Water → HCID 89442647、化合物

HRID 632725ノート

反応式

HRID 632725 の反応式
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][C:15]3[CH:20]=[C:19]([Cl:21])[C:18]([Cl:22])=[CH:17][C:16]=3[OH:23])[CH2:10][CH2:9]2)[C:3]=1[C:24]1[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=1.C(OC([N:38]1[CH2:41][CH:40](I)[CH2:39]1)=O)(C)(C)C.C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C=O)C>[NH:38]1[CH2:41][CH:40]([O:23][C:16]2[CH:17]=[C:18]([Cl:22])[C:19]([Cl:21])=[CH:20][C:15]=2[CH2:14][N:11]2[CH2:12][CH2:13][N:8]([C:4]3[N:5]=[CH:6][N:7]=[C:2]([NH2:1])[C:3]=3[C:24]3[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=3)[CH2:9][CH2:10]2)[CH2:39]1

参加物

6

反応物 4

HCID 962WaterHCID 10796Cesium carbonateHCID 11000522Tert-butyl 3-iodoazetidine-1-carboxylateHCID 89442445HCID 89442445、化合物

生成物 1

HCID 89442647HCID 89442647、化合物収率 40.8%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
90 °C

実験手順

A reaction mixture of 2-{4-[6-amino-5-(4-fluoro-phenyl)-pyrimidin-4-yl]-piperazin-1-ylmethyl}-4,5-dichloro-phenol (80.0 mg; 0.18 mmol; 1.00 eq.), 3-iodo-azetidine-1-carboxylic acid tert-butyl ester (60.6 mg; 0.21 mmol; 1.20 eq.) and cesium carbonate (116.2 mg; 0.36 mmol; 2.00 eq.) in DMF (1 ml) was stirred at 90° C. overnight. The reaction solution was poured to water and extracted with ethyl acetate, The separated organic layer was washed with brine, dried and concentrated, which was then dissolved in methanol (1 ml) followed by adding 4.0 M HCl in dioxane (2 ml) and stirred at RT overnight. The reaction mixture was concentrated and purified by Waters prep-HPLC (acidic condition) to yield the title compounds (37 mg, yield 33.6%). LC-MS: (M+1=504, obsd.=504/506).

後処理

  1. extractionextracted with ethyl acetate
  2. washThe separated organic layer was washed with brine
  3. customdried
  4. concentrationconcentrated
  5. dissolutionwhich was then dissolved in methanol (1 ml)
  6. additionby adding 4.0 M HCl in dioxane (2 ml)
  7. stirringstirred at RT overnight
  8. concentrationThe reaction mixture was concentrated
  9. custompurified by Waters prep-HPLC (acidic condition)

出典と根拠

ORDレコード
ord-291fb5e366ba4ebab0cba7a5a334f975
出典データセット
uspto-grants-2016_04
特許番号
US09321760B2

反応ノート

読み込み中…