An expedient synthesis of face b pyrido-annulated analogs of 1,5-benzothiazepines of medicinal interest

Article abstract of DOI:10.1080/17415993.2011.653666

An expedient protocol for the synthesis of face b pyrido-annulated analogs of 1,5-benzothiazepines, namely 4-(methylthio)-5-(1,3,4-oxadiazol-2-yl)-2- phenyl-5,11-dihydrobenzo[b] pyrido[2,3-e] [1,5] thiazepine-S,S-dioxides 9a-9f, of medicinal interest emerged to exploit the potential of 3-ketene dithioacetal-substituted derivatives of 4-(1,3,4-oxadiazol-2-yl)-2,3- dihydrobenzo[b] [1,5] thiazepin-2(1H)-one-S,S-dioxide 8. This latter compound 8 was obtained from the base-catalyzed condensation of CS2 x2032;,4′- oxadiazol-2′-yl)-2,3-dihydrobenzo[b] [1,5] thiazepin-2(1H)-one-S,S-dioxide (7). Compound 7 was available from ethyl-2-oxo-2,3,4,5-tetrahydro-[1,5]- benzothiazepin-4-carboxylate (3) on applying established synthetic procedures, which had been previously employed in the literature on related substrates. Treatment of 8 with the anions derived from substituted acetophenones formed the diones which underwent facile cyclocondensation with NH₄OAc in AcOH to yield the desired products 9a-9f in acceptable yields.

Full text of DOI:10.1080/17415993.2011.653666

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An expedient synthesis of face ‘b’
pyrido-annulated analogs of 1,5-
benzothiazepines of medicinal interest
Aarti Gupta a , Pragati Devi a & Dharma Kishore a
a Department of Chemistry , Banasthali University , Banasthali ,
304022 , Rajasthan , India
Published online: 31 Jan 2012.
To cite this article: Aarti Gupta , Pragati Devi & Dharma Kishore (2012) An expedient synthesis of
face ‘b’ pyrido-annulated analogs of 1,5-benzothiazepines of medicinal interest, Journal of Sulfur
Chemistry, 33:2, 171-178, DOI: 10.1080/17415993.2011.653666
To link to this article: http://dx.doi.org/10.1080/17415993.2011.653666
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Journal of Sulfur Chemistry
Vol. 33, No. 2, April 2012, 171–178
An expedient synthesis of face ‘b’ pyrido-annulated analogs of
1,5-benzothiazepines of medicinal interest
Aarti Gupta*, Pragati Devi and Dharma Kishore
Department of Chemistry, Banasthali University, Banasthali 304022, Rajasthan, India
(Received 19 October 2011; final version received 23 December 2011)
An expedient protocol for the synthesis of face ‘b’ pyrido-annulated analogs of 1,5-benzothiazepines,
namely 4-(methylthio)-5-(1ꢀ,3ꢀ,4ꢀ-oxadiazol-2ꢀ-yl)-2-phenyl-5,11-dihydrobenzo[b] pyrido[2,3-e] [1,5]
thiazepine-S,S-dioxides 9a–9f, of medicinal interest emerged to exploit the potential of 3-ketene
dithioacetal-substituted derivatives of 4-(1ꢀ,3ꢀ,4ꢀ-oxadiazol-2ꢀ-yl)-2,3-dihydrobenzo[b] [1,5] thiazepin-
2(1H)-one-S,S-dioxide 8. This latter compound 8 was obtained from the base-catalyzed condensation of
CS2 and MeI with 4-(1ꢀ,3ꢀ,4ꢀ-oxadiazol-2ꢀ-yl)-2,3-dihydrobenzo[b] [1,5] thiazepin-2(1H)-one-S,S-dioxide
(7). Compound 7 was available from ethyl-2-oxo-2,3,4,5-tetrahydro-[1,5]-benzothiazepin-4-carboxylate
(3) on applying established synthetic procedures, which had been previously employed in the literature
on related substrates. Treatment of 8 with the anions derived from substituted acetophenones formed the
diones which underwent facile cyclocondensation with NH4OAc in AcOH to yield the desired products
9a–9f in acceptable yields.
Keywords: 1,5-benzothiazepine; 1,5-benzothiazepin-S,S-dioxide; oxadiazole; oxoketenedithioacetals;
pyridobenzothiazepine
1. Introduction
Ever since the pyridine ring-annulated analog of 1,4-pyridodiazepine (the Nevirapine (1a);
Figure 1) received food and drug administration approval for its application in the treatment
of AIDS and in the combination therapy used in highly active anti-retroviral therapy [HAART]
(2), the interest on the various facets of the chemistry of pyridine-incorporated derivatives of 1,4-
*Corresponding author. Email: omaarti@rediffmail.com
ISSN 1741-5993 print/ISSN 1741-6000 online
© 2012 Taylor & Francis
http://dx.doi.org/10.1080/17415993.2011.653666
http://www.tandfonline.com

172 Aarti Gupta et al.
Figure 1. Nevirapine.
and 1,5-benzo (pyrido) diazepines and thiazepines has expanded exponentially. It triggered the
development of synthetically acceptable protocols for the annulations of the pyridine nucleus onto
heterocyclic scaffolds of medicinal importance.
Advent of impressive anti-HIV activity of molecules containing the oxadiazole (3) nucleus has
also recently attracted the attention of chemists, in the quest of developing bioactive materials
from this nucleus.
A perusal of literature (4) on 1,5-benzothiazepine and their S,S-dioxide derivatives revealed
that no attempt has been made to examine the feasibility of the annulation of face ‘b’ of these
molecules with the pyridine nucleus. This prompted us to undertake a study on the synthesis of face
‘b’ pyrido-annulated analogs of 1,5-benzothiazepin-S,S-dioxide substituted with an oxadiazole
nucleus at the 4-position on the premise that their presence in tandem in the same molecule, would
in all probability, provide a significant contribution to the biological efficacies of the resulting
molecules.
2. Results and discussion
Our interest in the synthesis of the 1,5-benzothiazepin-S,S-dioxide nucleus annulated on its face
‘b’with a pyridine ring and substituted at its 4-position with an oxadiazole nucleus, 9a–9f, inspired
us to examine the potential of an oxoketene dithioacetal synthon appended on 8 as a precursor
of a pyridine ring. In addition, we were also interested in simultaneously exploiting a carboxylic
ester substituent in the same synthetic route for the incorporation of an oxadiazole nucleus. The
synthetic plan which was conceived to achieve this goal envisioned 6 to be the most suitable
starting material (Scheme 1) from which 9a–9f were thought to emerge in three operations
overall (Scheme 2). The first stage of the strategy to produce the starting material 6 involved the
cyclocondensation of o-aminothiophenol (1) with maleic or (alternatively) fumaric acid esters (5)
2 followed by oxidation of the resulting 1,5-benzothiazepine nucleus 3 with H2O2 (AcOH) (6)
to give 4 in 76% yield (Scheme 1). The second phase of the strategy to produce 6 involved the
reaction of 4 with hydrazine hydrate (7) to afford the corresponding hydrazide derivative 5 which
in turn, upon its reaction with CS2 and KOH followed by acid treatment (8), gave oxadiazole
derivative 6 in 78% yield. The structural assignments of compounds 3–5 were based on their
elemental analysis, IR, 1H NMR and mass spectral data. The formation of 4 from 3 was indicated
by the IR spectrum of 4 that showed the absorption for the SO2 group at 1320 and 1128 cm−1
,
respectively. MS data for 4 agreed well with the sulfone structure since it exhibited a distinct peak
for M+-64 due to extrusion of SO2. Analytical and spectral data of 3–6 unequivocally established
their structures.

Journal of Sulfur Chemistry 173
Scheme 1. Synthesis of 4-(oxadiazolyl)-substituted 1,5-benzothiazepin-S,S-dioxide.
Scheme 2. Synthesis of face ‘b’pyridine-annulated 1,5-benzothiazepin-S,S-dioxide derivatives.

174 Aarti Gupta et al.
Table 1. Physical data of compounds 9a–9f
Compound
Ar
MP (◦C)
Yield (%)
Molecular formula (MW)
9a
9b
9c
9d
9e
9f
2,4-Dichlorophenyl
3-Bromophenyl
3-Nitrophenyl
Phenyl amino
2,4-Dibromolphenyl
p-Methoxyphenyl
130–132
139–140
145–147
110–112
120–122
155–156
70
75
70
79
65
80
C21H14Cl2N4O3S2(504.00)
C21H15BrN4O3S2 (514.00)
C21H15N5O5S2 (481.50)
C21H17N5O3S2 (451.52)
C21H14Br2N4O3S2 (592.20)
C22H18N4O4S2 (466.53)
The synthetic potential of oxoketene dithioacetals in heterocyclic synthesis has been well
established in the literature (9). We made use of its versatility in order to devise an elegant
strategy to generate the pyridine ring on face ‘b’ of the 1,5-benzothiazepine nucleus by adopting
the sequence of reactions outlined in Scheme 2. The strategy that allowed annulation of 6 with
a pyridine nucleus proceeded with the desulfurization (10) of 6 with Raney Ni to give 7 in 74%
yield. The reaction of 7 with CS2 and CH3I (11) in the presence of NaOEt afforded the key
oxoketene dithioacetal intermediate 8 in 66% yield which reacted smoothly with the anions of
several substituted acetophenones to give the 1,5-dione intermediates whose reaction in situ with
NH4OAc/AcOH (12) furnished the desired pyridine-annulated 1,5-benzothiazepine analogs 9a–
9f in 70–80% yield. The structural assignments of compounds 7, 8 and 9a–9f have been based
on their elemental analysis, IR, 1H NMR and mass spectral data. The MS data were in agreement
with structure 9a which exhibited a distinct pattern (13) in the presence of two chlorine atoms.
In a similar manner, the structures of compounds 9b–9f were established on the basis of their
elemental and spectral data. The physical data for the compounds are presented in Table 1.
3. Conclusion
The discovery of the exceedingly high anti-HIV potency-enhancing effect of the pyridine
nucleus in ‘Nevirapine’ prompted us to explore the possibility of its incorporation into the 1,5-
benzothiazepine nucleus. We made use of the versatility of the oxoketene dithioacetal substituent
appended on a 1,5-benzothiazepine nucleus to devise an elegant plan for its annulation onto the
pyridine ring. The biological evaluation of these materials is in progress.
4. Experimental
Melting points were determined in open glass capillaries and are uncorrected. Progress of the
reactions was monitored by using TLC on silica gel ‘G’-coated plates using benzene:methanol
(9:1). IR spectra on KBr were recorded with an FTIR-8400S, CE (Shimadzu). Mass spectra were
taken on a 3000 LC/MS System. 1H NMR spectra were recorded on a Bruker NMR model AC-
300F (Bruker) using CDCl3/DMSO-d6 as the solvent. Chemical shifts are expressed in δ (ppm)
relative to the signal for TMS as internal standard.
4.1. Preparation of ethyl-2-oxo-2,3,4,5-tetrahydro-[1,5]-benzothiazepin-4-carboxylate (3)
4.1.1. Method A
To o-aminothiophenol (1, 7.50 g, 0.06 mol) in dry xylene (50 ml) under reflux diethyl maleate or
diethyl fumerate (2, 10.32 g, 0.06 mol) was added, dropwise, 20.0 ml of dry xylene for 30 min.
Refluxing was continued for 15 h and about 50 ml of xylene was distilled off. The contents were

Journal of Sulfur Chemistry 175
left at room temperature overnight and the product thus obtained was recrystallized from dry
xylene to give 3, 7.35 g, at 75% yield, at an m.p. of 103–105 ◦C.
4.1.2. Method B
To o-aminothiophenol (1, 7.50 g, 0.06 mol) in dry xylene (50 ml) under reflux diethyl maleate
or diethyl fumerate (2, 10.32 g, 0.06 mol) was added, dropwise, 20 ml of dry xylene for 30 min.
Refluxing was continued further for 7 h and then a pinch of anhydrous NaH was added and
refluxing was continued again for 10 h. After completion of the reaction (monitored by TLC),
the reaction mixture was cooled to room temperature, then water was added to remove NaH,
the mixture was extracted with chloroform and the solvent was evaporated. The compound thus
obtained was recrystallized from dry xylene to give 3, 7.30 g, at 75% yield, at an m.p. of 103–
105 ◦C.
IR (cm−1): 3210 (NH), 3010 (Ar-H), 2980, 1425 ( CH2 next to C O), 1695, 1656 (C O),
−
=
=
1
=
− −
1580 (C C), 700 (C S C); H NMR (δ): 7.00–7.37 (4H, m, Ar-H), 8.00 (1H, s, NH), 3.59 (1H,
t, J = 12.7 Hz, CH of benzothiazepine), 2.95 (2H, d, J = 6.2 Hz, CH2 of benzothiazepine), 4.10
(2H, q, J = 7.1 Hz, CH2 of ester), 1.29 (3H, t, J = 7.1 Hz, CH3 of ester); MS: m/z 251.35 (M+
75%), 206.29 (100%), 178.28 (45%); Calcd. (%) for C12H13NO3S: C, 57.35; H, 5.21; N, 5.57; S,
12.76; Found: C, 57.06; H, 5.18; N, 5.53; S, 12.70.
4.2. Preparation of ethyl-2-oxo-2,3,4,5-tetrahydro-[1,5]-benzothiazepin-4-carboxylate-
S,S-dioxide (4)
A mixture of 3 (2.51 g, 0.01 mol) dissolved in 100 ml of glacial acetic acid and 3.50 ml of 30%
hydrogen peroxide was heated for 2 h at 100 ◦C, and then it was evaporated to dryness. The product
obtained was recrystallized from acetone to give 4, 2.15 g, at 76% yield, at an m.p. of 145–147 ◦C.
IR (cm−1): 3215 (NH), 3015 (Ar-H), 2985, 1420 ( CH2 next to C O), 1705, 1665 (C O),
−
=
=
1
=
1585 (C C), 1320, 1128 (SO2); H NMR (δ): 7.36–8.10 (4H, m, Ar-H), 8.00 (1H, s, NH), 4.05
(1H, t, J = 12.7 Hz, CH of benzothiazepine), 3.00 (2H, d, J = 6.2 Hz, CH2 of benzothiazepine),
4.25 (2H, q, J = 7.1 Hz, CH2 of ester), 1.29 (3H, t, J = 7.1 Hz, CH3 of ester); MS: m/z 283.05
(M+ 70%), 237.99 (25%), 219.12 (100%); Calcd. (%) for C12H13NO5S: C, 50.87; H, 4.63; N,
4.94; S, 11.32; Found: C, 50.62; H, 4.61; N, 4.92; S, 11.26.
4.3. Preparation of 2-oxo-2,3,4,5-tetrahydro-[1,5]-benzothiazepin-4-carbohydrazide-
S,S-dioxide (5)
To a solution of 4 (2.83 g, 0.01 mol) in ethanol (50 ml), hydrazine hydrate (1 ml, 0.024 mol) was
added. The reaction mixture was refluxed for 10 h and the product obtained was recrystallized
from ethanol to give 5, 2.00 g, at 75% yield, at an m.p. of 182–184 ◦C.
IR (cm−1): 3320, 3125 (NH, NH2), 3225 (NH), 3010 (Ar-H), 2980, 1425 ( CH2 next to C O),
−
=
1
=
=
1700, 1658 (C O), 1590 (C C), 1325, 1125 (SO2); H NMR (δ): 7.35–8.09 (4H, m, Ar-H), 8.02
(1H, s, NH), 4.15 (1H, t, J = 12.7 Hz, CH of benzothiazepine), 3.05 (2H, d, J = 6.2 Hz, CH2
of benzothiazepine), 8.00 (1H, s, NH), 2.00 (2H, s, NH2, amine); MS: m/z 269.26 (M+ 78%),
210.21 (32%), 146.15 (100%); Calcd. (%) for C10H11N3O4S: C, 44.60; H, 4.12; N, 15.60; S,
11.91; Found: C, 44.38; H, 4.10; N, 15.52; S, 11.85.
4.4. Preparation of 4-(5ꢀ-mercapto-1ꢀ,3ꢀ,4ꢀ-oxadiazol-2ꢀ-yl)-2,3-dihydro-[1,5]-
benzothiazepin-2(1H)-one-S,S-dioxide (6)
To a solution of carbohydrazide (5, 1.88 g, 0.007 mol) in dry ethanol (50 ml), a mixture of carbon
disulfide (4.50 ml, 0.06 mol) and potassium hydroxide (0.448 g, 0.008 mol) was added at 0 ◦C. The

176 Aarti Gupta et al.
resulting solution was refluxed for 46 h. After the completion of reaction (monitored by TLC), the
solvent was evaporated and the mixture was suspended in water and then brought to the neutral
point by adding dilute HCl. The solid obtained was filtered and recrystallized from methanol to
give 6, 1.70 g, at 78% yield, at an m.p. of 223–225 ◦C.
IR (cm−1): 3220 (NH), 3010 (Ar-H), 2980, 1425 ( CH2 next to C O), 2750 (weak, C-SH),
−
=
=
=
=
=
− −
1658 (C O), 1627 (C N), 1595 (C C), 1340, 1235 (C S), 1325, 1125 (SO2), 1165 (C O C);
1H NMR (δ): 7.37–8.10 (4H, m, Ar-H), 8.02 (1H, s, NH), 4.50 (1H, t, J = 12.7 Hz, CH of
benzothiazepine), 3.06 (2H, d, J = 6.2 Hz, CH2 of benzothiazepine), 13.05 (1H, s, aromatic C-
SH); MS: m/z 311.36 (M+ 84%), 278.29 (53%), 214.23 (100%); Calcd. (%) for C11H9N3O4S2:
C, 42.44; H, 2.91; N, 13.50; S, 20.60; Found: C, 42.23; H, 2.90; N, 13.43; S, 20.50.
4.5. Preparation of 4-(1ꢀ,3ꢀ,4ꢀ-oxadiazol-2ꢀ-yl)-2,3-dihydrobenzo[b] [1,5]
thiazepin-2(1H)-one-S,S-dioxide (7)
4.5.1. Method A
Compound 6 (1.60 g, 0.005 mol) was taken in dilute ammonium hydroxide (prepared by mixing
18 ml of concentrated ammonium hydroxide with 45 ml of water) and the mixture was heated
to boil. Raney Ni (2.5 g) was then added and the boiling was continued for 4 h until the initially
suspending nickel catalyst settled down. It was immediately filtered and the mixture was concen-
trated on a steam bath. The product obtained was recrystallized from ethanol to give 7, 1.50 g, at
74% yield, at an m.p. of 120–121 ◦C.
4.5.2. Method B
Raney Ni (6 g) was added to a solution of 6 (1.60 g, 0.005 mol) in ethanol (50 ml) and the mixture
was heated at 60–70 ◦C for 4 h. After the completion of reaction (monitored by TLC), Raney Ni
was filtered and the solvent was evaporated. The product obtained was recrystallized from ethanol
to give 7, 1.40 g, at 73% yield, at an m.p. of 120–121 ◦C.
IR (cm−1): 3160 (NH), 3035 (Ar-H), 2980, 1425 ( CH2 next to C O), 1690 (C O), 1627
−
=
=
1
=
=
− −
(C N), 1585 (C C), 1310, 1125 (SO2), 1165 (C O C); H NMR (δ): 7.36–8.10 (4H, m,Ar-H),
8.00 (1H, s, NH), 4.55 (1H, t, J = 12.7 Hz, CH of benzothiazepine), 3.25 (2H, d, J = 6.2 Hz, CH2
of benzothiazepine), 6.05 (1H, s, CH of oxadiazole ring); MS: m/z 279.30 (M+ 80%), 215.21
(100%), 187.20 (65%); Calcd. (%) for C11H9N3O4S: C, 47.31; H, 3.25; N, 15.05; S, 11.48; Found:
C, 47.07; H, 3.23; N, 14.97; S, 11.42.
4.6. Preparation of 3-(bis(methylthio)methylene)-4-(1ꢀ,3ꢀ,4ꢀ-oxadiazol-2ꢀ-yl)-2,3
dihydrobenzo[b] [1,5]thiazepin-2(1H)-one-S,S-dioxide (8)
A mixture of 7 (1.40 g, 0.005 mol) and CS2 (0.75 ml, 0.005 mol) was added to a well-stirred
and cold suspension of t-BuOK (1.30 g, 0.010 mol) in dry benzene (10 ml) and DMF (3 ml).
The reaction mixture was allowed to stand at room temperature for 6 h. Methyl iodide (2 ml,
0.010 mol) was gradually added with stirring under external cooling (exothermic reaction) and
the reaction mixture was allowed to stand for 5 h at room temperature with occasional shaking and
then refluxed on a water bath for 4 h. The mixture was poured onto crushed ice and the benzene
layer was separated. The aqueous portion was extracted with benzene and the combined extracts
were washed with water, dried over anhydrous sodium sulfate and the solvent was removed by
distillation. The product thus obtained was recrystallized from ethanol to give 8, 1.25 g, at 66%
yield, at an m.p. of 172–174 ◦C.

Journal of Sulfur Chemistry 177
IR (cm−1): 3160 (NH), 3045 (Ar-H), 2960 (C H str. CH3), 1685 (C O), 1630 (C N), 1575
−
−
=
=
1
=
− −
−
(C C), 1315, 1128 (SO2), 1160 (C O C), 690 (C S); H NMR (δ): 7.36–8.10 (4H, m, Ar-H),
8.00 (1H, s, NH), 4.96 (1H, s, CH of benzothiazepine), 2.80 [6H, s, (CH3)2 of SMe group], 6.04
(1H, s, CH of oxadiazole ring); MS: m/z 383.47 (M+ 88%), 336.37 (100%), 289.27 (46%); Calcd.
(%) for C14H13N3O4S3: C, 43.85. H, 3.42; N, 10.96; S, 25.09; Found: C, 43.63; H, 3.40; N, 10.91;
S, 24.96.
4.7. Preparation of 4-(methylthio)-5-(1ꢀ,3ꢀ,4ꢀ-oxadiazol-2ꢀ-yl)-2-phenyl-5,11-
dihydrobenzo[b] pyrido[2,3-e] [1,5]thiazepine-S,S-dioxide (9a–9f)
4.7.1. General method
A mixture of 8 (1.14 g, 0.003 mol) was added to a solution of acetophenone (0.003 mol) and
potassium tert-butoxide (0.7 g, 0.006 mol) in dry THF (25 ml). The solution was stirred at room
temperature overnight. Next, glacial acetic acid (25 ml) and ammonium acetate (2.4 g, 0.03 mol)
were added to the above solution which was then refluxed for 4 h with constant removal of THF.
The solution was then cooled to 20 ◦C, diluted with ice (10 g) and allowed to stand for 1 h. Water
(20 ml) was added and the precipitate was collected and crystallized with petroleum ether to give
9a (1.00 g), at 70% yield, at an m.p. of 130–132 ◦C. The other products 9b–9f were prepared
using the same procedure.
(9a). IR (cm−1): 3180 (NH), 3010 (Ar-H), 2965 (C H str. CH3), 1627 (C N), 1620–1400
−
−
=
=
=
− −
−
(C C aromatic and C N str. of pyridine), 1320, 1128 (SO2), 1165 (C O C), 800–600 (C Cl),
1
−
685 (C S); H NMR (δ): 6.91–7.61 (4H, m, Ar-H), 4.00 (1H, s, NH), 5.56 (1H, s, CH of ben-
zothiazepine), 6.04 (1H, s, CH of oxadiazole ring), 6.46 (1H, s, CH of pyridine), 2.53 (3H, s,
CH3 of SMe group), 7.53 (1H, s, Ar-H), 7.46 (1H, d, J = 7.4 Hz, Ar-H), 8.54 (1H, d, J = 8.3 Hz,
Ar-H); MS: m/z 504.00 (M+ 92%), 506.12 (58%), 508.18 (8.0%), 457.30 (100%); Calcd. (%) for
C21H14Cl2N4O3S2: C, 49.91; H, 2.79; N, 11.09; S, 12.69; Found: C, 49.66; H, 2.78; N, 11.03; S,
12.63.
(9b). IR (cm−1): 3190 (NH), 3010 (Ar-H), 2960 (C H str. CH3), 1627 (C N), 1620–1400
−
−
=
=
=
− −
−
(C C aromatic and C N str. of pyridine), 1320, 1128 (SO2), 1160 (C O C), 685 (C S),
1
−
600–500 (C Br); H NMR (δ): 6.91–7.61 (4H, m, Ar-H), 4.00 (1H, s, NH), 5.56 (1H, s, CH of
benzothiazepine), 6.04 (1H, s, CH of oxadiazole ring), 6.46 (1H, s, CH of pyridine), 2.53 (3H,
s, CH3 of SMe group), 7.97 (1H, s, Ar-H), 7.62, 7.95 (2H, d, J = 7.6 Hz, Ar-H), 7.43 (1H, t,
J = 7.1 Hz, Ar-H); MS: m/z 514.00 (M+ 84%), 516.28 (81%), 467.30 (100%); Calcd. (%) for
C21H15BrN4O3S2: C, 48.94; H, 2.93; N, 10.87; S, 12.44; Found: C, 48.70; H, 2.92; N, 10.82; S,
12.38.
(9c). IR (cm−1): 3185 (NH), 3010 (Ar-H), 2965 (C H str. CH3), 1627 (C N), 1620–1400
−
−
=
=
=
− −
(C C aromatic and C N str. of pyridine), 1510, 1360 (NO2), 1320, 1128 (SO2), 1165 (C O C),
1
−
690 (C S); H NMR (δ): 6.91–7.61 (4H, m, Ar-H), 4.00 (1H, s, NH), 5.56 (1H, s, CH of ben-
zothiazepine), 6.04 (1H, s, CH of oxadiazole ring), 6.46 (1H, s, CH of pyridine), 2.53 (3H, s, CH3
of SMe group), 9.16 (1H, s, Ar-H), 8.69, 8.28 (2H, d, J = 8.3 Hz, Ar-H), 7.80 (1H, t, J = 7.1 Hz,
Ar-H); MS: m/z 481.50 (M+ 91%), 434.40 (55%), 388.39 (100%); Calcd. (%) for C21H15N5O5S2:
C, 52.38; H, 3.14; N, 14.54; S, 13.32; Found: C, 52.12; H, 3.12; N, 14.47; S, 13.25.
(9d). IR (cm−1): 3310, 3190 (NH2, NH), 3025 (Ar-H), 2955 (C H str. CH3), 1627 (C N),
−
−
=
=
=
− −
1620–1400 (C C aromatic and C N str. of pyridine), 1320, 1125 (SO2), 1166 (C O C), 685
(C S); H NMR (δ): 6.91–7.61 (4H, m, Ar-H), 4.00 (1H, s, NH), 5.56 (1H, s, CH of benzoth-
iazepine), 6.04 (1H, s, CH of oxadiazole ring), 6.46 (1H, s, CH of pyridine), 2.53 (3H, s, CH3 of
1
−
−
SMe group), 6.27 (2H, s, NH of C NH), 6.61 (2H, d, J = 6.9 Hz,Ar-H), 8.05 (2H, d, J = 8.3 Hz,
Ar-H); MS: m/z 451.52 (M+ 72%), 404.42 (100%), 388.40 (30%); Calcd. (%) for C21H17N5O3S2:
C, 55.86; H, 3.79; N, 15.51; S, 14.20; Found: C, 55.58; H, 3.77; N, 15.43; S, 14.13.

178 Aarti Gupta et al.
(9e). IR (cm−1): 3180 (NH), 3015 (Ar-H), 2960 (C–H str.–CH3), 1627 (C N), 1620–1400
=
=
=
(C C aromatic and C N str. of pyridine), 1320, 1128 (SO2), 1165 (C–O–C), 690 (C–S), 600–500
1
(C–Br); H NMR (δ): 6.91–7.61 (4H, m, Ar-H), 4.00 (1H, s, NH), 5.56 (1H, s, CH benzoth-
iazepine), 6.04 (1H, s, CH of oxadiazole ring), 6.46 (1H, s, CH of pyridine), 2.53 (3H, s, CH3
of SMe group), 7.63 (1H, d, J=7.4 Hz, Ar-H), 8.08 (1H, d, J=8.1 Hz, Ar-H), 8.09 (1H, s, Ar-
H); MS: m/z 592.20 (M+ 65%), 594.35 (98%), 596.35 (61%), 545.20 (100%); Calcd. (%) for
C21H14Br2N4O3S2: C, 42.44; H, 2.37; N, 9.43; S, 10.79; Found: C, 42.23; H, 2.36; N, 9.38; S,
10.74.
(9f). IR (cm−1): 3190 (NH), 3010 (Ar-H), 2965 (C–H str.–CH3), 1668 (C O), 1627 (C N),
=
=
=
=
1620–1400 (C C aromatic and C N str. of pyridine), 1320, 1128 (SO2), 1165 (C–O–C), 675 (C–
S); 1H NMR (δ): 6.91–7.61 (4H, m,Ar-H), 4.00 (1H, s, NH), 5.56 (1H, s, CH of benzothiazepine),
6.04 (1H, s, CH of oxadiazole ring), 6.46 (1H, s, CH of pyridine), 2.53 (3H, s, CH3 of SMe group),
7.08 (2H, d, J = 7.2 Hz, Ar-H), 8.06 (2H, d, J = 8.1 Hz, Ar-H), 3.83 (3H, s, CH3 of –OCH3);
MS: m/z 466.53 (M+ 82%), 419.43 (45%), 374.37 (100%); Calcd. (%) for C22H18N4O4S2: C,
56.64; H, 3.89; N, 12.01; S, 13.75; Found: C, 56.36; H, 3.87; N, 11.95; S, 13.68.
Acknowledgements
The authors are thankful to the Director, CDRI Lucknow, SAIF-Chandigarh and Arbro Pharmaceutical Ltd-Delhi (India)
for providing the microanalyses and spectral data of the compounds and to the Department of Science and Technology,
New Delhi (India), for granting project to Banasthali Centre of Education for Research in Basic Sciences under their
CURIE (Consolidation of University Research for Innovation and Excellence in Women Universities) programme.
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