An Efficient Green Multi-Component Reaction Strategy for the Synthesis of Highly Functionalised Pyridines and Evaluation of Their Antibacterial Activities

Abstract

An efficient green multi-component reaction (MCR) method has been developed for the synthesis of 2-amino-4-aryl/heteroaryl-6-(pyridin-2-ylthio)pyridine-3,5-dicarbonitrile(s) via a 3-component reaction of aryl aldehyde(s), malononitrile and 2-mercaptopyridine in the presence of K₂CO₃ under solvent free reaction conditions (SFRC) using grinding technique at room temperature in a single step. The advantages of the present protocol is operationally simple, environmentally benign, solvent-free reaction conditions (SFRC), simple work up, excellent isolated yields of desired products and viable method for large scale applications in pharmaceutical industry. Interestingly, the synthesized compounds showed moderate to excellent antibacterial activities against Gram-positive and Gram-negative bacterial strains.

The pharmaceutical industry is increasingly under pressure to minimise its environmental impact.¹⁾ Demands for sustainable and environmental friendly organic syntheses^2,3) are stimulating the search for alternatives to the use of organic solvents in synthetic organic chemistry. Performing reaction under solvent-free reaction conditions (SFRC) using grinding technique is an important and interesting alternative, but reaction pathways, as well as the products formed may be modified significantly.^4–11) 2-Amino-3,5-dicarbonitrile-6-thiopyridines are among the most important N-heterocycles that exhibit miscellaneous pharmacological activities such as anti-prion,^12,13) anti-hepatitis B,¹⁴⁾ anticancer agents¹⁵⁾ and some of these compounds are recognized as highly selective ligands for adenosine receptors,¹⁶⁾ which are renowned as possible targets for the development of new drugs in the treatment of Parkinson’s disease, asthma, kidney disease, epilepsy, and cancer.¹⁷⁾ These utilities continue to drive the interest in the development of new synthetic routes for 2-amino-3,5-dicarbonitrile-6-thiopyridines which include a multi-component reactions (MCRs) under basic conditions^18–21) or basic ionic liquid medium²²⁾ and also MCR using Lewis acid catalysts such as (ZnCl₂)²³⁾ and boric acid,²⁴⁾ which show improved results when compared to base-catalyzed reactions. Ultrasonic-assisted synthesis also reported in literature.^25–29) However, this reported method is not accessible for large scale applications in pharmaceutical industry. Since grindstone chemistry³⁰⁾ is inexpensive and viable method for scale-up process when compared to Ultrasonic-assisted synthesis. Nevertheless, to the best of our knowledge, no reports on one-pot synthesis of 2-amino-4-aryl/heteroaryl-6-(pyridin-2-ylthio)pyridine-3,5-dicarbonitrile via MCR under SFRC using grindstone technology.

The present communication describes an one-pot three component synthesis of 2-amino-4-aryl/heteroaryl-6-(pyridin-2-ylthio)pyridine-3,5-dicarbonitrile (4) from aryl aldehyde (1), malononitrile (2) and 2-mercaptopyridine (3) in presence of K₂CO₃ under SFRC using grinding technique at room temperature as shown in Chart 1.

Chart 1. Green MCR Strategy for the Synthesis of 2-Amino-4-aryl/Heteroaryl-6-(pyridin-2-ylthio)pyridine-3,5-dicarbonitriles

Mechanistically, the reaction seems to proceed (Chart 2) via in situ generation of 2-alkylidenemalononitrile i.e., Knoevenagal adduct (5) from aryl aldehyde (1) and malononitrile (2) under basic conditions employed. Further, firstly, 1,2-addition between the thiol group of 2-mercaptopyridine and one of the nitrile group of another malononitrile and secondly, Michael addition between carbanion of malononitrile and Knoevenagel adduct (5) followed by cyclization afforded the intermediate (7) which tautomerises to 1,4-dihydropyridine intermediate (8) and subsequent aromatization in the presence of base and Knoevenagel adduct 5 (an in situ-oxidizing agent) provided the desired product 2-amino-4-aryl/heteroaryl-6-(pyridin-2-ylthio)pyridine-3,5-dicarbonitrile(s) 4a–i and compound 9.

Chart 2. Plausible Mechanism¹⁹⁾ for the Formation of 2-Amino-4-aryl/Heteroaryl-6-(pyridin-2-ylthio)pyridine-3,5-dicarbonitrile

Results and Discussion

In our initial study, the reaction of benzaldehyde (1a), malononitrile (2) and 2-mercaptopyridine (3) was carried out in the presence of Na₂CO₃ at room temperature give rise to 2-amino-3,5-dicarbonitrile-4-phenyl-6-thio pyridine 4a. It was isolated and yield is 42% in water and 63% under solvent-free reaction conditions (SFRC) (entry 1, Table 1). Then, we conducted the same reaction using K₂CO₃ and afforded 52% of yield in water and highest yield of 87% of product 4a was obtained under SFRC at room temperature. The use of other bases such as N-methyl-2-pyrrolidone, L-proline, basic Al₂O₃ and Cs₂CO₃ were examined, but were found to be less effective as the expected product 4a was isolated in 30–50% of yield (entries 3–6) in water and 40–70% of yield under SFRC. We also carried out the same reaction using tetra-n-butylammonium fluoride, KH₂PO₄, BaCl₂ both in water and under SFRC, but the obtained yield was not satisfactory (entries 7–9). From the above study we concluded that K₂CO₃ is the best option to get maximum yield of the desired product 4a under SFRC using grinding technique at room temperature.

Table 1. Optimization of Reaction Conditions for Synthesis of 2-Amino-4-phenyl-6-(pyridin-2-ylthio)pyridine-3,5-dicarbonitrile (4a) via MCR of 1a, 2 and 3^a)

Entry	Base	Time (min)		Yieldb) (%)
		Solvent (H2O)	SFRCc)	Solvent (H2O)	SFRCc)
1	Na2CO3	150	60	42	63
2	K2CO3	120	30	52	87
3	NMP	210	65	48	68
4	L-Proline	250	70	35	57
5	Basic Al2O3	300	60	20	46
6	Cs2CO3	330	60	40	61
7	TBAF	250	55	46	70
8	K2H2PO4	270	60	45	71
9	BaCl2	400	70	30	52

a) Reaction conditions: Benzaldehyde (1a) (0.00188 mol), malononitrile (2) (0.00377 mol), 2-mercaptopyridine (3) (0.0015 mol), base (1 eq) and H₂O (10 vol) or SFRC at room temperature. b) Isolated yields of the product. c) Reaction carried out under stirring. d) Reaction carried out under solvent free reaction conditions (SFRC) using grinding technique.

Further, the effect of temperature was examined under SFRC using K₂CO₃ (also with other bases stated in Table 1). In this connection, we raised the temperature of the reaction to 70–80°C and maintained at the same temperature for 30–70 min. The obtained yield of product 4a was comparatively low (50–65%). Based on obtained results, we concluded that room temperature is optimum for maximum conversion and highest isolated yield of product 4a.

Base concentration was optimized by varying its concentration from 0.5 to 2.0 eq (entries 1–5, Table 2). Increase in the product (4a) yield was observed on apply of 0.5 to 1.0 eq of base. Decrease in yield of the product 4a was observed on increase of base concentration (entries 4–5). Hence, 1 eq of base was considered as an optimum base concentration (entry 3).

Table 2. Effect of Base Load on Synthesis of 2-Amino-4-phenyl-6-(pyridin-2-ylthio)pyridine-3,5-dicarbonitrile (4a)^a)

Entry	K2CO3 (eq)	Time (min)	Yieldb) (%)
1	0.5	70	40
2	0.75	60	58
3	1	30	87
4	1.5	40	82
5	2.0	40	78

a) Reaction conditions: Benzaldehyde (1a) (0.00188 mol), malononitrile (2) (0.00377 mol), 2-mercaptopyridine (3) (0.0015 mol), K₂CO₃ at room temperature under SFRC. b) Isolated yields of product (4a).

To test the generality and scope of this MCR a range of aryl aldehydes (1a–i) were employed and obtained results were presented in Table 3. Consistent with the results in the optimization studies, the reactions smoothly proceeded to afford 2-amino-4-aryl/heteroaryl-6-(pyridin-2-ylthio)pyridine-3,5-dicarbonitriles in good to excellent isolated yields. Various electron donating e.g. OMe, Br, OH (entries 2, 5, 6, 8, Table 3) or electron withdrawing groups e.g. F, NO₂ (entries 3, 4, 7) present on the aryl aldehydes were well tolerated. The reaction proceeded well irrespective of the substituents present on aryl aldehydes (entries 1 vs. 2–8). The use of heteroaromatic aldehyde was also successful and afforded the desired product 4i in good yield (entry 9).

Entry	Aryl aldehyde (R) (1)	Time (min)	Product(s) (4)	Yieldb) (%)
1		30		87
2		20		82
3		25		91
4		30		90
5		20		88
6		28		83
7		35		85
8		15		92
9		20		90

a) Reaction conditions: Aryl aldehyde(s) (1a–i) (0.00188 mol), malononitrile (2) (0.00377 mol), 2-mercaptopyridine (3) (0.0015 mol), K₂CO₃ (1 eq) at room temperature under SFRC. b) Isolated yields of product(s) (4a–i).

Antibacterial Activity Studies

The primary antimicrobial activity screen was carried out by agar disc-diffusion method.^31–34) All the synthesized compounds were tested by the disk diffusion method against Gram-positive bacterial strains: Micrococcus luteus (MTCC 106) and Staphylococcus aureus (MTCC 737) and Gram-negative bacterial strains: Escherichia coli (MTCC 443), Klebsiella pneumoniae (MTCC 109). Chloramphenicol was used as positive control and dimethyl sulfoxide (DMSO) was used as negative control. The susceptibility was assessed on the basis of diameter of zone of inhibition against Gram-positive and Gram-negative strains of bacteria. Inhibition zones were measured and compared with the controls. The minimum inhibitory concentration (MIC) for the most active compounds 4c, 4d, 4g and 4i against the same microorganisms used in the preliminary screening was carried out using microdilution susceptibility method³²⁾ and presented in Table 4.

The results of preliminary antibacterial testing of compounds 4a–i are shown in Table S1 (see supplementary information). The results revealed that, compounds 4c, 4d, 4g and 4i displayed good activity against Gram-positive bacteria (inhibitory zone >25 mm) and excellent activity against Gram (−Ve) bacteria (inhibitory zone >27 mm). Compound 4e displayed low to moderate activity towards Gram (+Ve) bacteria (18–21 mm) and moderate activity (20–23 mm) towards Gram (−Ve) bacteria. Compounds 4a, 4b and 4h exhibited least activity against both bacteria.

On the other hand, the results of preliminary antibacterial testing of compounds 4a–i as shown in Table 4 revealed that, compounds 4d and 4i exhibited good activity against Gram (+Ve) bacteria (inhibitory zone >27 mm) and excellent activity against Gram (−Ve) bacteria (inhibitory zone >31 mm). Compounds 4c, 4e and 4g showed moderate activity towards Gram (+Ve) bacteria (19–27 mm) and moderate to good activity (23–29 mm) towards Gram (−Ve) bacteria.

The MIC values were determined as the lowest concentration that completely inhibited visible growth of the microorganisms as presented in Table S1. The structure–antimicrobial activity relationship of the synthesized compounds revealed that presence of electron withdrawing groups (F, Br, NO₂ on 4′-aryl substituent or presence of 4′-heterocycle of pyridine core displayed high activity. The compounds having electron donating groups (OH, OMe) on 4′-aryl substituent of pyridine core or without substitution exhibited low activity. Excellent activity was attained with the compounds (4c–d) having –F (fluorine) substituent on the 4′-aryl substituent of pyridine core. The maximum activity was observed with compound (4i) having 4′-heterocycle substituent of pyridine core.

Table 4. Minimum Inhibitory Concentration (MIC), µg/mL of 4

Compound	Minimum inhibitory concentration (µg/mL)
	Gram-positive bacteria		Gram-negative bacteria
	M. luteus	S. aureus	E. coli	K. pneumoniae
4c	100	100	100	100
4d	100	75	100	200
4g	50	100	100	100
4i	25	50	25	50
Chloramphenicol	6.5	6.5	6.25	6.0

Conclusion

In summary, we demonstrated an efficient Green MCR strategy for the synthesis of highly functionalized pyridines (4a–i) of potential medicinal interest via a three component reaction under SFRC by adopting Grindstone chemistry in presence of K₂CO₃ in a single step. The advantages of the grindstone technique include high yields, environmentally benign procedure, shorter reaction time, simpler workup procedure and less energy consumption. The methodology is also useful in constructing a diversity based library of molecules related to Pyridine framework. Among the synthetic analogues, compounds 4d and 4i showed excellent inhibition against multidrug resistant Gram-negative bacteria, E. coli and K. pneumoniae, nearly equivalent to that of reference drug Chloramphenicol. We have discerned that the inhibition rate was directly proportional either to strength of electron withdrawing groups on 4-aryl substituent or presence 4-heteroaryl group of 2-amino-4-aryl-6-(pyridin-2-ylthio)pyridine-3,5-dicarbonitrile, 4c–e, 4g and 4i.

Experimental

Melting points were determined using Buchi (B-540) melting point analyzer (Postfach, Flawil, Switzerland) and are uncorrected. NMR spectra were recorded on Varian 400 MHz (Varian, Inc., NMR Systems, Palo Alto, CA, U.S.A.). Chemical shifts were expressed in parts per million (ppm), coupling constants were expressed in Hertz (Hz). Splitting patterns describe apparent multiplicities and were designated as s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet) and br (broad). High Resolution Mass Spectra were recorded on a LCT-Premier XE mass spectrometer (Waters, Milford, MA, U.S.A.)-single quadrupole system equipped with electrospray ionization (ESI) source. Thin-layer chromatography was performed on 0.25 mm Merck silica gel plates and visualized with UV light. All chemicals and solvents are purchased from Sigma-Aldrich (St. Louis, MO, U.S.A.) and Merck (Mumbai, India) and are used without further purification.

General Experimental Procedure for Synthesis of Compounds 4a–i

A mixture of benzaldehyde (1a) (0.00188 mol, 0.2 g), malononitrile (2) (0.00377 mol, 0.249 g), K₂CO₃ (0.00188 mol, 0.138 g) and 2-mercaptopyridine (3) (0.00150 mol, 0.167 g) were thoroughly ground with a pestle in a mortar at room temperature in an open atmosphere until the mixture turned into a thick mass. The progress of the reaction was monitored by TLC. The mixture continued to be ground occasionally until completion of the reaction. After completion of the reaction as from TLC, water (100 mL) was added to the crude mass and product was extracted using ethyl acetate (3×50 mL). The organic layer was collected, dried over anhydrous Na₂SO₄ and the solvent was removed under vacuum. Pure product 4a was obtained from crude mass after recrystallisation from a mixture of EA–n-hexane (1 : 1 ratio, 10 vol) and the crude 2-benzylmalononitrile (9a) was isolated from the filtrate and purified by column chromatography using a mixture of EA–n-hexane (1 : 99 ratio). The obtained by-product 2-benzylmalononitrile (9a) was confirmed by ¹H-NMR and GC-MS. The same procedure for experimental and purification was followed for the preparation of all other compounds (4b–i). The synthesised compounds (4a–i) gave satisfactory spectroscopic data in accordance with their proposed structures.

2-Amino-4-phenyl-6-(pyridine-2-ylthio)pyridine-3,5-dicarbonitrile (4a): Off-white solid Yield=87%; mp 224–227°C; ¹H-NMR (400 MHz, DMSO-d₆) δ: 8.57 (d, 1H, J=3.6 Hz, arom H), 7.98 (br, 2H, –NH₂), 7.87 (t, 1H, J=8.0 Hz, arom H), 7.8 (d, 1H, J=8.0 Hz, arom H), 7.58 (s, 5H, arom H), 7.43 (t, 1H, J=6.0 Hz, arom H); ¹³C-NMR (100 MHz, DMSO-d₆) δ: 164.2, 159.8, 158.9, 152.4, 150.2, 137.8, 133.9, 130.5, 129.6, 129.4, 128.8 (2C), 128.6, 128.4 (2C), 123.5, 95.6, 88.0; high resolution (HR)-MS (ESI): m/z (M+H)⁺ Calcd for C₁₈H₁₂N₅S: 330.0813, Found 330.0808.

2-Benzylmalononitrile (9a): White solid; mp 88–90°C; ¹H-NMR (400 MHz, CDCl₃) δ: 7.43–7.38 (m, 2H, arom H), 7.36–7.30 (m, 2H, arom H), 3.90 (t, J=6.8 Hz, 1H), 3.27 (d, J=6.8 Hz, 2H); GC-MS: m/z (M)⁺ 156.

2-Amino-4-(4-methoxyphenyl)-6-(pyridine-2-ylthio)pyridine-3,5-dicarbonitrile (4b): Off-white solid; Yield=82%; mp 250–253°C; ¹H-NMR (400 MHz, DMSO-d₆) δ: 8.57 (d, 1H, J=4.0 Hz, arom H), 7.93 (br, 2H, –NH₂), 7.86 (td, 1H, J=8.0, 2.0 Hz, arom H), 7.80 (d, 1H, J=8.0 Hz, arom H), 7.53 (d, 2H, J=8.8 Hz, arom H), 7.42 (q, 1H, J=4.8 Hz, arom H), 7.13 (d, 2H, J=8.0 Hz, arom H), 3.85 (s, 3H, –OCH₃); ¹³C-NMR (100 MHz, DMSO-d₆) δ: 164.2, 160.9, 159.9, 158.5, 152.5. 150.2, 137.8, 130.3 (2C), 128.5, 125.7, 123.4, 115.5, 115.2, 114.1 (2C), 95.7, 87.9, 55.4; HR-MS (ESI): m/z (M+H)⁺ Calcd for C₁₉H₁₄N₃OS: 360.0919, Found: 360.0906.

2-Amino-4-(4-fluorophenyl)-6-(pyridine-2-ylthio)pyridine-3,5-dicarbonitrile (4c): Off-white solid; Yield=91%; mp 246–249°C; ¹H-NMR (400 MHz, DMSO-d₆) δ: 8.57 (d, 1H, J=4.0 Hz, arom H), 8.0 (br, 2H, –NH₂), 7.87 (td, 1H, J=8.0, 2.0 Hz, arom H), 7.80 (d, 1H, J=8.0 Hz, arom H), 7.67–7.64 (m, 2H, arom H), 7.46–7.41 (m, 3H, arom H); ¹³C-NMR (100 MHz, DMSO-d₆) δ: 164.2, 159.7, 157.9, 152.4, 150.2, 137.8 (2C), 131.2, 131.1, 128.6 (2C), 123.5, 116.0, 115.8, 115.2, 114.8, 95.7, 88.1; HR-MS (ESI): m/z (M+H)⁺ Calcd for C₁₈H₁₁N₅FS: 348.0719, Found: 348.0704.

2-Amino-4-(3,4-difluorophenyl)-6-(pyridine-2-ylthio)pyridine-3,5-dicarbonitrile (4d): Off-white solid; Yield=90%; mp 251–254°C; ¹H-NMR (400 MHz, DMSO-d₆) δ: 8.58 (d, 1H, J=4.8 Hz, arom H), 8.06 (br, 2H, –NH₂), 7.88 (t d, 2H, J=8.0, 2.0 Hz, arom H), 7.80 (d, 1H, J=7.6 Hz, arom H), 7.73–7.6 (m, 1H, arom H), 7.5–7.43 (m, 2H, arom H); ¹³C-NMR (100 MHz, DMSO-d₆) δ: 164.2, 159.6, 156.6, 152.2 (2C), 150.2, 137.8, 128.7, 126.2, 123.6, 118.49, 118.43, 118.3, 118.2, 115.0, 114.6, 95.5, 88.2; HR-MS (ESI): m/z (M+H)⁺ Calcd for C₁₈H₁₀N₅F₂S: 366.0625, Found: 366.0606.

2-Amino-4-(4-bromophenyl)-6-(pyridine-2-ylthio)pyridine-3,5-dicarbonitrile (4e): Off-white solid; Yield=88%; mp 260–263°C; ¹H-NMR (400 MHz, DMSO-d₆) δ: 8.57 (d, 1H, J=4.0 Hz, arom H), 8.0 (br, 2H, –NH₂), 7.87 (td, 2H, J=8.0, 1.6 Hz, arom H), 7.81 (d,t, 2H, J=8.4, 6.0 Hz, arom H), 7.54 (d, 2H, J=8.4 Hz, arom H), 7.44–7.41 (m, 1H, arom H); ¹³C-NMR (100 MHz, DMSO-d₆) δ: 164.2, 159.7, 157.7, 152.3, 150.2, 137.8, 133.1, 131.8 (2C), 130.6 (2C), 128.6, 124.2, 123.5, 115.1, 114.8, 95.4, 87.9; HR-MS (ESI): m/z (M+H)⁺ Calcd for C₁₈H₁₁N₅SBr: 407.9919, Found: 407.9904, other isotopic peaks found: 409.8890, 410. 9925

2-Amino-4-(3-hydroxyphenyl)-6-(pyridine-2-ylthio)pyridine-3,5-dicarbonitrile (4f): Off-white solid; Yield=83%; mp 222–226°C; ¹H-NMR (400 MHz, DMSO-d₆) δ: 9.89 (s, 1H, –OH), 8.56 (d, 1H, J=3.6 Hz, arom H), 7.95 (br, 2H, –NH₂), 7.87 (td, 1H, J=8.0, 2.0 Hz, arom H), 7.80 (d, 1H, J=8.0 Hz, arom H), 7.43–7.35 (m, 2H, arom H), 6.97–6.89 (m, 3H, arom H); ¹³C-NMR (100 MHz, DMSO-d₆) δ: 164.1, 159.8, 158.8, 157.3, 152.5, 150.1, 137.8, 135.0, 130.0, 128.5, 123.4, 118.9, 117.3, 115.2, 115.0, 114.8, 95.5, 87.9; HR-MS (ESI): m/z (M+H)⁺ Calcd for C₁₈H₁₂N₅OS: 346.0763, Found: 346.0746.

2-Amino-4-(4-nitrophenyl)-6-(pyridine-2-ylthio)pyridine-3,5-dicarbonitrile (4g): Off-white solid; Yield=85%; mp 245–248°C; ¹H-NMR (400 MHz, DMSO-d₆) δ: 8.58 (d, 1H, J=4.0 Hz, arom H), 8.44 (d, 2H, J=8.8 Hz, arom H), 8.11 (br, 2H, –NH₂), 7.90 (d, 2H, J=8.4 Hz, arom H), 7.87 (d, 1H, J=2.0 Hz, arom H), 7.81 (d, 1H, J=8.0 Hz, arom H), 7.44 (dd, 1H, J=6.8, 4.8 Hz, arom H); ¹³C-NMR (100 MHz, DMSO-d₆) δ: 164.4, 159.6, 156.9, 152.2, 150.2, 148.6, 140.1, 137.9, 130.3 (2C), 128.7, 123.9 (2C), 123.6, 114.9, 114.5, 95.1, 87.8; HR-MS (ESI): m/z (M+H)⁺ Calcd for C₁₈H₁₁N₆O₂S: 375.0664, Found: 375.0657.

2-Amino-4-(3,4,5-trimethoxyphenyl)-6-(pyridine-2-ylthio)pyridine-3,5-dicarbonitrile (4h): Off-white solid; Yield=92%; mp 265–268°C; ¹H-NMR (400 MHz, DMSO-d₆) δ: 8.57 (dd, 1H, J=4.8, 1.2 Hz, arom H), 7.95 (br, 2H, –NH₂), 7.87 (td, 1H, J=8.0, 1.6 Hz, arom H), 7.79 (d, 1H, J=8.0 Hz, arom H), 7.43 (td, 1H, J=5.6, 2.4 Hz, arom H), 6.94 (s, 2H, arom H), 3.82 (s, 6H, –2OCH₃), 3.76 (s, 3H, –OCH₃); ¹³C-NMR (100 MHz, DMSO-d₆) δ: 164.1, 159.7, 158.5, 152.7, 152.4, 150.1, 138.8, 137.7, 128.8, 128.6 (2C), 123.4, 115.4, 115.0, 106.4 (2C), 95.5, 87.9, 60.1, 56.1 (3C), HR-MS (ESI): m/z (M+H)⁺ Calcd for C₂₁H₁₈N₅O₃S: 420.1130, Found: 420.1117.

2-Amino-4-(pyridine-2-ylthio)-4-(pyridine-4-ylthio)pyridine-3,5-dicarbonitrile (4i): Off-white solid; Yield=90%; mp 233–235°C; ¹H-NMR (400 MHz, DMSO-d₆) δ: 8.82 (dd, 2H, J=4.4, 1.6 Hz, arom H), 8.58 (dd, 1H, J=4.8, 1.2 Hz, arom H), 8.1 (br, 2H, –NH₂), 7.88 (td, 1H, J=7.6, 2.0 Hz, arom H), 7.81 (d, 1H, J=8.4 Hz, arom H), 7.61 (d, 2H, J=6.4 Hz, arom H), 7.45–7.42 (m, 1H, arom H).; ¹³C-NMR (100 MHz, DMSO-d₆) δ: 164.3, 159.5, 156.3, 152.1, 150.2 (3C), 141.6, 137.8, 128.6, 123.5, 122.8 (2C), 114.8, 114.4, 94.8, 87.5.; HR-MS (ESI): m/z (M+H)⁺ Calcd for C₁₇H₁₁N₆S: 331.0766, Found: 331.0754.

Acknowledgment

The authors thank Dr. A. K. Roy, Dr. K. V. Raghu, Dr. V. Dahanukar and Analytical group of Dr. Reddy’s Laboratories, Hyderabad, India, for spectral data and DAE-BRNS (BARC), Govt. of India, Mumbai, for providing financial assistance (No. 2011/37C/52/BRNS/2264).

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