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Potassium Carbonate → 2-[2'-(1-Boc-pyrrolidin-2-yl)-3H,3'H-[5,5']bibenzoimidazolyl-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 2039015
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HRID 2039015 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[NH:17][C:16]2[CH:18]=[C:19](Br)[CH:20]=[CH:21][C:15]=2[N:14]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:23]([O:27][C:28]([N:30]1[CH2:34][CH2:33][CH2:32][CH:31]1[C:35]1[NH:39][C:38]2[CH:40]=[C:41](B3OC(C)(C)C(C)(C)O3)[CH:42]=[CH:43][C:37]=2[N:36]=1)=[O:29])([CH3:26])([CH3:25])[CH3:24].C(=O)([O-])[O-].[K+].[K+]>COCCOC.O.C(OCC)(=O)C.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>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[NH:17][C:16]2[CH:18]=[C:19]([C:41]3[CH:42]=[CH:43][C:37]4[N:36]=[C:35]([CH:31]5[CH2:32][CH2:33][CH2:34][N:30]5[C:28]([O:27][C:23]([CH3:24])([CH3:25])[CH3:26])=[O:29])[NH:39][C:38]=4[CH:40]=3)[CH:20]=[CH:21][C:15]=2[N:14]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
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참가 물질

8

반응물 3

HCID 11430Potassium CarbonateHCID 566054092-[5-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-benzoimidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl esterHCID 581852752-(6-bromo-1H-benzimidazol-2-yl)pyrrolidine-1-carboxylic acid tert-butyl ester

생성물 1

HCID 666207982-[2'-(1-Boc-pyrrolidin-2-yl)-3H,3'H-[5,5']bibenzoimidazolyl-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester수율 15.1%

시약·촉매·용매 4

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 80711,2-Dimethoxyethane용매HCID 8857Ethyl Acetate용매

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온도
110 °C

실험 절차

A mixture of 2-(6-bromo-1H-benzoimidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester (64 mg, 0.174 mmol), 2-[6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-benzoimidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester (72 mg, 0.174 mmol), tetrakis(triphenylphosphine)palladium (30 mg, 0.026 mmol) and potassium carbonate (48 mg, 0.35 mmol) in 2 ml 1,2-dimethoxyethane and 1 mL water was heated to 110° C. in microwave for 15 minutes. The reaction mixture was cooled and dissolved in ethyl acetate and washed with 5% lithium chloride aqueous solution. The organic layer dried (MgSO4), concentrated and purified by flash column chromatography (silica gel, 0 to 10% methanol/ethyl acetate) to give 2-[2′-(1-Boc-pyrrolidin-2-yl)-3H,3′H-[5,5]bibenzoimidazolyl-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester (15 mg, yield 15%). LCMS-ESI−: calc'd for C32H40N6O4: 572.70; Found: 573.1 (M+H+).

후처리

  1. temperatureThe reaction mixture was cooled
  2. washwashed with 5% lithium chloride aqueous solution
  3. dry with materialThe organic layer dried (MgSO4)
  4. concentrationconcentrated
  5. custompurified by flash column chromatography (silica gel, 0 to 10% methanol/ethyl acetate)

출처 및 근거

ORD 기록
ord-9e283c37b7a34c32bceffc197229ce45
출처 데이터셋
uspto-grants-2013_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08575118B2

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