Triethylamine → 2-chloro-5-[(4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-4-phenylpiperidin-1-yl)carbonyl]benzenesulfonamide

HRID 1992050노트

반응식

HRID 1992050 반응식
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:35][C:36]1[CH:37]=[C:38]([CH:42]=[CH:43][C:44]=1[S:45](=[O:48])(=[O:47])[NH2:46])C(O)=O.C(N(CC)CC)C.CN([C:59]([O:63]N1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.C(Cl)Cl>[Cl:35][C:36]1[CH:37]=[CH:38][C:42]([C:59]([N:22]2[CH2:21][CH2:20][C:19]([CH2:18][CH2:17][N:16]3[CH:14]4[CH2:13][CH2:12][CH:11]3[CH2:10][CH:9]([N:8]3[C:7]5[CH:31]=[CH:32][CH:33]=[CH:34][C:6]=5[N:5]=[C:4]3[CH3:3])[CH2:15]4)([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH2:24][CH2:23]2)=[O:63])=[CH:43][C:44]=1[S:45]([NH2:46])(=[O:47])=[O:48]

참가 물질

7

반응물 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 470031394-(Aminosulfonyl)-3-chlorobenzoic acidHCID 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 545840602-chloro-5-[(4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-4-phenylpiperidin-1-yl)carbonyl]benzenesulfonamide수율 47%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

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 (200 mg, 0.4 mmol) in DMF (8 mL) was added 3-chloro-4-sulfamoylbenzoic acid (94 mg, 0.4 mmol), triethylamine (166 μL, 1.2 mmol) and HATU (152 mg, 0.4 mmol). The resulting mixture was stirred at ambient temperature for 3 hours before being diluted with methylene chloride (50 mL). The reaction was then washed with saturated sodium bicarbonate solution. The organic phase was dried over anhydrous sodium sulfate. After evaporation of the solvent, the crude product was purified by flash chromatography on silical gel, eluting with a gradient of 0-10% methanol in ethyl acetate to afford 2-chloro-5-[(4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-4-phenylpiperidin-1-yl)carbonyl]benzenesulfonamide as amorphous solid (120 mg, 47%). 1H NMR (300 MHz, DMSO-d6) δ 7.87-7.71 (m, 3H), 7.57 (s, 1H), 7.50-7.47 (m, 2H), 7.38-7.33 (m, 4H), 7.24 (s, 1H), 7.14-7.06 (m, 2H), 4.49 (m, 1H), 3.98 (m, 1H), 3.42-3.23 (m, 5H), 3.06-3.00 (m, 1H), 2.43 (s, 3H), 2.39-2.22 (m, 2H), 2.17-2.08 (m, 2H), 1.92-1.76 (m, 10H), 1.58-1.56 (br, 2H). HRMS m/z (M+H)+ calcd: 646.2619; obsd: 646.2610.

후처리

  1. washThe reaction was then washed with saturated sodium bicarbonate solution
  2. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  3. customAfter evaporation of the solvent
  4. customthe crude product was purified by flash chromatography on silical gel
  5. washeluting with a gradient of 0-10% methanol in ethyl acetate

출처 및 근거

ORD 기록
ord-4310131b4c0a4995abf71171cfbc31dc
출처 데이터셋
uspto-grants-2010_01
특허 번호
US07645771B2

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