反应详情

Crude tert-butyl benzyl[2-(4-{[(4-fluorobenzyl)amino]carbonyl}-5,6-dihydroxypyrimidin-2-yl)ethyl]carbamate (prepared as described in Step 3) was taken in dichloromethane/trifluoroacetic acid (8/2 v/v) and the mixture was stirred 1 hour at room temperature. After evaporation of volatiles, the crude organic product was taken in methanol and treated with triethyl amine (1 equivalent), formaldehyde (2 equivalents), sodium cyanoborohydride (1.2 equivalents) and acetic acid (pH=5.5). The mixture was stirred at room temperature for 1 hour. Volatiles were evaporated and product was purified by RP HPLC (C18, 5 μM, H2O/MeCN with 1% of TFA as eluant). Lyophilization of appropriate fractions gave the title compound (TFA salt) as a white solid. 1H NMR (400 MHz, d6-DMS) δ 12.78 (bs, 1H), 12.32 (bs, 1H), 9.5-9.4 (m, 2H), 7.48 (s, 5H), 7.42-7.32 (m, 2H), 7.12 (t, J=8.7 Hz, 2H), 4.59-4.45 (m, 3H), 4.23 (bs, 1H), 3.75 (bs, 1H), 3.52 (bs, 1H), 3.08-3.00 (m, 2H), 2.72 (s, 3H); MS (ES) C22H23FN4O3 requires 410. Found: 411 (M+H+).

1. customAfter evaporation of volatiles
2. stirringThe mixture was stirred at room temperature for 1 hour
3. customVolatiles were evaporated
4. customproduct was purified by RP HPLC (C18, 5 μM, H2O/MeCN with 1% of TFA as eluant)