Sodium Bicarbonate → 3-(6-{7-[2-(1-tert-Butoxycarbonyl-pyrrolidin-2-yl)-3H-imidazol-4-yl]-9,10-dihydro-phenanthren-2-yl]-1H-benzoimidazol-2-yl)-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester

HRID 71895노트

반응식

HRID 71895 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[NH:14][C:15]([C:18]2[CH:31]=[CH:30][C:29]3[C:28]4[C:23](=[CH:24][C:25](Br)=[CH:26][CH:27]=4)[CH2:22][CH2:21][C:20]=3[CH:19]=2)=[CH:16][N:17]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:33]([O:37][C:38]([N:40]1[CH:45]([C:46]2[NH:50][C:49]3[CH:51]=[C:52](B4OC(C)(C)C(C)(C)O4)[CH:53]=[CH:54][C:48]=3[N:47]=2)[CH:44]2[CH2:64][CH:41]1[CH2:42][CH2:43]2)=[O:39])([CH3:36])([CH3:35])[CH3:34].C([O-])(O)=O.[Na+]>COCCOC.O>[C:33]([O:37][C:38]([N:40]1[CH:45]([C:46]2[NH:50][C:49]3[CH:51]=[C:52]([C:25]4[CH:26]=[CH:27][C:28]5[C:29]6[C:20](=[CH:19][C:18]([C:15]7[NH:14][C:13]([CH:9]8[CH2:10][CH2:11][CH2:12][N:8]8[C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])=[N:17][CH:16]=7)=[CH:31][CH:30]=6)[CH2:21][CH2:22][C:23]=5[CH:24]=4)[CH:53]=[CH:54][C:48]=3[N:47]=2)[CH:44]2[CH2:64][CH:41]1[CH2:42][CH2:43]2)=[O:39])([CH3:36])([CH3:34])[CH3:35]

참가 물질

6

반응물 3

HCID 516892Sodium BicarbonateHCID 66620440(1R,3S,4S)-3-[6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzimidazol-2-yl]-2-azabicyclo[2.2.1]heptane-2-carboxylic acid 1,1-dimethylethyl esterHCID 666209942-[5-(7-bromo-9,10-dihydro-phenanthren-2-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester

생성물 1

HCID 666211453-(6-{7-[2-(1-tert-Butoxycarbonyl-pyrrolidin-2-yl)-3H-imidazol-4-yl]-9,10-dihydro-phenanthren-2-yl]-1H-benzoimidazol-2-yl)-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester수율 59%

시약·촉매·용매 2

HCID 962Water용매HCID 80711,2-Dimethoxyethane용매

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온도
80 °C

실험 절차

Pd(Ph3)4 (20 mg, 0.017 mmol) was added to a mixture 2-[5-(7-bromo-9,10-dihydro-phenanthren-2-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester (173 mg, 0.35 mmol), 3-[6-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-benzoimidazol-2-yl]-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (154 mg, 0.35 mmol), NaHCO3 (103 mg, 1.22 mmol) in 1,2-dimethoxyethane (5 mL) and water (1 mL). The reaction mixture was flushed with nitrogen, heated at 80° C. for 16 hours, and then the volatile component was removed in vacuo. The residue was dissolved in ethyl acetate (100 mL), washed with NaHCO3 solution, water and brine, dried over Na2SO4, filtered and concentrated in vacuo. The obtained residue was purified by flash chromatography to provide the desired product 3-(6-{7-[2-(1-tert-Butoxycarbonyl-pyrrolidin-2-yl)-3H-imidazol-4-yl]-9,10-dihydro-phenanthren-2-yl}-1H-benzoimidazol-2-yl)-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester as a white solid (150 mg, 59%). m/z 727.4 (M+H)+.

후처리

  1. customThe reaction mixture was flushed with nitrogen
  2. customthe volatile component was removed in vacuo
  3. dissolutionThe residue was dissolved in ethyl acetate (100 mL)
  4. washwashed with NaHCO3 solution, water and brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe obtained residue was purified by flash chromatography

출처 및 근거

ORD 기록
ord-fbbfa3b52fef451391e9a0df4ca27782
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08822430B2

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