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Research ArticleA Simple and Advantageous Synthesis of the Privileged14-Benzodiazepine Nucleus
Neetu Jain and Dharma Kishore
Department of Chemistry Banasthali University Banasthali Rajasthan 304022 India
Correspondence should be addressed to Neetu Jain toneetuyahoocom
Received 30 April 2014 Revised 5 July 2014 Accepted 11 July 2014 Published 11 August 2014
Academic Editor Hideto Miyabe
Copyright copy 2014 N Jain and D Kishore This is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in any medium provided the original work is properlycited
A novel domino approach has been described for an easy access of the privileged nucleus of 5-carbomethoxy substituted14-benzodiazepin-2-ones 4(andashi) from an in situ methanolic hydrolysis of an incipient species formed from the interactionof 1-chloroacetylisatin 2(andashi) hexamethyldisilazane and n-butyl lithium The reaction is believed to take place through aconsecutive series of intramolecular reactions in a cascade to first generate a highly reactive carbene intermediate 3(andashi) from1-chloroacetylisatin and n-butyl lithium which is simultaneously trapped by hexamethyldisilazane before undergoing its in situhydrolysis with methanol to initiate its concomitant cyclocondensation to produce 4(andashi) in high yield and purity
1 Introduction
Exploration of synthetic processes that lead to the develop-ment of small molecules of medicinal interest by telescopingthemulticomponent operations into a single step or resortingto a process such as domino reactions is a rapidly emergingsubject in medicinal chemistry Ever since Koch et al [1]carried out a quantitative analysis of physiologically activenatural product scaffolds and showed that ones with twoor three rings were most often found in bioactive naturalproducts the interest on various facets of the chemistryof small molecules has expanded exponentially thereafterBenzodiazepines and their analogues have been recognizedrecently to belong to the class of privileged heterocyclicstructures [2ndash5] by virtue of their ability to form ligands toa number of functionally and structurally discrete biologicalreceptors [6ndash13] This property stimulated chemists to utilizetheir potential in the design and development of molecularprobes for biological evaluations Ubiquitous presence of thisnucleus in the psychopharmacologically active agents and inmolecules active against HIV infection for example TIBO(1) [14ndash17] and FDA approved dipyrido diazepine analoguenevirapine (2) [18ndash24] in Figure 1 provided an impetusfor an enormous research effort to be directed towards
the development of their structural analogues of medicinalimportance [25 26]
2 Results and Discussion
This communication reports the application of a noveldomino process for an easy access of the privileged nucleusof 5-carbomethoxy substituted 14-benzodiazepin-2-ones4(andashi) from the ring expansion of 1-chloroacetylisatins2(andashi) initiated by hexamethyldisilazane under the influenceof n-butyl lithiumN-Butyl lithium formed an obvious choicesince it has been used as a catalyst in amination of activealkyl halides with hexamethyldisilazane Amination of 1-chloroacetylisatin (2) formed the key step in allowing it toundergo ring expansion to give 4 Ogata and Matsumotorsquos[27] original procedure which employed Delepine reactionin the amination of 2 with methanolic solution of hexamineproduced 4 in low yieldThis called out to revisit this reactionto augment the scope of this reaction in view of the yield ofthis product
It is believed that Delepine reaction proceeded with theformation of the hexaminium ion We surmise that it wasthe bulky nature of hexamine which hindered its formation
Hindawi Publishing CorporationAdvances in ChemistryVolume 2014 Article ID 628326 6 pageshttpdxdoiorg1011552014628326
2 Advances in Chemistry
N
N
N NN
HN
O
S(O)
HN
Cl
CH3
CH3
H3C1 2
H3C
Figure 1
from 2 We assumed that this problem could possibly becircumvented by carrying out the amination of 2 with lessbulkier agents In consideration of the potential of hex-amethyldisilazane [28] in amination reaction in our initialattempt we replaced hexamine with this reagent Howevercontrary to our expectation 2 resisted its reaction with thisreagent and caused it to be recovered unchanged from thereaction mixture A search for possible use of a catalyst inthis reaction revealed that n-butyl lithium has been used inaminations employing hexamethyldisilazane This providedoptimism for this reaction too to succeed with the use ofthis catalyst This expectation turned into a reality in all theruns using a wide variety of substituted 1-chloroacetylisatinderivatives to produce 4 in an exceptionally high yield andpurity (Table 1)
We suggest that this reaction proceedswith the base catal-ysed dehydrochlorination of 2 to generate an acyl carbeneintermediate 3 which is subsequently trapped by hexam-ethyldisilazane The relatively small size of carbene precludesthe steric factor in the reaction with hexamethyldisilazaneThe hydrolysis of bis(trimethylsilyl) group from this withmethanol sets the stage for it to undergo ring expansion togive 4
In view of the extremely weak nucleophilic character ofisatinylamide nitrogen of 3 the possibility of the rearrange-ment of the acyl carbene intermediate had to be ruled out(No rearranged product was however traceable from thereaction mixture)
As the carbene was not likely to be trapped by thetertiary amine (hexamine) its reactionwith hexaminewas notexamined
3 Experiment
All the melting points were taken in open capillaries and areuncorrected The purity of all the compounds were checkedby TLC using the solvent systems (benzene methanol9 1 vv) and silica gel G as adsorbent IR spectra wererecorded on Shimadzu FTIR-8400 infrared spectrometerusing KBr 1H NMR were recorded on Bruker AC 300Fin CDCl
3+ DMSO-d
6(2 1 vv TMS as internal reference
and chemical shifts expressed in 120575 ppm) and mass spectra
were recorded on Jeol-JMS-D-D-300 mass spectrometerReagents 5-fluoro- 5-chloro- 5-bromo- 5-iodo- 5-methyl-5-methoxy- 5-nitro- and 57-dimethylisatins were procuredfrom commercial sources and used as such in the reactionwithout further purifications (see Scheme 1)
31 General Methods for the Preparation of 2(andashi) from 1(andashi)5-Fluoroisatin (1b 0068mol) was vigorously refluxed withchloroacetyl chloride (0090mol) for 7 h and themixturewascooled overnight at 0ndash5∘C The crude product which settledwas filtered washed with 20mL of ether air-dried and thenrecrystallised from ethyl acetate to give 2b yield 88 mp165-166∘C Other compounds 2(a cndashi) were prepared from1(a cndashi) using this procedure
32 General Methods for the Preparation of 4(andashi) from 2(andashi) 5-Fluoro-1-chloroacetylisatin (2b 001mol) was dissolvedin dry THF (20mL) and to this solution n-butyl lithium(001mol) and hexamethyldisilazane (001mol) were addedThe reactionmixture was magnetically stirred for 2 h at roomtemperature The progress of reaction was checked by TLCMethanol (20mL) was added to the reaction mass and themixture was refluxed for 5 h It was then poured on crushedice filtered air-dried and recrystallised from methanol togive 4b yield 87 mp 198ndash200∘C Other compounds 4(acndashi) were prepared from 2(a cndashi) using the same procedure
4 Conclusion
In summary a high yielding n-butyl lithium catalysedone-pot domino process has been developed to the facileaccess of the privileged nucleus of methyl-13-dihydro-2H-14-benzodiazepin-2-one-5-carboxylates 4(andashi) at ambienttemperature from the ring expansion of the corresponding 1-chloroacetylisatins 2(andashi) under the influence of hexamethyl-disilazane
Conflict of Interests
The authors declare that there is no conflict of interestsregarding the publication of this paper
Advances in Chemistry 3
Table1Ph
ysicalandspectraldataof
thec
ompo
unds
2(andashi)and4(andashi)
Entry
Molecular
form
ula
MW
MP
(∘ C)a
Yield(
)IR
(KBr)cmminus1
1 HNMR(C
DCl
3-DMSO
-d6)120575pp
mElem
entalanalysis
C(caldexp)
H(caldexp)
N(caldexp)
2aC 1
0H6C
lNO
322361
210ndash
1291
173516801675
756ndash
719(m
4HA
rH)432
(s2HC
H2)
53715
367
270265
626618
2bC 1
0H5C
lFNO
32416
0165ndash66
88175517251700
781ndash72
3(m
3HA
rH)433
(s2HC
H2)
49714
967
249240
580569
2cC 1
0H5C
l 2NO
325806
153ndash55
94178517401720
781ndash753(m
3HA
rH)432
(s2HC
H2)
465446
42
19519
0543531
2dC 1
0H5BrC
lNO
330251
178ndash79
90178017351710
796ndash
761(m3HA
rH)432
(s2HC
H2)
39703962
16715
6463459
2eC 1
0H5C
lINO
33495
1206ndash
0789
177017251690
780ndash
750(m
3HA
rH)428
(s2HC
H2)
28952889
1211
17338327
2fC 1
1H8C
lNO
32376
4185ndash86
92176517201690
772ndash70
3(m
3HA
rH)432
(s2HC
H2)
285
(s3HC
H3)
55605551
339328
589580
2gC 1
1H8C
lNO
425364
223ndash25
90178017401705
772ndash70
3(m
3HA
rH)432
(s2HC
H2)
373
(s3HO
CH3)
52095197
318312
552542
2hC 1
0H5C
lN2O
526861
130ndash
3291
178517451710
872ndash809(m
3HA
rH)452
(s2HC
H2)
44714
456
18817
110431037
2iC 1
2H10ClNO
32516
7168ndash70
921740
17001685
740ndash
712(m
2HA
rH)432
(s2HC
H2)
235
(s6HC
H3)
57275719
401397
557546
4aC 1
1H10N
2O3
21821
172ndash75
85319017251675
80(s1HN
H)79
8ndash76
5(m
4HA
rH)
448
(s2HC
H2)365(s3HO
CH3)
MS119898119911(
)21821(M+
100
)21020
(75
)10716(35
)
60556048
462452
12841279
4bC 1
1H9FN
2O3
23620
198ndash200
87322017351690
82(s1HN
H)808
(d1HA
rH)77
8(d
1HA
rH)
766(s1HA
rH)456
(s2HC
H2)378
(s3HO
CH3)
MS119898119911(
)23620(M
+75)20517
(100)17716(35
)
55935588
384379
11861176
4cC 1
1H9C
lN2O
325265
176ndash
7884
321517281684
81(s1H
NH)79
0(s1HA
rH)78
1(d
1HA
rH)
760(d1HA
rH)448
(s2HC
H2)370
(s3HO
CH3)MS119898119911(
)25265(M
+100
)25457
(M+2
33
)
52295223
359351
11091100
4dC 1
1H9BrN
2O3
2979
8243ndash45
86320817211675
80(s1HN
H)79
0(s1HA
rH)77
5(d
1HA
rH)
750(d1HA
rH)432
(s2HC
H2)312
(s3HO
CH3)MS119898119911(
)29798(M
+100
)2999
0(M
+2100)17716(35
)
444744
41
305299
94393
6
4eC 1
1H9IN
2O3
34411
187ndash88
90320017101670
80(s1HN
H)78
5(s1HA
rH)76
6(d
1HA
rH)
740(d1HA
rH)432
(s2HC
H2)312
(s3HO
CH3)
MS119898119911(
)344
11(M
+75)20517
(100)14716(35
)
3839
3829
264
259
814807
4 Advances in Chemistry
Table1Con
tinued
Entry
Molecular
form
ula
MW
MP
(∘ C)a
Yield
()
IR(K
Br)cmminus1
1 HNMR(C
DCl
3-DMSO
-d6)120575pp
mElem
entalanalysis
C(caldexp)
H(caldexp)
N(caldexp)
4fC 1
2H12N
2O3
23224
205ndash06
85318817231672
80(s1HN
H)78
4(s1HA
rH)75
6(d
1HA
rH)
742(d1HA
rH)432
(s2HC
H2)312
(s3HO
CH3)
234
(s3HC
H3)
MS119898119911(
)23224(M
+72)1772
5(25
)1491
7(100)
62606252
521517
12061196
4gC 1
2H12N
2O4
24808
182ndash85
87320217281677
80(s1HN
H)78
8(d1HA
rH)77
5(d
1HA
rH)
743(s1HA
rH)433
(s2HC
H2)312
(s3HO
CH3)
363
(s3HO
CH3)
MS119898119911(
)24808(M
+68)24011
(100)16345
(36
)
58065798
487479
11291119
4hC 1
1H9N
3O5
26305
202ndash05
83322817351698
80(s1HN
H)812
(s1HA
rH)79
8(d
1HA
rH)
766(d1HA
rH)455
(s2HC
H2)342
(s3HO
CH3)
MS119898119911(
)26305(M
+65)20117
(100)17080
(35
)
50205013
345334
15961589
4iC 1
3H14N
2O3
24626
215ndash17
88318517201670
80(s1HN
H)74
0(s2HA
rH)430
(s
2HC
H2)
310
(s3HO
CH3)234(s3Hfor
two
CH3)
MS119898119911(
)246
26(M
+100
)14517
(86
)10416
(27
)
63406331
573569
11381133
a Allthem
eltingpo
ints(M
P)w
erefou
ndto
beidenticalto
thea
uthenticsamples
prepared
accordingto
thep
rocedu
rerepo
rted
intheliterature
[22]
MWMolecular
Weightcaldexpcalculatedexp
erim
ental
Advances in Chemistry 5
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
CHR2
R2
R2
R2R2
R1
R1
R1
R1
R1
R1
R2
N
N
N
N
N
N
CC C
C
CH2Cl
n-BuLi THF
NH
SiMe3
SiMe3SiMe3
SiMe3HN
H
H
2
Me OH
MeOOCCOOMe
H2N
CH2
N CH
Δ2(andashi) 3(andashi)
4(andashi)
1 2 3 and 4(andashi)
R1 = R2 = H
R1 = Cl R2 = HR1 = Br R2 = HR1 = I R2 = HR1 = Me R2 = HR1 = OMe R2 = HR1 = NO2 R2 = HR1 = Me R2 = Me
(a)(b)(c)(d)(e)(f)(g)(h)(i)
R1 = F R2 = H
Scheme 1 Schematic presentation of the synthesis of the compounds
Acknowledgments
The authors are grateful to the Director of CDRI LucknowIndia for providing the spectral data of the compounds and tothe Department of Science and Technology DST New DelhiIndia for providing the financial assistance to ldquoBanasthaliCentre for Education and Research in Basic Sciencesrdquo undertheir CURIE (Consolidation of University Research for Inno-vation and Excellence in Women Universities) programme
References
[1] M A Koch A Schuffenhauer M Scheck et al ldquoChartingbiologically relevant chemical space a structural classificationof natural products (SCONP)rdquo Proceedings of the NationalAcademy of Sciences of the United States of America vol 102 no48 pp 17272ndash17277 2005
[2] W Nawroca B Sztuba A Opolski J Wietrzk MW Kowalskaand T Glowiak ldquoSynthesis and antiproliferative activity in vitro
of novel 15-benzodiazepines Part IIrdquo Archive der Pharmazie-Pharmaceutical and Medicinal Chemistry vol 334 no 1 pp 3ndash10 2000
[3] B E Evans K E Rittle M G Bock et al ldquoMethods fordrug discovery development of potent selective orally effectivecholecystokinin antagonistsrdquo Journal of Medicinal Chemistryvol 31 no 12 pp 2235ndash2246 1988
[4] R Yarchoan H Mitsuya R V Thomas et al ldquoIn vivoactivity against HIV and favorable toxicity profile of 2101584031015840-dideoxyinosinerdquo Science vol 245 no 4916 pp 412ndash415 1989
[5] J R Lokensgard C C Chao G Gekker S Hu and P KPeterson ldquoBenzodiazepines glia and HIV-1 neuropathogene-sisrdquoMolecular Neurobiology vol 18 no 1 pp 23ndash33 1998
[6] J Poupaert P Carato E Colacino and S Yous ldquo2(3H)-benzoxazolone and bioisosters as ldquoprivileged scaffoldrdquo in thedesign of pharmacological probesrdquo Current Medicinal Chem-istry vol 12 no 7 pp 877ndash885 2005
[7] D J Triggle ldquo14-dihydropyridines as calcium channel ligandsand privileged structuresrdquoCellular andMolecular Neurobiologyvol 23 no 3 pp 293ndash303 2003
6 Advances in Chemistry
[8] R W DeSimone K S Currie S A Mitchell J W Darrow andDA Pippin ldquoPrivileged structures applications in drug discov-eryrdquo Combinatorial Chemistry and High Throughput Screeningvol 7 no 5 pp 473ndash493 2004
[9] A A Patchett and R P Nargund ldquoChapter 26 Privilegedstructures an updaterdquo Annual Reports in Medicinal Chemistryvol 35 pp 289ndash298 2000
[10] J Yang Q Dang J Liu Z Wei J Wu and X Bai ldquoPreparationof a fully substituted purine libraryrdquo Journal of CombinatorialChemistry vol 7 no 3 pp 474ndash482 2005
[11] J Liu Q Dang ZWei H Zhang and X Bai ldquoParallel solution-phase synthesis of a 2689-tetrasubstituted purine library via asulfur intermediaterdquo Journal of Combinatorial Chemistry vol 7no 4 pp 627ndash636 2005
[12] Q Dang and J E Gomez-Galeno ldquoAn efficient synthesisof pyrrolo[23-d]pyrimidines via inverse electron demandDiels-Alder reactions of 2-amino-4-cyanopyrroles with 135-triazinesrdquo Journal of Organic Chemistry vol 67 no 24 pp8703ndash8705 2002
[13] P Bhuyan R C Boruah and J S Sandhu ldquoStudies on uracils 10A facile one-pot synthesis of pyrido[23-d]- and pyrazolo[34-d]pyrimidinesrdquo Journal of Organic Chemistry vol 55 no 2 pp568ndash571 1990
[14] R H Smith Jr W L Jorgen J Tirado-Rives et al ldquoPredictionof binding affinities for TIBO inhibitors of HIV-1 reverse tran-scriptase using Monte Carlo simulations in a linear responsemethodrdquo Journal of Medicinal Chemistry vol 41 no 26 pp5272ndash5286 1998
[15] B A Roberte K Andries J Desayter et al ldquoPotent and selectiveinhibition ofHIV-1 replication in vitro by a novel series of TIBOderivativesrdquo Nature vol 343 no 6257 pp 470ndash474 1990
[16] H J Breslin M J Kukla T Kromis et al ldquoSynthesis and anti-HIV activity of 1345-tetrahydro-2H-14- benzodiazepin-2-one (TBO) derivatives Truncated 4567-tetrahydro-5-methyl-imidazo[451-jk][14]benzodiazepin-2(1H)-ones (TIBO) ana-loguesrdquo Bioorganic and Medicinal Chemistry vol 7 no 11 pp2427ndash2436 1999
[17] W Ho M J Kukla H J Breslin et al ldquoSynthesis and anti-HIV-1 activity of 4567-tetrahydro-5-methylimidazo-[451-jk][14]benzodiazepin-2(1H)-one (TIBO) derivatives 4rdquo Jour-nal of Medicinal Chemistry vol 38 no 5 pp 794ndash802 1995
[18] B D Puodziunaite R Janciene L Kosychova and Z Stum-breviciute ldquoOn the synthetic way to novel peri-annelatedimidazo[15]benzodiazepinones as the potent non-nucleosidereverse transcriptase inhibitorsrdquo Arkivoc vol 2000 no 4 pp512ndash522 2000
[19] M D Braccio G Grossi G Roma L Vargiu M Muraand M E Marongiu ldquo15-Benzodiazepines Part XII Synthe-sis and biological evaluation of tricyclic and tetracyclic 15-benzodiazepine derivatives as nevirapine analoguesrdquo EuropeanJournal of Medicinal Chemistry vol 36 no 11-12 pp 935ndash9492001
[20] A Kamal M V Rao N Laxman G Ramesh and GS Reddy ldquoRecent developments in the design synthe-sis and structure-activity relationship studies of pyrrolo[21-c][14]benzodiazepines as DNA-interactive antitumour antibi-oticsrdquo Current Medicinal ChemistrymdashAnti-Cancer Agents vol2 no 2 pp 215ndash254 2002
[21] P Sharma B Vashistha R Tygai et al ldquoApplication ofmicrowave induced Delepine reaction to the facile one pot
synthesis of 7-substituted 13-dihydro-2H-[14]-benzodiazepin-2-one-5-methyl carboxylates from the corresponding 1-chloroacetylisatinsrdquo International Journal of Chemical Sciencesvol 8 no 1 2010
[22] A Singh R Sirohi S Shastri and D Kishore ldquoA facile one-potsynthesis of 7-substituted-5-methoxycarbonyl-1H-2 3-dihydro-1 4-benzodiazepin-2-ones from 5-substituted-119873-chloroacetylisatinsrdquo Indian Journal of Chemistry B vol 42B no 12 pp 3124ndash3127 2003
[23] P D Popp ldquoThe chemistry of isatinrdquo inAdvances in HeterocyclicChemistry vol 18 pp 1ndash58 1975
[24] M Pal N K Sharma Priyanka and K K Jha ldquoSynthetic andbiological multiplicity of isatin a reviewrdquo Journal of AdvancedScientific Research vol 2 no 2 pp 35ndash44 2011
[25] N Blazevic D Kolbah B Belin V Sunjic and F Kajfez ldquoHex-amethylenetetramine ldquoA versatile reagent in organic synthesisrdquordquoSynthesis pp 167ndash176 1979
[26] B Rigoa P Caulieza D Fasseurb and D Couturierb ldquoReactionof hexamethyldisilazane with diacylhydrazines an easy 134-oxadiazole synthesisrdquo Synthetic Communications vol 16 no 13pp 1665ndash1669 1986
[27] M Ogata and H Matsumoto ldquoA convenient synthesis of5-substituted 13-dihydro-2H-14-benzodiazepine-2-onesrdquoChemistry and Industry p 1067 1976
[28] H Fujishima H Takeshita S Suzuki M Toyota and MIhara ldquoHexamethyldisilazanes mediated one-pot intramolec-ular Michael addition-olefination reactions leading to ejvo-olefinated bicyclo[640]dodecanesrdquo Journal of the ChemicalSociety Perkin Transactions 1 no 18 pp 2609ndash2616 1999
Submit your manuscripts athttpwwwhindawicom
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Inorganic ChemistryInternational Journal of
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Carbohydrate Chemistry
International Journal of
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Journal of
Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Advances in
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Analytical Methods in Chemistry
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Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
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CatalystsJournal of
2 Advances in Chemistry
N
N
N NN
HN
O
S(O)
HN
Cl
CH3
CH3
H3C1 2
H3C
Figure 1
from 2 We assumed that this problem could possibly becircumvented by carrying out the amination of 2 with lessbulkier agents In consideration of the potential of hex-amethyldisilazane [28] in amination reaction in our initialattempt we replaced hexamine with this reagent Howevercontrary to our expectation 2 resisted its reaction with thisreagent and caused it to be recovered unchanged from thereaction mixture A search for possible use of a catalyst inthis reaction revealed that n-butyl lithium has been used inaminations employing hexamethyldisilazane This providedoptimism for this reaction too to succeed with the use ofthis catalyst This expectation turned into a reality in all theruns using a wide variety of substituted 1-chloroacetylisatinderivatives to produce 4 in an exceptionally high yield andpurity (Table 1)
We suggest that this reaction proceedswith the base catal-ysed dehydrochlorination of 2 to generate an acyl carbeneintermediate 3 which is subsequently trapped by hexam-ethyldisilazane The relatively small size of carbene precludesthe steric factor in the reaction with hexamethyldisilazaneThe hydrolysis of bis(trimethylsilyl) group from this withmethanol sets the stage for it to undergo ring expansion togive 4
In view of the extremely weak nucleophilic character ofisatinylamide nitrogen of 3 the possibility of the rearrange-ment of the acyl carbene intermediate had to be ruled out(No rearranged product was however traceable from thereaction mixture)
As the carbene was not likely to be trapped by thetertiary amine (hexamine) its reactionwith hexaminewas notexamined
3 Experiment
All the melting points were taken in open capillaries and areuncorrected The purity of all the compounds were checkedby TLC using the solvent systems (benzene methanol9 1 vv) and silica gel G as adsorbent IR spectra wererecorded on Shimadzu FTIR-8400 infrared spectrometerusing KBr 1H NMR were recorded on Bruker AC 300Fin CDCl
3+ DMSO-d
6(2 1 vv TMS as internal reference
and chemical shifts expressed in 120575 ppm) and mass spectra
were recorded on Jeol-JMS-D-D-300 mass spectrometerReagents 5-fluoro- 5-chloro- 5-bromo- 5-iodo- 5-methyl-5-methoxy- 5-nitro- and 57-dimethylisatins were procuredfrom commercial sources and used as such in the reactionwithout further purifications (see Scheme 1)
31 General Methods for the Preparation of 2(andashi) from 1(andashi)5-Fluoroisatin (1b 0068mol) was vigorously refluxed withchloroacetyl chloride (0090mol) for 7 h and themixturewascooled overnight at 0ndash5∘C The crude product which settledwas filtered washed with 20mL of ether air-dried and thenrecrystallised from ethyl acetate to give 2b yield 88 mp165-166∘C Other compounds 2(a cndashi) were prepared from1(a cndashi) using this procedure
32 General Methods for the Preparation of 4(andashi) from 2(andashi) 5-Fluoro-1-chloroacetylisatin (2b 001mol) was dissolvedin dry THF (20mL) and to this solution n-butyl lithium(001mol) and hexamethyldisilazane (001mol) were addedThe reactionmixture was magnetically stirred for 2 h at roomtemperature The progress of reaction was checked by TLCMethanol (20mL) was added to the reaction mass and themixture was refluxed for 5 h It was then poured on crushedice filtered air-dried and recrystallised from methanol togive 4b yield 87 mp 198ndash200∘C Other compounds 4(acndashi) were prepared from 2(a cndashi) using the same procedure
4 Conclusion
In summary a high yielding n-butyl lithium catalysedone-pot domino process has been developed to the facileaccess of the privileged nucleus of methyl-13-dihydro-2H-14-benzodiazepin-2-one-5-carboxylates 4(andashi) at ambienttemperature from the ring expansion of the corresponding 1-chloroacetylisatins 2(andashi) under the influence of hexamethyl-disilazane
Conflict of Interests
The authors declare that there is no conflict of interestsregarding the publication of this paper
Advances in Chemistry 3
Table1Ph
ysicalandspectraldataof
thec
ompo
unds
2(andashi)and4(andashi)
Entry
Molecular
form
ula
MW
MP
(∘ C)a
Yield(
)IR
(KBr)cmminus1
1 HNMR(C
DCl
3-DMSO
-d6)120575pp
mElem
entalanalysis
C(caldexp)
H(caldexp)
N(caldexp)
2aC 1
0H6C
lNO
322361
210ndash
1291
173516801675
756ndash
719(m
4HA
rH)432
(s2HC
H2)
53715
367
270265
626618
2bC 1
0H5C
lFNO
32416
0165ndash66
88175517251700
781ndash72
3(m
3HA
rH)433
(s2HC
H2)
49714
967
249240
580569
2cC 1
0H5C
l 2NO
325806
153ndash55
94178517401720
781ndash753(m
3HA
rH)432
(s2HC
H2)
465446
42
19519
0543531
2dC 1
0H5BrC
lNO
330251
178ndash79
90178017351710
796ndash
761(m3HA
rH)432
(s2HC
H2)
39703962
16715
6463459
2eC 1
0H5C
lINO
33495
1206ndash
0789
177017251690
780ndash
750(m
3HA
rH)428
(s2HC
H2)
28952889
1211
17338327
2fC 1
1H8C
lNO
32376
4185ndash86
92176517201690
772ndash70
3(m
3HA
rH)432
(s2HC
H2)
285
(s3HC
H3)
55605551
339328
589580
2gC 1
1H8C
lNO
425364
223ndash25
90178017401705
772ndash70
3(m
3HA
rH)432
(s2HC
H2)
373
(s3HO
CH3)
52095197
318312
552542
2hC 1
0H5C
lN2O
526861
130ndash
3291
178517451710
872ndash809(m
3HA
rH)452
(s2HC
H2)
44714
456
18817
110431037
2iC 1
2H10ClNO
32516
7168ndash70
921740
17001685
740ndash
712(m
2HA
rH)432
(s2HC
H2)
235
(s6HC
H3)
57275719
401397
557546
4aC 1
1H10N
2O3
21821
172ndash75
85319017251675
80(s1HN
H)79
8ndash76
5(m
4HA
rH)
448
(s2HC
H2)365(s3HO
CH3)
MS119898119911(
)21821(M+
100
)21020
(75
)10716(35
)
60556048
462452
12841279
4bC 1
1H9FN
2O3
23620
198ndash200
87322017351690
82(s1HN
H)808
(d1HA
rH)77
8(d
1HA
rH)
766(s1HA
rH)456
(s2HC
H2)378
(s3HO
CH3)
MS119898119911(
)23620(M
+75)20517
(100)17716(35
)
55935588
384379
11861176
4cC 1
1H9C
lN2O
325265
176ndash
7884
321517281684
81(s1H
NH)79
0(s1HA
rH)78
1(d
1HA
rH)
760(d1HA
rH)448
(s2HC
H2)370
(s3HO
CH3)MS119898119911(
)25265(M
+100
)25457
(M+2
33
)
52295223
359351
11091100
4dC 1
1H9BrN
2O3
2979
8243ndash45
86320817211675
80(s1HN
H)79
0(s1HA
rH)77
5(d
1HA
rH)
750(d1HA
rH)432
(s2HC
H2)312
(s3HO
CH3)MS119898119911(
)29798(M
+100
)2999
0(M
+2100)17716(35
)
444744
41
305299
94393
6
4eC 1
1H9IN
2O3
34411
187ndash88
90320017101670
80(s1HN
H)78
5(s1HA
rH)76
6(d
1HA
rH)
740(d1HA
rH)432
(s2HC
H2)312
(s3HO
CH3)
MS119898119911(
)344
11(M
+75)20517
(100)14716(35
)
3839
3829
264
259
814807
4 Advances in Chemistry
Table1Con
tinued
Entry
Molecular
form
ula
MW
MP
(∘ C)a
Yield
()
IR(K
Br)cmminus1
1 HNMR(C
DCl
3-DMSO
-d6)120575pp
mElem
entalanalysis
C(caldexp)
H(caldexp)
N(caldexp)
4fC 1
2H12N
2O3
23224
205ndash06
85318817231672
80(s1HN
H)78
4(s1HA
rH)75
6(d
1HA
rH)
742(d1HA
rH)432
(s2HC
H2)312
(s3HO
CH3)
234
(s3HC
H3)
MS119898119911(
)23224(M
+72)1772
5(25
)1491
7(100)
62606252
521517
12061196
4gC 1
2H12N
2O4
24808
182ndash85
87320217281677
80(s1HN
H)78
8(d1HA
rH)77
5(d
1HA
rH)
743(s1HA
rH)433
(s2HC
H2)312
(s3HO
CH3)
363
(s3HO
CH3)
MS119898119911(
)24808(M
+68)24011
(100)16345
(36
)
58065798
487479
11291119
4hC 1
1H9N
3O5
26305
202ndash05
83322817351698
80(s1HN
H)812
(s1HA
rH)79
8(d
1HA
rH)
766(d1HA
rH)455
(s2HC
H2)342
(s3HO
CH3)
MS119898119911(
)26305(M
+65)20117
(100)17080
(35
)
50205013
345334
15961589
4iC 1
3H14N
2O3
24626
215ndash17
88318517201670
80(s1HN
H)74
0(s2HA
rH)430
(s
2HC
H2)
310
(s3HO
CH3)234(s3Hfor
two
CH3)
MS119898119911(
)246
26(M
+100
)14517
(86
)10416
(27
)
63406331
573569
11381133
a Allthem
eltingpo
ints(M
P)w
erefou
ndto
beidenticalto
thea
uthenticsamples
prepared
accordingto
thep
rocedu
rerepo
rted
intheliterature
[22]
MWMolecular
Weightcaldexpcalculatedexp
erim
ental
Advances in Chemistry 5
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
CHR2
R2
R2
R2R2
R1
R1
R1
R1
R1
R1
R2
N
N
N
N
N
N
CC C
C
CH2Cl
n-BuLi THF
NH
SiMe3
SiMe3SiMe3
SiMe3HN
H
H
2
Me OH
MeOOCCOOMe
H2N
CH2
N CH
Δ2(andashi) 3(andashi)
4(andashi)
1 2 3 and 4(andashi)
R1 = R2 = H
R1 = Cl R2 = HR1 = Br R2 = HR1 = I R2 = HR1 = Me R2 = HR1 = OMe R2 = HR1 = NO2 R2 = HR1 = Me R2 = Me
(a)(b)(c)(d)(e)(f)(g)(h)(i)
R1 = F R2 = H
Scheme 1 Schematic presentation of the synthesis of the compounds
Acknowledgments
The authors are grateful to the Director of CDRI LucknowIndia for providing the spectral data of the compounds and tothe Department of Science and Technology DST New DelhiIndia for providing the financial assistance to ldquoBanasthaliCentre for Education and Research in Basic Sciencesrdquo undertheir CURIE (Consolidation of University Research for Inno-vation and Excellence in Women Universities) programme
References
[1] M A Koch A Schuffenhauer M Scheck et al ldquoChartingbiologically relevant chemical space a structural classificationof natural products (SCONP)rdquo Proceedings of the NationalAcademy of Sciences of the United States of America vol 102 no48 pp 17272ndash17277 2005
[2] W Nawroca B Sztuba A Opolski J Wietrzk MW Kowalskaand T Glowiak ldquoSynthesis and antiproliferative activity in vitro
of novel 15-benzodiazepines Part IIrdquo Archive der Pharmazie-Pharmaceutical and Medicinal Chemistry vol 334 no 1 pp 3ndash10 2000
[3] B E Evans K E Rittle M G Bock et al ldquoMethods fordrug discovery development of potent selective orally effectivecholecystokinin antagonistsrdquo Journal of Medicinal Chemistryvol 31 no 12 pp 2235ndash2246 1988
[4] R Yarchoan H Mitsuya R V Thomas et al ldquoIn vivoactivity against HIV and favorable toxicity profile of 2101584031015840-dideoxyinosinerdquo Science vol 245 no 4916 pp 412ndash415 1989
[5] J R Lokensgard C C Chao G Gekker S Hu and P KPeterson ldquoBenzodiazepines glia and HIV-1 neuropathogene-sisrdquoMolecular Neurobiology vol 18 no 1 pp 23ndash33 1998
[6] J Poupaert P Carato E Colacino and S Yous ldquo2(3H)-benzoxazolone and bioisosters as ldquoprivileged scaffoldrdquo in thedesign of pharmacological probesrdquo Current Medicinal Chem-istry vol 12 no 7 pp 877ndash885 2005
[7] D J Triggle ldquo14-dihydropyridines as calcium channel ligandsand privileged structuresrdquoCellular andMolecular Neurobiologyvol 23 no 3 pp 293ndash303 2003
6 Advances in Chemistry
[8] R W DeSimone K S Currie S A Mitchell J W Darrow andDA Pippin ldquoPrivileged structures applications in drug discov-eryrdquo Combinatorial Chemistry and High Throughput Screeningvol 7 no 5 pp 473ndash493 2004
[9] A A Patchett and R P Nargund ldquoChapter 26 Privilegedstructures an updaterdquo Annual Reports in Medicinal Chemistryvol 35 pp 289ndash298 2000
[10] J Yang Q Dang J Liu Z Wei J Wu and X Bai ldquoPreparationof a fully substituted purine libraryrdquo Journal of CombinatorialChemistry vol 7 no 3 pp 474ndash482 2005
[11] J Liu Q Dang ZWei H Zhang and X Bai ldquoParallel solution-phase synthesis of a 2689-tetrasubstituted purine library via asulfur intermediaterdquo Journal of Combinatorial Chemistry vol 7no 4 pp 627ndash636 2005
[12] Q Dang and J E Gomez-Galeno ldquoAn efficient synthesisof pyrrolo[23-d]pyrimidines via inverse electron demandDiels-Alder reactions of 2-amino-4-cyanopyrroles with 135-triazinesrdquo Journal of Organic Chemistry vol 67 no 24 pp8703ndash8705 2002
[13] P Bhuyan R C Boruah and J S Sandhu ldquoStudies on uracils 10A facile one-pot synthesis of pyrido[23-d]- and pyrazolo[34-d]pyrimidinesrdquo Journal of Organic Chemistry vol 55 no 2 pp568ndash571 1990
[14] R H Smith Jr W L Jorgen J Tirado-Rives et al ldquoPredictionof binding affinities for TIBO inhibitors of HIV-1 reverse tran-scriptase using Monte Carlo simulations in a linear responsemethodrdquo Journal of Medicinal Chemistry vol 41 no 26 pp5272ndash5286 1998
[15] B A Roberte K Andries J Desayter et al ldquoPotent and selectiveinhibition ofHIV-1 replication in vitro by a novel series of TIBOderivativesrdquo Nature vol 343 no 6257 pp 470ndash474 1990
[16] H J Breslin M J Kukla T Kromis et al ldquoSynthesis and anti-HIV activity of 1345-tetrahydro-2H-14- benzodiazepin-2-one (TBO) derivatives Truncated 4567-tetrahydro-5-methyl-imidazo[451-jk][14]benzodiazepin-2(1H)-ones (TIBO) ana-loguesrdquo Bioorganic and Medicinal Chemistry vol 7 no 11 pp2427ndash2436 1999
[17] W Ho M J Kukla H J Breslin et al ldquoSynthesis and anti-HIV-1 activity of 4567-tetrahydro-5-methylimidazo-[451-jk][14]benzodiazepin-2(1H)-one (TIBO) derivatives 4rdquo Jour-nal of Medicinal Chemistry vol 38 no 5 pp 794ndash802 1995
[18] B D Puodziunaite R Janciene L Kosychova and Z Stum-breviciute ldquoOn the synthetic way to novel peri-annelatedimidazo[15]benzodiazepinones as the potent non-nucleosidereverse transcriptase inhibitorsrdquo Arkivoc vol 2000 no 4 pp512ndash522 2000
[19] M D Braccio G Grossi G Roma L Vargiu M Muraand M E Marongiu ldquo15-Benzodiazepines Part XII Synthe-sis and biological evaluation of tricyclic and tetracyclic 15-benzodiazepine derivatives as nevirapine analoguesrdquo EuropeanJournal of Medicinal Chemistry vol 36 no 11-12 pp 935ndash9492001
[20] A Kamal M V Rao N Laxman G Ramesh and GS Reddy ldquoRecent developments in the design synthe-sis and structure-activity relationship studies of pyrrolo[21-c][14]benzodiazepines as DNA-interactive antitumour antibi-oticsrdquo Current Medicinal ChemistrymdashAnti-Cancer Agents vol2 no 2 pp 215ndash254 2002
[21] P Sharma B Vashistha R Tygai et al ldquoApplication ofmicrowave induced Delepine reaction to the facile one pot
synthesis of 7-substituted 13-dihydro-2H-[14]-benzodiazepin-2-one-5-methyl carboxylates from the corresponding 1-chloroacetylisatinsrdquo International Journal of Chemical Sciencesvol 8 no 1 2010
[22] A Singh R Sirohi S Shastri and D Kishore ldquoA facile one-potsynthesis of 7-substituted-5-methoxycarbonyl-1H-2 3-dihydro-1 4-benzodiazepin-2-ones from 5-substituted-119873-chloroacetylisatinsrdquo Indian Journal of Chemistry B vol 42B no 12 pp 3124ndash3127 2003
[23] P D Popp ldquoThe chemistry of isatinrdquo inAdvances in HeterocyclicChemistry vol 18 pp 1ndash58 1975
[24] M Pal N K Sharma Priyanka and K K Jha ldquoSynthetic andbiological multiplicity of isatin a reviewrdquo Journal of AdvancedScientific Research vol 2 no 2 pp 35ndash44 2011
[25] N Blazevic D Kolbah B Belin V Sunjic and F Kajfez ldquoHex-amethylenetetramine ldquoA versatile reagent in organic synthesisrdquordquoSynthesis pp 167ndash176 1979
[26] B Rigoa P Caulieza D Fasseurb and D Couturierb ldquoReactionof hexamethyldisilazane with diacylhydrazines an easy 134-oxadiazole synthesisrdquo Synthetic Communications vol 16 no 13pp 1665ndash1669 1986
[27] M Ogata and H Matsumoto ldquoA convenient synthesis of5-substituted 13-dihydro-2H-14-benzodiazepine-2-onesrdquoChemistry and Industry p 1067 1976
[28] H Fujishima H Takeshita S Suzuki M Toyota and MIhara ldquoHexamethyldisilazanes mediated one-pot intramolec-ular Michael addition-olefination reactions leading to ejvo-olefinated bicyclo[640]dodecanesrdquo Journal of the ChemicalSociety Perkin Transactions 1 no 18 pp 2609ndash2616 1999
Submit your manuscripts athttpwwwhindawicom
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Inorganic ChemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
International Journal ofPhotoenergy
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Carbohydrate Chemistry
International Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Advances in
Physical Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom
Analytical Methods in Chemistry
Journal of
Volume 2014
Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
SpectroscopyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Medicinal ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Chromatography Research International
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Applied ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Theoretical ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Spectroscopy
Analytical ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Quantum Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Organic Chemistry International
ElectrochemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
CatalystsJournal of
Advances in Chemistry 3
Table1Ph
ysicalandspectraldataof
thec
ompo
unds
2(andashi)and4(andashi)
Entry
Molecular
form
ula
MW
MP
(∘ C)a
Yield(
)IR
(KBr)cmminus1
1 HNMR(C
DCl
3-DMSO
-d6)120575pp
mElem
entalanalysis
C(caldexp)
H(caldexp)
N(caldexp)
2aC 1
0H6C
lNO
322361
210ndash
1291
173516801675
756ndash
719(m
4HA
rH)432
(s2HC
H2)
53715
367
270265
626618
2bC 1
0H5C
lFNO
32416
0165ndash66
88175517251700
781ndash72
3(m
3HA
rH)433
(s2HC
H2)
49714
967
249240
580569
2cC 1
0H5C
l 2NO
325806
153ndash55
94178517401720
781ndash753(m
3HA
rH)432
(s2HC
H2)
465446
42
19519
0543531
2dC 1
0H5BrC
lNO
330251
178ndash79
90178017351710
796ndash
761(m3HA
rH)432
(s2HC
H2)
39703962
16715
6463459
2eC 1
0H5C
lINO
33495
1206ndash
0789
177017251690
780ndash
750(m
3HA
rH)428
(s2HC
H2)
28952889
1211
17338327
2fC 1
1H8C
lNO
32376
4185ndash86
92176517201690
772ndash70
3(m
3HA
rH)432
(s2HC
H2)
285
(s3HC
H3)
55605551
339328
589580
2gC 1
1H8C
lNO
425364
223ndash25
90178017401705
772ndash70
3(m
3HA
rH)432
(s2HC
H2)
373
(s3HO
CH3)
52095197
318312
552542
2hC 1
0H5C
lN2O
526861
130ndash
3291
178517451710
872ndash809(m
3HA
rH)452
(s2HC
H2)
44714
456
18817
110431037
2iC 1
2H10ClNO
32516
7168ndash70
921740
17001685
740ndash
712(m
2HA
rH)432
(s2HC
H2)
235
(s6HC
H3)
57275719
401397
557546
4aC 1
1H10N
2O3
21821
172ndash75
85319017251675
80(s1HN
H)79
8ndash76
5(m
4HA
rH)
448
(s2HC
H2)365(s3HO
CH3)
MS119898119911(
)21821(M+
100
)21020
(75
)10716(35
)
60556048
462452
12841279
4bC 1
1H9FN
2O3
23620
198ndash200
87322017351690
82(s1HN
H)808
(d1HA
rH)77
8(d
1HA
rH)
766(s1HA
rH)456
(s2HC
H2)378
(s3HO
CH3)
MS119898119911(
)23620(M
+75)20517
(100)17716(35
)
55935588
384379
11861176
4cC 1
1H9C
lN2O
325265
176ndash
7884
321517281684
81(s1H
NH)79
0(s1HA
rH)78
1(d
1HA
rH)
760(d1HA
rH)448
(s2HC
H2)370
(s3HO
CH3)MS119898119911(
)25265(M
+100
)25457
(M+2
33
)
52295223
359351
11091100
4dC 1
1H9BrN
2O3
2979
8243ndash45
86320817211675
80(s1HN
H)79
0(s1HA
rH)77
5(d
1HA
rH)
750(d1HA
rH)432
(s2HC
H2)312
(s3HO
CH3)MS119898119911(
)29798(M
+100
)2999
0(M
+2100)17716(35
)
444744
41
305299
94393
6
4eC 1
1H9IN
2O3
34411
187ndash88
90320017101670
80(s1HN
H)78
5(s1HA
rH)76
6(d
1HA
rH)
740(d1HA
rH)432
(s2HC
H2)312
(s3HO
CH3)
MS119898119911(
)344
11(M
+75)20517
(100)14716(35
)
3839
3829
264
259
814807
4 Advances in Chemistry
Table1Con
tinued
Entry
Molecular
form
ula
MW
MP
(∘ C)a
Yield
()
IR(K
Br)cmminus1
1 HNMR(C
DCl
3-DMSO
-d6)120575pp
mElem
entalanalysis
C(caldexp)
H(caldexp)
N(caldexp)
4fC 1
2H12N
2O3
23224
205ndash06
85318817231672
80(s1HN
H)78
4(s1HA
rH)75
6(d
1HA
rH)
742(d1HA
rH)432
(s2HC
H2)312
(s3HO
CH3)
234
(s3HC
H3)
MS119898119911(
)23224(M
+72)1772
5(25
)1491
7(100)
62606252
521517
12061196
4gC 1
2H12N
2O4
24808
182ndash85
87320217281677
80(s1HN
H)78
8(d1HA
rH)77
5(d
1HA
rH)
743(s1HA
rH)433
(s2HC
H2)312
(s3HO
CH3)
363
(s3HO
CH3)
MS119898119911(
)24808(M
+68)24011
(100)16345
(36
)
58065798
487479
11291119
4hC 1
1H9N
3O5
26305
202ndash05
83322817351698
80(s1HN
H)812
(s1HA
rH)79
8(d
1HA
rH)
766(d1HA
rH)455
(s2HC
H2)342
(s3HO
CH3)
MS119898119911(
)26305(M
+65)20117
(100)17080
(35
)
50205013
345334
15961589
4iC 1
3H14N
2O3
24626
215ndash17
88318517201670
80(s1HN
H)74
0(s2HA
rH)430
(s
2HC
H2)
310
(s3HO
CH3)234(s3Hfor
two
CH3)
MS119898119911(
)246
26(M
+100
)14517
(86
)10416
(27
)
63406331
573569
11381133
a Allthem
eltingpo
ints(M
P)w
erefou
ndto
beidenticalto
thea
uthenticsamples
prepared
accordingto
thep
rocedu
rerepo
rted
intheliterature
[22]
MWMolecular
Weightcaldexpcalculatedexp
erim
ental
Advances in Chemistry 5
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
CHR2
R2
R2
R2R2
R1
R1
R1
R1
R1
R1
R2
N
N
N
N
N
N
CC C
C
CH2Cl
n-BuLi THF
NH
SiMe3
SiMe3SiMe3
SiMe3HN
H
H
2
Me OH
MeOOCCOOMe
H2N
CH2
N CH
Δ2(andashi) 3(andashi)
4(andashi)
1 2 3 and 4(andashi)
R1 = R2 = H
R1 = Cl R2 = HR1 = Br R2 = HR1 = I R2 = HR1 = Me R2 = HR1 = OMe R2 = HR1 = NO2 R2 = HR1 = Me R2 = Me
(a)(b)(c)(d)(e)(f)(g)(h)(i)
R1 = F R2 = H
Scheme 1 Schematic presentation of the synthesis of the compounds
Acknowledgments
The authors are grateful to the Director of CDRI LucknowIndia for providing the spectral data of the compounds and tothe Department of Science and Technology DST New DelhiIndia for providing the financial assistance to ldquoBanasthaliCentre for Education and Research in Basic Sciencesrdquo undertheir CURIE (Consolidation of University Research for Inno-vation and Excellence in Women Universities) programme
References
[1] M A Koch A Schuffenhauer M Scheck et al ldquoChartingbiologically relevant chemical space a structural classificationof natural products (SCONP)rdquo Proceedings of the NationalAcademy of Sciences of the United States of America vol 102 no48 pp 17272ndash17277 2005
[2] W Nawroca B Sztuba A Opolski J Wietrzk MW Kowalskaand T Glowiak ldquoSynthesis and antiproliferative activity in vitro
of novel 15-benzodiazepines Part IIrdquo Archive der Pharmazie-Pharmaceutical and Medicinal Chemistry vol 334 no 1 pp 3ndash10 2000
[3] B E Evans K E Rittle M G Bock et al ldquoMethods fordrug discovery development of potent selective orally effectivecholecystokinin antagonistsrdquo Journal of Medicinal Chemistryvol 31 no 12 pp 2235ndash2246 1988
[4] R Yarchoan H Mitsuya R V Thomas et al ldquoIn vivoactivity against HIV and favorable toxicity profile of 2101584031015840-dideoxyinosinerdquo Science vol 245 no 4916 pp 412ndash415 1989
[5] J R Lokensgard C C Chao G Gekker S Hu and P KPeterson ldquoBenzodiazepines glia and HIV-1 neuropathogene-sisrdquoMolecular Neurobiology vol 18 no 1 pp 23ndash33 1998
[6] J Poupaert P Carato E Colacino and S Yous ldquo2(3H)-benzoxazolone and bioisosters as ldquoprivileged scaffoldrdquo in thedesign of pharmacological probesrdquo Current Medicinal Chem-istry vol 12 no 7 pp 877ndash885 2005
[7] D J Triggle ldquo14-dihydropyridines as calcium channel ligandsand privileged structuresrdquoCellular andMolecular Neurobiologyvol 23 no 3 pp 293ndash303 2003
6 Advances in Chemistry
[8] R W DeSimone K S Currie S A Mitchell J W Darrow andDA Pippin ldquoPrivileged structures applications in drug discov-eryrdquo Combinatorial Chemistry and High Throughput Screeningvol 7 no 5 pp 473ndash493 2004
[9] A A Patchett and R P Nargund ldquoChapter 26 Privilegedstructures an updaterdquo Annual Reports in Medicinal Chemistryvol 35 pp 289ndash298 2000
[10] J Yang Q Dang J Liu Z Wei J Wu and X Bai ldquoPreparationof a fully substituted purine libraryrdquo Journal of CombinatorialChemistry vol 7 no 3 pp 474ndash482 2005
[11] J Liu Q Dang ZWei H Zhang and X Bai ldquoParallel solution-phase synthesis of a 2689-tetrasubstituted purine library via asulfur intermediaterdquo Journal of Combinatorial Chemistry vol 7no 4 pp 627ndash636 2005
[12] Q Dang and J E Gomez-Galeno ldquoAn efficient synthesisof pyrrolo[23-d]pyrimidines via inverse electron demandDiels-Alder reactions of 2-amino-4-cyanopyrroles with 135-triazinesrdquo Journal of Organic Chemistry vol 67 no 24 pp8703ndash8705 2002
[13] P Bhuyan R C Boruah and J S Sandhu ldquoStudies on uracils 10A facile one-pot synthesis of pyrido[23-d]- and pyrazolo[34-d]pyrimidinesrdquo Journal of Organic Chemistry vol 55 no 2 pp568ndash571 1990
[14] R H Smith Jr W L Jorgen J Tirado-Rives et al ldquoPredictionof binding affinities for TIBO inhibitors of HIV-1 reverse tran-scriptase using Monte Carlo simulations in a linear responsemethodrdquo Journal of Medicinal Chemistry vol 41 no 26 pp5272ndash5286 1998
[15] B A Roberte K Andries J Desayter et al ldquoPotent and selectiveinhibition ofHIV-1 replication in vitro by a novel series of TIBOderivativesrdquo Nature vol 343 no 6257 pp 470ndash474 1990
[16] H J Breslin M J Kukla T Kromis et al ldquoSynthesis and anti-HIV activity of 1345-tetrahydro-2H-14- benzodiazepin-2-one (TBO) derivatives Truncated 4567-tetrahydro-5-methyl-imidazo[451-jk][14]benzodiazepin-2(1H)-ones (TIBO) ana-loguesrdquo Bioorganic and Medicinal Chemistry vol 7 no 11 pp2427ndash2436 1999
[17] W Ho M J Kukla H J Breslin et al ldquoSynthesis and anti-HIV-1 activity of 4567-tetrahydro-5-methylimidazo-[451-jk][14]benzodiazepin-2(1H)-one (TIBO) derivatives 4rdquo Jour-nal of Medicinal Chemistry vol 38 no 5 pp 794ndash802 1995
[18] B D Puodziunaite R Janciene L Kosychova and Z Stum-breviciute ldquoOn the synthetic way to novel peri-annelatedimidazo[15]benzodiazepinones as the potent non-nucleosidereverse transcriptase inhibitorsrdquo Arkivoc vol 2000 no 4 pp512ndash522 2000
[19] M D Braccio G Grossi G Roma L Vargiu M Muraand M E Marongiu ldquo15-Benzodiazepines Part XII Synthe-sis and biological evaluation of tricyclic and tetracyclic 15-benzodiazepine derivatives as nevirapine analoguesrdquo EuropeanJournal of Medicinal Chemistry vol 36 no 11-12 pp 935ndash9492001
[20] A Kamal M V Rao N Laxman G Ramesh and GS Reddy ldquoRecent developments in the design synthe-sis and structure-activity relationship studies of pyrrolo[21-c][14]benzodiazepines as DNA-interactive antitumour antibi-oticsrdquo Current Medicinal ChemistrymdashAnti-Cancer Agents vol2 no 2 pp 215ndash254 2002
[21] P Sharma B Vashistha R Tygai et al ldquoApplication ofmicrowave induced Delepine reaction to the facile one pot
synthesis of 7-substituted 13-dihydro-2H-[14]-benzodiazepin-2-one-5-methyl carboxylates from the corresponding 1-chloroacetylisatinsrdquo International Journal of Chemical Sciencesvol 8 no 1 2010
[22] A Singh R Sirohi S Shastri and D Kishore ldquoA facile one-potsynthesis of 7-substituted-5-methoxycarbonyl-1H-2 3-dihydro-1 4-benzodiazepin-2-ones from 5-substituted-119873-chloroacetylisatinsrdquo Indian Journal of Chemistry B vol 42B no 12 pp 3124ndash3127 2003
[23] P D Popp ldquoThe chemistry of isatinrdquo inAdvances in HeterocyclicChemistry vol 18 pp 1ndash58 1975
[24] M Pal N K Sharma Priyanka and K K Jha ldquoSynthetic andbiological multiplicity of isatin a reviewrdquo Journal of AdvancedScientific Research vol 2 no 2 pp 35ndash44 2011
[25] N Blazevic D Kolbah B Belin V Sunjic and F Kajfez ldquoHex-amethylenetetramine ldquoA versatile reagent in organic synthesisrdquordquoSynthesis pp 167ndash176 1979
[26] B Rigoa P Caulieza D Fasseurb and D Couturierb ldquoReactionof hexamethyldisilazane with diacylhydrazines an easy 134-oxadiazole synthesisrdquo Synthetic Communications vol 16 no 13pp 1665ndash1669 1986
[27] M Ogata and H Matsumoto ldquoA convenient synthesis of5-substituted 13-dihydro-2H-14-benzodiazepine-2-onesrdquoChemistry and Industry p 1067 1976
[28] H Fujishima H Takeshita S Suzuki M Toyota and MIhara ldquoHexamethyldisilazanes mediated one-pot intramolec-ular Michael addition-olefination reactions leading to ejvo-olefinated bicyclo[640]dodecanesrdquo Journal of the ChemicalSociety Perkin Transactions 1 no 18 pp 2609ndash2616 1999
Submit your manuscripts athttpwwwhindawicom
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Inorganic ChemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
International Journal ofPhotoenergy
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Carbohydrate Chemistry
International Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Advances in
Physical Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom
Analytical Methods in Chemistry
Journal of
Volume 2014
Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
SpectroscopyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Medicinal ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Chromatography Research International
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Applied ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Theoretical ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Spectroscopy
Analytical ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Quantum Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Organic Chemistry International
ElectrochemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
CatalystsJournal of
4 Advances in Chemistry
Table1Con
tinued
Entry
Molecular
form
ula
MW
MP
(∘ C)a
Yield
()
IR(K
Br)cmminus1
1 HNMR(C
DCl
3-DMSO
-d6)120575pp
mElem
entalanalysis
C(caldexp)
H(caldexp)
N(caldexp)
4fC 1
2H12N
2O3
23224
205ndash06
85318817231672
80(s1HN
H)78
4(s1HA
rH)75
6(d
1HA
rH)
742(d1HA
rH)432
(s2HC
H2)312
(s3HO
CH3)
234
(s3HC
H3)
MS119898119911(
)23224(M
+72)1772
5(25
)1491
7(100)
62606252
521517
12061196
4gC 1
2H12N
2O4
24808
182ndash85
87320217281677
80(s1HN
H)78
8(d1HA
rH)77
5(d
1HA
rH)
743(s1HA
rH)433
(s2HC
H2)312
(s3HO
CH3)
363
(s3HO
CH3)
MS119898119911(
)24808(M
+68)24011
(100)16345
(36
)
58065798
487479
11291119
4hC 1
1H9N
3O5
26305
202ndash05
83322817351698
80(s1HN
H)812
(s1HA
rH)79
8(d
1HA
rH)
766(d1HA
rH)455
(s2HC
H2)342
(s3HO
CH3)
MS119898119911(
)26305(M
+65)20117
(100)17080
(35
)
50205013
345334
15961589
4iC 1
3H14N
2O3
24626
215ndash17
88318517201670
80(s1HN
H)74
0(s2HA
rH)430
(s
2HC
H2)
310
(s3HO
CH3)234(s3Hfor
two
CH3)
MS119898119911(
)246
26(M
+100
)14517
(86
)10416
(27
)
63406331
573569
11381133
a Allthem
eltingpo
ints(M
P)w
erefou
ndto
beidenticalto
thea
uthenticsamples
prepared
accordingto
thep
rocedu
rerepo
rted
intheliterature
[22]
MWMolecular
Weightcaldexpcalculatedexp
erim
ental
Advances in Chemistry 5
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
CHR2
R2
R2
R2R2
R1
R1
R1
R1
R1
R1
R2
N
N
N
N
N
N
CC C
C
CH2Cl
n-BuLi THF
NH
SiMe3
SiMe3SiMe3
SiMe3HN
H
H
2
Me OH
MeOOCCOOMe
H2N
CH2
N CH
Δ2(andashi) 3(andashi)
4(andashi)
1 2 3 and 4(andashi)
R1 = R2 = H
R1 = Cl R2 = HR1 = Br R2 = HR1 = I R2 = HR1 = Me R2 = HR1 = OMe R2 = HR1 = NO2 R2 = HR1 = Me R2 = Me
(a)(b)(c)(d)(e)(f)(g)(h)(i)
R1 = F R2 = H
Scheme 1 Schematic presentation of the synthesis of the compounds
Acknowledgments
The authors are grateful to the Director of CDRI LucknowIndia for providing the spectral data of the compounds and tothe Department of Science and Technology DST New DelhiIndia for providing the financial assistance to ldquoBanasthaliCentre for Education and Research in Basic Sciencesrdquo undertheir CURIE (Consolidation of University Research for Inno-vation and Excellence in Women Universities) programme
References
[1] M A Koch A Schuffenhauer M Scheck et al ldquoChartingbiologically relevant chemical space a structural classificationof natural products (SCONP)rdquo Proceedings of the NationalAcademy of Sciences of the United States of America vol 102 no48 pp 17272ndash17277 2005
[2] W Nawroca B Sztuba A Opolski J Wietrzk MW Kowalskaand T Glowiak ldquoSynthesis and antiproliferative activity in vitro
of novel 15-benzodiazepines Part IIrdquo Archive der Pharmazie-Pharmaceutical and Medicinal Chemistry vol 334 no 1 pp 3ndash10 2000
[3] B E Evans K E Rittle M G Bock et al ldquoMethods fordrug discovery development of potent selective orally effectivecholecystokinin antagonistsrdquo Journal of Medicinal Chemistryvol 31 no 12 pp 2235ndash2246 1988
[4] R Yarchoan H Mitsuya R V Thomas et al ldquoIn vivoactivity against HIV and favorable toxicity profile of 2101584031015840-dideoxyinosinerdquo Science vol 245 no 4916 pp 412ndash415 1989
[5] J R Lokensgard C C Chao G Gekker S Hu and P KPeterson ldquoBenzodiazepines glia and HIV-1 neuropathogene-sisrdquoMolecular Neurobiology vol 18 no 1 pp 23ndash33 1998
[6] J Poupaert P Carato E Colacino and S Yous ldquo2(3H)-benzoxazolone and bioisosters as ldquoprivileged scaffoldrdquo in thedesign of pharmacological probesrdquo Current Medicinal Chem-istry vol 12 no 7 pp 877ndash885 2005
[7] D J Triggle ldquo14-dihydropyridines as calcium channel ligandsand privileged structuresrdquoCellular andMolecular Neurobiologyvol 23 no 3 pp 293ndash303 2003
6 Advances in Chemistry
[8] R W DeSimone K S Currie S A Mitchell J W Darrow andDA Pippin ldquoPrivileged structures applications in drug discov-eryrdquo Combinatorial Chemistry and High Throughput Screeningvol 7 no 5 pp 473ndash493 2004
[9] A A Patchett and R P Nargund ldquoChapter 26 Privilegedstructures an updaterdquo Annual Reports in Medicinal Chemistryvol 35 pp 289ndash298 2000
[10] J Yang Q Dang J Liu Z Wei J Wu and X Bai ldquoPreparationof a fully substituted purine libraryrdquo Journal of CombinatorialChemistry vol 7 no 3 pp 474ndash482 2005
[11] J Liu Q Dang ZWei H Zhang and X Bai ldquoParallel solution-phase synthesis of a 2689-tetrasubstituted purine library via asulfur intermediaterdquo Journal of Combinatorial Chemistry vol 7no 4 pp 627ndash636 2005
[12] Q Dang and J E Gomez-Galeno ldquoAn efficient synthesisof pyrrolo[23-d]pyrimidines via inverse electron demandDiels-Alder reactions of 2-amino-4-cyanopyrroles with 135-triazinesrdquo Journal of Organic Chemistry vol 67 no 24 pp8703ndash8705 2002
[13] P Bhuyan R C Boruah and J S Sandhu ldquoStudies on uracils 10A facile one-pot synthesis of pyrido[23-d]- and pyrazolo[34-d]pyrimidinesrdquo Journal of Organic Chemistry vol 55 no 2 pp568ndash571 1990
[14] R H Smith Jr W L Jorgen J Tirado-Rives et al ldquoPredictionof binding affinities for TIBO inhibitors of HIV-1 reverse tran-scriptase using Monte Carlo simulations in a linear responsemethodrdquo Journal of Medicinal Chemistry vol 41 no 26 pp5272ndash5286 1998
[15] B A Roberte K Andries J Desayter et al ldquoPotent and selectiveinhibition ofHIV-1 replication in vitro by a novel series of TIBOderivativesrdquo Nature vol 343 no 6257 pp 470ndash474 1990
[16] H J Breslin M J Kukla T Kromis et al ldquoSynthesis and anti-HIV activity of 1345-tetrahydro-2H-14- benzodiazepin-2-one (TBO) derivatives Truncated 4567-tetrahydro-5-methyl-imidazo[451-jk][14]benzodiazepin-2(1H)-ones (TIBO) ana-loguesrdquo Bioorganic and Medicinal Chemistry vol 7 no 11 pp2427ndash2436 1999
[17] W Ho M J Kukla H J Breslin et al ldquoSynthesis and anti-HIV-1 activity of 4567-tetrahydro-5-methylimidazo-[451-jk][14]benzodiazepin-2(1H)-one (TIBO) derivatives 4rdquo Jour-nal of Medicinal Chemistry vol 38 no 5 pp 794ndash802 1995
[18] B D Puodziunaite R Janciene L Kosychova and Z Stum-breviciute ldquoOn the synthetic way to novel peri-annelatedimidazo[15]benzodiazepinones as the potent non-nucleosidereverse transcriptase inhibitorsrdquo Arkivoc vol 2000 no 4 pp512ndash522 2000
[19] M D Braccio G Grossi G Roma L Vargiu M Muraand M E Marongiu ldquo15-Benzodiazepines Part XII Synthe-sis and biological evaluation of tricyclic and tetracyclic 15-benzodiazepine derivatives as nevirapine analoguesrdquo EuropeanJournal of Medicinal Chemistry vol 36 no 11-12 pp 935ndash9492001
[20] A Kamal M V Rao N Laxman G Ramesh and GS Reddy ldquoRecent developments in the design synthe-sis and structure-activity relationship studies of pyrrolo[21-c][14]benzodiazepines as DNA-interactive antitumour antibi-oticsrdquo Current Medicinal ChemistrymdashAnti-Cancer Agents vol2 no 2 pp 215ndash254 2002
[21] P Sharma B Vashistha R Tygai et al ldquoApplication ofmicrowave induced Delepine reaction to the facile one pot
synthesis of 7-substituted 13-dihydro-2H-[14]-benzodiazepin-2-one-5-methyl carboxylates from the corresponding 1-chloroacetylisatinsrdquo International Journal of Chemical Sciencesvol 8 no 1 2010
[22] A Singh R Sirohi S Shastri and D Kishore ldquoA facile one-potsynthesis of 7-substituted-5-methoxycarbonyl-1H-2 3-dihydro-1 4-benzodiazepin-2-ones from 5-substituted-119873-chloroacetylisatinsrdquo Indian Journal of Chemistry B vol 42B no 12 pp 3124ndash3127 2003
[23] P D Popp ldquoThe chemistry of isatinrdquo inAdvances in HeterocyclicChemistry vol 18 pp 1ndash58 1975
[24] M Pal N K Sharma Priyanka and K K Jha ldquoSynthetic andbiological multiplicity of isatin a reviewrdquo Journal of AdvancedScientific Research vol 2 no 2 pp 35ndash44 2011
[25] N Blazevic D Kolbah B Belin V Sunjic and F Kajfez ldquoHex-amethylenetetramine ldquoA versatile reagent in organic synthesisrdquordquoSynthesis pp 167ndash176 1979
[26] B Rigoa P Caulieza D Fasseurb and D Couturierb ldquoReactionof hexamethyldisilazane with diacylhydrazines an easy 134-oxadiazole synthesisrdquo Synthetic Communications vol 16 no 13pp 1665ndash1669 1986
[27] M Ogata and H Matsumoto ldquoA convenient synthesis of5-substituted 13-dihydro-2H-14-benzodiazepine-2-onesrdquoChemistry and Industry p 1067 1976
[28] H Fujishima H Takeshita S Suzuki M Toyota and MIhara ldquoHexamethyldisilazanes mediated one-pot intramolec-ular Michael addition-olefination reactions leading to ejvo-olefinated bicyclo[640]dodecanesrdquo Journal of the ChemicalSociety Perkin Transactions 1 no 18 pp 2609ndash2616 1999
Submit your manuscripts athttpwwwhindawicom
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Inorganic ChemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
International Journal ofPhotoenergy
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Carbohydrate Chemistry
International Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Advances in
Physical Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom
Analytical Methods in Chemistry
Journal of
Volume 2014
Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
SpectroscopyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Medicinal ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Chromatography Research International
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Applied ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Theoretical ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Spectroscopy
Analytical ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Quantum Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Organic Chemistry International
ElectrochemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
CatalystsJournal of
Advances in Chemistry 5
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
CHR2
R2
R2
R2R2
R1
R1
R1
R1
R1
R1
R2
N
N
N
N
N
N
CC C
C
CH2Cl
n-BuLi THF
NH
SiMe3
SiMe3SiMe3
SiMe3HN
H
H
2
Me OH
MeOOCCOOMe
H2N
CH2
N CH
Δ2(andashi) 3(andashi)
4(andashi)
1 2 3 and 4(andashi)
R1 = R2 = H
R1 = Cl R2 = HR1 = Br R2 = HR1 = I R2 = HR1 = Me R2 = HR1 = OMe R2 = HR1 = NO2 R2 = HR1 = Me R2 = Me
(a)(b)(c)(d)(e)(f)(g)(h)(i)
R1 = F R2 = H
Scheme 1 Schematic presentation of the synthesis of the compounds
Acknowledgments
The authors are grateful to the Director of CDRI LucknowIndia for providing the spectral data of the compounds and tothe Department of Science and Technology DST New DelhiIndia for providing the financial assistance to ldquoBanasthaliCentre for Education and Research in Basic Sciencesrdquo undertheir CURIE (Consolidation of University Research for Inno-vation and Excellence in Women Universities) programme
References
[1] M A Koch A Schuffenhauer M Scheck et al ldquoChartingbiologically relevant chemical space a structural classificationof natural products (SCONP)rdquo Proceedings of the NationalAcademy of Sciences of the United States of America vol 102 no48 pp 17272ndash17277 2005
[2] W Nawroca B Sztuba A Opolski J Wietrzk MW Kowalskaand T Glowiak ldquoSynthesis and antiproliferative activity in vitro
of novel 15-benzodiazepines Part IIrdquo Archive der Pharmazie-Pharmaceutical and Medicinal Chemistry vol 334 no 1 pp 3ndash10 2000
[3] B E Evans K E Rittle M G Bock et al ldquoMethods fordrug discovery development of potent selective orally effectivecholecystokinin antagonistsrdquo Journal of Medicinal Chemistryvol 31 no 12 pp 2235ndash2246 1988
[4] R Yarchoan H Mitsuya R V Thomas et al ldquoIn vivoactivity against HIV and favorable toxicity profile of 2101584031015840-dideoxyinosinerdquo Science vol 245 no 4916 pp 412ndash415 1989
[5] J R Lokensgard C C Chao G Gekker S Hu and P KPeterson ldquoBenzodiazepines glia and HIV-1 neuropathogene-sisrdquoMolecular Neurobiology vol 18 no 1 pp 23ndash33 1998
[6] J Poupaert P Carato E Colacino and S Yous ldquo2(3H)-benzoxazolone and bioisosters as ldquoprivileged scaffoldrdquo in thedesign of pharmacological probesrdquo Current Medicinal Chem-istry vol 12 no 7 pp 877ndash885 2005
[7] D J Triggle ldquo14-dihydropyridines as calcium channel ligandsand privileged structuresrdquoCellular andMolecular Neurobiologyvol 23 no 3 pp 293ndash303 2003
6 Advances in Chemistry
[8] R W DeSimone K S Currie S A Mitchell J W Darrow andDA Pippin ldquoPrivileged structures applications in drug discov-eryrdquo Combinatorial Chemistry and High Throughput Screeningvol 7 no 5 pp 473ndash493 2004
[9] A A Patchett and R P Nargund ldquoChapter 26 Privilegedstructures an updaterdquo Annual Reports in Medicinal Chemistryvol 35 pp 289ndash298 2000
[10] J Yang Q Dang J Liu Z Wei J Wu and X Bai ldquoPreparationof a fully substituted purine libraryrdquo Journal of CombinatorialChemistry vol 7 no 3 pp 474ndash482 2005
[11] J Liu Q Dang ZWei H Zhang and X Bai ldquoParallel solution-phase synthesis of a 2689-tetrasubstituted purine library via asulfur intermediaterdquo Journal of Combinatorial Chemistry vol 7no 4 pp 627ndash636 2005
[12] Q Dang and J E Gomez-Galeno ldquoAn efficient synthesisof pyrrolo[23-d]pyrimidines via inverse electron demandDiels-Alder reactions of 2-amino-4-cyanopyrroles with 135-triazinesrdquo Journal of Organic Chemistry vol 67 no 24 pp8703ndash8705 2002
[13] P Bhuyan R C Boruah and J S Sandhu ldquoStudies on uracils 10A facile one-pot synthesis of pyrido[23-d]- and pyrazolo[34-d]pyrimidinesrdquo Journal of Organic Chemistry vol 55 no 2 pp568ndash571 1990
[14] R H Smith Jr W L Jorgen J Tirado-Rives et al ldquoPredictionof binding affinities for TIBO inhibitors of HIV-1 reverse tran-scriptase using Monte Carlo simulations in a linear responsemethodrdquo Journal of Medicinal Chemistry vol 41 no 26 pp5272ndash5286 1998
[15] B A Roberte K Andries J Desayter et al ldquoPotent and selectiveinhibition ofHIV-1 replication in vitro by a novel series of TIBOderivativesrdquo Nature vol 343 no 6257 pp 470ndash474 1990
[16] H J Breslin M J Kukla T Kromis et al ldquoSynthesis and anti-HIV activity of 1345-tetrahydro-2H-14- benzodiazepin-2-one (TBO) derivatives Truncated 4567-tetrahydro-5-methyl-imidazo[451-jk][14]benzodiazepin-2(1H)-ones (TIBO) ana-loguesrdquo Bioorganic and Medicinal Chemistry vol 7 no 11 pp2427ndash2436 1999
[17] W Ho M J Kukla H J Breslin et al ldquoSynthesis and anti-HIV-1 activity of 4567-tetrahydro-5-methylimidazo-[451-jk][14]benzodiazepin-2(1H)-one (TIBO) derivatives 4rdquo Jour-nal of Medicinal Chemistry vol 38 no 5 pp 794ndash802 1995
[18] B D Puodziunaite R Janciene L Kosychova and Z Stum-breviciute ldquoOn the synthetic way to novel peri-annelatedimidazo[15]benzodiazepinones as the potent non-nucleosidereverse transcriptase inhibitorsrdquo Arkivoc vol 2000 no 4 pp512ndash522 2000
[19] M D Braccio G Grossi G Roma L Vargiu M Muraand M E Marongiu ldquo15-Benzodiazepines Part XII Synthe-sis and biological evaluation of tricyclic and tetracyclic 15-benzodiazepine derivatives as nevirapine analoguesrdquo EuropeanJournal of Medicinal Chemistry vol 36 no 11-12 pp 935ndash9492001
[20] A Kamal M V Rao N Laxman G Ramesh and GS Reddy ldquoRecent developments in the design synthe-sis and structure-activity relationship studies of pyrrolo[21-c][14]benzodiazepines as DNA-interactive antitumour antibi-oticsrdquo Current Medicinal ChemistrymdashAnti-Cancer Agents vol2 no 2 pp 215ndash254 2002
[21] P Sharma B Vashistha R Tygai et al ldquoApplication ofmicrowave induced Delepine reaction to the facile one pot
synthesis of 7-substituted 13-dihydro-2H-[14]-benzodiazepin-2-one-5-methyl carboxylates from the corresponding 1-chloroacetylisatinsrdquo International Journal of Chemical Sciencesvol 8 no 1 2010
[22] A Singh R Sirohi S Shastri and D Kishore ldquoA facile one-potsynthesis of 7-substituted-5-methoxycarbonyl-1H-2 3-dihydro-1 4-benzodiazepin-2-ones from 5-substituted-119873-chloroacetylisatinsrdquo Indian Journal of Chemistry B vol 42B no 12 pp 3124ndash3127 2003
[23] P D Popp ldquoThe chemistry of isatinrdquo inAdvances in HeterocyclicChemistry vol 18 pp 1ndash58 1975
[24] M Pal N K Sharma Priyanka and K K Jha ldquoSynthetic andbiological multiplicity of isatin a reviewrdquo Journal of AdvancedScientific Research vol 2 no 2 pp 35ndash44 2011
[25] N Blazevic D Kolbah B Belin V Sunjic and F Kajfez ldquoHex-amethylenetetramine ldquoA versatile reagent in organic synthesisrdquordquoSynthesis pp 167ndash176 1979
[26] B Rigoa P Caulieza D Fasseurb and D Couturierb ldquoReactionof hexamethyldisilazane with diacylhydrazines an easy 134-oxadiazole synthesisrdquo Synthetic Communications vol 16 no 13pp 1665ndash1669 1986
[27] M Ogata and H Matsumoto ldquoA convenient synthesis of5-substituted 13-dihydro-2H-14-benzodiazepine-2-onesrdquoChemistry and Industry p 1067 1976
[28] H Fujishima H Takeshita S Suzuki M Toyota and MIhara ldquoHexamethyldisilazanes mediated one-pot intramolec-ular Michael addition-olefination reactions leading to ejvo-olefinated bicyclo[640]dodecanesrdquo Journal of the ChemicalSociety Perkin Transactions 1 no 18 pp 2609ndash2616 1999
Submit your manuscripts athttpwwwhindawicom
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Inorganic ChemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
International Journal ofPhotoenergy
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Carbohydrate Chemistry
International Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Advances in
Physical Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom
Analytical Methods in Chemistry
Journal of
Volume 2014
Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
SpectroscopyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Medicinal ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Chromatography Research International
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Applied ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Theoretical ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Spectroscopy
Analytical ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Quantum Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Organic Chemistry International
ElectrochemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
CatalystsJournal of
6 Advances in Chemistry
[8] R W DeSimone K S Currie S A Mitchell J W Darrow andDA Pippin ldquoPrivileged structures applications in drug discov-eryrdquo Combinatorial Chemistry and High Throughput Screeningvol 7 no 5 pp 473ndash493 2004
[9] A A Patchett and R P Nargund ldquoChapter 26 Privilegedstructures an updaterdquo Annual Reports in Medicinal Chemistryvol 35 pp 289ndash298 2000
[10] J Yang Q Dang J Liu Z Wei J Wu and X Bai ldquoPreparationof a fully substituted purine libraryrdquo Journal of CombinatorialChemistry vol 7 no 3 pp 474ndash482 2005
[11] J Liu Q Dang ZWei H Zhang and X Bai ldquoParallel solution-phase synthesis of a 2689-tetrasubstituted purine library via asulfur intermediaterdquo Journal of Combinatorial Chemistry vol 7no 4 pp 627ndash636 2005
[12] Q Dang and J E Gomez-Galeno ldquoAn efficient synthesisof pyrrolo[23-d]pyrimidines via inverse electron demandDiels-Alder reactions of 2-amino-4-cyanopyrroles with 135-triazinesrdquo Journal of Organic Chemistry vol 67 no 24 pp8703ndash8705 2002
[13] P Bhuyan R C Boruah and J S Sandhu ldquoStudies on uracils 10A facile one-pot synthesis of pyrido[23-d]- and pyrazolo[34-d]pyrimidinesrdquo Journal of Organic Chemistry vol 55 no 2 pp568ndash571 1990
[14] R H Smith Jr W L Jorgen J Tirado-Rives et al ldquoPredictionof binding affinities for TIBO inhibitors of HIV-1 reverse tran-scriptase using Monte Carlo simulations in a linear responsemethodrdquo Journal of Medicinal Chemistry vol 41 no 26 pp5272ndash5286 1998
[15] B A Roberte K Andries J Desayter et al ldquoPotent and selectiveinhibition ofHIV-1 replication in vitro by a novel series of TIBOderivativesrdquo Nature vol 343 no 6257 pp 470ndash474 1990
[16] H J Breslin M J Kukla T Kromis et al ldquoSynthesis and anti-HIV activity of 1345-tetrahydro-2H-14- benzodiazepin-2-one (TBO) derivatives Truncated 4567-tetrahydro-5-methyl-imidazo[451-jk][14]benzodiazepin-2(1H)-ones (TIBO) ana-loguesrdquo Bioorganic and Medicinal Chemistry vol 7 no 11 pp2427ndash2436 1999
[17] W Ho M J Kukla H J Breslin et al ldquoSynthesis and anti-HIV-1 activity of 4567-tetrahydro-5-methylimidazo-[451-jk][14]benzodiazepin-2(1H)-one (TIBO) derivatives 4rdquo Jour-nal of Medicinal Chemistry vol 38 no 5 pp 794ndash802 1995
[18] B D Puodziunaite R Janciene L Kosychova and Z Stum-breviciute ldquoOn the synthetic way to novel peri-annelatedimidazo[15]benzodiazepinones as the potent non-nucleosidereverse transcriptase inhibitorsrdquo Arkivoc vol 2000 no 4 pp512ndash522 2000
[19] M D Braccio G Grossi G Roma L Vargiu M Muraand M E Marongiu ldquo15-Benzodiazepines Part XII Synthe-sis and biological evaluation of tricyclic and tetracyclic 15-benzodiazepine derivatives as nevirapine analoguesrdquo EuropeanJournal of Medicinal Chemistry vol 36 no 11-12 pp 935ndash9492001
[20] A Kamal M V Rao N Laxman G Ramesh and GS Reddy ldquoRecent developments in the design synthe-sis and structure-activity relationship studies of pyrrolo[21-c][14]benzodiazepines as DNA-interactive antitumour antibi-oticsrdquo Current Medicinal ChemistrymdashAnti-Cancer Agents vol2 no 2 pp 215ndash254 2002
[21] P Sharma B Vashistha R Tygai et al ldquoApplication ofmicrowave induced Delepine reaction to the facile one pot
synthesis of 7-substituted 13-dihydro-2H-[14]-benzodiazepin-2-one-5-methyl carboxylates from the corresponding 1-chloroacetylisatinsrdquo International Journal of Chemical Sciencesvol 8 no 1 2010
[22] A Singh R Sirohi S Shastri and D Kishore ldquoA facile one-potsynthesis of 7-substituted-5-methoxycarbonyl-1H-2 3-dihydro-1 4-benzodiazepin-2-ones from 5-substituted-119873-chloroacetylisatinsrdquo Indian Journal of Chemistry B vol 42B no 12 pp 3124ndash3127 2003
[23] P D Popp ldquoThe chemistry of isatinrdquo inAdvances in HeterocyclicChemistry vol 18 pp 1ndash58 1975
[24] M Pal N K Sharma Priyanka and K K Jha ldquoSynthetic andbiological multiplicity of isatin a reviewrdquo Journal of AdvancedScientific Research vol 2 no 2 pp 35ndash44 2011
[25] N Blazevic D Kolbah B Belin V Sunjic and F Kajfez ldquoHex-amethylenetetramine ldquoA versatile reagent in organic synthesisrdquordquoSynthesis pp 167ndash176 1979
[26] B Rigoa P Caulieza D Fasseurb and D Couturierb ldquoReactionof hexamethyldisilazane with diacylhydrazines an easy 134-oxadiazole synthesisrdquo Synthetic Communications vol 16 no 13pp 1665ndash1669 1986
[27] M Ogata and H Matsumoto ldquoA convenient synthesis of5-substituted 13-dihydro-2H-14-benzodiazepine-2-onesrdquoChemistry and Industry p 1067 1976
[28] H Fujishima H Takeshita S Suzuki M Toyota and MIhara ldquoHexamethyldisilazanes mediated one-pot intramolec-ular Michael addition-olefination reactions leading to ejvo-olefinated bicyclo[640]dodecanesrdquo Journal of the ChemicalSociety Perkin Transactions 1 no 18 pp 2609ndash2616 1999
Submit your manuscripts athttpwwwhindawicom
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Inorganic ChemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
International Journal ofPhotoenergy
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Carbohydrate Chemistry
International Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Advances in
Physical Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom
Analytical Methods in Chemistry
Journal of
Volume 2014
Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
SpectroscopyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Medicinal ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Chromatography Research International
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Applied ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Theoretical ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Spectroscopy
Analytical ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Quantum Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Organic Chemistry International
ElectrochemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
CatalystsJournal of
Submit your manuscripts athttpwwwhindawicom
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Inorganic ChemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
International Journal ofPhotoenergy
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Carbohydrate Chemistry
International Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Advances in
Physical Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom
Analytical Methods in Chemistry
Journal of
Volume 2014
Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
SpectroscopyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Medicinal ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Chromatography Research International
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Applied ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Theoretical ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Spectroscopy
Analytical ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Quantum Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Organic Chemistry International
ElectrochemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
CatalystsJournal of