Hydrochloric Acid → N4-{4-[(3-Cyclopropyl-1H-pyrrolo[2,3-b]pyridin-4-yl)oxy]-3,5-difluorophenyl}-6-(trifluoromethyl)-pyrimidine-2,4-diamine

HRID 2192196ノート

反応式

HRID 2192196 の反応式
[CH:1]1([C:4]2[C:12]3[C:7](=[N:8][CH:9]=[CH:10][C:11]=3[O:13][C:14]3[C:20]([F:21])=[CH:19][C:17]([NH2:18])=[CH:16][C:15]=3[F:22])[NH:6][CH:5]=2)[CH2:3][CH2:2]1.Cl[C:24]1[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[N:27]=[C:26]([NH2:34])[N:25]=1.Cl.[OH-].[Na+]>O.C(O)C>[CH:1]1([C:4]2[C:12]3[C:7](=[N:8][CH:9]=[CH:10][C:11]=3[O:13][C:14]3[C:15]([F:22])=[CH:16][C:17]([NH:18][C:24]4[CH:29]=[C:28]([C:30]([F:33])([F:31])[F:32])[N:27]=[C:26]([NH2:34])[N:25]=4)=[CH:19][C:20]=3[F:21])[NH:6][CH:5]=2)[CH2:3][CH2:2]1

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 130869074-Chloro-6-(trifluoromethyl)pyrimidin-2-amine2 回HCID 597409994-[(3-cyclopropyl-1H-pyrrolo[2,3-b]pyridin-4-yl)oxy]-3,5-difluoroaniline

生成物 1

HCID 11496330N4-{4-[(3-Cyclopropyl-1H-pyrrolo[2,3-b]pyridin-4-yl)oxy]-3,5-difluorophenyl}-6-(trifluoromethyl)-pyrimidine-2,4-diamine

試薬・触媒・溶媒 2

HCID 702Ethanol溶媒HCID 962Water溶媒

実験手順

330 mg (1.10 mmol) of 4-[(3-cyclopropyl-1H-pyrrolo[2,3-b]pyridin-4-yl)oxy]-3,5-difluoroaniline and 320 mg (1.64 mmol) of 4-chloro-6-(trifluoromethyl)pyrimidine-2-amine are suspended in 4 ml of water and 2 ml of ethanol. 0.55 ml (2.2 mmol) of 4N hydrochloric acid is added, and the mixture is heated at reflux for 1 h. Another 107 mg (0.55 mmol) of 4-chloro-6-(trifluoromethyl)pyrimidine-2-amine are then added, and the mixture is heated for a further 2 hours. The mixture is made alkaline by addition of 1N aqueous sodium hydroxide solution and extracted with ethyl acetate, and the organic phase is washed with water. The organic phase is dried over sodium sulfate and the solvent is removed under reduced pressure. The product is purified by preparative HPLC.

後処理

  1. temperaturethe mixture is heated
  2. temperatureat reflux for 1 h
  3. temperaturethe mixture is heated for a further 2 hours
  4. extractionextracted with ethyl acetate
  5. washthe organic phase is washed with water
  6. dry with materialThe organic phase is dried over sodium sulfate
  7. customthe solvent is removed under reduced pressure
  8. customThe product is purified by preparative HPLC

出典と根拠

ORDレコード
ord-6b4d92bc41f7442a80ceb93c1c0005f4
出典データセット
uspto-grants-2012_12
特許番号
US08329716B2

反応ノート

読み込み中…