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Supporting Information
Cobalt-Catalyzed C–H Cyanation of (Hetero)arenes and 6-Arylpurines with N-Cyanosuccinimide as a New Cyanating
Agent
Amit B. Pawar†,‡ and Sukbok Chang*†,‡
† Center for Catalytic Hydrocarbon Functionalizations, Institute for Basic Science (IBS), Daejeon, 305-701,
Republic of Korea, Email: [email protected]
‡ Department of Chemistry, Korea Advanced Institute of Science & Technology (KAIST), Daejeon 305-701,
Republic of Korea
Table of Content S-1
1. General Methods S-2
2. General Procedures for the Preparation of Starting Materials S-2
3. Experimental Procedure of the Optimization Study S-6
4. Experimental Procedure of the Co-Catalyzed C‒H Cyanation
4.1. General Procedure for the Co-Catalyzed C‒H Cyanation with N-
cyanosuccinimide
4.2. Spectroscopic Data of Cyanated Compounds Obtained in this Study
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5. H/D Exchange Experiment S-24
6. Kinetic Isotope Effect Study S-25
7. References S-26
8. Appendix
Copies of 1H and 13C NMR Spectral Data of Compounds Obtained in this Study
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Crystallographic Data of 3j, 5g and 7b S-86
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1. General Methods
Unless otherwise stated, all commercial reagents and solvents were used without additional purification. Analytical thin layer chromatography (TLC) was performed on pre-coated silica gel 60 F254 plates. Visualization on TLC was achieved by the use of UV light (254 nm). Column chromatography was undertaken on silica gel (400‒630mesh) using a proper eluent system. 1H NMR was recorded on Agilent Technologies DD2 (600 MHz). Chemical shifts were quoted in parts per million (ppm) referenced to the appropriate solvent peak or 0.0 ppm for tetramethylsilane. The following abbreviations were used to describe peak splitting patterns when appropriate: br = broad, s = singlet, d = doublet, t = triplet, q = quartet, quin = quintet, sext = sextet, sep = septet, dd = doublet of doublet, td = triplet of doublet, ddd = doublet of doublet of doublet, m = multiplet. Coupling constants, J, were reported in hertz unit (Hz). 13C NMR was recorded on Agilent Technologies DD2 (150 MHz) and was fully decoupled by broad band proton decoupling. Chemical shifts were reported in ppm referenced to the center of a triplet at 77.0 ppm of chloroform-d. Infrared (IR) spectra were recorded using diamond ATR module of ALPHA FT-IR Spectrometer from Bruker Co., Ltd. Frequencies are given in reciprocal centimeters (cm-1) and only selected absorbance peaks are reported. High resolution mass spectra were obtained from the Korea Basic Science Institute (Daegu) by using EI method. Materials were obtained from commercial suppliers or prepared according to standard procedures unless otherwise noted. Cp*Co(CO)I2 was synthesized according to the literature.S1 Various N-cyanoimidesS2 were prepared according to the literature procedure. 2-PhenylpyridineS3 substrates were prepared according to reported procedure.
2. General Procedure for the Preparation of Starting Materials
2.1. General Procedure for the Preparation of Arylpyridines
To a solution of arylboronic acid (2.6 mmol) in toluene (7.0 mL), H2O (7.0 mL), ethanol (2.0 mL), Pd(PPh3)4 (0.069 g, 0.06 mmol), Na2CO3 (1.6 g, 15 mmol), and 2-bromopyridine (0.19 mL, 2.0 mmol) were added under argon atmosphere. The reaction mixture was allowed to stir at 95 °C for 18 h, and then cooled to room temperature. Saturated NH4Cl solution (15 mL) was added and the aqueous mixture was extracted with EtOAc (25 mL x 3). The combined organic extracts were dried over Na2SO4, and concentrated under reduced pressure. The crude product
S-3
was purified by silica gel column chromatography with n-hexane/EtOAc to give the desired 2-arylpyridines.
2.2. Preparation of 2-[4-(1,3-dioxolan-2-yl)phenyl]pyridine (1d)(S4)
A two-neck round bottom flask equiped with Dean-Stark distillation apparatus was charged with 4-(pyridin-2-yl)benzaldehyde (0.37 g, 2.0 mmol) and p-toluenesulfonic acid monohydrate (76 mg, 20 mol%). Benzene (20 mL) and ethylene glycol (0.22 mL, 4.0 mmol) were added, and refluxed for 36 h. The reaction mixture was then cooled to room temperature, evaporated under reduced pressure, and poured into saturated aqueous NaHCO3 solution. The water phase was extracted with CH2Cl2 (20 mL x 3) and the combined organic phase was dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (EtOAc/n-hexane, 3:7) to furnish 1d as white solid (0.30 g, 63%).
2.3. Preparation of (E)-ethyl 3-[4-(pyridin-2-yl)phenyl]acrylate (1f)
To a slurry of NaH (0.12 g of 60% suspension in mineral oil, 3.0 mmol) in dry THF (6.0 mL) was added triethyl phosphonoacetate (0.60 mL, 3.0 mmol) dropwise at -15 °C and stirred at same temperature for 30 min. A solution of 4-(pyridin-2-yl)benzaldehyde (0.37 g, 2.0 mmol) in THF (6.0 mL) was introduced into the reaction mixture and stirred at the same temperature for 30 min. It was warmed to room temperature and stirred for another 30 min. After completion of the reaction (TLC), it was quenched with sat. NH4Cl solution (15 mL) and extracted with EtOAc (2 x 20 mL). Combined organic layers were washed with brine (25 mL) and dried over Na2SO4. Evaporation of solvent and then silica gel column chromatography (EtOAc/n-hexane, 3:7) of the residue yielded 1f (0.37 g, 73%) as white solid; m.p. 84 – 85 °C; 1H NMR (600 MHz, CDCl3) δ 8.73 – 8.68 (m, 1H), 8.04 (d, J = 8.3 Hz, 2H), 7.79 – 7.75 (m, 2H), 7.73 (d, J = 16.1 Hz, 1H), 7.64 (d, J = 8.3 Hz, 2H), 7.28 – 7.22 (m, 1H), 6.50 (d, J = 16.0 Hz, 1H), 4.28 (q, J = 7.1 Hz, 2H), 1.35 (t, J = 7.1 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 166.9, 156.4, 149.8, 143.9, 141.0, 136.8, 135.0, 128.5, 127.3, 122.5, 120.6, 118.7, 60.5, 14.3; IR (diamond) 3070, 2985, 1710, 1628, 1581, 1466, 1176, 984, 775 cm-1; HRMS (EI) m/z calcd. for C16H15NO2 [M]+: 253.1103, found: 253.1102.
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2.4. Preparation of 4-(pyridin-2-yl)benzyl acetate (1ga)
To a solution of [4-(pyridin-2-yl)phenyl]methanol (0.26 g, 1.4 mmol) in CH2Cl2 (2.0 mL) were added triethylamine (0.40 mL, 2.8 mmol) and acetic anhydride (Ac2O, 1.0 mL) at room temperature. After stirring for 12 h, the reaction mixture was quenched with water (20 mL). and extracted with CH2Cl2 (20 mL x 2). The comdined organic layers were washed with brine (20 mL) and dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was further purified by silica gel column chromatography (EtOAc/n-hexane, 2:8) to furnish 1ga as colourless liquid (0.25 g, 80%); 1H NMR (600 MHz, CDCl3) δ 8.70 (d, J = 4.8 Hz, 1H), 7.99 (d, J = 7.9 Hz, 2H), 7.77 – 7.68 (m, 2H), 7.46 (d, J = 7.8 Hz, 2H), 7.27 – 7.20 (m, 1H), 5.16 (s, 2H), 2.12 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 170.8, 156.9, 149.6, 139.3, 136.8, 136.7, 128.5, 127.1, 122.2, 120.5, 65.9, 21.0; IR (diamond) 3285, 2950, 1734, 1587, 1466, 1435, 1376, 1224, 1016, 776 cm-1; HRMS (EI) m/z calcd. for C14H13NO2 [M]+: 227.0946, found: 227.0944.
2.5. Preparation of 2-{4-[(tert-butyldimethylsilyloxy)methyl]phenyl}pyridine (1gb)
To a solution of [4-(pyridin-2-yl)phenyl]methanol (0.37 g, 2.0 mmol) in CH2Cl2 (4.0 mL) were added imidazole (0.27 g, 4.0 mmol), TBDMSCl (0.45 g, 3.0 mmol) and DMAP (50 mg, 20 mol %) at room temperature. After stirring for 12 h, the reaction mixture was quenched with water (20 mL). The organic layer was separated and aqueous phase was extracted with CH2Cl2 (20 mL x 2). The comdined organic layers were washed with brine (20 mL), dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (EtOAc/n-hexane, 1:9) to afford 1gb as white solid (0.50 g, 83%); m.p. 72 – 73 °C; 1H NMR (600 MHz, CDCl3) δ 8.68 (d, J = 4.9 Hz, 1H), 7.96 (d, J = 8.1 Hz, 2H), 7.81 – 7.64 (m, 2H), 7.43 (d, J = 8.0 Hz, 2H), 7.24 – 7.15 (m, 1H), 4.80 (s, 2H), 0.96 (s, 9H), 0.11 (s, 6H); 13C NMR (150 MHz, CDCl3) δ 157.4, 149.6, 142.4, 138.1, 136.6, 126.8, 126.4, 121.9, 120.4, 64.8, 25.9, 18.4, -5.2; IR (diamond) 2953, 2925, 2882, 2852, 1585, 1466, 1434, 1296, 1252, 1207, 1083, 833, 775 cm-1; HRMS (EI) m/z calcd. for C18H25NOSi [M]+: 299.1705, found: 299.1704.
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2.6. Preparation of 2-{4-[(methoxymethoxy)methyl]phenyl}pyridine (1gc)
To a solution of [4-(pyridin-2-yl)phenyl]methanol (0.30 g, 1.6 mmol) in CH2Cl2 (4.0 mL) were added diisopropylethylamine (0.56 mL, 3.2 mmol), DMAP (40 mg, 20 mol%) and MOMCl (0.18 mL, 3.3 mmol) at 0 °C. After stirring for 15 min at the same temperature, the recation mixture was refluxed for 5 h. After completion of the reaction, it was cooled to room temperature and quenched with water (20 mL). The organic layer was separated. The aqueous phase was extracted with CH2Cl2 (20 mL x 2). The comdined organic layers were washed brine (20 mL), dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (EtOAc/n-hexane, 1:9) to afford 1gc as colorless oil (0.27 g, 74%); 1H NMR (600 MHz, CDCl3) δ 8.69 (d, J = 4.6 Hz, 1H), 7.99 (d, J = 8.0 Hz, 2H), 7.78 – 7.70 (m, 2H), 7.47 (d, J = 8.0 Hz, 2H), 7.25 – 7.19 (m, 1H), 4.74 (s, 2H), 4.66 (s, 2H), 3.43 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 157.2, 149.7, 138.8, 138.7, 136.7, 128.2, 126.9, 122.1, 120.5, 95.7, 68.8, 55.4; IR (diamond) 2929, 2881, 1586, 1561, 1434, 1376, 1210, 1147, 1099, 1042, 775 cm-1; HRMS (EI) m/z calcd. for C14H15NO2 [M]+: 229.1103, found: 229.1100.
2.7. Preparation of 2-{4-[(4-methoxybenzyloxy)methyl]phenyl}pyridine (1gd)
To a solution of [4-(pyridin-2-yl)phenyl]methanol (0.15 g, 0.81 mmol) in dry DMF (4 mL) were added NaH (48 mg of 60% suspension in mineral oil, 1.2 mmol), Bu4NI (30 mg, 10 mol%) and PMBCl (98 μL, 0.97 mmol) at 0 °C. After stirring for 15 min at the same temperature, the reaction mixture was warmed to room temperature. After stirring for 12 h, the reaction mixture was quenched with water (20 mL) and extracted with CH2Cl2 (20 mL x 2). The combined organic layers were wased with brine (20 mL), dried over Na2SO, and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (EtOAc/n-hexane, 1:9) to afford 1gd as colourless liquid (0.16 g, 63%); 1H NMR (600 MHz, CDCl3) δ 8.71 – 8.67 (m, 1H), 7.98 (d, J = 8.2 Hz, 2H), 7.78 – 7.70 (m, 2H), 7.47 (d, J = 8.2 Hz, 2H), 7.32 – 7.28 (m, 2H), 7.25 – 7.20 (m, 1H), 6.93 – 6.86 (m, 2H), 4.59 (s, 2H), 4.51 (s, 2H), 3.81 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 159.2, 157.2, 149.6, 139.2, 138.7, 136.7, 130.3, 129.4, 128.1, 126.9, 122.1, 120.5, 113.8, 71.8, 71.4, 55.3; IR (diamond) 3003, 2854, 2834, 1610, 1585, 1561, 1244, 1078, 1030, 775 cm-1; HRMS (EI) m/z calcd. for C20H19NO2 [M]+: 305.1416, found: 305.1418.
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3. Experimental Procedure of the Optimization Study
To a screw capped vial with a spinvane triangular-shaped Teflon stirbar were added 2-phenylpyridine (1a, 15.5 mg, 0.10 mmol), cyanating agent (2a-2d, 0.15 mmol), catalyst, Ag salt, additive, and solvent (0.5 mL) under argon atmosphere. The reaction mixture was stirred
in a pre-heated oil bath at 120 C for 12 h. The reaction mixture was cooled to room temperature, filtered through a pad of celite and then washed with EtOAc (10 mL x 3). Solvents were removed under reduced pressure and crude yield was measured by 1H NMR using an internal standard (1,1,2,2-tetrachloroethane).
Table S1. Optimization of the Co-Catalyzed C−H Cyanation Reaction
Entry Catalyst (mol %) Ag salt (mol %)
CN source
Additives (mol %)
Solvent Yield (%)a
1 Cp*Co(CO)I2 (10) AgNTf2 (20) 2a - 1,2-DCE 31
2 Cp*Co(CO)I2 (10) AgNTf2 (20) 2a K2CO3 (20) 1,2-DCE 31
3 Cp*Co(CO)I2 (10) AgNTf2 (20) 2a Na2CO3 (20) 1,2-DCE 25
4 Cp*Co(CO)I2 (10) AgNTf2 (20) 2a Li2CO3 (20) 1,2-DCE 40
5 Cp*Co(CO)I2 (10) AgNTf2 (20) 2a Ag2CO3 (20) 1,2-DCE 22
6 Cp*Co(CO)I2 (10) AgNTf2 (20) 2a KOAc (20) 1,2-DCE 60
7 Cp*Co(CO)I2 (10) AgNTf2 (20) 2a NaOAc (20) 1,2-DCE 58
8 Cp*Co(CO)I2 (10) AgNTf2 (20) 2a CsOAc (20) 1,2-DCE 57
9 Cp*Co(CO)I2 (10) AgNTf2 (20) 2a LiOAc (20) 1,2-DCE 57
10 Cp*Co(CO)I2 (10) AgNTf2 (20) 2a Cu(OAc)2 (20) 1,2-DCE 25
11 Cp*Co(CO)I2 (10) AgNTf2 (20) 2a AgOAc (20) 1,2-DCE 66
12 Cp*Co(CO)I2 (10) AgNTf2 (20) 2b AgOAc (20) 1,2-DCE 42
13 Cp*Co(CO)I2 (10) AgNTf2 (20) 2c AgOAc (20) 1,2-DCE 74
14 Cp*Co(CO)I2 (10) AgNTf2 (20) 2d AgOAc (20) 1,2-DCE 80(74)
15b Cp*Co(CO)I2 (10) AgNTf2 (20) 2d AgOAc (20) 1,2-DCE 72
16c Cp*Co(CO)I2 (10) AgNTf2 (20) 2d AgOAc (20) 1,2-DCE 57
17 Cp*Co(CO)I2 (10) AgNTf2 (20) 2d AgOTf (20) 1,2-DCE 23
18 Cp*Co(CO)I2 (10) AgNTf2 (20) 2d AgOTs (20) 1,2-DCE 29
19 Cp*Co(CO)I2 (10) AgNTf2 (20) 2d AgOAc (20) 1,4-Dioxane 67
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20 Cp*Co(CO)I2 (10) AgNTf2 (20) 2d AgOAc (20) THF 60
21 Cp*Co(CO)I2 (10) AgNTf2 (20) 2d AgOAc (20) Acetone 38
22 Cp*Co(CO)I2 (10) AgNTf2 (20) 2d AgOAc (20) o-Xylene 30
23 Cp*Co(CO)I2 (10) AgNTf2 (20) 2d AgOAc (20) DMF N.R.
24 Cp*Co(CO)I2 (10) AgSbF6 (20) 2d AgOAc (20) 1,2-DCE 61
25 Cp*Co(CO)I2 (5) AgNTf2 (10) 2d AgOAc (10) 1,2-DCE 67
26 - AgNTf2 (20) 2d AgOAc (20) 1,2-DCE N.R.
27 Cp*Co(CO)I2 (10) - 2d AgOAc (20) 1,2-DCE N.R.
28 Co(OAc)2 (10) AgNTf2 (20) 2d AgOAc (20) 1,2-DCE N.R.
29 Co(acac)3 (10) AgNTf2 (20) 2d AgOAc (20) 1,2-DCE N.R.
30 Co(TPP) (10) AgNTf2 (20) 2d AgOAc (20) 1,2-DCE N.R.
Reaction conditions: 1a (0.10 mmol), 2a–2d (0.15 mmol), catalyst, additive and solvent (0.5 mL) at the 120 C
for 12 h. a NMR yields are given and isolated yield is shown in parenthesis. b Reaction carried out at 110 C. c Run for 9 h. N.R. = no reaction.
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4. Experimental Procedure of the Co-Catalyzed C‒H Cyanation
4.1. General Procedure for the Co-Catalyzed C‒H Cyanation with N-Cyanosuccinimide
To a screw capped vial with a spinvane triangular-shaped Teflon stirbar were added arene (0.10 mmol), N-cyanosuccinimide (2d, 18.6 mg, 0.15 mmol), Cp*Co(CO)I2 (4.8 mg, 10 mol %), AgNTf2 (7.8 mg, 20 mol %), AgOAc (3.3 mg, 20 mol %), and 1,2-dichloroethane (0.5
mL) under argon atmosphere. The reaction mixture was stirred at 120 C for 12 h, cooled to room temerature, filtered through a pad of celite and then washed with EtOAc (10 mL x 3). The organic layer was washed with 1N NaOH (15 mL) followed by H2O (15 mL), dried over Na2SO4 and filtered. Solvents were removed under reduced pressure and the residue was purified by column chromatography on silica gel (n-hexane/EtOAc) to give the desired cyanated product.
4.2. Spectroscopic Data of Cyanated Compounds Obtained in this Study.
2-(Pyridin-2-yl)benzonitrile (Scheme 2, 3aa)S5
White solid; m.p. 47 – 48 °C; 1H NMR (600 MHz, CDCl3) δ 8.81 – 8.75 (m, 1H), 7.86 – 7.82 (m, 2H), 7.82 – 7.77 (m, 2H), 7.70 (td, J = 7.7, 1.4 Hz, 1H), 7.51 (td, J = 7.7, 1.1 Hz, 1H), 7.36 (ddd, J = 7.4, 4.8, 1.1 Hz, 1H); 13C NMR (150 MHz, CDCl3) δ 155.2, 149.9, 143.4, 136.7, 134.1, 132.8, 129.9, 128.7, 123.3, 123.2, 118.6, 111.0.
5-Methyl-2-(pyridin-2-yl)benzonitrile (Scheme 2, 3ab)S5
White solid; m.p. 76 – 77 °C; 1H NMR (600 MHz, CDCl3) δ 8.76 (d, J = 4.5 Hz, 1H), 7.82 (td, J = 7.7, 1.8 Hz, 1H), 7.79 – 7.70 (m, 2H), 7.60 (brs, 1H), 7.49 (d, J = 7.8 Hz, 1H), 7.34 (dd, J = 7.4, 4.8 Hz, 1H), 2.44 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 155.2, 149.7, 140.5, 139.1, 136.8, 134.4, 133.7, 129.9, 123.11, 123.09, 118.8, 110.8, 20.8.
5-(tert-Butyl)-2-(pyridin-2-yl)benzonitrile (Scheme 2, 3ac)S6
Colorless liquid; 1H NMR (600 MHz, CDCl3) δ 8.76 (d, J = 4.4 Hz, 1H), 7.83 (td, J = 7.7, 1.8 Hz, 1H), 7.81 – 7.76 (m, 3H), 7.71 (dd, J = 8.3, 2.1 Hz, 1H), 7.34 (ddd, J = 7.5, 4.9, 1.3 Hz,
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1H), 1.37 (s, 9H); 13C NMR (150 MHz, CDCl3) δ 155.2, 152.4, 149.8, 140.5, 136.8, 131.1, 130.2, 129.7, 123.08, 123.07, 119.2, 110.6, 34.8, 31.0.
4-(Pyridin-2-yl)-[1,1'-biphenyl]-3-carbonitrile (Scheme 2, 3ad)S5
White solid; m.p. 68 – 69 °C; 1H NMR (600 MHz, CDCl3) δ 8.80 (d, J = 4.8 Hz, 1H), 8.02 (d, J = 1.9 Hz, 1H), 7.95 (d, J = 8.1 Hz, 1H), 7.91 (dd, J = 8.1, 1.9 Hz, 1H), 7.89 – 7.83 (m, 2H), 7.63 (d, J = 7.6 Hz, 2H), 7.51 (t, J = 7.6 Hz, 2H), 7.44 (t, J = 7.4 Hz, 1H), 7.40 – 7.35 (m, 1H); 13C NMR (150 MHz, CDCl3) δ 154.8, 149.9, 142.0, 141.8, 138.3, 136.9, 132.6, 131.4, 130.5, 129.1, 128.5, 127.0, 123.3, 123.2, 118.7, 111.5.
5-(Dimethylamino)-2-(pyridin-2-yl)benzonitrile (Scheme 2, 3ae)
Colorless solid; m.p. 77 – 78 °C; 1H NMR (600 MHz, CDCl3) δ 8.73 – 8.64 (m, 1H), 7.81 – 7.68 (m, 3H), 7.24 (ddd, J = 6.7, 4.9, 1.8 Hz, 1H), 7.00 (d, J = 2.8 Hz, 1H), 6.95 (dd, J = 8.8, 2.8 Hz, 1H), 3.04 (s, 6H); 13C NMR (150 MHz, CDCl3) δ 155.5, 149.9, 149.6, 136.5, 130.7, 130.4, 122.4, 122.0, 119.7, 116.5, 116.0, 111.3, 40.1; IR (diamond) 3002, 2916, 2895, 2223, 1602, 1543, 1468, 1369, 1230, 989, 789 cm-1; HRMS (EI) m/z calcd. for C14H13N3 [M]+: 223.1109, found: 223.1109.
5-(Methylthio)-2-(pyridin-2-yl)benzonitrile (Scheme 2, 3af)
White solid; m.p. 50 – 51 °C; 1H NMR (600 MHz, CDCl3) δ 8.76 (d, J = 4.3 Hz, 1H), 7.83 (td, J = 7.7, 1.8 Hz, 1H), 7.79 – 7.75 (m, 2H), 7.58 (d, J = 2.1 Hz, 1H), 7.52 (dd, J = 8.3, 2.1 Hz, 1H), 7.39 – 7.30 (m, 1H), 2.55 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 154.6, 149.7, 141.0, 139.3, 137.0, 130.5, 130.2, 130.1, 123.2, 123.0, 118.4, 111.5, 15.3; IR (diamond) 3048, 2987, 2918, 2225, 1589. 1565, 1460, 1182, 780 cm-1; HRMS (EI) m/z calcd. for C13H10N2S [M]+: 226.0565, found: 226.0567.
5-Methoxy-2-(pyridin-2-yl)benzonitrile (Scheme 2, 3ba)S5
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White solid; m.p. 105 – 106 °C; 1H NMR (600 MHz, CDCl3) δ 8.75 (d, J = 4.6 Hz, 1H), 7.86 – 7.72 (m, 3H), 7.32 (ddd, J = 7.4, 4.8, 1.2 Hz, 1H), 7.27 (d, J = 2.7 Hz, 1H), 7.22 (dd, J = 8.7, 2.7 Hz, 1H), 3.89 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 159.6, 154.9, 149.6, 136.9, 135.8, 131.4, 122.9, 122.8, 119.4, 118.6, 118.5, 111.8, 55.7.
5-(Benzyloxy)-2-(pyridin-2-yl)benzonitrile (Scheme 2, 3bb)S6
White solid; m.p. 84 – 85 °C; 1H NMR (600 MHz, CDCl3) δ 8.75 (d, J = 4.6 Hz, 1H), 7.86 – 7.69 (m, 3H), 7.47 – 7.40 (m, 4H), 7.39 – 7.34 (m, 2H), 7.32 (dd, J = 7.4, 4.9 Hz, 1H), 7.29 (dd, J = 8.7, 2.7 Hz, 1H), 5.15 (s, 2H); 13C NMR (150 MHz, CDCl3) δ 158.7, 154.9, 149.7, 136.8, 136.2, 135.7, 131.4, 128.8, 128.4, 127.5, 122.9, 122.8, 120.2, 119.6, 118.5, 111.8, 70.5.
5-Phenoxy-2-(pyridin-2-yl)benzonitrile (Scheme 2, 3bc)
White solid; m.p. 45 – 46 °C; 1H NMR (600 MHz, CDCl3) δ 8.76 (d, J = 4.7 Hz, 1H), 7.85 – 7.80 (m, 2H), 7.78 (d, J = 7.9 Hz, 1H), 7.42 (t, J = 7.9 Hz, 2H), 7.36 – 7.29 (m, 3H), 7.23 (t, J = 7.4 Hz, 1H), 7.08 (d, J = 8.0 Hz, 2H); 13C NMR (150 MHz, CDCl3) δ 158.1, 155.4, 154.7, 149.8, 137.7, 136.9, 131.7, 130.2, 124.8, 123.1, 123.0, 122.7, 122.6, 119.8, 118.1, 112.1; IR (diamond) 3053, 3008, 2985, 2227, 1584, 142, 1225, 951, 788 cm-1; HRMS (EI) m/z calcd. for C18H12N2O [M]+: 272.0950, found: 272.0946.
3-Cyano-N,N-dimethyl-4-(pyridin-2-yl)benzamide (Scheme 2, 3ca)
White solid; m.p. 94 – 95 °C; 1H NMR (600 MHz, CDCl3) δ 8.79 (d, J = 5.4 Hz, 1H), 7.91 (d, J = 8.1 Hz, 1H), 7.89 – 7.85 (m, 2H), 7.81 (d, J = 7.9 Hz, 1H), 7.75 (dd, J = 8.0, 1.7 Hz, 1H), 7.40 (dd, J = 7.5, 4.8 Hz, 1H), 3.15 (s, 3H), 3.03 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 168.9, 154.4, 150.0, 144.3, 136.9, 132.7, 131.4, 130.2, 123.7, 123.2, 117.9, 111.3, 39.5, 35.5; IR (diamond) 3051, 2922, 2852, 2229, 1620, 1582, 1400, 1170, 794 cm-1; HRMS (EI) m/z calcd. for C15H13N3j [M]+: 251.1059, found: 251.1058.
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5-Acetyl-2-(pyridin-2-yl)benzonitrile (Scheme 2, 3cb)
White solid; m.p. 102 – 103 °C; 1H NMR (600 MHz, CDCl3) δ 8.81 (d, J = 4.8 Hz, 1H), 8.37 (brs, 1H), 8.24 (d, J = 8.2 Hz, 1H), 7.99 (d, J = 8.2 Hz, 1H), 7.93 – 7.81 (m, 2H), 7.44 – 7.39 (m, 1H), 2.68 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 195.5, 154.0, 150.1, 146.8, 137.0, 136.9, 134.2, 132.1, 130.5, 124.0, 123.4, 117.9, 111.7, 26.6; IR (diamond) 3075, 3059, 2924, 2226, 1684, 1570, 1466, 1259, 785 cm-1; HRMS (EI) m/z calcd. for C14H10N2O [M]+: 222.0793, found: 222.0794.
Methyl 3-cyano-4-(pyridin-2-yl)benzoate (Scheme 2, 3cc)S5
White solid; m.p. 91 – 92 °C; 1H NMR (600 MHz, CDCl3) δ 8.81 (dt, J = 4.8, 1.3 Hz, 1H), 8.47 (d, J = 1.8 Hz, 1H), 8.33 (dd, J = 8.2, 1.8 Hz, 1H), 7.96 (d, J = 8.2 Hz, 1H), 7.88 (td, J = 7.6, 1.8 Hz, 1H), 7.86 – 7.82 (m, 1H), 7.41 (ddd, J = 7.3, 4.8, 1.4 Hz, 1H), 3.99 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 165.0, 154.2, 150.1, 147.0, 136.9, 135.4, 133.5, 130.7, 130.5, 123.9, 123.4, 117.8, 111.5, 52.7.
5-(1,3-Dioxolan-2-yl)-2-(pyridin-2-yl)benzonitrile (Scheme 2, 3d)
White solid; m.p. 103 – 104 °C; 1H NMR (600 MHz, CDCl3) δ 8.78 (d, J = 4.5 Hz, 1H), 7.93 (s, 1H), 7.90 – 7.81 (m, 2H), 7.81 – 7.76 (m, 2H), 7.36 (dd, J = 7.5, 4.8 Hz, 1H), 5.90 (s, 1H), 4.17 – 4.04 (m, 4H); 13C NMR (150 MHz, CDCl3) δ 154.9, 150.0, 143.9, 139.4, 136.1, 132.2, 130.9, 130.1, 123.4, 123.2, 118.5, 111.1, 102.1, 65.4; IR (diamond) 2958, 2893, 2850, 2226, 1589, 1470, 1098, 947, 785 cm-1; HRMS (EI) m/z calcd. for C15H12N2O2 [M]+: 252.0899, found: 252.0896.
2-(Pyridin-2-yl)-5-(trifluoromethyl)benzonitrile (Scheme 2, 3e)S7
S-12
White solid; m.p. 65 – 66 °C; 1H NMR (600 MHz, CDCl3) δ 8.82 (d, J = 4.7 Hz, 1H), 8.07 (brs, 1H), 8.03 (d, J = 8.2 Hz, 1H), 7.94 (d, J = 8.2 Hz, 1H), 7.90 (td, J = 7.7, 1.7 Hz, 1H), 7.84 (d, J = 7.8 Hz, 1H), 7.43 (dd, J = 7.5, 4.8 Hz, 1H); 13C NMR (150 MHz, CDCl3) δ 153.7, 150.2, 146.5, 137.0, 131.3 (q, J C-F = 33.9 Hz), 131.0 (d, J C-F = 3.8 Hz), 130.7, 129.4 (q, J C-F = 3.6 Hz), 124.1, 123.3, 122.9 (d, J C-F = 271.3 Hz), 117.3, 111.9.
(E)-Ethyl 3-(3-cyano-4-(pyridin-2-yl)phenyl)acrylate (Scheme 2, 3f)
White solid; m.p. 138 – 139 °C; 1H NMR (600 MHz, CDCl3) δ 8.79 (dt, J = 4.8, 1.3 Hz, 1H), 7.93 (d, J = 1.8 Hz, 1H), 7.91 (d, J = 8.2 Hz, 1H), 7.86 (td, J = 7.6, 1.8 Hz, 1H), 7.84 – 7.81 (m, 2H), 7.69 (d, J = 16.0 Hz, 1H), 7.38 (ddd, J = 7.3, 4.8, 1.3 Hz, 1H), 6.54 (d, J = 16.0 Hz, 1H), 4.30 (q, J = 7.1 Hz, 2H), 1.36 (t, J = 7.1 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 166.1, 154.4, 150.0, 144.2, 141.3, 136.9, 135.3, 133.5, 131.7, 130.6, 123.6, 123.1, 121.2, 118.1, 111.8, 60.9, 14.2; IR (diamond) 3076, 2986, 2873, 2223, 1712, 1634, 1465, 1181, 783 cm-1; HRMS (EI) m/z calcd. for C17H14N2O2 [M]+: 278.1055, found: 278.1056.
3-Cyano-4-(pyridin-2-yl)benzyl acetate (Scheme 2, 3ga)
N
CNO
O White solid; m.p. 44 – 45 °C; 1H NMR (600 MHz, CDCl3) δ 8.78 (d, J = 4.2 Hz, 1H), 7.88 – 7.83 (m, 2H), 7.81 – 7.77 (m, 2H), 7.69 – 7.63 (m, 1H), 7.37 (ddd, J = 7.5, 4.9, 1.2 Hz, 1H), 5.18 (s, 2H), 2.15 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 170.5, 154.7, 150.0, 143.1, 137.2, 136.8, 133.3, 132.3, 130.2, 123.4, 123.1, 118.4, 111.3, 64.6, 20.8; IR (diamond) 3048, 2992, 2921, 2229, 1739, 1586, 1249, 1027, 751 cm-1; HRMS (EI) m/z calcd. for C15H12N2O2 [M]+: 252.0899, found: 252.0898.
5-[(tert-Butyldimethylsilyloxy)methyl]-2-(pyridin-2-yl)benzonitrile (Scheme 2, 3gb)
White solid; m.p. 40 – 41 °C; 1H NMR (600 MHz, CDCl3) δ 8.77 (d, J = 4.8 Hz, 1H), 7.86 – 7.74 (m, 4H), 7.62 (d, J = 8.1 Hz, 1H), 7.35 (ddd, J = 7.4, 4.9, 1.2 Hz, 1H), 4.81 (s, 2H), 0.96 (s, 9H), 0.13 (s, 6H); 13C NMR (150 MHz, CDCl3) δ 155.2, 149.9, 142.7, 142.0, 136.7, 131.4, 130.3, 129.9, 123.16, 123.13, 118.9, 110.8, 63.7, 25.9, 18.4, -5.3; IR (diamond) 2951, 2927,
S-13
2855, 2223, 1585, 1460, 1252, 1088, 833, 774 cm-1; HRMS (EI) m/z calcd. for C19H24N2OSi [M]+: 324.1658, found: 324.1655.
5-[(Methoxymethoxy)methyl]-2-(pyridin-2-yl)benzonitrile (Scheme 2, 3gc)
Pale yellow oil; 1H NMR (600 MHz, CDCl3) δ 8.79 – 8.75 (m, 1H), 7.86 – 7.75 (m, 4H), 7.67 (dd, J = 8.1, 1.8 Hz, 1H), 7.36 (ddd, J = 7.5, 4.8, 1.2 Hz, 1H), 4.75 (s, 2H), 4.68 (s, 2H), 3.43 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 155.0, 149.9, 142.6, 139.4, 136.8, 132.9, 131.8, 130.0, 123.3, 123.2, 118.6, 111.1, 96.0, 67.7, 55.6; IR (diamond) 2928, 2886, 2225, 1586, 1463, 1214, 1044, 789 cm-1; HRMS (EI) m/z calcd. for C15H14N2O2 [M]+: 254.1055, found: 254.1056.
5-[(4-Methoxybenzyloxy)methyl]-2-(pyridin-2-yl)benzonitrile (Scheme 2, 3gd)
Pale yellow oil; 1H NMR (600 MHz, CDCl3) δ 8.77 (dt, J = 4.8, 1.3 Hz, 1H), 7.85 – 7.81 (m, 2H), 7.81 – 7.77 (m, 2H), 7.66 (dd, J = 8.1, 1.7 Hz, 1H), 7.35 (ddd, J = 7.5, 4.8, 1.2 Hz, 1H), 7.33 – 7.28 (m, 2H), 6.95 – 6.86 (m, 2H), 4.59 (s, 2H), 4.54 (s, 2H), 3.82 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 159.4, 155.1, 149.9, 142.6, 139.8, 136.8, 132.9, 131.8, 130.0, 129.6, 129.5, 123.3, 123.2, 118.7, 114.0, 111.0, 72.3, 70.2, 55.3; IR (diamond) 2854, 2835, 2224, 1610, 1511, 1244, 1085, 789 cm-1; HRMS (EI) m/z calcd. for C21H18N2O2 [M]+: 330.1368, found: 330.1366.
3-(Pyridin-2-yl)-2-naphthonitrile (Scheme 2, 3h)S5
White solid; m.p. 154 – 155 °C; 1H NMR (600 MHz, CDCl3) δ 8.82 (d, J = 4.8 Hz, 1H), 8.39 (s, 1H), 8.28 (s, 1H), 7.99 – 7.90 (m, 2H), 7.86 (d, J = 4.2 Hz, 2H), 7.72 – 7.58 (m, 2H), 7.42 – 7.33 (m, 1H); 13C NMR (150 MHz, CDCl3) δ 155.5, 149.9, 137.7, 136.8, 136.1, 134.6, 131.8, 129.7, 129.4, 128.5, 128.04, 128.02, 123.3, 123.1, 118.9, 108.8.
S-14
5-Chloro-2-(pyridin-2-yl)benzonitrile (Scheme 2, 3ia)S7
White solid; m.p. 165 – 166 °C; 1H NMR (600 MHz, CDCl3) δ 8.78 (d, J = 4.9 Hz, 1H), 7.88 – 7.76 (m, 4H), 7.67 (dd, J = 8.5, 2.2 Hz, 1H), 7.44 – 7.34 (m, 1H); 13C NMR (150 MHz, CDCl3) δ 154.0, 150.0, 141.7, 137.0, 135.0, 133.6, 133.2, 131.3, 123.6, 123.1, 117.4, 112.5.
5-Bromo-2-(pyridin-2-yl)benzonitrile (Scheme 2, 3ib)S6
White solid; m.p. 145 – 146 °C; 1H NMR (600 MHz, CDCl3) δ 8.78 (d, J = 4.3 Hz, 1H), 7.93 (d, J = 2.0 Hz, 1H), 7.86 (td, J = 7.8, 1.7 Hz, 1H), 7.82 (dd, J = 8.5, 2.0 Hz, 1H), 7.81 – 7.78 (m, 1H), 7.77 – 7.73 (m, 1H), 7.39 (dd, J = 7.5, 4.8 Hz, 1H); 13C NMR (150 MHz, CDCl3) δ 154.1, 150.0, 142.1, 137.0, 136.4, 136.1, 131.4, 123.6, 123.1, 122.6, 117.3, 112.7.
5-Fluoro-2-(pyridin-2-yl)benzonitrile (Scheme 2, 3ic)S5,7
White solid; m.p. 133 – 134 °C; 1H NMR (600 MHz, CDCl3) δ 8.77 (d, J = 4.9 Hz, 1H), 7.89 – 7.81 (m, 2H), 7.77 (d, J = 7.9 Hz, 1H), 7.50 (dd, J = 8.1, 2.6 Hz, 1H), 7.41 (td, J = 8.3, 2.7 Hz, 1H), 7.37 (dd, J = 7.5, 4.9 Hz, 1H); 13C NMR (150 MHz, CDCl3) δ 162.0 (d, J C-F = 251.9 Hz), 154.2, 149.9, 139.9, 136.9, 132.1 (d, J C-F = 8.5 Hz), 123.4, 123.1, 120.7 (d, J C-F = 24.8 Hz), 120.5 (d, J C-F = 21.2 Hz), 117.4 (d, J C-F = 2.4 Hz), 112.5 (d, J C-F = 9.4 Hz).
5-(Methylsulfonyl)-2-(pyridin-2-yl)benzonitrile (Scheme 2, 3j)
Colorless solid; m.p. 130 – 131 °C; 1H NMR (600 MHz, CDCl3) δ 8.83 (d, J = 4.7 Hz, 1H), 8.38 (d, J = 1.9 Hz, 1H), 8.24 (dd, J = 8.3, 1.9 Hz, 1H), 8.10 (d, J = 8.3 Hz, 1H), 7.91 (td, J = 7.7, 1.8 Hz, 1H), 7.87 (d, J = 7.9 Hz, 1H), 7.45 (ddd, J = 7.5, 4.8, 1.2 Hz, 1H), 3.14 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 153.3, 150.3, 148.0, 141.2, 137.2, 133.2, 131.3, 124.4, 123.5, 116.9, 112.5, 44.5; IR (diamond) 3058, 3012, 2919, 2236, 1709, 1144, 765 cm-1; HRMS (EI) m/z calcd. for C13H10N2O2S [M]+: 258.0463, found: 258.0466.
S-15
4-Methoxy-2-(pyridin-2-yl)benzonitrile (Scheme 2, 3ka)S6
White solid; m.p. 70 – 71 °C; 1H NMR (600 MHz, CDCl3) δ 8.77 (dt, J = 4.8, 1.3 Hz, 1H), 7.87 – 7.79 (m, 2H), 7.71 (d, J = 8.6 Hz, 1H), 7.41 – 7.32 (m, 2H), 7.01 (dd, J = 8.6, 2.6 Hz, 1H), 3.92 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 162.8, 155.2, 149.9, 145.6, 136.8, 135.7, 123.4, 123.3, 119.1, 115.1, 115.0, 102.7, 55.7.
4-Methyl-2-(pyridin-2-yl)benzonitrile (Scheme 2, 3kb)S5
White solid; m.p. 59 – 60 °C; 1H NMR (600 MHz, CDCl3) δ 8.77 (dt, J = 4.9, 1.3 Hz, 1H), 7.83 (td, J = 7.6, 1.8 Hz, 1H), 7.81 – 7.77 (m, 1H), 7.71 – 7.65 (m, 2H), 7.35 (ddd, J = 7.4, 4.8, 1.3 Hz, 1H), 7.31 (dd, J = 7.9, 1.7 Hz, 1H), 2.48 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 155.4, 149.9, 143.8, 143.3, 136.7, 134.0, 130.7, 129.5, 123.3, 123.2, 118.9, 108.0, 21.8.
4-Acetyl-2-(pyridin-2-yl)benzonitrile (Scheme 2, 3kc)S8
N
CN
O
White solid; m.p. 131 – 132 °C; 1H NMR (600 MHz, CDCl3) δ 8.81 (dt, J = 4.8, 1.3 Hz, 1H), 8.41 (d, J = 1.7 Hz, 1H), 8.06 (dd, J = 8.1, 1.7 Hz, 1H), 7.92 (d, J = 8.0 Hz, 1H), 7.88 (td, J = 7.7, 1.8 Hz, 1H), 7.86 – 7.83 (m, 1H), 7.41 (ddd, J = 7.4, 4.8, 1.2 Hz, 1H), 2.70 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 196.5, 154.3, 150.1, 144.0, 140.0, 137.0, 134.5, 129.6, 127.9, 123.7, 123.2, 117.9, 114.8, 26.8.
2-(5-Acetylpyridin-2-yl)benzonitrile (Scheme 2, 3l)
White solid; m.p. 121 – 122 °C; 1H NMR (600 MHz, CDCl3) δ 9.31 (d, J = 2.3 Hz, 1H), 8.38 (dd, J = 8.2, 2.2 Hz, 1H), 7.92 – 7.87 (m, 2H), 7.84 (dd, J = 7.7, 1.3 Hz, 1H), 7.74 (td, J = 7.7, 1.3 Hz, 1H), 7.57 (td, J = 7.7, 1.2 Hz, 1H), 2.70 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 196.2, 158.7, 150.0, 142.2, 136.5, 134.4, 132.9, 131.5, 130.1, 129.6, 123.0, 118.4, 111.3, 26.8; IR
S-16
(diamond) 3280, 3213, 3090, 3063, 2954, 1728, 1632, 1587, 1524, 1475, 1442, 1215, 1077, 1021, 942 cm-1; HRMS (EI) m/z calcd. for C14H10N2O [M]+: 222.0793, found: 222.0793.
2-(4-Methylpyridin-2-yl)benzonitrile (Scheme 2, 3ma)S6
White solid; m.p. 55 – 56 °C; 1H NMR (600 MHz, CDCl3) δ 8.62 (d, J = 5.0 Hz, 1H), 7.82 (dd, J = 7.9, 1.2 Hz, 1H), 7.79 (dd, J = 7.8, 1.3 Hz, 1H), 7.68 (td, J = 7.7, 1.4 Hz, 1H), 7.59 (brs, 1H), 7.50 (td, J = 7.6, 1.3 Hz, 1H), 7.20 – 7.15 (m, 1H), 2.45 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 155.1, 149.7, 148.0, 143.7, 134.0, 132.7, 129.9, 128.6, 124.3, 124.1, 118.7, 111.1, 21.2.
2-(5-Methylpyridin-2-yl)benzonitrile (Scheme 2, 3mb)S6
White solid; m.p. 79 – 80 °C; 1H NMR (600 MHz, CDCl3) δ 8.60 (brs, 1H), 7.83 (dd, J = 8.0, 1.2 Hz, 1H), 7.79 (dd, J = 7.8, 1.4 Hz, 1H), 7.71 – 7.61 (m, 3H), 7.48 (td, J = 7.6, 1.3 Hz, 1H), 2.42 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 152.5, 150.4, 143.5, 137.2, 134.0, 133.1, 132.7, 129.8, 128.4, 122.7, 118.8, 110.9, 18.3.
2-(1H-Pyrazol-1-yl)benzonitrile (Scheme 2, 3n)S7
Colorless oil; 1H NMR (600 MHz, CDCl3) δ 8.15 (d, J = 2.6 Hz, 1H), 7.83 – 7.76 (m, 3H), 7.74 – 7.68 (m, 1H), 7.43 (t, J = 7.6 Hz, 1H), 6.55 (brs, 1H); 13C NMR (150 MHz, CDCl3) δ 142.2, 142.0, 134.4, 134.0, 129.5, 127.2, 124.3, 116.9, 108.5, 105.3.
2-(Pyrimidin-2-yl)benzonitrile (Scheme 2, 3o)S5
Colorless solid; m.p. 138 – 139 °C; 1H NMR (600 MHz, CDCl3) δ 8.93 (d, J = 4.8 Hz, 2H), 8.38 (d, J = 7.9 Hz, 1H), 7.86 (d, J = 7.7 Hz, 1H), 7.72 (t, J = 7.6 Hz, 1H), 7.58 (t, J = 7.6 Hz,
S-17
1H), 7.34 (t, J = 4.8 Hz, 1H); 13C NMR (150 MHz, CDCl3) δ 162.9, 157.3, 140.3, 135.1, 132.5, 130.4, 130.2, 120.1, 118.9, 111.9.
Benzo[h]quinoline-10-carbonitrile (Scheme 2, 3p)S5
White solid; m.p. 133 – 134 °C; 1H NMR (600 MHz, CDCl3) δ 9.14 (dd, J = 4.3, 1.8 Hz, 1H), 8.22 (dd, J = 8.1, 1.7 Hz, 1H), 8.16 (d, J = 7.3 Hz, 1H), 8.12 (d, J = 8.0 Hz, 1H), 7.83 (d, J = 8.8 Hz, 1H), 7.79 (d, J = 8.8 Hz, 1H), 7.73 (t, J = 7.7 Hz, 1H), 7.63 (dd, J = 8.0, 4.3 Hz, 1H); 13C NMR (150 MHz, CDCl3) δ 148.5, 144.5, 136.2, 135.7, 134.1, 132.7, 130.8, 127.4, 127.2, 127.1, 127.0, 123.0, 120.7, 109.1. 2-(Pyridin-2-yl)thiophene-3-carbonitrile (Scheme 3, 5a)
White solid; m.p. 72 – 73 °C; 1H NMR (600 MHz, CDCl3) δ 8.64 (d, J = 4.6 Hz, 1H), 8.24 (d, J = 8.0 Hz, 1H), 7.83 (td, J = 7.8, 1.8 Hz, 1H), 7.43 (d, J = 5.3 Hz, 1H), 7.35 – 7.28 (m, 2H); 13C NMR (150 MHz, CDCl3) δ 153.6, 149.8, 149.6, 137.3, 130.8, 127.7, 123.9, 120.1, 115.9, 105.9; IR (diamond) 311, 2921, 2851, 2224, 1578, 1462, 947, 782 cm-1; HRMS (EI) m/z calcd. for C10H6N2S [M]+: 186.0252, found: 186.0249.
3-(Pyridin-2-yl)thiophene-2-carbonitrile (Scheme 3, 5ba)
White solid; m.p. 38 – 39 °C; 1H NMR (600 MHz, CDCl3) δ 8.75 – 8.70 (m, 1H), 7.95 (d, J = 7.9 Hz, 1H), 7.82 (td, J = 7.7, 1.8 Hz, 1H), 7.69 (d, J = 5.0 Hz, 1H), 7.62 (d, J = 5.2 Hz, 1H), 7.36 – 7.30 (m, 1H); 13C NMR (150 MHz, CDCl3) δ 150.9, 150.0, 149.9, 137.1, 131.7, 128.3, 123.6, 121.9, 114.7, 106.2; IR (diamond) 3079, 2921, 2850, 2209, 1582, 1463, 1150, 990 cm-1; HRMS (EI) m/z calcd. for C10H6N2S [M]+: 186.0252, found: 186.0251.
2-(Pyridin-2-yl)furan-3-carbonitrile (Scheme 3, 5bb)
Pale yellow solid; m.p. 81 – 82 °C; 1H NMR (600 MHz, CDCl3) δ 8.76 (d, J = 4.8 Hz, 1H), 7.91 (d, J = 7.9 Hz, 1H), 7.83 (td, J = 7.8, 1.8 Hz, 1H), 7.55 (d, J = 2.0 Hz, 1H), 7.34 (dd, J =
S-18
7.5, 4.8 Hz, 1H), 6.76 (d, J = 1.9 Hz, 1H); 13C NMR (150 MHz, CDCl3) δ 158.5, 150.2, 146.8, 143.2, 136.9, 124.1, 120.1, 114.3, 114.0, 94.8; IR (diamond) 3115, 2922, 2227, 1505, 1216, 887 cm-1; HRMS (EI) m/z calcd. for C10H6N2O [M]+: 170.0480, found: 170.0478.
1-(Pyrimidin-2-yl)-1H-pyrrole-2-carbonitrile (Scheme 3, 5c)S9
White solid; m.p. 118 – 119 °C; 1H NMR (600 MHz, CDCl3) δ 8.75 (d, J = 4.8 Hz, 2H), 7.99 (dd, J = 3.1, 1.7 Hz, 1H), 7.23 (t, J = 4.8 Hz, 1H), 7.09 (dd, J = 3.7, 1.7 Hz, 1H), 6.38 (t, J = 3.4 Hz, 1H); 13C NMR (150 MHz, CDCl3) δ 158.6, 155.1, 126.1, 125.0, 118.8, 114.0, 111.8, 102.9.
2-(Pyridin-2-yl)benzo[b]thiophene-3-carbonitrile (Scheme 3, 5da)
White solid; m.p. 159 – 160 °C; 1H NMR (600 MHz, CDCl3) δ 8.74 – 8.67 (m, 1H), 8.43 (d, J = 8.0 Hz, 1H), 8.00 (d, J = 8.0 Hz, 1H), 7.92 – 7.85 (m, 2H), 7.56 – 7.51 (m, 1H), 7.51 – 7.46 (m, 1H), 7.41 – 7.33 (m, 1H); 13C NMR (150 MHz, CDCl3) δ 155.0, 150.0, 149.7, 139.5, 138.3, 137.3, 126.7, 126.0, 124.6, 122.8, 122.6, 121.2, 115.1, 101.9; IR (diamond) 3056, 2921, 2851, 2218, 1582, 1431, 991, 753 cm-1; HRMS (EI) m/z calcd. for C14H8N2S [M]+: 236.0408, found: 236.0409.
2-(Pyridin-2-yl)benzofuran-3-carbonitrile (Scheme 3, 5db)
White solid; m.p. 126 – 127 °C; 1H NMR (600 MHz, CDCl3) δ 8.85 (d, J = 4.2 Hz, 1H), 8.11 (d, J = 7.9 Hz, 1H), 7.89 (td, J = 7.8, 1.7 Hz, 1H), 7.80 (d, J = 7.6 Hz, 1H), 7.64 (d, J = 8.2 Hz, 1H), 7.48 (td, J = 7.8, 1.4 Hz, 1H), 7.45 – 7.38 (m, 2H); 13C NMR (150 MHz, CDCl3) δ 159.9, 153.9, 150.4, 146.8, 137.0, 127.19, 127.16, 124.97, 124.95, 121.3, 120.5, 113.7, 112.1, 91.2; IR (diamond) 2921, 2851, 2224, 1777, 1452, 1158, 742 cm-1; HRMS (EI) m/z calcd. for C14H8N2O [M]+: 220.0637, found: 220.0636.
S-19
4-(Pyridin-2-yl)dibenzo[b,d]thiophene-3-carbonitrile (Scheme 3, 5ea)
Colorless; m.p. 141 – 142 °C; 1H NMR (600 MHz, CDCl3) δ 8.91 – 8.88 (m, 1H), 8.26 (d, J = 8.1 Hz, 1H), 8.24 – 8.20 (m, 1H), 8.01 (d, J = 7.9 Hz, 1H), 7.94 (td, J = 7.7, 1.8 Hz, 1H), 7.90 – 7.85 (m, 2H), 7.58 – 7.49 (m, 2H), 7.49 – 7.42 (m, 1H); 13C NMR (150 MHz, CDCl3) δ 154.3, 149.6, 142.3, 140.1, 139.8, 138.4, 137.1, 134.1, 129.5, 128.4, 124.9, 124.5, 123.9, 122.7, 122.5, 121.5, 119.0, 108.4; IR (diamond) 2919, 2850, 2214, 1583, 1373, 758 cm-1; HRMS (EI) m/z calcd. for C18H10N2S [M]+: 286.0565, found: 286.0563.
4-(Pyridin-2-yl)dibenzo[b,d]furan-3-carbonitrile (Scheme 3, 5eb)
White solid; m.p. 138 – 139 °C; 1H NMR (600 MHz, CDCl3) δ 8.91 (brs, 1H), 8.06 (d, J = 8.0 Hz, 1H), 8.04 (d, J = 7.8 Hz, 1H), 8.01 – 7.97 (m, 1H), 7.95 (td, J = 7.6, 1.7 Hz, 1H), 7.81 (d, J = 8.0 Hz, 1H), 7.63 – 7.60 (m, 1H), 7.59 – 7.53 (m, 1H), 7.49 – 7.40 (m, 2H); 13C NMR (150 MHz, CDCl3) δ 157.4, 153.0, 151.2, 149.9, 136.8, 129.2, 128.9, 128.7, 128.3, 125.5, 123.8, 123.7, 122.8, 121.5, 121.0, 118.7, 112.3, 109.7; IR (diamond) 3057, 2923, 2219, 1628, 1405, 1192, 750 cm-1; HRMS (EI) m/z calcd. for C18H10N2O [M]+: 270.0793, found: 270.0791.
1-(Pyridin-2-yl)-1H-indole-2-carbonitrile (Scheme 3, 5fa)S10
White solid; m.p. 74 – 75 °C; 1H NMR (600 MHz, CDCl3) δ 8.70 (dd, J = 5.0, 1.9 Hz, 1H), 7.96 (td, J = 7.8, 1.9 Hz, 1H), 7.78 (d, J = 8.5 Hz, 1H), 7.71 (d, J = 8.0 Hz, 1H), 7.60 (d, J = 8.1 Hz, 1H), 7.46 – 7.40 (m, 2H), 7.40 – 7.37 (m, 1H), 7.31 – 7.27 (m, 1H); 13C NMR (150 MHz, CDCl3) δ 149.7, 149.6, 138.8, 137.1, 126.9, 126.8, 122.8, 122.7, 122.3, 118.8, 117.3, 113.7, 112.2, 109.0.
S-20
1-(Pyrimidin-2-yl)-1H-indole-2-carbonitrile (Scheme 3, 5fb)S10
White solid; m.p. 121 – 122 °C; 1H NMR (600 MHz, CDCl3) δ 8.81 (d, J = 5.0 Hz, 2H), 8.67 (d, J = 8.5 Hz, 1H), 7.66 (d, J = 8.0 Hz, 1H), 7.48 (t, J = 7.8 Hz, 1H), 7.46 – 7.43 (m, 1H), 7.31 (t, J = 7.6 Hz, 1H), 7.24 – 7.17 (m, 1H); 13C NMR (150 MHz, CDCl3) δ 158.2, 156.4,
136.4, 127.6, 127.4, 123.4, 121.9, 120.8, 117.9, 116.0, 114.1, 108.8.
4-Oxo-1-(pyrimidin-2-yl)-4,5,6,7-tetrahydro-1H-indole-2-carbonitrile (Scheme 3, 5g)
Colorless solid; m.p. 216 – 218 °C; 1H NMR (600 MHz, CDCl3) δ 8.86 (d, J = 4.8 Hz, 2H), 7.42 (s, 1H), 7.39 (t, J = 4.9 Hz, 1H), 3.27 (t, J = 6.3 Hz, 2H), 2.57 (t, J = 6.3 Hz, 2H), 2.27 – 2.10 (m, 2H); 13C NMR (150 MHz, CDCl3) δ 193.4, 158.7, 155.3, 148.0, 122.9, 121.0, 120.0, 113.7, 105.6, 37.7, 25.3, 23.2; IR (diamond) 3228, 2955, 2923, 2216, 1678, 1410, 1215, 824 cm-1; HRMS (EI) m/z calcd. for C13H10N4O [M]+: 238.0855, found: 238.0853.
2-(9-Phenyl-9H-purin-6-yl)benzonitrile (Scheme 4, 7a)
White solid; m.p. 198 – 200 °C; 1H NMR (600 MHz, CDCl3) δ 9.22 (s, 1H), 8.48 (d, J = 7.8 Hz, 1H), 8.45 (s, 1H), 7.94 (d, J = 7.6 Hz, 1H), 7.81 (t, J = 7.7 Hz, 1H), 7.77 (d, J = 7.8 Hz, 2H), 7.69 – 7.59 (m, 3H), 7.53 (t, J = 7.5 Hz, 1H); 13C NMR (150 MHz, CDCl3) δ 153.7, 153.0, 152.3, 144.3, 138.1, 134.9, 134.1, 132.5, 132.0, 131.9, 130.3, 130.0, 128.8, 123.7, 118.3, 112.4; IR (diamond) 3095, 3083, 3048, 2923, 2223, 1590, 1507, 1331, 1182, 927, 755 cm-1; HRMS (EI) m/z calcd. for C18H11N5 [M]+: 297.1014, found: 297.1011.
S-21
2-(9-Ethyl-9H-purin-6-yl)benzonitrile (Scheme 4, 7b)
Colorless solid; m.p. 165 – 166 °C; 1H NMR (600 MHz, CDCl3) δ 9.16 (s, 1H), 8.45 (d, J = 7.9 Hz, 1H), 8.20 (s, 1H), 7.92 (d, J = 7.7 Hz, 1H), 7.78 (t, J = 7.7 Hz, 1H), 7.62 (t, J = 7.7 Hz, 1H), 4.42 (q, J = 7.4 Hz, 2H), 1.63 (t, J = 7.4 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 153.0, 152.4, 152.2, 144.8, 138.3, 134.9, 132.4, 132.0, 131.5, 130.1, 118.4, 112.3, 39.2, 15.3; IR (diamond) 2968, 2923, 2223, 1577, 1324, 1214, 958, 770 cm-1; HRMS (EI) m/z calcd. for C14H11N5 [M]+: 249.1014, found: 249.1013.
2-(9-Butyl-9H-purin-6-yl)benzonitrile (Scheme 4, 7c)
White solid; m.p. 94 – 95 °C; 1H NMR (600 MHz, CDCl3) δ 9.15 (s, 1H), 8.46 (d, J = 7.9 Hz, 1H), 8.17 (s, 1H), 7.92 (d, J = 7.7 Hz, 1H), 7.78 (t, J = 7.7 Hz, 1H), 7.62 (t, J = 7.7 Hz, 1H), 4.36 (t, J = 7.3 Hz, 2H), 1.97 (quin, J = 7.4 Hz, 2H), 1.42 (sext, J = 7.4 Hz, 2H), 1.00 (t, J = 7.4 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 153.0, 152.6, 152.2, 145.3, 138.3, 134.9, 132.4, 132.0, 131.4, 130.1, 118.4, 112.2, 43.9, 31.9, 19.9, 13.5; IR (diamond) 2957, 2925, 2871, 2217, 1576, 1328, 1208, 760 cm-1; HRMS (EI) m/z calcd. for C16H15N5 [M]+: 277.1327, found: 277.1325.
2-(9-Benzyl-9H-purin-6-yl)benzonitrile (Scheme 4, 7d)
N
N
N
N
CN
Ph
White solid; m.p. 155 – 157 °C; 1H NMR (600 MHz, CDCl3) δ 9.19 (s, 1H), 8.46 (d, J = 7.8 Hz, 1H), 8.14 (s, 1H), 7.91 (d, J = 7.7 Hz, 1H), 7.77 (t, J = 7.7 Hz, 1H), 7.61 (t, J = 7.6 Hz, 1H), 7.43 – 7.31 (m, 5H), 5.52 (s, 2H); 13C NMR (150 MHz, CDCl3) δ 153.1, 152.6, 152.5, 145.1, 138.1, 135.0, 134.8, 132.4, 132.0, 131.3, 130.2, 129.2, 128.7, 127.9, 118.4, 112.3, 47.52.; IR (diamond) 3054, 2921, 2221, 1580, 1501, 1213, 765 cm-1; HRMS (EI) m/z calcd. for C19H13N5 [M]+: 311.1171, found: 311.1169
S-22
2-(9-Isopropyl-9H-purin-6-yl)-5-methoxybenzonitrile (Scheme 4, 7e)
White solid; m.p. 116 – 118 °C; 1H NMR (600 MHz, CDCl3) δ 9.10 (s, 1H), 8.52 (d, J = 8.8 Hz, 1H), 8.20 (s, 1H), 7.40 (d, J = 2.7 Hz, 1H), 7.32 – 7.25 (m, 1H), 5.00 (sep, J = 6.8 Hz, 1H), 3.92 (s, 3H), 1.70 (d, J = 6.8 Hz, 6H).; 13C NMR (150 MHz, CDCl3) δ 160.6, 152.7, 152.0, 151.8, 142.6, 133.7, 131.4, 130.7, 120.1, 118.5, 113.3, 55.8, 47.6, 22.5; IR (diamond) 3107, 2922, 2850, 2226, 1601, 1181, 1057, 802 cm-1; HRMS (EI) m/z calcd. for C16H15N5O [M]+: 293.1277, found: 293.1276.
5-Acetyl-2-(9-isopropyl-9H-purin-6-yl) (Scheme 4, 7f)
Yellow solid; m.p. 122 – 124 °C; 1H NMR (600 MHz, CDCl3) δ 9.17 (s, 1H), 8.63 (d, J = 8.2 Hz, 1H), 8.47 (d, J = 1.8 Hz, 1H), 8.31 (dd, J = 8.3, 1.9 Hz, 1H), 8.26 (s, 1H), 5.03 (sep, J = 6.8 Hz, 1H), 2.70 (s, 3H), 1.72 (d, J = 6.9 Hz, 6H); 13C NMR (150 MHz, CDCl3) δ 195.5, 152.4, 151.9, 151.6, 143.5, 141.9, 137.8, 134.7, 132.5, 132.0, 131.7, 117.7, 112.9, 47.8, 26.7, 22.5; IR (diamond) 2988, 2922, 2852, 2212, 1688, 1578, 1223, 934 cm-1; HRMS (EI) m/z calcd. for C17H15N5O [M]+: 305.1277, found: 305.1277.
5-Chloro-2-(9-isopropyl-9H-purin-6-yl) (Scheme 4, 7g)
White solid; m.p. 165 – 166 °C; 1H NMR (600 MHz, CDCl3) δ 9.13 (s, 1H), 8.51 (d, J = 8.5 Hz, 1H), 8.23 (s, 1H), 7.88 (d, J = 2.2 Hz, 1H), 7.74 (dd, J = 8.5, 2.2 Hz, 1H), 5.02 (sep, J =
S-23
6.9 Hz, 1H), 1.71 (d, J = 6.8 Hz, 6H); 13C NMR (150 MHz, CDCl3) δ 152.3, 151.9, 151.6, 143.2, 136.7, 136.4, 134.6, 133.3, 132.7, 131.7, 117.2, 113.7, 47.8, 22.5; IR (diamond) 3103, 3042, 2970, 2925, 2228, 1553, 1217, 934 cm-1; HRMS (EI) m/z calcd. for C15H12ClN5 [M]+: 297.0781, found: 297.0780.
2-(7-Isopropyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)benzonitrile (Scheme 4, 7h)
White solid; m.p. 141 – 143 °C; 1H NMR (600 MHz, CDCl3) δ 9.02 (s, 1H), 7.89 (dd, J = 7.5, 1.4 Hz, 2H), 7.75 (td, J = 7.6, 1.4 Hz, 1H), 7.60 (td, J = 7.4, 1.4 Hz, 1H), 7.42 (d, J = 3.7 Hz, 1H), 6.59 (d, J = 3.6 Hz, 1H), 5.21 (sep, J = 6.8 Hz, 1H), 1.57 (d, J = 6.8 Hz, 6H); 13C NMR (150 MHz, CDCl3) δ 154.6, 150.9, 150.9, 141.4, 134.4, 132.5, 130.5, 129.4, 126.2, 118.1, 116.9, 112.1, 99.7, 46.2, 22.7; IR (diamond) 2970, 2924, 2224, 1558, 1357, 1226, 924, 742 cm-1; HRMS (EI) m/z calcd. for C16H14N4 [M]+: 262.1218, found: 262.1218.
5. H/D
To a drie(18.5 mAgOAc under artemeratuorganic under reanalysis
Figure S
9.09.5
8.6
546
8.6
568
Exchang
ed screw camg, 0.10 mm
(3.3 mg, 2rgon atmospure, filteredlayer was w
educed pressof the crud
MeO
S1. Crude 1H
8.08.5
1.02
1.02
0.98
0.97
7.7
114
7.7
144
7.9
424
7.9
576
8.6
444
8.6
464
8.6
488
8.6
526
ge Experim
apped vial wmol), Cp*C20 mol%), phere. The r
d through a washed withsure and the
de mixture.
N
1ba
H NMR of
6.57.07.5
2.00
1.00
6.9
924
6.9
950
6.9
996
7.0
067
7.6
601
7.6
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7.7
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ment
with a spinvCo(CO)I2 (4CD3OD (16reaction mipad of celi
h brine (15e extents of
1
C
CD3OD
(4.0 equiv)
a H/D expe
5.56.0
S-24
vane triangu4.8 mg, 106 μL, 0.40 ixture was site and then
5 mL) and df deuterium
AgOAc (20 mol 1,2-DCE, 120 °C,
Cp*Co(CO)I 2 (10 mAgNTf2 (20 mo
eriment of 1
4.04.55.0f1 (ppm)
ular-shaped 0 mol %), A
mmol) andstirred at 12n washed wdried over Nincorporati
MeO%) 12 h
mol %)l %)
ba with CD
3.03.50
3.15
3.8
666
Teflon stirbAgNTf2 (7d 1,2-dichlo20 °C for 12with EtOAcNa2SO4. Soion was me
N
H/D
H/D
51% D
[D]n-1ba
D3jD.
12.02.5
bar were ad.8 mg, 20 oroethane (2 h, cooled c (10 mL xolvent was reasured by 1
51% D
0.51.0.5
dded 1ba mol %)
(0.5 mL) to room 3). The removed 1H NMR
-0.50.0
0.0
004
S-25
6. Kinetic Isotope Effect Study
6.1. Parallel Experiments
2-Phenylpyridine (1a) (15.5 mg, 0.10 mmol) or [D5]-2-phenylpyridine ([D5]-1a) (16.0 mg, 0.10 mmol) were added to two separate dried screw capped vials with a spinvane triangular-shaped Teflon stirbar along with N-cyanosuccinimide (2d) (18.6 mg, 0.15 mmol), Cp*Co(CO)I2 (10 mol %), AgNTf2 (20 mol %), AgOAc (20 mol%) and 1,2-dichloroethane (0.5 mL) under argon atmosphere. Each of the reaction mixture was stirred at 120 °C for 10 min. Then it was cooled to room temerature, filtered through a pad of silica and the silica pad was washed with EtOAc (10 mL x 2). The solvent was removed under reduced pressure and the residue was analyzed by 1H NMR by using 1,1,2,2-tetrachloroethane (0.10 mmol) as internal standard. Product yield of 3aa was 26% and that of [D4]-3aa was 24% leading to KIE value of 1.1.
6.2. Competitive experiment
To a dried screw capped vial with a spinvane triangular-shaped Teflon stirbar were added 2-phenylpyridine (1a) (15.5 mg, 0.10 mmol), [D5]-2-phenylpyridine ([D5]-1a) (16.0 mg, 0.10 mmol), N-cyanosuccinimide (2d) (37.2 mg, 0.30 mmol), Cp*Co(CO)I2 (10 mol %), AgNTf2 (20 mol %), AgOAc (20 mol%) and 1,2-dichloroethane (1.0 mL) under argon atmosphere. The reaction mixture was stirred at 120 °C for 100 min, cooled to room temerature, filtered through a pad of silica and then washed with EtOAc (15 mL x 2). Solvent was removed under reduced pressure and the residue was purified by column chromatography on silica gel (EtOAc/n-hexane, 3:7) to give a mixture of desired products 3aa + [D4]-3aa. The ratio of 3aa/[D4]-3aa was determined by 1H NMR analysis to give a KIE value of 1.2.
Figure Sand [D5]
7. Refe
(S1) (a)
(b)
Ino
(S2) Ste
(S3) (a)
Go
J.;
Y.
(S4) Ra
(S5) Ki
(S6) Xu
9.09.5
S2. 1H NMR]-2-phenylpy
erences
) Sun, B.; Y
) Frith, S. A
org. Chem.
ephens, R. W
) Grohmann
oodhue, C. E
Iwasawa, N
-X.; Li, J.-H
ao, M. L. N
im, J.; Chan
u, H.; Liu, P
8.08.50
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N
CN
3aa
54%
R of a mixtuyridine ([D5
Yoshino, T.
A.; Spencer
Commun. 2
W.; Domeie
n, C.; Wan
E.; Yu, J.-Q
N. J. Am. C
H. Eur. J. O
.; Dhanorka
ng, S. J. Am
P.-T.; Li, Y.
6.7.07.5
1.00
0.54
0.54
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7.4
971
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7.5
226
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826
7.6
877
7.6
958
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788
7.7
921
[D4]-3a
D
D
D
D
+
46%
ure of 3aa a]-1a) in one
; Matsunag
r, J. Inorg.
2004, 7, 117
er L. A. Syn
ng, H.; Glo
Q. J. Am. Ch
Chem. Soc.
Org. Chem. 2
ar, R. J. Eur
. Chem. Soc
.-H.; Han, F
5.56.0.5
7.2
673
7.3
500
7.3
580
7.3
624
N
CN
aa
S-26
and [D4]-3ae vessel.
ga, S.; Kana
Synth. 199
74.
nth. Commu
orius, F. O
hem. Soc. 2
2011, 133,
2007, 1457
r. J. Org. Ch
c. 2010, 132
F.-S. Org. L
44.55.0f1 (ppm)
aa from a re
ai, M. Adv. S
0, 28, 273.
un. 1991, 21
Org. Lett. 20
006, 128, 1
1251. (d)
.
hem. 2014,
2, 10272.
ett. 2013, 1
3.03.54.0
action of 2-
Synth. Cata
(c) Li, W.
, 2025.
013, 15, 30
2634. (c) M
Deng, C.-L
5214.
5, 3354.
12.02.5
-phenylpyrid
al. 2014, 35
; Weng, L.
014. (b) C
Mizuno, H.;
L.; Guo, S.-M
0.51.01.5
dine (1a)
56, 1491.
; Jin, G.
hen, X.;
Takaya,
M.; Xie,
-0.50.0
-0.0
003
S-27
(S7) Jin, J.; Wen, Q.; Lu, P.; Wang, Y. Chem. Commun. 2012, 9933.
(S8) Peng, J.; Zhao, J.; Hu, Z.; Liang, D.; Huang, J.; Zhu, Q. Org. Lett. 2012, 14, 4966.
(S9) Xu, S.; Huang, X.; Hong, X.; Xu, B. Org. Lett. 2012, 14, 4614.
(S10) Kou, X.; Zhao, M.; Qiao, X.; Zhu, Y.; Tong, X.; Shen, Z. Chem. Eur. J. 2013, 19, 16880.
S-29
(E)-Ethyl 3-(4-(pyridin-2-yl)phenyl)acrylate (1f)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
3.00
2.04
1.02
1.61
2.06
1.14
1.88
2.01
0.94
0.00
0
1.33
91.
351
1.36
3
4.26
44.
276
4.28
84.
300
6.49
06.
517
7.25
07.
254
7.25
77.
261
7.26
57.
268
7.63
17.
645
7.75
97.
762
8.02
98.
043
8.70
38.
705
8.70
88.
711
8.71
38.
715
0102030405060708090100110120130140150160170180190f1 (ppm)
14.3
3
60.5
4
76.7
9 c
dc
l377
.00
cd
cl3
77.2
1 c
dc
l3
118
.72
120.
57
122.
52
127.
29
128.
47
134.
99
136.
81
140.
97
143.
94
149.
82
156.
40
166.
92
NEtO
O 1f
S-30
4-(Pyridin-2-yl)benzyl acetate (1ga)
-0.0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
3.01
2.10
1.00
2.04
2.12
2.08
0.99
0.00
1
2.12
2
5.16
4
7.22
77.
236
7.23
97.
247
7.26
27.
457
7.47
07.
712
7.72
57.
736
7.73
97.
749
7.75
27.
762
7.76
57.
982
7.99
58.
698
8.70
6
0102030405060708090100110120130140150160170180190f1 (ppm)
20.9
7
65.9
1
76.7
9 c
dc
l377
.00
cd
cl3
77.2
1 c
dc
l3
120.
55
122.
23
127.
09
128.
53
136.
68
136.
78
139.
27
149.
65
156.
90
170.
80
S-31
2-{4-[(tert-Butyldimethylsilyloxy)methyl]phenyl}pyridine (1gb)
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0f1 (ppm)
5.90
9.20
2.12
1.00
2.01
2.05
2.04
0.95
-0.0
000.
115
0.95
5
4.80
3
7.19
47.
198
7.20
27.
205
7.20
97.
213
7.21
77.
255
7.42
27.
436
7.70
87.
719
7.72
27.
730
7.73
37.
956
7.96
9
8.67
88.
686
-100102030405060708090100110120130140150160170180190f1 (ppm)
-5.2
1
18.4
3
25.9
6
64.7
7
76.7
9 c
dc
l377
.00
cd
cl3
77.2
1 c
dc
l3
120.
37
121.
90
126.
39
126.
77
136.
64
138.
09
142.
35
149.
63
157.
40
S-32
2-{4-[(Methoxymethoxy)methyl]phenyl}pyridine (1gc)
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.04
2.17
2.13
1.04
2.12
2.16
2.13
1.00
-0.0
00
3.43
1
4.66
04.
736
7.21
47.
217
7.22
27.
225
7.22
87.
233
7.23
67.
260
7.46
27.
476
7.71
87.
732
7.74
47.
747
7.75
77.
760
7.98
27.
995
8.68
88.
695
0102030405060708090100110120130140150160170180190f1 (ppm)
55.3
9
68.8
4
76.7
9 c
dc
l377
.00
cd
cl3
77.2
1 c
dc
l3
95.7
4
120.
46
122.
07
126.
95
128.
16
136.
69
138.
72
138.
81
149.
67
157.
16
S-33
2-{4-[(4-Methoxybenzyloxy)methyl]phenyl}pyridine (1gd)
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
3.13
2.15
2.16
2.01
1.00
2.00
2.06
2.11
2.10
1.01
-0.0
00
3.81
1
4.51
14.
590
6.88
66.
891
6.89
46.
901
6.90
56.
910
7.29
67.
310
7.46
17.
474
7.72
97.
732
7.73
57.
975
7.98
9
8.68
48.
686
8.68
98.
692
8.69
48.
697
0102030405060708090100110120130140150160170180f1 (ppm)
55.2
7
71.4
471
.76
76.7
9 c
dc
l377
.00
cd
cl3
77.2
1 c
dc
l3
113
.82
120.
48
122.
05
126.
93
128.
1112
9.4
513
0.2
6
136.
71
138.
71
139.
23
149.
65
157.
22
159.
23
S-34
2-(Pyridin-2-yl)benzonitrile (3aa)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
1.05
1.08
1.09
2.08
2.10
1.00
0.0
002
7.2
682
7.3
493
7.3
511
7.3
574
7.3
592
7.3
617
7.3
635
7.3
699
7.3
716
7.4
963
7.4
982
7.5
090
7.5
108
7.5
218
7.5
237
7.6
817
7.6
840
7.6
946
7.6
969
7.7
074
7.7
097
7.7
790
7.7
921
7.7
970
7.7
993
7.8
100
7.8
123
7.8
264
7.8
293
7.8
394
7.8
421
7.8
526
7.8
551
8.7
745
8.7
762
8.7
783
8.7
826
8.7
843
8.7
863
0102030405060708090100110120130140150160170180190f1 (ppm)
76.7
888
cd
cl3
77.0
009
cd
cl3
77.2
128
cd
cl3
111
.00
79
118.
620
012
3.1
559
123.
264
9
128.
679
312
9.9
088
132.
758
413
4.0
566
136.
752
8
143.
419
2
149.
875
0
155.
183
2
122.2122.6123.0123.4123.824.2f1 (ppm)
123
.15
59
123
.26
49
S-35
5-Methyl-2-(pyridin-2-yl)benzonitrile (3ab)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.13
1.00
1.01
0.96
1.98
1.01
0.99
2.44
1
7.26
37.
327
7.33
57.
340
7.34
87.
488
7.50
17.
602
7.74
27.
755
7.76
47.
777
7.81
07.
813
7.82
37.
826
7.83
57.
838
8.75
88.
765
0102030405060708090100110120130140150160170180190f1 (ppm)
20.
845
76.
789
cd
cl3
77.
001
cd
cl3
77.
213
cd
cl3
110.
789
118.
827
123
.08
71
23.1
10
129
.87
31
33.7
24
134
.42
01
36.8
51
139
.13
41
40.5
48
149
.73
3
155
.16
5
123.00123.05123.10123.15123.20f1 (ppm)
123
.087
123
.110
S-36
5-(tert-Butyl)-2-(pyridin-2-yl)benzonitrile (3ac)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
9.04
1.00
1.03
2.95
1.01
1.05
1.36
8
7.26
37.
329
7.33
17.
337
7.33
97.
341
7.34
37.
349
7.35
17.
715
7.71
87.
780
7.78
77.
788
7.79
47.
798
7.83
0
8.76
08.
767
0102030405060708090100110120130140150160170180f1 (ppm)
30.
983
34.
807
76.
788
cd
cl3
77.
000
cd
cl3
77.
212
cd
cl3
110.
623
119.
202
123
.07
51
23.0
86
129
.72
31
30.1
99
131
.11
9
136
.82
5
140
.46
3
149
.77
81
52.3
62
155
.17
2
7.37.47.57.67.77.8f1 (ppm)
1.00
1.03
2.95
1.01
7.2
637
.329
7.3
317
.337
7.3
397
.341
7.3
437
.349
7.3
51
7.7
017
.705
7.7
157
.718
7.7
807
.787
7.7
887
.794
7.7
98
S-37
4-(Pyridin-2-yl)-[1,1'-biphenyl]-3-carbonitrile (3ad)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
1.03
1.03
2.15
2.14
2.09
1.09
1.09
1.00
1.04
7.26
37.
366
7.37
17.
375
7.38
07.
385
7.38
97.
426
7.43
87.
450
7.49
27.
505
7.51
87.
623
7.63
67.
847
7.85
67.
860
7.86
57.
868
7.87
87.
881
7.90
27.
906
7.91
67.
919
7.94
37.
957
8.02
08.
023
8.80
08.
808
0102030405060708090100110120130140150160170180190f1 (ppm)
76.
789
cd
cl3
77.
000
cd
cl3
77.
212
cd
cl3
111.
496
118.
732
123
.16
91
23.3
29
127
.03
51
28.5
26
129
.15
41
30.4
71
131
.38
61
32.5
96
136
.90
61
38.3
45
141
.79
21
41.9
78
149
.90
1
154
.85
3
S-38
5-(Dimethylamino)-2-(pyridin-2-yl)benzonitrile (3ae)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
6.15
1.04
0.98
1.00
3.02
0.96
-0.0
00
3.03
8
6.94
46.
949
6.95
96.
964
7.00
27.
007
7.23
07.
233
7.23
87.
241
7.24
47.
249
7.25
27.
264
7.72
77.
732
7.74
27.
745
7.74
77.
750
7.75
97.
762
8.70
58.
713
0102030405060708090100110120130140150160170180190f1 (ppm)
40.
118
76.
788
cd
cl3
77.
000
cd
cl3
77.
211
cd
cl3
111.
267
116.
032
116.
546
119.
729
122
.02
31
22.3
64
130
.45
51
30.7
08
136
.53
1
149
.59
51
49.8
91
155
.55
5
S-39
5-(Methylthio)-2-(pyridin-2-yl)benzonitrile (3af)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
3.07
1.00
1.01
0.95
2.02
1.06
1.02
2.54
7
7.26
47.
336
7.34
47.
346
7.34
97.
357
7.51
17.
515
7.52
57.
529
7.58
27.
586
7.77
27.
787
7.81
87.
821
7.83
17.
834
7.84
47.
847
8.75
68.
763
0102030405060708090100110120130140150160170180190f1 (ppm)
15.
292
76.
789
cd
cl3
77.
001
cd
cl3
77.
213
cd
cl3
111.
546
118.
410
122
.98
11
23.2
02
130
.07
81
30.2
48
130
.51
2
136
.98
31
39.3
09
141
.04
8
149
.72
5
154
.58
7
121122123124125126127128129130131f1 (ppm)
122.
981
123.
202
130.
078
130.
248
130.
512
S-40
5-Methoxy-2-(pyridin-2-yl)benzonitrile (3ba)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
3.02
1.00
0.93
1.01
3.05
1.04
3.88
8
7.21
17.
216
7.22
67.
230
7.26
37.
271
7.27
57.
312
7.31
47.
320
7.32
27.
325
7.32
77.
333
7.33
57.
754
7.76
77.
790
7.80
57.
808
7.81
87.
821
7.83
3
8.74
38.
751
0102030405060708090100110120130140150160170180f1 (ppm)
55.
747
76.
789
cd
cl3
77.
001
cd
cl3
77.
212
cd
cl3
111.
761
118.
530
118.
583
119.
380
122
.84
11
22.9
28
131
.40
01
35.8
00
136
.90
8
149
.62
3
154
.86
6
159
.60
2
118.4118.6118.8119.0119.2119.4f1 (ppm)
118.
530
118.
583
119.
380
122.6122.75122.85122.95123.05f1 (ppm)
122.
841
122.
928
S-41
5-(Benzyloxy)-2-(pyridin-2-yl)benzonitrile (3bb)
-0.0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
2.09
1.05
1.00
1.93
3.95
3.05
1.01
5.14
9
7.26
37.
278
7.28
27.
292
7.29
77.
309
7.31
77.
321
7.32
97.
348
7.35
37.
364
7.37
67.
403
7.41
67.
428
7.43
57.
447
7.45
07.
749
7.76
27.
784
7.79
97
.811
7.81
47.
824
7.82
7
8.74
28.
750
0102030405060708090100110120130140150160170180190f1 (ppm)
70.
526
76.
788
cd
cl3
77.
001
cd
cl3
77.
213
cd
cl3
111.
794
118.
543
119.
565
120
.17
41
22.8
45
122
.88
81
27.4
55
128
.38
81
28.7
59
131
.41
41
35.7
19
136
.16
21
36.8
20
149
.70
9
154
.89
1
158
.66
8
7.257.307.357.407.457.50f1 (ppm)
1.0
5
1.0
0
1.9
3
3.9
5
7.26
287.
2777
7.28
227.
2923
7.29
687.
3089
7.31
697.
3211
7.32
947.
3482
7.35
267.
3644
7.37
627.
4032
7.41
597.
4280
7.43
497.
4466
7.44
98
S-42
5-Phenoxy-2-(pyridin-2-yl)benzonitrile (3bc)
-0.0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0f1 (ppm)
1.96
1.00
2.98
1.96
1.02
2.05
1.00
7.07
67.
089
7.21
67.
229
7.24
17.
263
7.30
67.
311
7.32
17.
325
7.33
77.
341
7.34
57.
350
7.35
87.
410
7.42
37.
436
7.77
07.
783
7.81
47.
824
7.82
87.
834
7.83
7
8.75
88.
765
0102030405060708090100110120130140150160170180f1 (ppm)
76.7
88 c
dcl
377
.000
cd
cl3
77.2
12 c
dcl
3
112
.084
118
.148
119
.841
122.
616
122.
678
123.
008
123.
093
124.
841
130.
224
131.
669
136.
928
137.
743
149.
767
154.
664
155.
435
158.
106
S-43
3-Cyano-N,N-dimethyl-4-(pyridin-2-yl)benzamide (3ca)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
3.04
3.04
1.00
1.01
1.00
1.92
1.01
0.96
0.0
004
3.0
271
3.1
489
7.2
702
7.3
851
7.3
929
7.3
973
7.4
056
7.7
559
7.7
588
7.8
201
7.8
614
7.8
647
7.8
698
7.9
082
7.9
217
8.7
888
8.7
978
0102030405060708090100110120130140150160170180f1 (ppm)
35.4
857
39.4
719
76.7
881
cd
cl3
77.0
000
cd
cl3
77.2
117
cd
cl3
111
.31
22
117.
928
9
123.
246
712
3.6
815
130.
180
713
1.4
409
132.
718
113
6.9
444
144.
264
7
150.
054
5
154.
416
3
168.
897
3
S-44
5-Acetyl-2-(pyridin-2-yl)benzonitrile (3cb)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
3.16
1.02
2.08
1.09
1.06
1.00
1.07
2.67
7
7.26
47.
406
7.41
37.
416
7.41
87.
426
7.85
57.
871
7.88
47.
982
7.99
68.
236
8.25
08.
372
8.80
88.
816
0102030405060708090100110120130140150160170180190200210f1 (ppm)
26.
634
76.
789
cd
cl3
77.
001
cd
cl3
77.
212
cd
cl3
111.
670
117.
906
123
.40
11
23.9
92
130
.46
81
32.0
98
134
.22
61
36.9
52
137
.03
5
146
.84
61
50.1
06
154
.05
2
195
.53
6
S-45
Methyl 3-cyano-4-(pyridin-2-yl)benzoate (3cc)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
3.14
1.00
2.07
1.03
1.02
0.95
0.96
-0.0
00
3.9
90
7.2
667
.397
7.3
997
.405
7.4
077
.409
7.4
117
.417
7.4
197
.850
7.8
527
.952
7.9
66
8.3
228
.336
8.4
708
.473
8.8
028
.804
8.8
078
.810
8.8
128
.815
0102030405060708090100110120130140150160170180f1 (ppm)
52.
709
76.
788
cd
cl3
77.
000
cd
cl3
77.
212
cd
cl3
111.
481
117.
827
123
.38
91
23.9
19
130
.24
01
30.7
02
133
.53
91
35.3
58
136
.95
3
146
.96
01
50.1
33
154
.20
4
164
.97
3
S-46
5-(1,3-Dioxolan-2-yl)-2-(pyridin-2-yl)benzonitrile (3d)
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
4.13
0.96
1.00
1.96
2.02
0.96
0.99
0.00
1
4.05
74.
067
4.07
84.
084
4.09
04.
106
4.11
24.
120
4.12
44.
125
4.12
84.
133
4.14
44.
154
7.26
67.
354
7.36
27.
366
7.37
47.
780
7.79
37.
839
7.84
27.
865
7.87
87.
930
8.77
68.
784
0102030405060708090100110120130140150160170180f1 (ppm)
65.
419
76.
788
cd
cl3
77.
000
cd
cl3
77.
212
cd
cl3
102
.13
7
111.
088
118.
456
123
.24
01
23.4
21
130
.05
81
30.9
111
32.1
64
136
.81
51
39.3
91
143
.93
1
149
.97
2
154
.87
2
112114116118120122124126128130132f1 (ppm)
111.
088
118.
456
123.
240
123.
421
130.
058
130.
911
132.
164
S-47
2-(Pyridin-2-yl)-5-(trifluoromethyl)benzonitrile (3e)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
1.01
1.00
1.04
1.02
1.03
0.96
1.00
7.26
37.
422
7.43
07.
434
7.44
27.
850
7.89
57.
897
7.95
08.
020
8.03
48.
064
8.06
8
8.81
28.
820
0102030405060708090100110120130140150160170180f1 (ppm)
76.7
879
cd
cl3
77.0
001
cd
cl3
77.2
115
cd
cl3
111
.934
611
7.3
502
123.
309
712
4.06
38
129.
408
712
9.43
25
130.
724
313
0.98
41
131.
009
713
1.03
50
137.
040
8
146.
511
215
0.20
66
153.
751
9
7.27.37.47.57.67.77.87.98.08.1f1 (ppm)
1.01
1.00
1.04
1.02
1.03
0.96
7.2
63
7.4
227
.430
7.4
347
.442
7.8
377
.850
7.8
827
.885
7.8
957
.897
7.9
087
.910
7.9
367
.950
8.0
208
.034
8.0
648
.068
120121122123124125126f1 (ppm)
12
0.2
23
7
12
2.0
32
8
12
3.3
09
7
12
3.8
42
11
24.
06
38
12
5.6
51
4
129.0129.5130.0130.5131.0131.52.0f1 (ppm)
12
9.3
85
61
29.
40
87
12
9.4
32
51
29.
45
61
13
0.7
24
31
30.
95
54
13
0.9
84
11
31.
00
97
13
1.0
35
01
31.
06
06
13
1.1
80
41
31.
40
57
13
1.6
31
5
S-48
(E)-Ethyl 3-[3-cyano-4-(pyridin-2-yl)phenyl]acrylate (3f)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
3.12
2.12
1.05
1.00
1.06
2.08
1.05
1.02
1.02
0.97
0.00
0
1.34
61.
358
1.37
0
1.65
6
4.28
04.
292
4.30
44.
316
6.52
96.
555
7.26
77.
382
7.38
47.
386
7.39
27.
394
7.67
37.
700
7.83
27.
902
7.93
07.
933
8.78
58.
787
8.79
08.
793
8.79
68.
798
0102030405060708090100110120130140150160170180f1 (ppm)
14.
253
60.
872
76.
788
cd
cl3
77.
000
cd
cl3
77.
212
cd
cl3
111.
820
118.
107
121
.19
91
23.1
45
123
.63
3
130
.56
01
31.6
75
133
.46
91
35.2
63
136
.89
01
41.3
03
144
.19
1
150
.04
3
154
.36
4
166
.13
3
S-49
3-Cyano-4-(pyridin-2-yl)benzyl acetate (3ga)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
2.99
2.10
1.00
1.04
1.95
2.05
0.97
0.00
0
2.15
4
5.18
1
7.26
87.
357
7.35
97.
366
7.36
87.
370
7.37
27.
378
7.38
07.
677
7.79
57.
798
7.80
17.
844
7.84
77.
852
7.86
5
8.77
68.
783
0102030405060708090100110120130140150160170180190f1 (ppm)
20.
839
64.
569
76.
788
cd
cl3
77.
000
cd
cl3
77.
212
cd
cl3
111.
304
118.
370
123
.15
01
23.4
22
130
.211
132
.25
81
33.3
36
136
.83
31
37.2
04
143
.111
149
.97
1
154
.74
5
170
.51
5
S-50
5-[(tert-Butyldimethylsilyloxy)methyl]-2-(pyridin-2-yl)benzonitrile (3gb)
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
6.10
9.66
2.15
1.04
1.09
4.16
1.00
-0.0
000.
135
0.96
3
4.80
9
7.26
37.
334
7.33
67.
343
7.34
57.
347
7.34
97.
355
7.35
77.
618
7.63
27.
765
7.76
77.
777
7.79
07.
812
7.81
67.
819
7.82
57.
828
7.83
17.
841
7.84
48.
767
8.77
5
-100102030405060708090100110120130140150160170180f1 (ppm)
-5.3
01
18.
377
25.
888
63.
727
76.
788
cd
cl3
77.
000
cd
cl3
77.
211
cd
cl3
110.
847
118.
888
123
.14
51
23.1
69
129
.85
91
30.2
89
131
.37
7
136
.75
4
142
.02
61
42.7
43
149
.89
7
155
.20
9
123.00123.05123.10123.15123.20123.25f1 (ppm)
12
3.1
45
12
3.1
69
S-51
5-[(Methoxymethoxy)methyl]-2-(pyridin-2-yl)benzonitrile (3gc)
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
2.95
2.10
2.05
1.03
1.08
4.14
1.00
-0.0
00
3.43
2
4.67
84.
749
7.34
77.
349
7.35
57.
357
7.35
97.
361
7.36
77.
369
7.79
57.
811
7.81
47.
837
7.83
97.
852
8.77
18.
773
8.77
58.
779
8.78
18.
783
0102030405060708090100110120130140150160170180f1 (ppm)
55.
563
67.
669
76.
789
cd
cl3
77.
001
cd
cl3
77.
212
cd
cl3
95.
991
111.
070
118.
614
123
.17
11
23.3
02
130
.03
41
31.7
94
132
.88
21
36.8
08
139
.35
61
42.5
91
149
.92
9
154
.97
7
122122.7122.9123.1123.3123.5123.7f1 (ppm)
123.
171
123.
302
S-52
5-[(4-Methoxybenzyloxy)methyl]-2-(pyridin-2-yl)benzonitrile (3gd)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
3.04
2.12
2.14
2.04
2.05
1.05
1.10
2.04
2.11
1.00
-0.0
00
3.82
3
4.54
54.
591
6.90
86.
911
6.91
96.
922
7.26
17.
296
7.31
07.
788
7.79
07.
791
7.79
37.
826
7.83
9
8.76
88.
770
8.77
28.
776
8.77
88.
780
0102030405060708090100110120130140150160170180f1 (ppm)
55.
302
70.
208
72.
331
76.
788
cd
cl3
76.
999
cd
cl3
77.
211
cd
cl3
111.
031
113.
960
118.
667
123
.17
71
23.2
75
129
.48
61
29.6
46
130
.02
91
31.7
95
132
.88
81
36.7
94
139
.81
51
42.5
57
149
.93
4
155
.06
2
159
.45
2
123124125126127128129130131132133f1 (ppm)
123
.177
123
.275
129
.486
129
.646
130
.029
131
.795
132
.888
S-53
3-(Pyridin-2-yl)-2-naphthonitrile (3h)
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
1.00
1.02
1.02
1.98
2.08
1.00
0.99
0.98
0.00
1
7.26
27.
363
7.37
07.
378
7.38
57.
616
7.62
87.
641
7.66
07.
672
7.68
47.
861
7.86
87.
926
7.93
97.
950
7.96
48.
279
8.39
4
8.81
48.
822
0102030405060708090100110120130140150160170180f1 (ppm)
76.
788
cd
cl3
77.
000
cd
cl3
77.
212
cd
cl3
108
.77
7
118.
940
123
.06
71
23.3
03
128
.01
91
28.0
43
128
.53
41
29.4
30
129
.68
51
31.8
34
134
.56
81
36.5
13
136
.79
81
37.7
30
149
.90
2
155
.52
5
127.8127.9128.0128.1128.2128.3128.4128.5128.6128.7f1 (ppm)
128.
019
128.
043
128.
534
S-54
5-Chloro-2-(pyridin-2-yl)benzonitrile (3ia)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
1.00
0.98
1.85
1.98
1.02
7.26
37.
369
7.37
77.
381
7.38
97.
671
7.67
57.
774
7.77
97.
794
7.81
97.
834
7.85
3
8.77
38.
781
0102030405060708090100110120130140150160170180f1 (ppm)
76.
788
cd
cl3
77.
000
cd
cl3
77.
212
cd
cl3
112.
462
117.
386
123
.11
01
23.6
08
131
.32
31
33.1
59
133
.60
11
35.0
01
137
.01
81
41.7
26
149
.97
4
154
.05
3
S-55
5-Bromo-2-(pyridin-2-yl)benzonitrile (3ib)
-0.0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
1.00
1.02
1.00
0.98
1.00
0.90
1.03
7.26
37.
375
7.38
37.
388
7.39
67.
745
7.75
97.
796
7.81
57.
818
7.92
97.
932
8.77
48.
781
0102030405060708090100110120130140150160170180f1 (ppm)
76.
789
cd
cl3
77.
001
cd
cl3
77.
212
cd
cl3
112.
691
117.
268
122
.64
81
23.0
79
123
.63
4
131
.41
91
36.0
86
136
.45
31
37.0
31
142
.15
1
150
.00
1
154
.10
1
122124126128130132134136138f1 (ppm)
122
.648
123
.079
123
.634
131
.419
136
.086
136
.453
137
.031
S-56
5-Fluoro-2-(pyridin-2-yl)benzonitrile (3ic)
-0.0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
1.02
1.03
0.97
1.00
2.03
1.00
7.26
37.
360
7.36
87.
372
7.38
07.
396
7.40
17.
410
7.41
57.
424
7.42
97.
492
7.49
67.
505
7.51
07.
761
7.77
57.
832
7.83
57.
845
7.84
87.
858
7.86
27.
872
8.76
58.
773
0102030405060708090100110120130140150160170180f1 (ppm)
76.
789
cd
cl3
77.
001
cd
cl3
77.
212
cd
cl3
112.
438
112.
501
117.
432
117.
445
120
.43
11
20.5
71
120
.63
21
20.7
97
123
.09
61
23.4
10
132
.12
21
32.1
78
136
.95
61
39.8
69
149
.93
0
154
.21
9
161
.16
11
62.8
32
S-57
5-(Methylsulfonyl)-2-(pyridin-2-yl)benzonitrile (3j)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
3.19
1.04
1.04
1.06
1.06
1.04
0.95
1.00
-0.0
00
3.13
7
7.26
67.
442
7.44
47.
450
7.45
27.
454
7.45
67.
462
7.46
47.
874
8.09
78.
110
8.22
98.
232
8.38
08.
383
8.82
38.
831
0102030405060708090100110120130140150160170180f1 (ppm)
44.
469
76.
788
cd
cl3
77.
000
cd
cl3
77.
212
cd
cl3
112.
545
116.
915
123
.46
01
24.3
86
131
.26
91
33.2
43
137
.15
71
41.1
80
147
.99
01
50.3
37
153
.30
7
N
CNS
3j
Me
O
O
S-58
4-Methoxy-2-(pyridin-2-yl)benzonitrile (3ka)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
3.20
1.05
2.02
1.00
1.02
1.02
0.98
0.00
0
3.92
4
6.99
77.
001
7.01
17.
015
7.26
67.
351
7.35
47.
356
7.36
17.
366
7.37
17.
374
7.70
77.
721
7.81
57.
817
7.81
97.
841
8.76
28.
764
8.76
68.
770
8.77
28.
774
0102030405060708090100110120130140150160170180f1 (ppm)
55.
711
76.
788
cd
cl3
77.
000
cd
cl3
77.
212
cd
cl3
102
.69
5
115.
047
115.
117
119.
061
123
.32
11
23.4
20
135
.69
71
36.7
93
145
.58
5
149
.89
7
155
.15
7
162
.83
7
114.0114.5115.0115.5116.0f1 (ppm)
115
.04
711
5.1
17
122.2122.6123.0123.4123.8124.2f1 (ppm)
12
3.3
21
12
3.4
20
S-59
4-Methyl-2-(pyridin-2-yl)benzonitrile (3kb)
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
3.06
1.01
1.00
1.96
0.99
1.03
0.97
0.00
0
2.48
4
7.26
67.
304
7.30
67.
317
7.32
07.
340
7.34
27.
348
7.35
07.
352
7.35
47.
360
7.36
27.
669
7.67
07.
678
7.69
27.
799
7.83
4
8.76
38.
766
8.76
88.
772
8.77
48.
776
0102030405060708090100110120130140150160170180f1 (ppm)
21.
798
76.
788
cd
cl3
77.
000
cd
cl3
77.
212
cd
cl3
108
.00
1
118.
936
123
.21
81
23.3
01
129
.52
91
30.7
02
133
.96
11
36.7
41
143
.34
51
43.8
28
149
.89
7
155
.36
4
122.7122.9123.1123.3123.5123.7f1 (ppm)
123.
218
123.
301
S-60
4-Acetyl-2-(pyridin-2-yl)benzonitrile (3kc)
-0.0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
3.06
1.00
1.00
1.02
0.99
1.04
0.99
0.97
-0.0
00
2.69
6
7.26
57.
400
7.40
37.
408
7.41
17.
413
7.41
57.
421
7.42
37.
850
7.90
97.
922
8.05
9
8.40
58.
407
8.80
48.
806
8.80
88.
812
8.81
48.
816
0102030405060708090100110120130140150160170180190200210f1 (ppm)
26.
848
76.
789
cd
cl3
77.
001
cd
cl3
77.
212
cd
cl3
114
.82
411
7.8
97
123
.22
31
23.7
61
127
.89
01
29.6
15
134
.53
21
37.0
19
140
.04
11
43.9
90
150
.09
6
154
.33
6
196
.49
3
S-61
2-(5-Acetylpyridin-2-yl)benzonitrile (3l)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.5
f1 (ppm)
3.05
1.02
1.05
0.98
2.02
1.02
1.00
2.69
8
7.26
37.
574
7.88
57.
898
7.90
27.
916
8.37
38.
377
8.38
78.
390
9.31
19.
315
0102030405060708090100110120130140150160170180190200210f1 (ppm)
26.
830
76.
788
cd
cl3
77.
000
cd
cl3
77.
211
cd
cl3
111.
282
118.
369
123
.01
8
129
.55
81
30.0
71
131
.46
11
32.9
34
134
.38
51
36.5
21
142
.20
0
150
.01
2
158
.69
1
196
.15
8
N
CN3l
O
S-62
2-(4-Methylpyridin-2-yl)benzonitrile (3ma)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
3.06
1.00
1.03
0.98
1.05
0.97
1.00
0.97
0.0
00
2.4
55
7.1
73
7.1
76
7.1
82
7.1
85
7.2
66
7.4
82
7.4
84
7.4
94
7.4
96
7.5
07
7.5
09
7.5
87
7.6
66
7.6
69
7.6
79
7.6
81
7.6
92
7.6
94
7.7
85
7.7
88
7.7
98
7.8
01
7.8
14
7.8
16
7.8
27
7.8
29
8.6
20
8.6
28
0102030405060708090100110120130140150160170180f1 (ppm)
21.
155
76.
789
cd
cl3
77.
001
cd
cl3
77.
213
cd
cl3
111.
085
118.
675
124
.14
71
24.2
59
128
.57
61
29.9
19
132
.71
91
34.0
29
143
.68
51
48.0
22
149
.66
0
155
.14
7
124125126127128129f1 (ppm)
124.
147
124.
259
128.
576
S-63
2-(5-Methylpyridin-2-yl)benzonitrile (3mb)
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
3.08
1.00
2.96
0.95
0.99
0.96
-0.0
00
2.41
5
7.26
57.
468
7.47
07.
481
7.48
37.
494
7.49
67.
630
7.63
47.
643
7.64
77.
662
7.66
47.
675
7.67
87.
687
7.69
07.
692
7.77
77.
780
7.79
07.
793
7.81
97.
821
7.83
27.
834
8.60
2
0102030405060708090100110120130140150160170180f1 (ppm)
18.
258
76.
789
cd
cl3
77.
001
cd
cl3
77.
212
cd
cl3
110.
944
118.
795
122
.66
4
128
.41
51
29.8
02
132
.74
61
33.1
23
134
.02
61
37.2
41
143
.55
1
150
.40
01
52.4
86
S-64
2-(1H-Pyrazol-1-yl)benzonitrile (3n)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
0.94
1.00
1.02
2.99
0.95
6.5
485
6.5
518
6.5
553
7.2
629
7.4
330
7.4
458
7.7
108
7.7
770
7.7
898
7.7
939
7.8
078
7.8
172
8.1
458
8.1
501
0102030405060708090100110120130140150160170180f1 (ppm)
76.
789
cd
cl3
77.
000
cd
cl3
77.
212
cd
cl3
105
.34
9
108
.46
2
116.
949
124
.29
61
27.1
94
129
.511
133
.95
61
34.4
24
142
.04
71
42.2
38
141.6141.8142.0142.2142.4142.6f1 (ppm)
142.
047
142.
238
S-65
2-(Pyrimidin-2-yl)benzonitrile (3o)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
1.05
1.02
1.04
0.99
1.00
2.03
7.26
37.
327
7.33
57.
343
7.56
77.
580
7.59
27.
708
7.72
17.
734
7.85
17.
864
8.36
98.
382
8.92
28.
930
0102030405060708090100110120130140150160170180f1 (ppm)
76.
789
cd
cl3
77.
000
cd
cl3
77.
212
cd
cl3
111.
900
118.
876
120
.11
7
130
.20
71
30.4
34
132
.52
81
35.0
58
140
.30
4
157
.32
9
162
.86
5
S-66
Benzo[h]quinoline-10-carbonitrile (3p)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
1.01
0.99
1.04
1.00
1.00
0.95
1.00
1.00
7.26
37.
730
7.78
37.
797
7.82
28.
112
8.12
58.
150
8.16
28.
216
8.21
9
9.13
29.
135
9.14
09.
143
0102030405060708090100110120130140150160170180f1 (ppm)
76.
788
cd
cl3
77.
000
cd
cl3
77.
212
cd
cl3
109
.02
5
120
.73
51
23.0
33
126
.97
41
27.0
79
127
.23
41
27.3
65
130
.78
01
32.6
76
134
.07
61
35.6
71
136
.24
0
144
.51
7
148
.48
4
126.8126.9127.0127.1127.2127.3127.4127.5127.6f1 (ppm)
126.
974
127.
079
127.
234
127.
365
S-67
3-(Pyridin-2-yl)thiophene-2-carbonitrile (5a)
-0.0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
1.05
1.01
1.03
1.07
1.04
1.00
-0.0
00
7.26
47.
315
7.32
37.
328
7.33
67.
614
7.62
27.
688
7.69
77.
939
7.95
2
8.72
58.
727
8.72
98.
733
8.73
58.
737
0102030405060708090100110120130140150160170180f1 (ppm)
76.
788
cd
cl3
77.
000
cd
cl3
77.
212
cd
cl3
106
.23
6
114.
690
121
.89
61
23.6
08
128
.35
01
31.7
15
137
.07
4
149
.94
61
49.9
77
150
.93
2
149.90149.95150.00f1 (ppm)
149.
946
149.
977
S-68
2-(Pyridin-2-yl)thiophene-3-carbonitrile (5ba)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
1.99
0.98
1.03
0.98
1.00
7.26
47.
300
7.30
87.
315
7.32
07.
324
7.42
17.
430
7.81
57.
825
7.82
8
8.23
88.
251
8.63
88.
646
0102030405060708090100110120130140150160170180f1 (ppm)
76.7
89 c
dc
l377
.001
cd
cl3
77.2
12 c
dc
l3
105
.88
4
115.
876
120
.07
912
3.9
23
127
.72
513
0.8
35
137
.33
3
149
.60
614
9.8
28
153
.59
8
149150151152153154f1 (ppm)
149.
606
149.
828
153.
598
S-69
2-(Pyridin-2-yl)furan-3-carbonitrile (5bb)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
0.98
1.03
1.00
1.03
1.00
1.02
6.76
36.
766
7.26
37.
326
7.33
47.
338
7.34
67.
553
7.55
67.
825
7.82
87.
838
7.84
17.
903
7.91
7
8.76
08.
768
0102030405060708090100110120130140150160170180f1 (ppm)
76.7
88 c
dc
l377
.000
cd
cl3
77.2
11 c
dc
l3
94.8
30
113.
991
114.
261
120
.15
3
124
.15
2
136
.88
9
143
.23
714
6.8
29
150
.18
2
158
.49
2
113114115116117118119120121122123124125f1 (ppm)
113.
991
114.
261
120.
153
124.
152
S-70
1-(Pyrimidin-2-yl)-1H-pyrrole-2-carbonitrile (5c)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
1.03
1.01
1.04
1.00
2.00
6.37
46.
380
6.38
6
7.08
17.
084
7.08
87.
090
7.22
67.
234
7.24
27.
267
7.99
07.
993
7.99
67.
998
8.74
28.
750
0102030405060708090100110120130140150160170180f1 (ppm)
76.7
88 c
dc
l377
.000
cd
cl3
77.2
12 c
dc
l3
102
.88
8
111.
758
114.
043
118.
844
124
.97
612
6.1
24
155
.13
5
158
.57
6
S-71
2-(Pyridin-2-yl)benzo[b]thiophene-3-carbonitrile (5da)
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
1.07
1.07
1.07
2.07
1.01
1.00
0.99
-0.0
00
7.36
57.
366
7.37
37.
374
7.37
87.
379
7.38
67.
387
7.47
17.
473
7.48
57.
496
7.49
87.
521
7.52
37.
535
7.54
67.
548
7.88
97.
903
7.99
4
8.42
78.
440
8.71
18.
712
8.71
58.
719
8.72
18.
723
0102030405060708090100110120130140150160170180f1 (ppm)
76.7
89 c
dc
l377
.001
cd
cl3
77.2
12 c
dc
l3
101
.90
7
115.
143
121
.21
612
2.6
00
122
.85
112
4.6
33
126
.05
212
6.6
76
137
.31
813
8.3
06
139
.45
7
149
.70
514
9.9
96
154
.98
7
13613814014214414614815015215456f1 (ppm)
137.
318
138.
306
139.
457
149.
705
149.
996
154.
987
10105110115120125f1 (ppm)
101.
907
115.
143
121.
216
122.
600
122.
851
124.
633
126.
052
126.
676
S-72
2-(Pyridin-2-yl)benzofuran-3-carbonitrile (5db)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
2.01
1.00
1.01
0.97
1.02
1.00
1.08
7.26
47.
400
7.40
77.
412
7.41
57.
420
7.42
87.
441
7.46
27.
465
7.47
67.
478
7.48
87.
491
7.63
07.
644
7.79
37.
805
7.87
47.
877
7.88
77.
890
7.90
07.
903
8.10
58.
118
8.84
58.
851
0102030405060708090100110120130140150160170180f1 (ppm)
76.7
88 c
dc
l377
.000
cd
cl3
77.2
12 c
dc
l3
91.2
51
112.
075
113.
669
120
.52
212
1.3
36
124
.95
312
4.9
70
127
.16
312
7.1
86
136
.99
6
146
.78
515
0.4
22
153
.87
3
159
.89
7
125.0125.5126.0126.5127.0f1 (ppm)
124.
953
124.
970
127.
163
127.
186
S-73
4-(Pyridin-2-yl)dibenzo[b,d]thiophene-3-carbonitrile (5ea)
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
1.05
2.15
2.04
1.07
1.02
1.07
1.09
1.00
0.00
0
7.26
07.
447
7.44
97.
455
7.45
77.
460
7.46
27.
468
7.47
07.
508
7.51
07.
520
7.52
27.
532
7.53
57.
538
7.54
77.
550
7.56
07.
562
7.86
97.
874
7.88
78.
006
8.25
68.
269
8.89
18.
893
8.89
58.
900
8.90
28.
904
0102030405060708090100110120130140150160170180f1 (ppm)
76.
788
cd
cl3
77.
000
cd
cl3
77.
212
cd
cl3
108
.43
9
118.
978
121
.49
21
22.5
24
122
.65
71
23.9
37
124
.55
01
24.8
73
128
.38
01
29.5
07
134
.07
81
37.0
60
138
.36
01
39.7
92
140
.08
21
42.3
44
149
.64
1
154
.33
4
110115120125130135140145150155f1 (ppm)
108.439
118.978
121.492
122.524
122.657
123.937
124.550
124.873
128.380
129.507
134.078
137.060
138.360
139.792
140.082
142.344
149.641
154.334
SN
CN
5ea
S-74
4-(Pyridin-2-yl)dibenzo[b,d]furan-3-carbonitrile (5eb)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
2.00
1.02
1.00
0.98
1.95
1.99
1.06
7.41
97.
421
7.43
27.
444
7.44
67.
450
7.45
67.
458
7.46
07.
463
7.46
87.
471
7.54
97.
551
7.56
17.
563
7.56
57.
575
7.57
77.
607
7.62
17.
800
7.81
37.
937
7.94
07.
950
7.95
37.
963
7.96
67.
981
7.99
48.
029
8.04
28.
053
8.06
78.
913
0102030405060708090100110120130140150160170180f1 (ppm)
76.7
89 c
dc
l377
.001
cd
cl3
77.2
13 c
dc
l3
109
.73
311
2.27
112
0.9
61
121
.55
512
2.8
18
123
.71
312
3.8
27
128
.69
812
8.9
37
129
.24
5
136
.76
3
149
.85
815
1.1
65
152
.95
615
7.3
55
118119120121122123124125126127128129130f1 (ppm)
118
.661
120
.961
121
.555
122
.818
123
.713
123
.827
125
.530
128
.285
128
.698
128
.937
129
.245
S-75
1-(Pyridin-2-yl)-1H-indole-2-carbonitrile (5fa)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
1.07
1.04
2.02
1.04
1.04
1.04
1.06
1.00
0.00
0
7.25
67.
270
7.28
37.
295
7.37
57.
383
7.38
77.
396
7.41
17.
423
7.42
67.
428
7.43
77.
439
7.59
87.
611
7.70
77.
720
7.76
97.
783
7.94
17.
944
7.95
47.
957
7.96
77.
970
8.69
18.
694
8.69
98.
703
0102030405060708090100110120130140150160170180f1 (ppm)
76.7
89 c
dc
l377
.000
cd
cl3
77.2
12 c
dc
l3
109
.05
211
2.24
411
3.68
111
7.34
811
8.79
312
2.3
03
122
.68
412
2.7
70
126
.82
912
6.9
19
137
.03
913
8.8
51
149
.62
714
9.6
57
S-76
1-(Pyrimidin-2-yl)-1H-indole-2-carbonitrile (5fb)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
1.00
1.04
0.93
1.04
1.03
1.01
1.97
7.20
17.
209
7.21
77.
263
7.29
77.
309
7.32
27.
447
7.47
07.
483
7.49
67.
652
7.66
5
8.65
98.
673
8.80
38.
812
0102030405060708090100110120130140150160170180f1 (ppm)
76.7
88 c
dc
l377
.000
cd
cl3
77.2
12 c
dc
l3
108
.79
4
114.
101
116.
050
117.
856
120
.85
312
1.8
82
123
.38
712
7.4
06
127
.63
2
136
.43
4
156
.39
915
8.1
77
120121122123124125126127128f1 (ppm)
120.
853
121.
882
123.
387
127.
406
127.
632
S-77
4-Oxo-1-(pyrimidin-2-yl)-4,5,6,7-tetrahydro-1H-indole-2-carbonitrile (5g)
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
2.21
2.22
2.18
1.00
0.89
1.99
0.00
0
2.17
62.
187
2.19
72.
208
2.21
92.
564
2.57
42.
585
3.26
33.
273
3.28
4
7.26
77.
377
7.38
57.
393
7.41
5
8.85
68.
864
0102030405060708090100110120130140150160170180190200210f1 (ppm)
23.2
4625
.321
37.6
63
76.7
89 c
dc
l377
.001
cd
cl3
77.2
12 c
dc
l3
105
.60
1
113.
158
119.
953
120
.97
012
2.9
29
148
.03
0
155
.33
915
8.7
13
193
.42
8
N
NN
CN
O
5g
S-78
2-(9-Phenyl-9H-purin-6-yl)benzonitrile (7a)
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
1.03
3.12
2.04
1.08
1.00
0.95
1.01
0.94
-0.0
00
7.26
67.
517
7.53
07.
542
7.62
47.
637
7.65
07.
663
7.76
77.
780
7.80
17.
814
7.82
67.
937
7.95
08.
450
8.47
68.
489
9.21
7
0102030405060708090100110120130140150160170180f1 (ppm)
76.7
89 c
dc
l377
.001
cd
cl3
77.2
13 c
dc
l3
112.
364
118.
318
123
.711
128
.77
613
0.0
49
130
.29
613
2.0
28
132
.50
613
4.9
50
138
.08
3
144
.27
9
152
.27
915
2.9
92
153
.72
2
129130131132133134135f1 (ppm)
128.
776
130.
049
130.
296
131.
903
132.
028
132.
506
134.
109
134.
950
N
N
N
NPh
CN
7a
S-79
2-(9-Ethyl-9H-purin-6-yl)benzonitrile (7b)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.22
2.19
1.07
1.09
1.00
0.99
1.03
0.95
-0.0
00
1.61
81.
631
1.64
3
4.40
14.
414
4.42
64.
438
7.27
37.
605
7.61
87.
631
7.77
07.
781
7.79
57.
911
7.92
48.
196
8.44
08.
453
9.15
6
0102030405060708090100110120130140150160170180f1 (ppm)
15.3
23
39.1
86
76.7
8977
.000
77.2
12
112.
257
118.
376
130.
099
131.
554
131.
958
132.
443
134.
903
138.
274
144.
843
152.
164
152.
426
152.
989
152.0152.2152.4152.6152.8153.0153.2f1 (ppm)
152.
164
152.
426
152.
989
130.0130.5131.0131.5132.0132.5f1 (ppm)
130.
099
131.
554
131.
958
132.
443
S-80
2-(9-Butyl-9H-purin-6-yl)benzonitrile (7c)
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.01
2.12
2.06
2.02
1.02
1.04
0.98
1.01
1.00
0.92
-0.0
00
0.98
81.
000
1.01
31.
414
1.42
71.
440
1.94
11.
953
1.96
61.
979
1.99
1
4.34
44.
356
4.36
8
7.27
27.
604
7.61
77.
630
7.76
87.
781
7.79
47.
911
7.92
48.
167
8.45
08.
464
9.15
3
0102030405060708090100110120130140150160170180f1 (ppm)
13.4
61
19.9
03
31.8
81
43.9
24
76.7
88 c
dc
l377
.000
cd
cl3
77.2
12 c
dc
l3
112.
255
118.
392
130
.09
813
1.4
35
131
.97
813
2.4
29
134
.92
313
8.2
62
145
.29
5
152
.18
615
2.5
96
152
.95
6
136138140142144146148150152154f1 (ppm)
134.
923
138.
262
145.
295
152.
186
152.
596
152.
956
118120122124126128130132f1 (ppm)
118.
392
130.
098
131.
435
131.
978
132.
429
S-81
2-(9-Benzyl-9H-purin-6-yl)benzonitrile (7d)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
2.16
4.95
1.06
1.09
1.00
1.03
1.03
0.99
-0.0
00
5.51
8
7.26
47.
346
7.35
37.
358
7.36
57.
369
7.38
07.
391
7.39
97.
404
7.60
07.
613
7.62
67.
759
7.77
27.
785
7.90
77.
920
8.14
58.
450
8.46
3
9.18
6
0102030405060708090100110120130140150160170180f1 (ppm)
47.5
20
76.7
88 c
dc
l377
.000
cd
cl3
77.2
12 c
dc
l3
112.
266
118.
387
127
.94
412
8.7
36
129
.22
513
0.1
61
132
.02
613
2.4
44
134
.85
313
4.9
64
138
.15
3
145
.12
9
152
.49
015
2.6
08
153
.10
9
152152.4152.6152.8153.0153.253.4f1 (ppm)
152.
490
152.
608
153.
109
128129130131132133134135f1 (ppm)
127.
944
128.
736
129.
225
130.
161
131.
306
132.
026
132.
444
134.
853
134.
964
N
N
N
N
CN
7dPh
S-82
2-(9-Isopropyl-9H-purin-6-yl)-5-methoxybenzonitrile (7e)
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
6.58
3.01
1.08
0.96
0.95
1.00
1.00
0.93
-0.0
00
1.69
01.
702
3.92
4
4.98
14.
992
5.00
45.
015
5.02
6
7.26
87.
273
7.27
77.
287
7.29
27.
396
7.40
0
8.19
9
8.51
18.
525
9.10
1
0102030405060708090100110120130140150160170180f1 (ppm)
22.5
12
47.5
68
55.8
02
76.7
88 c
dc
l377
.000
cd
cl3
77.2
12 c
dc
l3
113.
304
118.
506
120
.09
0
130
.65
813
1.4
48
133
.68
6
142
.58
0
151
.84
115
2.0
33
152
.68
2
160
.61
2
N
N
N
N
CN
7e
OMe
S-83
5-Acetyl-2-(9-isopropyl-9H-purin-6-yl)benzonitrile (7f)
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
6.74
3.05
1.09
1.01
1.06
0.99
1.00
0.93
-0.0
01
1.71
21.
724
2.70
2
4.99
75.
008
5.02
05.
031
5.04
25.
054
5.06
5
7.27
3
8.26
08.
304
8.30
78.
318
8.32
18.
464
8.46
78.
620
8.63
49.
168
0102030405060708090100110120130140150160170180190200210f1 (ppm)
22.4
94
26.6
91
47.8
33
76.7
88 c
dc
l377
.000
cd
cl3
77.2
12 c
dc
l3
112.
919
117.
695
131
.68
513
1.9
72
132
.52
813
4.7
55
137
.80
714
1.9
07
143
.51
215
1.5
96
151
.91
215
2.4
27
195
.52
6
S-84
5-Chloro-2-(9-isopropyl-9H-purin-6-yl)benzonitrile (7g)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
6.35
1.02
0.93
1.00
1.03
0.91
0.00
0
1.70
11.
712
4.98
24.
994
5.00
55.
016
5.02
85.
039
5.05
0
7.26
97.
738
7.74
87.
752
7.88
37.
887
8.23
18.
507
8.52
2
9.13
3
0102030405060708090100110120130140150160170180f1 (ppm)
22.5
03
47.7
65
76.7
88 c
dc
l376
.999
cd
cl3
77.2
11 c
dc
l3
113.
698
117.
210
131
.67
513
2.7
38
133
.32
413
4.6
33
136
.41
313
6.6
84
143
.17
7
151
.62
515
1.8
73
152
.30
6
150.8151.2151.6152.0152.4152.8f1 (ppm)
151.
625
151.
873
152.
306
131132133134135136137f1 (ppm)
131.
675
132.
738
133.
324
134.
633
136.
413
136.
684
N
N
N
N
CN
7g
Cl
S-85
2-(7-Isopropyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)benzonitrile (7h)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
6.22
1.03
0.96
0.99
1.00
1.03
1.89
0.88
0.00
0
1.57
31.
585
5.19
25.
204
5.21
55.
227
5.23
85.
249
5.26
1
6.59
16.
597
7.27
07.
419
7.42
57.
594
7.59
67.
608
7.60
97.
732
7.74
57.
747
7.75
87.
760
7.88
37.
886
7.89
67.
898
9.03
1
0102030405060708090100110120130140150160170180f1 (ppm)
22.6
96
46.2
42
76.7
93 c
dc
l377
.005
cd
cl3
77.2
16 c
dc
l3
99.7
22
112.
098
116.
894
118.
117
126
.24
312
9.4
32
130
.46
413
2.5
28
134
.44
0
141
.41
6
150
.91
315
0.9
39
154
.57
1
150.86150.88150.90150.92150.94150.96150.98151.00f1 (ppm)
150.
913
150.
939
S-88
Table S2. Crystal data and structure refinement for 3j.
Identification code 3j
Empirical formula C13H10N2O2S
Formula weight 258.29
Temperature 273(2) K
Wavelength 0.71073 Å
Crystal system Monoclinic
Space group P2(1)/c
Unit cell dimensions a = 11.9124(16) Å = 90°.
b = 7.5041(10) Å = 111.533(5)°.
c = 14.670(2) Å = 90°.
Volume 1219.9(3) Å3
Z 4
Density (calculated) 1.406 Mg/m3
Absorption coefficient 0.260 mm-1
F(000) 536
Crystal size 0.10 x 0.10 x 0.08 mm3
Theta range for data collection 2.87 to 31.75°.
Index ranges -16<=h<=17, -10<=k<=11, -21<=l<=16
Reflections collected 35311
Independent reflections 4009 [R(int) = 0.0726]
Completeness to theta = 25.00° 99.9 %
Absorption correction Semi-empirical from equivalents
Max. and min. transmission 0.9795 and 0.9745
Refinement method Full-matrix least-squares on F2
Data / restraints / parameters 4009 / 0 / 163
Goodness-of-fit on F2 1.033
Final R indices [I>2sigma(I)] R1 = 0.0543, wR2 = 0.1185
R indices (all data) R1 = 0.1170, wR2 = 0.1396
Largest diff. peak and hole 0.303 and -0.391 e.Å-3
S-89
Table S3. Atomic coordinates ( x 104) and equivalent isotropic displacement parameters (Å2x
103) for 3j. U(eq) is defined as one third of the trace of the orthogonalized Uij tensor.
____________________________________________________________________________
x y z U(eq)
____________________________________________________________________________
S(1) 1144(1) 1105(1) 3935(1) 41(1)
O(1) 1558(1) 1889(3) 3226(1) 69(1)
O(2) 243(1) 2006(2) 4193(1) 55(1)
N(1) 5204(1) 1043(2) 8551(1) 42(1)
N(2) 2683(2) -1226(3) 8165(1) 57(1)
C(1) 6138(2) 1007(3) 9403(1) 49(1)
C(2) 7284(2) 497(3) 9503(1) 50(1)
C(3) 7494(2) -29(3) 8683(2) 51(1)
C(4) 6541(2) -33(3) 7790(1) 43(1)
C(5) 5417(1) 525(2) 7755(1) 34(1)
C(6) 4368(1) 593(2) 6809(1) 32(1)
C(7) 4518(2) 1176(2) 5960(1) 36(1)
C(8) 3556(2) 1309(2) 5074(1) 37(1)
C(9) 2415(1) 813(2) 5032(1) 34(1)
C(10) 2236(1) 186(2) 5856(1) 36(1)
C(11) 3206(1) 88(2) 6744(1) 32(1)
C(12) 618(2) -1049(3) 3557(2) 60(1)
C(13) 2960(2) -607(3) 7572(1) 39(1)
____________________________________________________________________________
S-90
Table S4. Bond lengths [Å] and angles [°] for 3j.
_____________________________________________________
S(1)-O(1) 1.4315(16)
S(1)-O(2) 1.4323(14)
S(1)-C(12) 1.749(2)
S(1)-C(9) 1.7718(16)
N(1)-C(1) 1.335(2)
N(1)-C(5) 1.340(2)
N(2)-C(13) 1.137(2)
C(1)-C(2) 1.373(3)
C(2)-C(3) 1.374(3)
C(3)-C(4) 1.383(2)
C(4)-C(5) 1.386(2)
C(5)-C(6) 1.489(2)
C(6)-C(7) 1.391(2)
C(6)-C(11) 1.405(2)
C(7)-C(8) 1.387(2)
C(8)-C(9) 1.388(2)
C(9)-C(10) 1.385(2)
C(10)-C(11) 1.391(2)
C(11)-C(13) 1.447(2)
O(1)-S(1)-O(2) 119.31(10)
O(1)-S(1)-C(12) 109.18(12)
O(2)-S(1)-C(12) 107.65(10)
O(1)-S(1)-C(9) 107.67(8)
O(2)-S(1)-C(9) 107.01(8)
C(12)-S(1)-C(9) 105.14(9)
C(1)-N(1)-C(5) 116.81(16)
N(1)-C(1)-C(2) 124.07(19)
C(1)-C(2)-C(3) 118.69(17)
C(2)-C(3)-C(4) 118.67(18)
C(3)-C(4)-C(5) 118.74(18)
N(1)-C(5)-C(4) 123.00(15)
N(1)-C(5)-C(6) 116.11(14)
C(4)-C(5)-C(6) 120.88(15)
C(7)-C(6)-C(11) 118.16(14)
C(7)-C(6)-C(5) 120.37(14)
C(11)-C(6)-C(5) 121.47(14)
S-91
C(8)-C(7)-C(6) 121.88(15)
C(7)-C(8)-C(9) 118.77(16)
C(10)-C(9)-C(8) 120.98(15)
C(10)-C(9)-S(1) 118.70(12)
C(8)-C(9)-S(1) 120.21(13)
C(9)-C(10)-C(11) 119.66(15)
C(10)-C(11)-C(6) 120.52(15)
C(10)-C(11)-C(13) 116.84(14)
C(6)-C(11)-C(13) 122.60(15)
N(2)-C(13)-C(11) 174.05(19)
_____________________________________________________________
Symmetry transformations used to generate equivalent atoms:
S-92
Table S5. Anisotropic displacement parameters (Å2x 103) for 3j. The anisotropic
displacement factor exponent takes the form: -22[ h2 a*2U11 + ... + 2 h k a* b* U12 ]
____________________________________________________________________________
__
U11 U22 U33 U23 U13 U12
____________________________________________________________________________
__
S(1) 31(1) 52(1) 35(1) 2(1) 5(1) 5(1)
O(1) 48(1) 108(1) 45(1) 28(1) 9(1) 6(1)
O(2) 37(1) 57(1) 64(1) -6(1) 10(1) 12(1)
N(1) 43(1) 47(1) 32(1) -5(1) 10(1) 0(1)
N(2) 54(1) 79(1) 41(1) 2(1) 21(1) -14(1)
C(1) 54(1) 52(1) 33(1) -7(1) 7(1) -2(1)
C(2) 45(1) 51(1) 38(1) 2(1) -4(1) -6(1)
C(3) 32(1) 59(1) 54(1) 6(1) 7(1) 2(1)
C(4) 36(1) 52(1) 38(1) 1(1) 12(1) 1(1)
C(5) 33(1) 34(1) 31(1) 0(1) 9(1) -3(1)
C(6) 30(1) 34(1) 30(1) -3(1) 9(1) -1(1)
C(7) 30(1) 45(1) 34(1) 0(1) 12(1) -5(1)
C(8) 35(1) 46(1) 31(1) 2(1) 13(1) -1(1)
C(9) 30(1) 38(1) 30(1) -2(1) 7(1) 2(1)
C(10) 28(1) 42(1) 37(1) -2(1) 12(1) -2(1)
C(11) 33(1) 35(1) 32(1) -2(1) 14(1) 0(1)
C(12) 44(1) 65(1) 57(1) -24(1) 4(1) 2(1)
C(13) 34(1) 49(1) 35(1) -1(1) 12(1) -2(1)
____________________________________________________________________________
__
S-93
Table S6. Hydrogen coordinates ( x 104) and isotropic displacement parameters (Å2x 10 3)
for 3j.
____________________________________________________________________________
____
x y z U(eq)
____________________________________________________________________________
____
H(1A) 6001 1355 9977 59
H(2A) 7920 508 10128 60
H(3A) 8279 -382 8728 61
H(4A) 6655 -411 7212 51
H(7A) 5304 1493 5990 44
H(8A) 3674 1731 4505 45
H(10A) 1454 -175 5814 43
H(12A) -94 -987 2950 89
H(12B) 399 -1630 4068 89
H(12C) 1251 -1740 3443 89
____________________________________________________________________________
____
S-94
Table S7. Torsion angles [°] for 3j.
________________________________________________________________
C(5)-N(1)-C(1)-C(2) 0.8(3)
N(1)-C(1)-C(2)-C(3) -0.7(3)
C(1)-C(2)-C(3)-C(4) -0.3(3)
C(2)-C(3)-C(4)-C(5) 1.2(3)
C(1)-N(1)-C(5)-C(4) 0.1(3)
C(1)-N(1)-C(5)-C(6) -179.37(16)
C(3)-C(4)-C(5)-N(1) -1.1(3)
C(3)-C(4)-C(5)-C(6) 178.35(17)
N(1)-C(5)-C(6)-C(7) 139.95(17)
C(4)-C(5)-C(6)-C(7) -39.6(2)
N(1)-C(5)-C(6)-C(11) -39.6(2)
C(4)-C(5)-C(6)-C(11) 140.92(18)
C(11)-C(6)-C(7)-C(8) 1.6(3)
C(5)-C(6)-C(7)-C(8) -177.93(16)
C(6)-C(7)-C(8)-C(9) -1.2(3)
C(7)-C(8)-C(9)-C(10) -0.4(3)
C(7)-C(8)-C(9)-S(1) 175.68(13)
O(1)-S(1)-C(9)-C(10) 175.54(15)
O(2)-S(1)-C(9)-C(10) 46.14(16)
C(12)-S(1)-C(9)-C(10) -68.13(16)
O(1)-S(1)-C(9)-C(8) -0.63(18)
O(2)-S(1)-C(9)-C(8) -130.03(15)
C(12)-S(1)-C(9)-C(8) 115.70(16)
C(8)-C(9)-C(10)-C(11) 1.5(3)
S(1)-C(9)-C(10)-C(11) -174.66(13)
C(9)-C(10)-C(11)-C(6) -1.0(3)
C(9)-C(10)-C(11)-C(13) -179.00(16)
C(7)-C(6)-C(11)-C(10) -0.5(2)
C(5)-C(6)-C(11)-C(10) 179.04(15)
C(7)-C(6)-C(11)-C(13) 177.38(16)
C(5)-C(6)-C(11)-C(13) -3.1(3)
C(10)-C(11)-C(13)-N(2) 24(2)
C(6)-C(11)-C(13)-N(2) -154.4(19)
________________________________________________________________
Symmetry transformations used to generate equivalent atoms:
S-96
Table S8. Crystal data and structure refinement for 5g.
Identification code 5g
Empirical formula C13 H10 N4 O
Formula weight 238.25
Temperature 120(2) K
Wavelength 0.71073 Å
Crystal system Triclinic
Space group P-1
Unit cell dimensions a = 6.9373(6) Å = 85.814(4)°.
b = 8.2261(7) Å = 78.171(4)°.
c = 9.7516(8) Å = 89.197(4)°.
Volume 543.22(8) Å3
Z 2
Density (calculated) 1.457 Mg/m3
Absorption coefficient 0.098 mm-1
F(000) 248
Crystal size 0.57 x 0.30 x 0.17 mm3
Theta range for data collection 3.00 to 28.00°.
Index ranges -9<=h<=9, -10<=k<=10, -12<=l<=12
Reflections collected 33282
Independent reflections 2612 [R(int) = 0.0243]
Completeness to theta = 28.00° 99.9 %
Absorption correction Semi-empirical from equivalents
Max. and min. transmission 0.9835 and 0.9462
Refinement method Full-matrix least-squares on F2
Data / restraints / parameters 2612 / 0 / 163
Goodness-of-fit on F2 1.093
Final R indices [I>2sigma(I)] R1 = 0.0359, wR2 = 0.1014
R indices (all data) R1 = 0.0378, wR2 = 0.1033
Largest diff. peak and hole 0.334 and -0.297 e.Å-3
S-97
Table S9. Atomic coordinates ( x 104) and equivalent isotropic displacement parameters (Å2x
103) for 5g. U(eq) is defined as one third of the trace of the orthogonalized Uij tensor.
____________________________________________________________________________
____
x y z U(eq)
____________________________________________________________________________
____
O(1) -1893(1) 1785(1) 8855(1) 31(1)
N(1) 419(1) 2726(1) 4115(1) 17(1)
N(2) 2986(1) 1750(1) 2442(1) 22(1)
N(3) 1105(1) 4080(1) 1899(1) 24(1)
N(4) -3722(2) 4596(1) 2911(1) 29(1)
C(1) 1250(2) 564(1) 7998(1) 22(1)
C(2) -548(2) 1582(1) 7859(1) 21(1)
C(3) -579(1) 2248(1) 6433(1) 18(1)
C(4) 950(1) 2024(1) 5307(1) 17(1)
C(5) 2853(1) 1209(1) 5419(1) 20(1)
C(6) 3095(2) 1166(1) 6949(1) 22(1)
C(7) -2097(1) 3125(1) 5932(1) 20(1)
C(8) -1466(1) 3408(1) 4510(1) 18(1)
C(9) 1585(1) 2862(1) 2730(1) 17(1)
C(10) 2210(2) 4202(1) 596(1) 26(1)
C(11) 3754(2) 3154(1) 166(1) 24(1)
C(12) 4085(2) 1933(1) 1139(1) 24(1)
C(13) -2612(2) 4090(1) 3560(1) 21(1)
S-98
Table S10. Bond lengths [Å] and angles [°] for 5g.
_____________________________________________________
O(1)-C(2) 1.2206(12)
N(1)-C(4) 1.3758(12)
N(1)-C(8) 1.4060(12)
N(1)-C(9) 1.4231(11)
N(2)-C(9) 1.3266(13)
N(2)-C(12) 1.3405(13)
N(3)-C(9) 1.3241(13)
N(3)-C(10) 1.3409(13)
N(4)-C(13) 1.1485(14)
C(1)-C(2) 1.5160(14)
C(1)-C(6) 1.5289(14)
C(2)-C(3) 1.4613(13)
C(3)-C(4) 1.3825(13)
C(3)-C(7) 1.4162(13)
C(4)-C(5) 1.4923(13)
C(5)-C(6) 1.5327(13)
C(7)-C(8) 1.3691(13)
C(8)-C(13) 1.4215(14)
C(10)-C(11) 1.3815(15)
C(11)-C(12) 1.3802(15)
C(4)-N(1)-C(8) 107.94(8)
C(4)-N(1)-C(9) 127.26(8)
C(8)-N(1)-C(9) 124.67(8)
C(9)-N(2)-C(12) 114.48(9)
C(9)-N(3)-C(10) 114.81(9)
C(2)-C(1)-C(6) 112.29(8)
O(1)-C(2)-C(3) 122.66(10)
O(1)-C(2)-C(1) 122.49(9)
C(3)-C(2)-C(1) 114.82(8)
C(4)-C(3)-C(7) 108.49(8)
C(4)-C(3)-C(2) 122.59(9)
C(7)-C(3)-C(2) 128.86(9)
N(1)-C(4)-C(3) 107.99(8)
N(1)-C(4)-C(5) 127.43(8)
C(3)-C(4)-C(5) 124.55(9)
C(4)-C(5)-C(6) 108.88(8)
S-99
C(1)-C(6)-C(5) 113.00(8)
C(8)-C(7)-C(3) 106.77(8)
C(7)-C(8)-N(1) 108.82(8)
C(7)-C(8)-C(13) 125.83(9)
N(1)-C(8)-C(13) 124.90(9)
N(3)-C(9)-N(2) 128.92(9)
N(3)-C(9)-N(1) 115.10(8)
N(2)-C(9)-N(1) 115.98(8)
N(3)-C(10)-C(11) 122.38(10)
C(12)-C(11)-C(10) 116.65(9)
N(2)-C(12)-C(11) 122.72(9)
N(4)-C(13)-C(8) 172.16(11)
_____________________________________________________________
Symmetry transformations used to generate equivalent atoms:
S-100
Table S11. Anisotropic displacement parameters (Å2x 103) for 5g. The anisotropic
displacement factor exponent takes the form: -22[ h2 a*2U11 + ... + 2 h k a* b* U12 ]
____________________________________________________________________________
__
U11 U22 U33 U23 U13 U12
____________________________________________________________________________
__
O(1) 28(1) 40(1) 18(1) 2(1) 6(1) 7(1)
N(1) 15(1) 19(1) 15(1) 0(1) -1(1) 3(1)
N(2) 22(1) 24(1) 16(1) -1(1) 0(1) 5(1)
N(3) 22(1) 26(1) 20(1) 4(1) -1(1) 4(1)
N(4) 25(1) 35(1) 27(1) 3(1) -6(1) 7(1)
C(1) 22(1) 26(1) 18(1) 3(1) -3(1) 2(1)
C(2) 20(1) 23(1) 16(1) 0(1) 0(1) -1(1)
C(3) 17(1) 20(1) 16(1) -1(1) 0(1) 1(1)
C(4) 17(1) 17(1) 15(1) -1(1) -2(1) 1(1)
C(5) 17(1) 25(1) 17(1) 0(1) -2(1) 5(1)
C(6) 19(1) 29(1) 18(1) 1(1) -4(1) 3(1)
C(7) 16(1) 22(1) 19(1) -1(1) 0(1) 3(1)
C(8) 15(1) 19(1) 19(1) -1(1) -1(1) 2(1)
C(9) 17(1) 20(1) 15(1) -1(1) -2(1) -1(1)
C(10) 25(1) 32(1) 18(1) 6(1) -2(1) 2(1)
C(11) 22(1) 33(1) 15(1) -1(1) 0(1) -1(1)
C(12) 23(1) 30(1) 18(1) -4(1) 1(1) 5(1)
C(13) 19(1) 22(1) 22(1) 0(1) -1(1) 3(1)
____________________________________________________________________________
__
S-101
Table S12. Hydrogen coordinates ( x 104) and isotropic displacement parameters (Å2x 10 3)
for 5g.
____________________________________________________________________________
____
x y z U(eq)
____________________________________________________________________________
____
H(1A) 995 -584 7846 27
H(1B) 1482 597 8964 27
H(5A) 3961 1817 4801 24
H(5B) 2859 86 5117 24
H(6A) 4212 442 7064 27
H(6B) 3421 2275 7163 27
H(7A) -3317 3453 6477 24
H(10A) 1922 5039 -56 31
H(11A) 4547 3267 -754 29
H(12A) 5136 1193 875 29
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____
S-102
Table S13. Torsion angles [°] for 5g.
________________________________________________________________
C(6)-C(1)-C(2)-O(1) -149.55(10)
C(6)-C(1)-C(2)-C(3) 32.63(12)
O(1)-C(2)-C(3)-C(4) 179.62(10)
C(1)-C(2)-C(3)-C(4) -2.56(14)
O(1)-C(2)-C(3)-C(7) -3.47(17)
C(1)-C(2)-C(3)-C(7) 174.35(10)
C(8)-N(1)-C(4)-C(3) 0.46(11)
C(9)-N(1)-C(4)-C(3) 176.41(9)
C(8)-N(1)-C(4)-C(5) -177.45(9)
C(9)-N(1)-C(4)-C(5) -1.50(16)
C(7)-C(3)-C(4)-N(1) -0.52(11)
C(2)-C(3)-C(4)-N(1) 176.94(9)
C(7)-C(3)-C(4)-C(5) 177.46(9)
C(2)-C(3)-C(4)-C(5) -5.07(15)
N(1)-C(4)-C(5)-C(6) 159.83(9)
C(3)-C(4)-C(5)-C(6) -17.76(13)
C(2)-C(1)-C(6)-C(5) -57.01(12)
C(4)-C(5)-C(6)-C(1) 47.69(11)
C(4)-C(3)-C(7)-C(8) 0.38(11)
C(2)-C(3)-C(7)-C(8) -176.88(10)
C(3)-C(7)-C(8)-N(1) -0.10(11)
C(3)-C(7)-C(8)-C(13) 172.49(9)
C(4)-N(1)-C(8)-C(7) -0.22(11)
C(9)-N(1)-C(8)-C(7) -176.30(8)
C(4)-N(1)-C(8)-C(13) -172.89(9)
C(9)-N(1)-C(8)-C(13) 11.03(15)
C(10)-N(3)-C(9)-N(2) -0.73(17)
C(10)-N(3)-C(9)-N(1) 179.92(9)
C(12)-N(2)-C(9)-N(3) 2.09(16)
C(12)-N(2)-C(9)-N(1) -178.57(8)
C(4)-N(1)-C(9)-N(3) -154.87(10)
C(8)-N(1)-C(9)-N(3) 20.44(14)
C(4)-N(1)-C(9)-N(2) 25.70(14)
C(8)-N(1)-C(9)-N(2) -158.99(9)
C(9)-N(3)-C(10)-C(11) -1.18(16)
N(3)-C(10)-C(11)-C(12) 1.51(17)
C(9)-N(2)-C(12)-C(11) -1.59(16)
S-103
C(10)-C(11)-C(12)-N(2) -0.02(17)
C(7)-C(8)-C(13)-N(4) -17.6(9)
N(1)-C(8)-C(13)-N(4) 153.8(8)
________________________________________________________________
Symmetry transformations used to generate equivalent atoms:
S-105
Table S14. Crystal data and structure refinement for 7b.
Identification code 7b
Empirical formula C14 H11 N5
Formula weight 249.28
Temperature 120(2) K
Wavelength 0.71073 Å
Crystal system Triclinic
Space group P-1
Unit cell dimensions a = 7.9667(3) Å = 109.198(2)°.
b = 8.6666(4) Å = 107.554(2)°.
c = 9.6847(4) Å = 92.006(2)°.
Volume 595.36(4) Å3
Z 2
Density (calculated) 1.391 Mg/m3
Absorption coefficient 0.089 mm-1
F(000) 260
Crystal size 0.40 x 0.34 x 0.15 mm3
Theta range for data collection 2.71 to 34.95°.
Index ranges -12<=h<=12, -13<=k<=13, -15<=l<=15
Reflections collected 30635
Independent reflections 5059 [R(int) = 0.0546]
Completeness to theta = 25.00° 99.9 %
Absorption correction Semi-empirical from equivalents
Max. and min. transmission 0.9867 and 0.9652
Refinement method Full-matrix least-squares on F2
Data / restraints / parameters 5059 / 0 / 172
Goodness-of-fit on F2 1.045
Final R indices [I>2sigma(I)] R1 = 0.0557, wR2 = 0.1267
R indices (all data) R1 = 0.1012, wR2 = 0.1462
Largest diff. peak and hole 0.455 and -0.280 e.Å-3
S-106
Table S15. Atomic coordinates ( x 104) and equivalent isotropic displacement parameters
(Å2x 103) for 7b. U(eq) is defined as one third of the trace of the orthogonalized Uij tensor.
____________________________________________________________________________
____
x y z U(eq)
____________________________________________________________________________
____
N(3) 5401(1) 6287(1) 9142(1) 22(1)
N(2) 7034(1) 4620(1) 7630(1) 22(1)
N(4) 2145(1) 3563(1) 5655(1) 25(1)
N(5) 2214(1) 5565(1) 7870(1) 22(1)
N(1) 9576(1) 1733(1) 7878(1) 34(1)
C(7) 5719(1) 2395(1) 5152(1) 19(1)
C(10) 3948(1) 5429(1) 7973(1) 19(1)
C(9) 3897(1) 4175(1) 6598(1) 19(1)
C(2) 7109(1) 1437(1) 5323(1) 20(1)
C(1) 8448(1) 1673(1) 6791(1) 24(1)
C(11) 6881(1) 5816(1) 8867(1) 23(1)
C(8) 5538(1) 3758(1) 6476(1) 18(1)
C(12) 1223(1) 4430(1) 6467(1) 26(1)
C(3) 7212(2) 137(1) 4049(1) 26(1)
C(6) 4467(2) 2002(1) 3683(1) 25(1)
C(13) 1540(2) 6678(2) 9013(1) 27(1)
C(5) 4584(2) 715(2) 2425(1) 29(1)
C(4) 5950(2) -224(2) 2604(1) 30(1)
C(14) 769(2) 8046(2) 8515(2) 35(1)
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____
S-107
Table S16. Bond lengths [Å] and angles [°] for 7b.
_____________________________________________________
N(3)-C(10) 1.3309(13)
N(3)-C(11) 1.3340(14)
N(2)-C(11) 1.3429(13)
N(2)-C(8) 1.3466(13)
N(4)-C(12) 1.3114(14)
N(4)-C(9) 1.3869(13)
N(5)-C(12) 1.3631(15)
N(5)-C(10) 1.3663(13)
N(5)-C(13) 1.4620(13)
N(1)-C(1) 1.1438(15)
C(7)-C(6) 1.3919(14)
C(7)-C(2) 1.4099(14)
C(7)-C(8) 1.4788(14)
C(10)-C(9) 1.4031(14)
C(9)-C(8) 1.3977(14)
C(2)-C(3) 1.3965(14)
C(2)-C(1) 1.4423(15)
C(3)-C(4) 1.3818(17)
C(6)-C(5) 1.3853(15)
C(13)-C(14) 1.5048(17)
C(5)-C(4) 1.3851(18)
C(10)-N(3)-C(11) 111.60(9)
C(11)-N(2)-C(8) 118.51(9)
C(12)-N(4)-C(9) 103.48(9)
C(12)-N(5)-C(10) 105.45(9)
C(12)-N(5)-C(13) 126.60(9)
C(10)-N(5)-C(13) 127.95(9)
C(6)-C(7)-C(2) 117.88(9)
C(6)-C(7)-C(8) 119.83(9)
C(2)-C(7)-C(8) 122.27(9)
N(3)-C(10)-N(5) 127.46(9)
N(3)-C(10)-C(9) 126.42(9)
N(5)-C(10)-C(9) 106.12(9)
N(4)-C(9)-C(8) 133.66(9)
N(4)-C(9)-C(10) 109.96(9)
C(8)-C(9)-C(10) 116.32(9)
S-108
C(3)-C(2)-C(7) 120.55(10)
C(3)-C(2)-C(1) 116.03(9)
C(7)-C(2)-C(1) 123.37(9)
N(1)-C(1)-C(2) 173.31(12)
N(3)-C(11)-N(2) 128.49(10)
N(2)-C(8)-C(9) 118.60(9)
N(2)-C(8)-C(7) 118.10(9)
C(9)-C(8)-C(7) 123.30(9)
N(4)-C(12)-N(5) 115.00(10)
C(4)-C(3)-C(2) 120.30(10)
C(5)-C(6)-C(7) 121.18(10)
N(5)-C(13)-C(14) 112.16(10)
C(4)-C(5)-C(6) 120.57(10)
C(3)-C(4)-C(5) 119.53(10)
_____________________________________________________________
Symmetry transformations used to generate equivalent atoms:
S-109
Table S17. Anisotropic displacement parameters (Å2x 103) for 7b. The anisotropic
displacement factor exponent takes the form: -22[ h2 a*2U11 + ... + 2 h k a* b* U12 ]
____________________________________________________________________________
__
U11 U22 U33 U23 U13 U12
____________________________________________________________________________
__
N(3) 22(1) 22(1) 20(1) 3(1) 7(1) 4(1)
N(2) 19(1) 21(1) 21(1) 2(1) 6(1) 4(1)
N(4) 18(1) 23(1) 26(1) 5(1) 3(1) 3(1)
N(5) 19(1) 24(1) 26(1) 8(1) 10(1) 7(1)
N(1) 30(1) 36(1) 30(1) 7(1) 7(1) 12(1)
C(7) 20(1) 17(1) 19(1) 4(1) 8(1) 1(1)
C(10) 18(1) 19(1) 21(1) 7(1) 8(1) 5(1)
C(9) 18(1) 17(1) 19(1) 4(1) 5(1) 3(1)
C(2) 21(1) 18(1) 21(1) 4(1) 9(1) 2(1)
C(1) 23(1) 22(1) 26(1) 5(1) 12(1) 7(1)
C(11) 19(1) 22(1) 21(1) 2(1) 5(1) 3(1)
C(8) 19(1) 17(1) 18(1) 4(1) 6(1) 3(1)
C(12) 18(1) 25(1) 30(1) 9(1) 6(1) 3(1)
C(3) 31(1) 21(1) 28(1) 4(1) 16(1) 6(1)
C(6) 27(1) 24(1) 21(1) 6(1) 6(1) 4(1)
C(13) 27(1) 31(1) 30(1) 10(1) 17(1) 12(1)
C(5) 35(1) 27(1) 18(1) 3(1) 6(1) -1(1)
C(4) 41(1) 22(1) 24(1) 0(1) 16(1) 1(1)
C(14) 39(1) 31(1) 35(1) 9(1) 14(1) 15(1)
____________________________________________________________________________
__
S-110
Table S18. Hydrogen coordinates ( x 104) and isotropic displacement parameters (Å2x 10 3)
for 7b.
____________________________________________________________________________
____
x y z U(eq)
____________________________________________________________________________
____
H(11A) 7969 6402 9648 27
H(12A) -42 4277 6104 31
H(3A) 8153 -502 4178 32
H(6A) 3515 2627 3540 30
H(13A) 2522 7165 10014 33
H(13B) 610 6037 9175 33
H(5A) 3720 475 1431 35
H(4A) 6020 -1111 1739 36
H(14A) 333 8760 9310 53
H(14B) -219 7571 7534 53
H(14C) 1692 8699 8375 53
____________________________________________________________________________
____
S-111
Table S19. Torsion angles [°] for 7b.
________________________________________________________________
C(11)-N(3)-C(10)-N(5) 178.95(10)
C(11)-N(3)-C(10)-C(9) -0.07(16)
C(12)-N(5)-C(10)-N(3) -179.80(11)
C(13)-N(5)-C(10)-N(3) -0.15(18)
C(12)-N(5)-C(10)-C(9) -0.62(11)
C(13)-N(5)-C(10)-C(9) 179.04(10)
C(12)-N(4)-C(9)-C(8) 176.61(12)
C(12)-N(4)-C(9)-C(10) -0.38(12)
N(3)-C(10)-C(9)-N(4) 179.84(10)
N(5)-C(10)-C(9)-N(4) 0.64(12)
N(3)-C(10)-C(9)-C(8) 2.26(16)
N(5)-C(10)-C(9)-C(8) -176.93(9)
C(6)-C(7)-C(2)-C(3) -0.07(15)
C(8)-C(7)-C(2)-C(3) 178.62(10)
C(6)-C(7)-C(2)-C(1) -177.46(10)
C(8)-C(7)-C(2)-C(1) 1.24(16)
C(3)-C(2)-C(1)-N(1) 0.7(11)
C(7)-C(2)-C(1)-N(1) 178.2(10)
C(10)-N(3)-C(11)-N(2) -1.51(17)
C(8)-N(2)-C(11)-N(3) 0.68(18)
C(11)-N(2)-C(8)-C(9) 1.75(15)
C(11)-N(2)-C(8)-C(7) -177.30(10)
N(4)-C(9)-C(8)-N(2) -179.86(11)
C(10)-C(9)-C(8)-N(2) -3.01(14)
N(4)-C(9)-C(8)-C(7) -0.87(18)
C(10)-C(9)-C(8)-C(7) 175.98(9)
C(6)-C(7)-C(8)-N(2) -149.17(10)
C(2)-C(7)-C(8)-N(2) 32.16(14)
C(6)-C(7)-C(8)-C(9) 31.83(15)
C(2)-C(7)-C(8)-C(9) -146.84(11)
C(9)-N(4)-C(12)-N(5) -0.03(13)
C(10)-N(5)-C(12)-N(4) 0.43(13)
C(13)-N(5)-C(12)-N(4) -179.24(10)
C(7)-C(2)-C(3)-C(4) 0.11(17)
C(1)-C(2)-C(3)-C(4) 177.68(11)
C(2)-C(7)-C(6)-C(5) -0.23(16)
C(8)-C(7)-C(6)-C(5) -178.96(10)