tert-butyl 4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate → 10-bromo-9-fluoro-3-(1H-pyrazol-4-yl)-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine-2-carboxamide
反応式
[Br:1][C:2]1[C:3]([F:20])=[CH:4][C:5]2[O:11][CH2:10][CH2:9][N:8]3[C:12](I)=[C:13]([C:15]([NH2:17])=[O:16])[N:14]=[C:7]3[C:6]=2[CH:19]=1.C([N:28]1[CH:32]=[C:31](B2OC(C)(C)C(C)(C)O2)[CH:30]=[N:29]1)(OC(C)(C)C)=O>>[Br:1][C:2]1[C:3]([F:20])=[CH:4][C:5]2[O:11][CH2:10][CH2:9][N:8]3[C:12]([C:31]4[CH:32]=[N:28][NH:29][CH:30]=4)=[C:13]([C:15]([NH2:17])=[O:16])[N:14]=[C:7]3[C:6]=2[CH:19]=1参加物
3
反応物 2
生成物 1
実験手順
10-Bromo-9-fluoro-3-iodo-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine-2-carboxamide (0.14 g) was reacted with 1-Boc-4-pyrazoleboronic acid pinacol ester similar to as described in Example 4 and triturated from water followed by methanol to give 100 mg of 10-bromo-9-fluoro-3-(1H-pyrazol-4-yl)-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine-2-carboxamide. This intermediate was reacted with 2-Methyl-3-butyne-ol via similar to as described in Procedure E to afford 47.5 mg of 9-fluoro-10-(3-hydroxy-3-methyl-but-1-ynyl)-3-(1H-pyrazol-4-yl)-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine-2-carboxamide following reverse phase hplc purification. MS (Q1) 396 (M)+. 1H NMR (400 MHz, DMSO) δ 13.10 (s, 1H), 8.62 (s, 1H), 8.10 (s, 1H), 7.81 (s, 1H), 7.57 (s, 1H), 7.01 (s, 1H), 6.99 (s, 1H), 5.50 (s, 1H), 4.54-4.41 (m, 2H), 4.38-4.20 (m, 2H), 2.07 (s, 1H), 1.51 (s, 6H).