Med Chem Res (2013) 22:211–218
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2-(4-Methyl-4H-1,2,4-triazol-3-yl)sulfanyl-N-(5-methyl-
isoxazol-3-yl)acetamide (3c)
compounds were routinely checked for purity by TLC on
silica gel 60. IR spectra were recorded on a Shimadzu,
1
8400 FTIR spectrometer as KBr pellets. H NMR spectra
Yield 82 %. m.p. 184–185 °C. IR (KBr) mmax(cm-1): 3337
(N–H), 1668 (C=O), 1605–1408 (C=C and C=N). 1H-NMR
(500 MHz) (DMSO-d6) d(ppm): 2.36 (3H, s, isoxazole C3–
CH3), 3.65 (3H, s, triazole N–CH3), 4.46 (2H, s, CO–CH2),
6.63 (H, s, isoxazole C2–H), 8.61 (H, s, triazole C2–H),
10.67 (H, s, NH–CO). Es-Ms (m/z): M?1: 254.1. Anal.
calcd. for C9H11N5O2S: C, 42.68; H, 4.38; N, 27.65.
Found: C, 42.78; H, 4.38; N, 27.61.
were recorded on a Bruker UltraShield 500 MHz spec-
trometer in DMSO-d6. MS data were obtained on an Agi-
lent 1100 Series LC/MSD Trap VL&SL spectrometer.
Elemental analyses (C, H, and N) were determined on a
Perkin Elmer analyser.
Synthesis of the compounds (3a–3j)
3-Amino-5-methyl-isoxazole (4.9 g, 50 mmol) was dis-
solved in 50 mL of tetrahydrofuran and triethylamine
(8.5 mL, 60 mmol) was added. This mixture was allowed
to stir on an ice bath. Chloroacetyl chloride (0.06 mol,
4.8 mL) in 10 mL of tetrahydrofuran was added drop by
drop. After completion of dropping, reaction mixture was
stirred for 1 h at room temperature. Tetrahydrofuran was
evaporated and the residue was recrystallized from ethanol
to give 2-chloro-N-(5-methyl-isoxazol-3-yl)acetamide (2).
A mixture of the starting compound (1) (0.349 g, 2 mmol),
appropriate thiol-azole derivative (2 mmol), and K2CO3
(0.276 g, 2 mmol) in acetone (30 mL) was refluxed for
2 h. After cooling, the solution was evaporated until dry-
ness. The residue was washed with cold water and
recrystallized from ethanol to give target compounds (3a–3j).
2-(1-Methyl-1H-1,2,3,4-tetrazol-5-yl)sulfanyl-N-(5-methyl-
isoxazol-3-yl)acetamide (3d)
Yield 76 %. m.p. 198–199 °C. IR (KBr) mmax(cm-1): 3364
(N–H), 1670 (C=O), 1605–1410 (C=C and C=N). 1H NMR
(500 MHz) (DMSO-d6) d(ppm): 2.37 (3H, s, isoxazole C3–
CH3), 4.05 (3H, s, tetrazole N–CH3), 4.49 (2H, s, CO–
CH2), 6.62 (H, s, isoxazole C2–H), 10.68 (H, s, NH–CO).
Es-Ms (m/z): M?1: 255.1 Anal. calcd. for C8H10N6O2S: C,
37.79; H, 3.96; N, 33.05. Found: C, 37.71; H, 3.98; N,
33.01.
2-(1-Phenyl-1H-1,2,3,4-tetrazol-5-yl)sulfanyl-N-(5-methyl-
isoxazol-3-yl)acetamide (3e)
Yield 83 %. m.p. 179–180 °C. IR (KBr) mmax(cm-1): 3368
(N–H), 1672 (C=O), 1607–1409 (C=C and C=N). 1H NMR
(500 MHz) (DMSO-d6) d(ppm): 2.36 (3H, s, isoxazole C3–
CH3), 4.45 (2H, s, CO–CH2), 6.61 (H, s, isoxazole C2–H),
7.60–7.66 (m, 3H, tetrazole N–Ph C3,4,5–H), 8.02 (d, 2H,
J = 8.48 Hz, tetrazole N–Ph C2,6–H), 10.70 (H, s, NH–
CO). Es-Ms (m/z): M?1: 317.2. Anal. calcd. for
C13H12N6O2S: C, 49.36; H, 3.82; N, 26.57. Found: C,
49.48; H, 3.81; N, 26.51.
2-(1-Methyl-1H-imidazol-2-yl)sulfanyl-N-(5-methyl-
isoxazol-3-yl)acetamide (3a)
Yield 74 %. m.p. 143–144 °C. IR (KBr) mmax(cm-1): 3341
(N–H), 1672 (C=O), 1611–1413 (C=C and C=N). 1H NMR
(500 MHz) (DMSO-d6) d(ppm): 2.35 (3H, s, isoxazole C3–
CH3), 2.93 (3H, s, imidazole N–CH3), 4.44 (2H, m, CO–
CH2), 6.62 (H, s, isoxazole C2–H), 7.94 (H, d, J = 8.16,
imidazole C3–H), 8.24 (H, d, J = 8.05, imidazole C2–H),
10.70 (H, s, NH–CO). Es-Ms (m/z): M?1: 253.1. Anal.
calcd. for C10H12N4O2S: C, 47.61; H, 4.79; N, 22.21.
Found: C, 47.58; H, 4.78; N, 22.14.
2-(5-Methyl-1,3,4-thiadiazol-2-yl)sulfanyl-N-(5-methyl-
isoxazol-3-yl)acetamide (3f)
Yield 72 %. m.p. 225 °C. IR (KBr) mmax(cm-1): 3364 (N–
H), 1673 (C=O), 1606–1411 (C=C and C=N). H NMR
1
2-(4H-1,2,4-triazol-3-yl)sulfanyl-N-(5-methyl-isoxazol-3-
yl)acetamide (3b)
(500 MHz) (DMSO-d6) d(ppm): 2.35 (3H, s, isoxazole
C3–CH3), 2.71 (3H, s, thiadiazole C2–CH3), 4.48 (2H, s,
CO–CH2), 6.63 (H, s, isoxazole C2–H), 10.68 (H, s, NH–CO).
Es-Ms (m/z): M?1: 271.1. Anal. calcd. for C9H10N4O2S2: C,
39.99; H, 3.73; N, 20.73. Found: C, 39.88; H, 3.74; N, 20.71.
Yield 79 %. m.p. 196–197 °C. IR (KBr) mmax(cm-1): 3346
(N–H), 1671 (C=O), 1604–1412 (C=C and C=N). 1H NMR
(500 MHz) (DMSO-d6) d(ppm): 2.35 (3H, s, isoxazole C3–
CH3), 4.46 (2H, s, CO–CH2), 6.64 (H, s, isoxazole C2–H),
8.62 (H, s, triazole C2–H), 10.65 (H, s, NH–CO), 12.91 (br,
H, triazole NH). Es-Ms (m/z): M?1: 240.2. Anal. calcd. for
C8H9N5O2S: C, 40.16; H, 3.79; N, 29.27. Found: C, 40.08;
H, 3.80; N, 29.31.
2-(1H-benzimidazol-2-yl)sulfanyl-N-(5-methyl-isoxazol-3-
yl)acetamide (3g)
Yield 83 %. m.p. 187–188 °C. IR (KBr) mmax(cm-1): 3388
(N–H), 1675 (C=O), 1611–1407 (C=C and C=N). 1H NMR
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