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Potassium Carbonate → 2-(4-fluoro-2-(hydroxymethyl)phenoxy)-N-(2-oxo-1,2-dihydropyridin-4-yl)-4-(trifluoromethyl)benzamide

HRID 1053173
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HRID 1053173 반응식
F[C:2]1[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[CH:14][C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][NH:10][C:9](=[O:13])[CH:8]=1)=[O:5].C(=O)([O-])[O-].[K+].[K+].[F:28][C:29]1[CH:34]=[CH:33][C:32]([OH:35])=[C:31]([CH2:36][OH:37])[CH:30]=1>CN1CCCC1=O>[F:28][C:29]1[CH:34]=[CH:33][C:32]([O:35][C:2]2[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[CH:14][C:3]=2[C:4]([NH:6][C:7]2[CH:12]=[CH:11][NH:10][C:9](=[O:13])[CH:8]=2)=[O:5])=[C:31]([CH2:36][OH:37])[CH:30]=1
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5

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HCID 11430Potassium CarbonateHCID 106068384-Fluoro-2-(hydroxymethyl)phenolHCID 867284632-fluoro-N-(2-oxo-1H-pyridin-4-yl)-4-(trifluoromethyl)benzamide

생성물 1

HCID 867284862-(4-fluoro-2-(hydroxymethyl)phenoxy)-N-(2-oxo-1,2-dihydropyridin-4-yl)-4-(trifluoromethyl)benzamide수율 1.2%

시약·촉매·용매 1

HCID 13387
N-methyl-2-pyrrolidone
용매

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온도
80 °C

실험 절차

2-Fluoro-N-(2-oxo-1H-pyridin-4-yl)-4-(trifluoromethyl)benzamide (625.3 mg, 2.08 mmol), potassium carbonate (287.9 mg, 2.08 mmol) and 4-fluoro-2-(hydroxymethyl)phenol (296 mg, 2.08 mmol) were added to 1-methylpyrrolidin-2-one (3.0 mL) and the reaction was stirred at 80° C. for 10 minutes. The reaction was filtered and the compound was purified by reverse phase preparative chromatography utilizing a gradient of 10-99% acetonitrile in water containing HCl as a modifier to yield 2-[4-fluoro-2-(hydroxymethyl)phenoxy]-N-(2-oxo-1H-pyridin-4-yl)-4-(trifluoromethyl)benzamide (157) (10.3 mg, 1%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 11.44 (s, 1H), 10.66 (s, 1H), 7.86 (d, J=7.9 Hz, 1H), 7.61 (d, J=8.0 Hz, 1H), 7.41-7.27 (m, 2H), 7.24-7.12 (m, 1H), 7.12-7.07 (m, 1H), 7.04 (s, 1H), 6.80 (d, J=2.1 Hz, 1H), 6.43 (dd, J=7.3, 2.2 Hz, 1H), 4.47 (s, 2H) ppm. ESI-MS m/z calc. 422.09. found 423.2 (M+1)+; Retention time: 1.32 minutes (3 minutes run).

후처리

  1. filtrationThe reaction was filtered
  2. customthe compound was purified by reverse phase preparative chromatography
  3. additioncontaining HCl as a modifier

출처 및 근거

ORD 기록
ord-a7f87d11827b4777a6cd6cf06f1edcdc
출처 데이터셋
uspto-grants-2016_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09393235B2

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