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

HRID 476361ノート

反応式

HRID 476361 の反応式
[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

参加物

6

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-dc9a2079720c431098d0573e8fa3522f
出典データセット
uspto-grants-2014_01
特許番号
US08637672B2

反応ノート

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