反应详情

To a solution containing (±)-2-[4-(4-amino-quinazolin-7-ylmethyl)-3-methoxycarbonyl-5-oxo-piperazin-1-ylmethyl]-5-chloro-indole-1-carboxylic acid tert-butyl ester (26 mg, 0.03 mmol) in CH2Cl2 (4 mL) is added trifluoroacetic acid (1 mL) at ambient temperature. After 4 h, the reaction mixture is concentrated in vacuo and then dissolved in water/CH3CN and purified by reverse-phase HPLC [Buffer A: water w/0.1% TFA; Buffer B: CH3CN w/0.1% TFA; Gradient: 0% B to 60% B over 30 min] to provide 10 mg (47%) of the title compound as a white solid. 1H NMR (300 MHz, d6-DMSO) δ2.62 (m, 1H), 3.05-3.51 (m, 4H), 3.59 (s, 3H), 3.81 (d, J=14.0 Hz, 1H), 4.26 (m, 1H), 4.69 (ABq, ΔAB=310 Hz, JAB=16.4 Hz, 2H), 6.26 (s, 1H), 7.02 (dd, J=8.6, 2.0 Hz, 1H), 7.31 (d, J=8.6 Hz, 1H), 7.49 (d, J=2.0 Hz, 1H), 7.52 (s, 1H), 7.61 (d, J=8.7 Hz, 1H), 8.30 (d, J=8.6 Hz, 1H), 8.47 (s, 1H), 8.77 (s, 1H), 9.69 (br s, 2H), 11.17 (s, 1H) ppm; MS (ion spray): m/z 479 (M+H).

1. concentrationthe reaction mixture is concentrated in vacuo
2. dissolutiondissolved in water/CH3CN
3. custompurified by reverse-phase HPLC [Buffer A: water