Tetrahydrofuran → (s,e)-n-(3,3-Dimethyl-1-(methylamino)-1-oxobutan-2-yl)-8-methyl-3-(3-morpholinoprop-1-enyl)-6,7,8,9-tetrahydro-5h-imidazo[1,5-a][1,4]diazepine-1-carboxamide

反応式

[Si](OC[CH2:10]/[CH:11]=[CH:12]/[C:13]1[N:17]2[CH2:18][CH2:19][CH2:20][N:21]([CH3:23])[CH2:22][C:16]2=[C:15]([C:24]([NH:26][C@@H:27]([C:32]([CH3:35])([CH3:34])[CH3:33])[C:28]([NH:30][CH3:31])=[O:29])=[O:25])[N:14]=1)(C(C)(C)C)(C)C.CC[CH2:38][CH2:39][N+:40](CCCC)(CCCC)[CH2:41][CH2:42]CC.[F-].C1C[O:57]CC1>>[CH3:35][C:32]([CH3:34])([CH3:33])[C@H:27]([NH:26][C:24]([C:15]1[N:14]=[C:13](/[CH:12]=[CH:11]/[CH2:10][N:40]2[CH2:41][CH2:42][O:57][CH2:38][CH2:39]2)[N:17]2[CH2:18][CH2:19][CH2:20][N:21]([CH3:23])[CH2:22][C:16]=12)=[O:25])[C:28]([NH:30][CH3:31])=[O:29]

参加物

反応物 3

HCID 8028Tetrahydrofuran

HCID 2724141Tetrabutylammonium Fluoride

HCID 57635634HCID 57635634、化合物

生成物 1

HCID 57635710(s,e)-n-(3,3-Dimethyl-1-(methylamino)-1-oxobutan-2-yl)-8-methyl-3-(3-morpholinoprop-1-enyl)-6,7,8,9-tetrahydro-5h-imidazo[1,5-a][1,4]diazepine-1-carboxamide収率 70%

実験手順

Compound 47A (0.126 g, 0.25 mmol) was dissolved in THF and TBAF (1M in THF, 0.50 mL, 0.50 mmol) solution was added. The resulting mixture was stirred for 18 h. The mixture was concentrated, diluted with NaCl saturated solution and extracted with DCM. The organic layer was dried over anhydrous Na2SO4 and concentrated. The residue was purified by Prep LC/MS using 5-95% gradient of acetonitrile/water with 0.1% formic acid. The resulting material was purified by ion exchange chromatography using a Strata SPE SCX column to remove t-butyl dimethylsilane impurity. Compound 514 (0.070 g, 70%) was isolated as a free base. 1H-NMR (400 MHz, CDCl3) δ: 1.07 (s, 9H), 1.85 (m, 3H), 2.37 (s, 3H), 2.53 (m, 2H), 2.80 (d, 3H), 2.95 (m, 2H), 3.82 (t, 2H), 4.06 (m, 2H), 4.29 (m, 3H), 5.93 (m, 1H), 6.34 (d, 1H), 6.73 (m, 1H), 7.86 (m, 1H); LCMS (+ESI) m/z 392.2 [M+H]+.