2
Tatsuki Nakagawa et al.
Scheme 2. Synthesis of the TPy derivatives 2–4.
Scheme 1. Cypridina oxyluciferin, its analogue (OCLA) and the TPy
derivatives 1–4, together with a synthesis of TPy ring.
9.2 Hz), 7.54 (2 H, t, J 7.5 Hz), 7.61 (1 H, t, J 7.5 Hz), 7.91 (2 H, d, J
9.2 Hz), 7.98 (2 H, d, J 7.5 Hz), 8.47 (1 H, br s), 8.75 (1 H, s) and 9.47
(1 H, s). m (KBr)/cmꢀ1 3436, 1673, 1610, 1538, 1423 and 1269. m/z
(ESI) 319 ([M+H]+) and 341 ([M+Na]+).
(2 H, br s), 6.77 (2 H, d, J 9.2 Hz), 7.79 (1 H, s), 7.86 (2 H, d, J
8.6 Hz) and 8.31 (1 H, s). m (KBr)/cmꢀ1 3427, 3134, 1610, 1521, 1434
and 1286. m/z (ESI) 237 ([M+Na]+).
6-(4-Methoxyphenyl)pyrazinamine (7b). 96% yield. Yellow crystals,
mp 139–140°C. dH (CDCl3) 3.86 (3 H, s), 4.55 (2 H, br s), 6.98 (2 H, d,
J 8.6 Hz), 7.87 (1 H, s), 7.90 (2 H, d, J 9.2 Hz) and 8.32 (1 H, s). m
(KBr)/cmꢀ1 3438, 3110, 1608, 1533, 1434 and 1249. m/z (ESI) 202
([M+H]+).
60-(4-Methoxyphenyl)benzamidopyrazine (8b). Approximately 100%
yield. Yellow crystals, mp 149–150°C. dH (CDCl3) 3.88 (3 H, s), 7.03 (2
H, d, J 8.6 Hz), 7.54 (2 H, t, J 8.0 Hz), 7.62 (1 H, t, J 7.8 Hz), 7.94-
8.00 (4 H, m), 8.50 (1 H, br s), 8.78 (1 H, s) and 9.57 (1 H, s). m (KBr)/
cmꢀ1 3430, 3054, 1668, 1608, 1533, 1419 and 1259. m/z (ESI) 306
([M+H]+) and 328 ([M+Na]+).
6-(4-Methoxyphenyl)-2-phenylthiazolo[4,5-b]pyrazine (2b). To a solu-
tion of 50-(4-methoxyphenyl)benzamidopyrazine (90 mg, 0.30 mmol) in
chlorobenzene (1.0 mL), Lawesson’s reagent (72 mg, 0.18 mmol) was
added and the reaction mixture was heated under reflux overnight. For
completing the reaction, Lawesson’s reagent (72 mg, 0.18 mmol) was
added again, and the solution was heated under reflux for 4 h. The reac-
tion mixture was directly purified by silica gel thin layer chromatography
[CHCl3/ethyl acetate (15:1)] and the product was washed with n-hexane
to give 2b (35 mg, 37%) as yellow crystals: mp 191–192°C. dH (CDCl3)
3.90 (3 H, s), 7.06 (2 H, d, J 8.6 Hz), 7.53–7.59 (3 H, m), 8.08 (2 H, t,
J 8.6 Hz), 8.21 (2 H, m) and 9.08 (1 H, s). m (KBr)/cmꢀ1 2840, 1606,
1514, 1442 and 1325. m/z (ESI) Found: 342.0659 ([M+Na]+).
C18H13N3NaOS requires 342.0677.
5-(4-Dimethylaminophenyl)-2-phenylthiazolo[4,5-b]pyrazine (3a). 51%
yield. Orange crystals, mp 201–203°C. dH (CDCl3) 3.07 (6 H, s), 6.83 (2
H, d, J 8.6 Hz), 7.51-7.58 (3 H, m), 8.13 (2 H, d, J 9.2 Hz), 8.22 (2 H,
m) and 8.92 (1 H, s). m (KBr)/cmꢀ1 1610, 1514, 1466, 1369, 1236 and
1200. m/z (ESI) Found: 355.0946 ([M+Na]+). C19H16N4NaS requires
355.0993.
5-(4-Methoxyphenyl)-2-phenylthiazolo[4,5-b]pyrazine (3b). 59% yield.
Yellow crystals, mp 182–183°C. dH (CDCl3) 3.90 (3 H, s), 7.06 (2 H, d,
J 9.2 Hz), 7.51-7.60 (3 H, m), 8.16 (2 H, d, J 9.2 Hz), 8.23 (2 H, m)
and 8.95 (1 H, s). m (KBr)/cmꢀ1 1610, 1514, 1326, 1261 and 1201. m/z
(ESI) Found: 342.0639 ([M+Na]+). C18H13N3NaOS requires 342.0677.
2-(4-Cyanophenyl)-6-(4-dimethylaminophenyl)thiazolo[4,5-b]pyrazine
(4a). 30% yield. Orange crystals, mp >300°C. dH (CDCl3) 3.08 (6 H, s),
6.82 (2 H, d, J 8.6 Hz), 7.82 (2 H, d, J 8.0 Hz), 8.05 (2 H, d, J 8.6 Hz),
50-(4-Methoxyphenyl)benzamidopyrazine (6a). To a solution of 5-(4-
methoxyphenyl)pyrazinamine (150 mg, 0.75 mmol) in pyridine (1.0 mL),
benzoyl chloride (105 lL, 0.90 mol) was added under Ar, and the reaction
mixture was stirred at room temperature for 2 h. The reaction was
quenched by adding saturated NaHCO3 aqueous solution (50 mL), and
the product was extracted with chloroform (50 mL 9 3). The organic
layer was washed with brine, dried over Na2SO4 and concentrated in
vacuo, to give 6a (230 mg, 100%) as yellow crystals: mp 189–190°C. dH
(CDCl3) 3.88 (3 H, s), 7.02 (2 H, d, J 8.6 Hz), 7.53 (2 H, t, J 8.0 Hz),
7.61 (1 H, t, J 6.9 Hz), 7.95-7.97 (4 H, m), 8.49 (1 H, br s), 8.66 (1 H, d,
J 1.8 Hz) and 9.71 (1 H, d, J 1.8 Hz). m (KBr)/cmꢀ1 3369, 1668, 1610,
1513, 1419, 1353 and 1249. m/z (ESI) 306 ([M+H]+) and 328 ([M+Na]+).
4-Cyano-60-(4-dimethylaminophenyl)benzamidopyrazine (6b). ~100%
yield. Yellow crystals, mp 200°C (decomp.). dH (CDCl3) 3.04 (6 H, s),
6.80 (2 H, d, J 9.2 Hz), 7.83 (2 H, d, J 8.6 Hz), 7.92 (2 H, d, J 8.6 Hz),
8.05 (2 H, d, J 8.6 Hz), 8.43 (1 H, br s), 8.65 (1 H, d, J 1.7 Hz) and
9.62 (1 H, d, J 1.2 Hz). m (KBr)/cmꢀ1 3369, 2229, 1670, 1610, 1496
and 1357. m/z (ESI) 344 ([M+H]+) and 366 ([M+Na]+).
4-Cyano-60-(4-methoxyphenyl)benzamidopyrazine (6c). 95% yield.
Yellow crystals, mp 238–239°C. dH (CDCl3) 3.88 (3 H, s), 7.03 (2 H, d,
J 9.2 Hz), 7.84 (2 H, d, J 8.6 Hz), 7.97 (2 H, d, J 8.6 Hz), 8.06 (2 H, d,
J 8.6 Hz), 8.46 (1 H, br s), 8.68 (1 H, d, J 1.7 Hz) and 9.67 (1 H, d, J
1.2 Hz). m (KBr)/cmꢀ1 3307, 2229, 1654, 1610, 1542, 1498 1357, and
1250. m/z (ESI) 331 ([M+H]+) and 353 ([M+Na]+).
60-(4-Dimethylaminophenyl)benzamidopyrazine (8a). 88% yield. Yel-
low crystals, mp 200–201°C. dH (CDCl3) 3.05 (6 H, s), 6.79 (2 H, d, J