反应详情

To a solution of 4-(4-amino-quinazoline-7-ylmethyl)-2-methoxymethyl-3-oxo-piperazine-1-carboxylic acid benzyl ester, EXAMPLE 75, (0.69 g, 2.29 mmol) in 9 mL of DMF is added N,N-diisopropylethyl amine (0.89 g, 6.87 mmol), TBTU (0.76 g, 2.36 mmol), and 5-chloro-2-thienyloxyacetic acid, EXAMPLE 24, (0.40 g, 2.08 mmol). The solution is stirred for 16 hours. After this time the solution is concentrated. The crude material is purified by RP-HPLC eluting with a gradient of 10% CH3CN/H2O (0.1% TFA) to 80% CH3CN/H2O (0.1% TFA). The product fractions are lyophilized to give product as a white solid (1.0 g, 1.57 mmol). 1H NMR (d6-DMSO, 300 MHz) δ9.70 (bs, 2H), 8.78 (s, 1H), 8.29 (m, 1H), 7.55 (m, 2H), 6.72 (m, 1H), 6.22 (m, 1H), 4.80 (m, 4H), 3.78 (m, 4H), 3.59 (m, 3H), 3.31 and 3.2 (s, 3H rotational isomers).MS (ion spray) M+H=476. Elemental Analysis: C21H22ClN5O4S.1.4CF3CO2H cal: C=45.03%, H=3.68%, N=11.04%; found C=44.98%, H=3.71%, N=11.02%.

1. concentrationAfter this time the solution is concentrated
2. customThe crude material is purified by RP-HPLC
3. washeluting with a gradient of 10% CH3CN/H2O (0.1% TFA) to 80% CH3CN/H2O (0.1% TFA)