Cesium carbonate → 4-{3-(5-Chloro-2-difluoromethoxyphenyl)-4-[(pyrazolo[1,5-a]pyrimidine-3-carbonyl)amino]pyrazol-1-yl}piperidine-1-carboxylic acid tert-butyl ester

HRID 529753ノート

反応式

HRID 529753 の反応式
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:25][CH:26]([F:28])[F:27])=[C:6]([C:8]2[C:12]([NH:13][C:14]([C:16]3[CH:17]=[N:18][N:19]4[CH:24]=[CH:23][CH:22]=[N:21][C:20]=34)=[O:15])=[CH:11][NH:10][N:9]=2)[CH:7]=1.[C:29]([O:33][C:34]([N:36]1[CH2:41][CH2:40][CH:39](OS(C2C=CC(C)=CC=2)(=O)=O)[CH2:38][CH2:37]1)=[O:35])([CH3:32])([CH3:31])[CH3:30].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.O>[C:29]([O:33][C:34]([N:36]1[CH2:41][CH2:40][CH:39]([N:10]2[CH:11]=[C:12]([NH:13][C:14]([C:16]3[CH:17]=[N:18][N:19]4[CH:24]=[CH:23][CH:22]=[N:21][C:20]=34)=[O:15])[C:8]([C:6]3[CH:7]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=3[O:25][CH:26]([F:28])[F:27])=[N:9]2)[CH2:38][CH2:37]1)=[O:35])([CH3:32])([CH3:30])[CH3:31]

参加物

6

反応物 3

HCID 10796Cesium carbonateHCID 157347131-(tert-Butoxycarbonyl)-4-(p-toluenesulfonyloxy)piperidineHCID 178522413HCID 178522413、化合物

生成物 1

HCID 1185223724-{3-(5-Chloro-2-difluoromethoxyphenyl)-4-[(pyrazolo[1,5-a]pyrimidine-3-carbonyl)amino]pyrazol-1-yl}piperidine-1-carboxylic acid tert-butyl ester

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
90 °C

実験手順

Pyrazolo[1,5-a]pyrimidine-3-carboxylic acid [3-(5-chloro-2-difluoromethoxyphenyl)-1H-pyrazol-4-yl]amide (200 mg, 0.49 mmol) was dissolved in DMF (5 mL), 4-(toluene-4-sulfonyloxy)piperidine-1-carboxylic acid tert-butyl ester (263 mg, 0.74 mmol) and cesium carbonate (240 mg, 0.74 mmol) were added and the mixture heated at 90° C. for 2 hours. The mixture was allowed to cool to room temperature, diluted with water and extracted with DCM (×3). The combined organic extract was washed with brine, dried (Na2SO4), filtered and evaporated. The resultant yellow oil was purified by flash chromatography on silica eluting with 0-2% MeOH in DCM. The appropriate fractions were collected and evaporated to afford 4-{3-(5-chloro-2-difluoromethoxyphenyl)-4-[(pyrazolo[1,5-a]pyrimidine-3-carbonyl)amino]pyrazol-1-yl}piperidine-1-carboxylic acid tert-butyl ester a yellow oil. The crude product was taken onto the next step without further purification. LCMS (Method 4) [M+Na]+=610.0; RT=4.30 min.

後処理

  1. temperatureto cool to room temperature
  2. extractionextracted with DCM (×3)
  3. extractionThe combined organic extract
  4. washwas washed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated
  8. customThe resultant yellow oil was purified by flash chromatography on silica eluting with 0-2% MeOH in DCM
  9. customThe appropriate fractions were collected
  10. customevaporated

出典と根拠

ORDレコード
ord-6ae026a3acd24f1792c8fc0e7f350d07
出典データセット
uspto-grants-2016_05
特許番号
US09346815B2

反応ノート

読み込み中…