1248
D. Kumar et al. / European Journal of Medicinal Chemistry 45 (2010) 1244–1249
5.1.2.13. 4-(10-Benzenesulfonylindol-30-yl)-2-(40-hydroxy-30-methox-
162.82,145.58,137.39,130.59,130.39,130.30,129.69,124.86,122.90,
122.36, 120.76, 115.38, 112.05, 111.97 (Ar-C). HRMS for C17H11FN2O,
calcd (M þ H)þ: 279.0934, found: 279.1013 (M þ H)þ.
yphenyl)oxazole(4m). Yield 82%; mp 192–194 ꢀC. 1H NMR
(400 MHz, CDCl3, d ppm): 3.61 (s, 3H, OCH3), 5.37 (s, 1H, OH), 7.32–
7.36 (m, 5H, Ar-H), 7.41–7.45 (m, 3H, Ar-H), 7.51–7.54 (m, 2H, Ar-H),
7.55 (s, 1H, Ar-H), 7.78 (s, 1H, Ar-H), 7.92–7.95 (m, 2H, Ar-H). HRMS
for C24H18N2O5S, calcd (M)þ: 446.0936, found: 446.1101 (M)þ.
5.1.3.5. 2-(40-Hydroxyphenyl)-4-(30-indolyl)oxazole (5e). Yield 84%;
mp 138 ꢀC. 1H NMR (400 MHz, CDCl3,
d ppm): 5.36 (s, 1H, OH),
7.22–7.29 (m, 1H, Ar-H), 7.42–7.51 (m, 4H, Ar-H), 7.77 (d, 1H,
J ¼ 2.52 Hz, Ar-H), 7.86 (dd,1H, J ¼ 6.56,1.76 Hz, Ar-H), 8.01 (s,1H, Ar-
H), 8.11–8.16 (m, 2H, Ar-H), 8.38 (s, 1H, NH). 13C NMR (100 MHz,
5.1.2.14. 4-(10-Benzenesulfonylindol-30-yl)-2-(40-benzyloxy-30-
methoxyphenyl)oxazole (4n). Yield 70%; mp 142–144 ꢀC. 1H NMR
(400 MHz, CDCl3,
d
ppm): 3.44 (s, 3H, OCH3), 5.02 (s, 2H, CH2, Ar-H),
DMSO-d6, d ppm): 168.78, 162.58, 145.61, 140.79, 137.21, 136.18,
7.29–7.41 (m, 5H, Ar-H), 7.49–7.55 (m, 3H, Ar-H), 7.6–7.64 (m, 2H,
Ar-H), 7.83 (d, J ¼ 8.4 Hz, 2H, Ar-H), 7.93–7.98 (m, 4H, Ar-H), 7.99 (s,
1H, Ar-H), 8.21 (d, J ¼ 8.1 Hz, 1H, Ar-H), 8.36 (s, 1H, Ar-H). IR (KBr,
v cmꢂ1): 3360, 3169, 1633, 1454, 1126, 750. HRMS for C31H24N2O5S,
calcd (M)þ: 536.14, found: 536.15 (M)þ.
133.51, 132.64, 131.14, 129.56, 128.64, 126.47, 125.62, 124.45, 113.84
(Ar-C). HRMS for C17H12N2O2, calcd (M þ H)þ: 277.0977, found:
277.0982 (M þ H)þ.
5.1.3.6. 4-(30-Indolyl)-2-(styryl)oxazole (5f). Yield 85%; mp 162 ꢀC.
1H NMR (400 MHz, CDCl3,
d ppm): 6.82 (m, 2H, C-H), 7.12–7.23 (m,
5.1.2.15. 4-(10-Benzenesulfonylindol-30-yl)-2-(40-piperidinyl)oxazole
5H, Ar-H), 7.31–7.33 (m, 2H, Ar-H), 7.56 (d, 1H, J ¼ 2.53 Hz, Ar-H),
(4o). Yield 50%; mp 124–128 ꢀC. 1H NMR (400 MHz, CDCl3,
d
ppm):
7.58–7.60 (m, 2H, Ar-H), 7.72 (s, 1H, Ar-H), 8.38 (s, 1H, NH). 13C NMR
2.1–2.4 (m, 4H), 2.6–2.8 (m, 4H, CH2), 2.9 (m, 1H, CH), 7.43–7.52 (m,
5H, Ar-H), 7.68(s, 1H, Ar-H), 7.93–7.98 (m, 4H, Ar-H), 7.9 (s, 1H, Ar-
H). HRMS for C22H21N3O3S, calcd (M þ H)þ: 408.1304, found:
408.1401 (M þ H)þ.
(100 MHz, DMSO-d6, d ppm): 160.72, 137.52, 136.95, 135.52 (C]C),
131.50, 129.23, 127.90, 127.21, 126.00 (C]C), 124.72, 123.64, 121.95,
119.92, 119.70, 114.02, 112.10, 107.09 (Ar-C). LCMS for C19H14N2O,
calcd (M)þ: 286.1, found: 286.1 (M)þ.
5.1.3. General procedure for the synthesis of 4-(30-indolyl)-2-
substituted oxazole (5)
5.1.3.7. 4-(30-Indolyl)-2-(40-pyridyl)oxazole (5g). Yield 85%; mp
122 ꢀC. 1H NMR (400 MHz, CDCl3,
d ppm): 7.15–7.19 (m, 2H, Ar-H),
A stirred solution of 4 (1 mmol), sodium hydroxide (3 mmol) in
ethanol (10 mL) and water (3 mL) was refluxed till the completion
of reaction. The ethanol was evaporated under vacuum, and the
remaining aqueous solution was extracted with dichloromethane
(3 ꢁ10 mL). The organic phase was dried over anhydrous sodium
sulfate and concentrated under vacuum to afford 5 in excellent
yield.
7.52–7.55 (m, 2H, Ar-H), 7.57 (d,1H, J ¼ 2.53 Hz, Ar-H), 7.62–7.64 (m,
2H, Ar-H), 7.78 (s, 1H, Ar-H), 7.93–7.96 (m, 2H, Ar-H), 8.42 (s, 1H,
NH). 13C NMR (100 MHz, DMSO-d6,
d ppm): 159.50, 148.63, 133.17,
130.99, 129.66, 128.95, 128.14, 127.43, 126.46, 125.95, 124.41, 122.18,
120.06, 112.40 (Ar-C). HRMS for C16H11N3O, calcd (M þ H)þ:
262.0980, found: 262.1056 (M þ H)þ.
5.1.3.8. 2-(Benzyl)4-(30-indolyl) oxazole (5h). Yield 80%; mp 138 ꢀC.
5.1.3.1. 4-(30-Indolyl)-2-phenyloxazole (5a). Yield 82%; mp 172 ꢀC.
1H NMR (400 MHz, CDCl3,
d
ppm): 4.39 (s, 2H, CH2). 7.15–7.40 (m,
9H, Ar-H), 7.69 (d, 1H, J ¼ 2.54 Hz, Ar-H), 8.00 (s, 1H, Ar-H), 8.61 (s,
1H, NH). 13C NMR (100 MHz, DMSO-d6,
ppm): 166.58, 143.66,
1H NMR (400 MHz, CDCl3,
d ppm): 7.28–7.32 (m, 2H, Ar-H), 7.39–
7.50 (m, 5H, Ar-H), 7.94 (d, 1H, J ¼ 7.92 Hz, Ar-H), 7.97–8.01 (m, 2H,
d
Ar-H), 8.03 (s, 1H, Ar-H), 8.49 (s, 1H, NH). 13C NMR (100 MHz,
140.26, 137.84, 136.96, 132.96, 129.58, 128.46, 126.75, 125.30,
123.06, 122.15, 121.04, 111.36, 109.88 (Ar-C), 33.19 (CH2). HRMS for
C18H14N2O, calcd (M þ H)þ: 275.1184, found: 275.2200 (M þ H)þ.
DMSO-d6,
d ppm): 162.54, 153.07, 147.00, 137.52, 136.97, 131.87,
129.22, 128.63, 127.90, 126.01, 121.93, 119.90, 116.12, 112.12, 107.03
(Ar-C). HRMS for C17H12N2O, calcd (M þ H)þ: 261.1028, found:
261.1800 (M þ H)þ.
5.1.3.9. 2-(40-Chlorophenyl)4-(30-indolyl) oxazole (5i). Yield 84%;
mp 158–162 ꢀC. 1H NMR (400 MHz, CDCl3,
d ppm): 7.25–7.32 (m,
5.1.3.2. 4-(30-Indolyl)-2-methyloxazole (5b). Yield 80%; mp 163 ꢀC.
4H, Ar-H), 7.39–7.41 (m, 2H, Ar-H), 7.59 (d, 1H, J ¼ 2.54 Hz, Ar-H),
1H NMR (400 MHz, CDCl3,
d
ppm): 2.75 (s, 3H, CH3), 7.21–7.30 (m,
7.78 (s, 1H, Ar-H), 7.93–8.03 (m, 2H, Ar-H), 8.41 (s, 1H, NH). 13C NMR
2H, Ar-H), 7.39–7.44 (m, 2H, Ar-H), 7.79 (s, 1H, Ar-H), 7.87 (d, 1H,
(100 MHz, DMSO-d6, d ppm): 159.70, 148.31, 137.68, 135.64, 133.45,
J ¼ 7.84 Hz, Ar-H), 8.36 (s, 1H, NH). 13C NMR (100 MHz, DMSO-d6,
131.39, 129.82, 128.20, 127.65, 126.27, 124.78, 122.21, 120.30, 112.44,
106.75 (Ar-C). HRMS for C17H11ClN2O, calcd (M þ H)þ: 295.0638,
found: 295.0739 (M þ H)þ.
d
ppm): 165.0, 150.30, 136.56, 125.10, 123.72, 122.49, 120.57, 120.02,
112.80, 111.47, 109.62 (Ar-C), 19.25 (CH3). HRMS for C12H10N2O,
calcd (M þ H)þ: 199.0871, found: 199.0932 (M þ H)þ.
5.1.3.10. 4-(30-Indolyl)-2-(40-methoxyphenyl)oxazole (5j). Yield 86%;
5.1.3.3. 2-(30,40-Dimethoxyphenyl)-4-(30-indolyl)oxazole (5c). Yield
mp 164 ꢀC. 1H NMR (400 MHz, CDCl3,
d ppm): 3.39 (s, 3H, OCH3),
83%; mp 182–185 ꢀC. 1H NMR (400 MHz, CDCl3,
d
ppm): 3.62 (s, 3H,
7.39–7.43 (m, 4H, Ar-H), 7.54 (d, 1H, J ¼ 2.54 Hz, Ar-H), 7.65 (d, 2H,
OCH3), 3.64 (s, 3H, OCH3), 7.35–7.39 (m, 2H, Ar-H), 7.42 (s,1H, Ar-H),
7.49–7.52 (m, 2H, Ar-H), 7.95–7.97 (m, 4H, Ar-H), 8.33 (s, 1H, NH).
J ¼ 8 Hz, Ar-H), 7.79 (s, 1H, Ar-H), 7.96 (d, 2H, J ¼ 5.96 Hz, Ar-H), 8.20
(s, 1H, NH). 13C NMR (100 MHz, DMSO-d6,
d ppm): 162.44, 162.16,
13C NMR (100 MHz, DMSO-d6,
d
ppm): 163.13, 151.71, 148.66,
144.87, 137.49, 136.23, 130.56, 129.78, 126.55, 124.83, 123.06, 122.52,
120.80, 114.10, 112.57, 112.29 (Ar-C), 55.86 (OCH3). LCMS for
C18H14N2O2, calcd (M þ H)þ: 291.1, found: 291.1 (M þ H)þ.
145.04, 137.34, 129.26, 126.59,124, 90, 122.85, 122.30,121.15, 120.71,
112.21, 112.02, 111.91, 111.25, 110.74 (Ar-C), 56.06 (OCH3), 56.02
(OCH3). HRMS for C19H16N2O3, calcd (M þ H)þ: 321.1239, found:
321.1252 (M þ H)þ.
5.1.3.11. 4-(30-Indolyl)oxazole (5k). Yield 83%; mp 110 ꢀC. 1H NMR
(400 MHz, CDCl3,
J ¼ 2.55 Hz, Ar-H), 7.71 (s, 1H, Ar-H), 7.92 (s, 1H, Ar-H), 8.35 (s, 1H,
NH). 13C NMR (100 MHz, DMSO-d6,
ppm): 152.26, 148.60, 128.96,
d ppm): 7.22–7.30 (m, 4H, Ar-H), 7.56 (d, 1H,
5.1.3.4. 2-(40-Fluorophenyl)-4-(30-indolyl)oxazole (5d). Yield 81%;
mp 145–148 ꢀC. 1H NMR (400 MHz, CDCl3,
d
ppm): 7.22–7.29 (m,
d
1H, Ar-H), 7.42–7.51 (m, 4H, Ar-H), 7.78 (d, 1H, J ¼ 2.52 Hz, Ar-H),
128.14, 125.95, 124.64, 124.40, 123.50, 121.45, 120.50, 119.50 (Ar-C).
HRMS for C11H8N2O, calcd (M þ H)þ: 185.0715, found: 185.0813
(M þ H)þ.
7.84–7.87 (m, 1H, Ar-H), 8.01 (s, 1H, Ar-H), 8.16–8.19 (m, 2H, Ar-H),
8.38 (s, 1H, NH). 13C NMR (100 MHz, DMSO-d6,
d ppm): 165.71,