Chloroacetyl chloride → 4-(3-chloro-2-fluoroanilino)-7-methoxy-6-{[(2S)-1-(chloroacetyl)pyrrolidin-2-yl]methoxy}quinazoline

HRID 1948951ノート

反応式

HRID 1948951 の反応式
Cl.[Cl:2][C:3]1[C:4]([F:29])=[C:5]([CH:26]=[CH:27][CH:28]=1)[NH:6][C:7]1[C:16]2[C:11](=[CH:12][C:13]([O:24][CH3:25])=[C:14]([O:17][CH2:18][C@@H:19]3[CH2:23][CH2:22][CH2:21][NH:20]3)[CH:15]=2)[N:10]=[CH:9][N:8]=1.C(N(C(C)C)CC)(C)C.[Cl:39][CH2:40][C:41](Cl)=[O:42]>C(Cl)Cl>[Cl:2][C:3]1[C:4]([F:29])=[C:5]([CH:26]=[CH:27][CH:28]=1)[NH:6][C:7]1[C:16]2[C:11](=[CH:12][C:13]([O:24][CH3:25])=[C:14]([O:17][CH2:18][C@@H:19]3[CH2:23][CH2:22][CH2:21][N:20]3[C:41](=[O:42])[CH2:40][Cl:39])[CH:15]=2)[N:10]=[CH:9][N:8]=1

参加物

5

反応物 3

HCID 6577Chloroacetyl chlorideHCID 81531DiisopropylethylamineHCID 685223024-(3-chloro-2-fluoroanilino)-7-methoxy-6-[(2S)-pyrrolidin-2-ylmethoxy]quinazoline hydrochloride

生成物 1

HCID 685201434-(3-chloro-2-fluoroanilino)-7-methoxy-6-{[(2S)-1-(chloroacetyl)pyrrolidin-2-yl]methoxy}quinazoline収率 95.1%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
4 °C

実験手順

4-(3-chloro-2-fluoroanilino)-7-methoxy-6-[(2S)-pyrrolidin-2-ylmethoxy]quinazoline hydrochloride (1.1 g, 2.5 mmol; prepared as described in Example 31-starting materials) was dissolved in a mixture methylene chloride (20 ml) and diisopropylethylamine (1.0 ml) under a nitrogen atmosphere. The solution was cooled in an ice/water bath to 4° C. and chloroacetyl chloride (0.2 ml, 2.63 mmole) was added. The reaction mixture was stirred cold for two 25 hours and then partitioned between methylene chloride and saturated aqueous NaHCO3. The organic layer was separated, washed with brine, dried over Na2SO4, filtered and evaporated to give 4-(3-chloro-2-fluoroanilino)-7-methoxy-6-{[(2S)-1-(chloroacetyl)pyrrolidin-2-yl]methoxy}quinazoline (1.14 g, 94.9%); Mass Spectrum: (M+H)+ 479.

後処理

  1. custompartitioned between methylene chloride and saturated aqueous NaHCO3
  2. customThe organic layer was separated
  3. washwashed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customevaporated

出典と根拠

ORDレコード
ord-cb0d70a5bfda4109b7e979913a9738f2
出典データセット
uspto-grants-2013_03
特許番号
US08399667B2

反応ノート

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