Reaction Steps
Under an argon atmosphere, 5-(4-acetoxyphenyl)-2-amino-3-benzylpyrazine (c-19) (367 mg, 1.15 mmol) was dissolved in anhydrous dichloromethane (9 mL) and to this was added triethylamine (480 μL, 3.44 mmol), and cooled to 0° C. To this was added benzylsulfonyl chloride (658 mg, 3.45 mmol) and stirred for 4.5 h after warming to room temperature. To this was further added benzylsulfonyl chloride (658 mg, 3.45 mmol) and the mixture was stirred for 1.5 h. To this was added 2 M hydrochloric acid to stop the reaction and after separating the aqueous layer and organic layer, the organic layer was washed once with water and once with saturated brine, and then dried over anhydrous sodium sulfate. After removing anhydrous sodium sulfate by filtration, the filtrate was concentrated under reduced pressure with a rotary evaporator. The residue was purified by silica gel column chromatography (23 g, n-hexane/ethyl acetate=4/1→7/3) to give 5-(4-acetoxyphenyl)-3-benzyl-2-bis(benzylsulfonyl)aminopyrazine (c-20) as a yellow amorphous (487 mg, 67.4%). Rf=0.53 (n-hexane/ethyl acetate=3/2). Mp. 84-86.5° C. UV (MeOH) λmax (log ε) 307 (4.26), 293.5 (4.21), 259.5 (4.19). UV (pH 7.4 PB) λmax (log ε) 320 (4.30), 298.5 (4.25), 265 (4.29). 1H NMR (400 MHz, DMSO-d6) δ 2.29 (s, 3H), 3.90 (s, 2H), 5.00 (s, 1H), 5.03 (s, 1H), 5.18 (s, 1H), 5.22 (s, 1H), 7.13-7.17 (m, 2H), 7.18-7.23 (m, 1H), 7.25-7.33 (m, 4H), 7.39-7.45 (m, 10H), 8.09-8.14 (AA′BB′, 2H), 9.21 (s, 1H). 13C NMR (75.5 MHz, DMSO-d6) δ 20.9, 37.4, 61.0 (1C×2), 122.7 (2C), 126.4, 126.8 (1C×2), 128.2 (2C), 128.5 (2C), 128.8 (2C×2), 129.3, 129.6 (2C), 131.6 (2C×2), 132.1, 137.5, 139.2, 141.0, 151.3, 152.5, 155.6, 169.0. IR (KBr, cm−1) 509, 534, 611, 696, 777, 876, 912, 1144, 1163, 1198, 1354, 1375, 1416, 1433, 1757. HRMS (FAB+) m/z 628.1582 (M+H, C33H30N3O6S2 requires 628.1576).
