Potassium Carbonate → N-[4-(4-amino-2,5-difluorophenoxy)-6-chloropyrimidin-2-yl]acetamide

HRID 476361노트

반응식

HRID 476361 반응식
[NH2:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([OH:9])=[C:4]([F:10])[CH:3]=1.[Cl:11][C:12]1[CH:17]=[C:16](Cl)[N:15]=[C:14]([NH:19][C:20](=[O:22])[CH3:21])[N:13]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O>[NH2:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([O:9][C:16]2[CH:17]=[C:12]([Cl:11])[N:13]=[C:14]([NH:19][C:20](=[O:22])[CH3:21])[N:15]=2)=[C:4]([F:10])[CH:3]=1

참가 물질

6

반응물 3

HCID 11430Potassium CarbonateHCID 27787624-Amino-2,5-difluorophenolHCID 12611964N-(4,6-Dichloropyrimidin-2-yl)acetamide

생성물 1

HCID 86662870N-[4-(4-amino-2,5-difluorophenoxy)-6-chloropyrimidin-2-yl]acetamide수율 44%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

A solution of 4-amino-2,5-difluoro-phenol (3.5 g, 24 mmol), N-(4,6-dichloro-pyrimidin-2-yl)-acetamide (5.30 g, 24 mmol) and potassium carbonate (3.4 g, 24 mmol) in DMF (100 mL) was stirred at 50° C. under nitrogen overnight. After cooling to room temperature the reaction mixture was suspended in water (300 mL) and extracted with ethyl acetate (3×200 mL). The combined organic layers was washed with brine, dried over sodium sulfate and concentrated. The crude product was purified by silica gel chromatography (15%-20% ethyl acetate in petroleum ether) to give N-[4-(4-amino-2,5-difluoro-phenoxy)-6-chloro-pyrimidin-2-yl]-acetamide (3.3 g, 44% yield) as a white solid. 1HNMR (400 MHz, DMSO-d6): δ 10.72 (s, 1H), 7.20-7.24 (dd, J=11.2 Hz, J=7.6 Hz, 1H), 7.00 (s, 1H), 6.64 (dd, J=12.0 Hz, J=8.4 Hz, 1H), 5.48 (s, 2H), 2.03 (s, 3H).

후처리

  1. extractionextracted with ethyl acetate (3×200 mL)
  2. washThe combined organic layers was washed with brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. customThe crude product was purified by silica gel chromatography (15%-20% ethyl acetate in petroleum ether)

출처 및 근거

ORD 기록
ord-dc9a2079720c431098d0573e8fa3522f
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08637672B2

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