Boron tribromide → 4-amino-6-[[(1S)-1-[6-fluoro-1-(3-hydroxycyclobutyl)benzimidazol-2-yl]ethyl]amino]pyrimidine-5-carbonitrile
반응식
[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([NH:10][C@H:11]([C:13]2[N:17]([C@H:18]3[CH2:21][C@H:20]([O:22]CC4C=CC=CC=4)[CH2:19]3)[C:16]3[CH:30]=[C:31]([F:34])[CH:32]=[CH:33][C:15]=3[N:14]=2)[CH3:12])[N:5]=[CH:4][N:3]=1.B(Br)(Br)Br>C(Cl)Cl>[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([NH:10][C@H:11]([C:13]2[N:17]([CH:18]3[CH2:21][CH:20]([OH:22])[CH2:19]3)[C:16]3[CH:30]=[C:31]([F:34])[CH:32]=[CH:33][C:15]=3[N:14]=2)[CH3:12])[N:5]=[CH:4][N:3]=1참가 물질
4
실험 절차
4-Amino-6-[(S)-1-[1-(trans-3-benzyloxycyclobutyl)-6-fluoro-1H-benzoimidazol-2-yl]ethylamino]-pyrimidine-5-carbonitrile (0.06 g, 0.13 mmol) in DCM (5 mL) cooled to 0° C. To this mixture was added boron tribromide (1M solution in DCM, 0.26 mL, 0.23 mmol) dropwise and the resulting mixture stirred at RT for 2 h. The reaction mixture was quenched with MeOH (2 mL) and concentrated in vacuo. The resulting yellow solid was purified by column chromatography (Si—PCC, gradient 0-10% MeOH in DCM) to afford 392 as a colourless glassy solid (75 mg, quantitative). LCMS (Method K): RT 2.41 min [M+H]+ 368.3. 1H NMR (DMSO-d6): δ 8.17 (1H, d, J=6.44 Hz), 8.07 (1H, s), 7.92 (1H, d, J=9.28 Hz), 7.81 (1H, dd, J=8.98, 4.77 Hz), 7.59 (2H, s), 7.41 (1H, t, J=9.27 Hz), 5.83-5.75 (1H, m), 5.49-5.39 (1H, m), 4.59-4.53 (1H, m), 3.16-2.97 (2H, m), 2.46-2.28 (2H, m), 1.67 (3H, d, J=6.81 Hz