Acetic Acid → HCID 136166734, compound

Participants

Reaction Steps

Both diethyl N-(4-amino-3-fluorobenzoyl)-(L)-glutamate (2.21 g, 6.49 mmoles) and 3-(2-acetylamino-4-diacetylamino-1,6-dihydro-6-oxo-5-pyrimidinyl)propionaldehyde (2.00 g, 6.49 mmoles) were stirred in absolute ethanol (50 mL) under nitrogen while glacial acetic acid (3mL) was added dropwise during 1 minute. After solution was achieved (1 hour), activated 3 Å molecular sieves (10 mL) were added and stirring was continued 5 hours. The reaction mixture was chilled (ice bath) and sodium cyanoborohydride (408 mg, 6.49 mmoles) added in one portion. After stirring cold 0.5 hour, the bath was removed. The reaction mixture was allowed to warm to ambient temperature and stir 16 hours. The reaction mixture was filtered and the solids rinsed with ethanol (100 mL). The filtrate was spin evaporated to a brown residue that was partitioned between ethyl acetate and water (100 mL each). The organic phase was separated, washed (1×100 mL 1:1 water/brine), dried (MgSO4), filtered, and spin evaporated to a small volume (20 mL). The solution was chromatographed on silica gel (175 g) using an ethyl acetate rinse (450 mL) followed by elution of the product with 5% added methanol. Like fractions were combined by spin evaporation and dried to give a white solid; yield, 2.66 g (65%); mp 76°-84° C. (dec); 1H-NMR (DMSO-d6) δ 1.15 and 1.16 (2t overlapped, 6H), 1.64 (m, 2H), 2.00 (m, 2H), 2.11 (s, 3H), 2.20 (s, 6H), 2.27 (m, 2H), 2.40 (t, 2H), 3.10 (m, 2H), 3.9-4.1 (2q overlapped, 4H), 4.35 (m, 1H), 6.10 (m, 1H), 6.66 (t, JoH,H and JmF,H =9 Hz, 1H), 7.5-7.6 (m, 2H), 8.35 (d, 1H), 11.9 (v br d, 1H); uv (MeOH) 299 nm max (28000), 257 min (7500); mass spec (FAB) m/e 633 (23%), 430 (100), 388 (87).

Provenance & Evidence