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Nitrogen → 2-[5-(3'-tert-Butoxycarbonylamino-biphenyl-4-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid benzyl ester

HRID 1185754
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HRID 1185754 반응식
[CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH2:14][CH2:13][CH:12]1[C:16]1[NH:17][C:18]([C:21]2[CH:26]=[CH:25][C:24](Br)=[CH:23][CH:22]=2)=[CH:19][N:20]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:28]([O:32][C:33]([NH:35][C:36]1[CH:37]=[C:38](B(O)O)[CH:39]=[CH:40][CH:41]=1)=[O:34])([CH3:31])([CH3:30])[CH3:29].C([O-])([O-])=O.[K+].[K+].N#N>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.COCCOC>[CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH2:14][CH2:13][CH:12]1[C:16]1[NH:17][C:18]([C:21]2[CH:26]=[CH:25][C:24]([C:38]3[CH:39]=[CH:40][CH:41]=[C:36]([NH:35][C:33]([O:32][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:34])[CH:37]=3)=[CH:23][CH:22]=2)=[CH:19][N:20]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
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참가 물질

7

반응물 4

HCID 947NitrogenHCID 11430Potassium CarbonateHCID 2773228(3-Boc-aminophenyl)boronic acidHCID 666210362-[5-(4-Bromo-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid benzyl ester

생성물 1

HCID 666209592-[5-(3'-tert-Butoxycarbonylamino-biphenyl-4-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid benzyl ester수율 64.1%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 80711,2-Dimethoxyethane용매

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온도
85 °C

실험 절차

2-[5-(4-Bromo-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid benzyl ester (2.14 g, 5.01 mmol), (3-tert-Butoxycarbonylaminophenyl)-boronic acid (1.19 g, 5.01 mmol), Pd(PPh3)4 (289 mg, 0.251 mmol) and K2CO3 (5.5 mL of 2 M aqueous solution, 11.02 mmol) were combined with 1,2-dimethoxyethane (20 mL). The suspension was stirred while N2 was bubbled through the solution for 24 min. A reflux condenser was attached and the suspension was heated to 85° C. for 17 hours. It was then cooled, diluted with ethyl acetate (150 mL), washed with water and brine, dried over sodium sulfate and concentrated. The crude product was purified by silica column chromatography (25% to 50% EtOAc/hexanes) to provide 2-[5-(3′-tert-Butoxycarbonylamino-biphenyl-4-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid benzyl ester (1.73 g, 64%).

후처리

  1. customwas bubbled through the solution for 24 min
  2. customA reflux condenser was attached
  3. temperatureIt was then cooled
  4. additiondiluted with ethyl acetate (150 mL)
  5. washwashed with water and brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. customThe crude product was purified by silica column chromatography (25% to 50% EtOAc/hexanes)

출처 및 근거

ORD 기록
ord-b1d1dcd0b13c4f3ba837785ea69d170a
출처 데이터셋
uspto-grants-2014_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08669234B2

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