(Diethylamino)sulfur trifluoride → (S)-6-fluoromethyl-5-(4-fluoro-phenyl)-2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one
反応式
CCN(S(F)(F)[F:7])CC.[F:10][C:11]1[CH:16]=[CH:15][C:14]([N:17]2[C@H:22]([CH2:23]O)[CH2:21][N:20]3[N:25]=[C:26]([CH2:28][O:29][C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)[CH:27]=[C:19]3[C:18]2=[O:36])=[CH:13][CH:12]=1>C(Cl)Cl>[F:7][CH2:23][C@@H:22]1[CH2:21][N:20]2[N:25]=[C:26]([CH2:28][O:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[CH:27]=[C:19]2[C:18](=[O:36])[N:17]1[C:14]1[CH:13]=[CH:12][C:11]([F:10])=[CH:16][CH:15]=1参加物
4
反応物 2
生成物 1
試薬・触媒・溶媒 1
実験手順
DAST (0.067 mL, 0.55 mmol) was added to a solution of (S)-5-(4-fluoro-phenyl)-6-hydroxymethyl-2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (135 mg, 0.37 mmol) in DCM (2 mL) at −10° C. The mixture was stirred at room temperature for 15 minutes. Then quenched with a 1N solution of HCl and extracted with AcOEt. The organic layer was separated, dried (Na2SO4), filtered and the solvent evaporated in vacuo. The residue was purified by flash column chromatography (silica; AcOEt in heptane 20/80 to 80/20). Desired fractions were collected and the solvents evaporated in vacuo. The residue was triturated with DIPE to yield (S)-6-fluoromethyl-5-(4-fluoro-phenyl)-2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (81 mg, 60% yield) as an off-white solid. 1H NMR (400 MHz, CDCl3) δ ppm 4.32-4.37 (m, 1H), 4.37-4.42 (m, 0.5H), 4.42-4.52 (m, 1H), 4.59 (dd, J=9.4, 4.5 Hz, 0.5H), 4.66-4.77 (m, 2H), 5.13 (s, 2H), 6.95-7.03 (m, 3H), 7.03 (s, 1H), 7.13-7.20 (m, 2H), 7.27-7.35 (m, 4H).