2-Methyl-3-butyn-2-ol → 9-fluoro-10-(3-hydroxy-3-methylbut-1-ynyl)-3-(3-methyl-1-(2,2,2-trifluoroethyl)-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide

温度

85 °C

The title compound was prepared similarly according to Procedure E. To a solution of 10-bromo-9-fluoro-3-[5-methyl-2-(2,2,2-trifluoroethyl)-1,2,4-triazol-3-yl]-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine-2-carboxamide (200 mg, 0.41 mmol), PdCl2(PPh3)2 (0.05 equiv., 14.5 mg, 0.02 mmol) and copper (I) iodide (0.05 equiv., 4.0 mg, 0.02 mmol) in diisopropylamine (1.1 mL, 2.6 mL/mmol) and DMF (0.53 mL, 1.3 mL/mmol) was added 2-methyl-3-butyn-2-ol (2.0 equiv., 0.08 mL, 0.82 mmol). The reaction was heated to 85° C. for 30 minutes. The reaction mixture was cooled to room temperature, diluted with methylene chloride and filtered over celite. The crude was purified by reverse-phase HPLC to afford 73 mg (36.3% yield) of a fluffy white solid. 1H NMR (400 MHz, DMSO) δ 8.66 (d, J=8.5 Hz, 1H), 7.99 (br s, 1H), 7.48 (br s, 1H), 7.05 (d, J=10.5 Hz, 1H), 5.53 (s, 1H), 5.12-4.96 (m, 2H), 4.56-4.47 (m, 2H), 4.30-3.98 (m, 2H), 2.37 (s, 3H), 1.50 (s, 6H). M+H=493.2.

1. temperatureThe reaction mixture was cooled to room temperature
2. filtrationfiltered over celite
3. customThe crude was purified by reverse-phase HPLC

ORDレコード

ord-3e3914a52a904526980f7fae502de9a5

出典データセット

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09034866B2