反应详情

To a mixture containing (±)-1-(4-amino-quinazolin-7-ylmethyl)-4-(6-chloro-benzo[b]thiophene-2-sulfonyl)-6-oxo-piperazine-2-carboxylic acid (45 mg, 0.08 mmol), EXAMPLE 800, N-methylmorpholine (18 mg, 0.18 mmol), and HATU (35 mg, 0.09 mmol) in anhydrous DMF (1 mL) is added NH3 (7N in MeOH, 2 drops, approx. 0.5 mmol). The heterogeneous mixture is stirred 16 h at ambient temprature and then concentrated to dryness. The residue is dissolved in water 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 25 mg (46%) of the title compound as a white solid. 1H NMR (300 MHz, d6-DMSO) δ3.63 (d, J=16.0 Hz, 1H), 4.01 (m, 4H), 5.17 (d, J=16.6 Hz, 1H), 7.58 (m, 3H), 8.08 (d, J=8.6 Hz, 1H), 8.17 (s, 1H), 8.26 (d, J=8.6 Hz, 1H), 8.34 (d, J=1.9 Hz, 1H), 8.74 (s, 1H), 9.63 (br s, 2H) ppm; MS (ISP loop): m/z 531 (M+H).

1. concentrationconcentrated to dryness
2. dissolutionThe residue is dissolved in water
3. custompurified by reverse-phase HPLC [Buffer A: water