反应详情

6-Amino-4-methyl-2,3-dihydro-1,4-benzoxazepin-5-one (151 mg, 0.79 mmol, see Example 3.22) and N-(1,3-dimethylpyrazol-4-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine (150 mg, 0.39 mmol) were reacted using the procedure in Example 5.02. The reaction mixture was purified by preparative HPLC using a Waters X-Bridge reverse-phase column (C-18, 5 microns silica, 19 mm diameter, 100 mm length, flow rate of 40 ml/minute) and decreasingly polar mixtures of water (containing 0.2% ammonium carbonate) and acetonitrile as eluent, followed by flash chromatography on silica gel eluting with 0 to 5% MeOH in EtOAc/DCM (1:1). The solvent was evaporated to dryness and triturated in a mixture of 30% tBuOMe in pentane to give the title compounds as a light white foam (95 mg, 54%). 1H NMR spectrum (500 MHz, CDCl3): 2.15 (s, 3H), 3.21 (s, 3H), 3.50 (t, 2H), 3.81 (s, 3H), 4.35 (t, 2H), 6.19 (s, 1H), 6.30 (s, 1H), 6.70 (dd, 1H), 7.19 (dd, 1H), 7.23 (dd, 1H), 7.38 (s, 1H), 8.20 (s, 1H), 9.21 (s, 1H); Mass spectrum: ESI+ MH+ 447.

1. customThe reaction mixture was purified by preparative HPLC
2. customThe solvent was evaporated to dryness
3. customtriturated in a mixture of 30% tBuOMe in pentane