Triethylamine → 2-methyl-1-{8-[2-(4-phenyl-1-pyrimidin-2-ylpiperidin-4-yl)ethyl]-8-azabicyclo[3.2.1]oct-3-yl}-1H-benzimidazole

HRID 1992077노트

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Cl.Cl.[CH3:3][C:4]1[N:8]([CH:9]2[CH2:15][CH:14]3[N:16]([CH2:17][CH2:18][C:19]4([C:25]5[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=5)[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]4)[CH:11]([CH2:12][CH2:13]3)[CH2:10]2)[C:7]2[CH:31]=[CH:32][CH:33]=[CH:34][C:6]=2[N:5]=1.Cl[C:36]1[N:41]=[CH:40][CH:39]=[CH:38][N:37]=1.C(N(CC)CC)C>>[CH3:3][C:4]1[N:8]([CH:9]2[CH2:15][CH:14]3[N:16]([CH2:17][CH2:18][C:19]4([C:25]5[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=5)[CH2:20][CH2:21][N:22]([C:36]5[N:41]=[CH:40][CH:39]=[CH:38][N:37]=5)[CH2:23][CH2:24]4)[CH:11]([CH2:12][CH2:13]3)[CH2:10]2)[C:7]2[CH:31]=[CH:32][CH:33]=[CH:34][C:6]=2[N:5]=1

참가 물질

반응물 3

HCID 8471Triethylamine

HCID 744042-Chloropyrimidine

HCID 686757782-methyl-1-{8-[2-(4-phenyl piperidin-4-yl)ethyl]-8-azabicyclo[3.2.1]oct-3-yl}-1H-benzimidazole dihydrochloride

생성물 1

HCID 566714482-methyl-1-{8-[2-(4-phenyl-1-pyrimidin-2-ylpiperidin-4-yl)ethyl]-8-azabicyclo[3.2.1]oct-3-yl}-1H-benzimidazole수율 65%

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온도: 80 °C

실험 절차

To a stirred solution of 2-methyl-1-{8-[2-(4-phenylpiperidin-4-yl)ethyl]-8-azabicyclo[3.2.1]oct-3-yl}-1H-benzimidazole dihydrochloride (25.3 mg, 0.05 mmol) in N,N-dimethylformade (2 mL) was added 2-chloropyrimidine (8.6 mg, 0.075 mmol) and triethylamine (21 μL, 0.15 mmol). The resulting mixture was stirred at 80° C. for 2.5 hours. After evaporation of the solvent, the crude product was directly purified by flash chromatography on silical gel, eluting with a gradient of 0-10% triethylamine in methanol to afford 2-methyl-1-{8-[2-(4-phenyl-1-pyrimidin-2-ylpiperidin-4-yl)ethyl]-8-azabicyclo[3.2.1]oct-3-yl}-1H-benzimidazole as amorphous solid (16.2 mg, 65%). 1H NMR (300 MHz, CDCl3) δ 8.30 (d, J=6.0 Hz, 2H), 7.67 (dd, J=2.6, 7.0 Hz, 1H), 7.39-7.37 (m, 4H), 7.35-7.22 (m, 3H), 7.21-7.14 (m, 2H), 6.45 (t, J=4.7 Hz, 1H), 4.64 (m, 1H), 4.17-4.09 (m, 2H), 3.61-3.52 (m, 2H), 3.28-3.25 (m, 2H), 2.59 (s, 3H), 2.44-2.33 (m, 2H), 2.29-2.22 (m, 2H), 1.97-1.85 (m, 10H), 1.62 (d, J=7.7 Hz, 2H). HRMS m/z (M+H)+ calcd: 507.3236; obsd: 507.3248.

후처리

customAfter evaporation of the solvent
customthe crude product was directly purified by flash chromatography on silical gel
washeluting with a gradient of 0-10% triethylamine in methanol

출처 및 근거

ORD 기록: ord-126bf68c6c5240f89fc8a1a04430ed48
출처 데이터셋: uspto-grants-2010_01
DOI: 10.6084/m9.figshare.5104873.v1
특허 번호: US07645771B2

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