Acetic Acid → tert-Butyl (3R)-3-{[2-({3-methyl-5-[2-(3-oxo-1,4-diazepan-1-yl)-1,3-thiazol-5-yl]-phenyl}amino)pyrimidin-4-yl]oxy}pyrrolidine-1-carboxylate

HRID 1028128ノート

反応式

HRID 1028128 の反応式
[NH2:1][C:2]1[CH:3]=[C:4]([C:9]2[S:13][C:12]([N:14]3[CH2:20][CH2:19][CH2:18][NH:17][C:16](=[O:21])[CH2:15]3)=[N:11][CH:10]=2)[CH:5]=[C:6]([CH3:8])[CH:7]=1.Cl[C:23]1[N:28]=[C:27]([O:29][C@@H:30]2[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31]2)[CH:26]=[CH:25][N:24]=1.CC(O)=O>O1CCOCC1.C(=O)(O)[O-].[Na+]>[CH3:8][C:6]1[CH:7]=[C:2]([NH:1][C:23]2[N:28]=[C:27]([O:29][C@@H:30]3[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31]3)[CH:26]=[CH:25][N:24]=2)[CH:3]=[C:4]([C:9]2[S:13][C:12]([N:14]3[CH2:20][CH2:19][CH2:18][NH:17][C:16](=[O:21])[CH2:15]3)=[N:11][CH:10]=2)[CH:5]=1

参加物

6

反応物 3

HCID 176Acetic Acid3 回HCID 60137519(R)-tert-Butyl 3-((2-chloropyrimidin-4-yl)oxy)pyrrolidine-1-carboxylateHCID 67236328HCID 67236328、化合物2 回

生成物 1

HCID 86674326tert-Butyl (3R)-3-{[2-({3-methyl-5-[2-(3-oxo-1,4-diazepan-1-yl)-1,3-thiazol-5-yl]-phenyl}amino)pyrimidin-4-yl]oxy}pyrrolidine-1-carboxylate収率 26%

試薬・触媒・溶媒 2

HCID 312751,4-Dioxane溶媒HCID 516892Sodium Bicarbonate溶媒

反応条件

温度
120 °C

実験手順

To a stirred solution of the 4-[5-(3-amino-5-methylphenyl)-1,3-thiazol-2-yl]-1,4-diazepan-2-one (Intermediate XX, 165 mg, 0.55 mmol) and tert-butyl (3R)-3-[(2-chloropyrimidin-4-yl)oxy]pyrrolidine-1-carboxylate (164 mg, 0.55 mmol) in dioxane (2.7 ml) was added AcOH (66 μl, 1.15 mmol). The mixture was heated to 120° C. for 5 h, treated with additional portion of AcOH (66 μl, 1.15 mmol), and left to stir overnight. Additional AcOH (66 μl, 1.15 mmol) was then added and the resultant mixture was left to stir overnight. The mixture was then cooled to room temperature, diluted with saturated sodium bicarbonate solution, and extracted with ethyl acetate (×3). The combined organics were washed with brine, dried over sodium sulfate, concentrated, and purified by Combiflash. (ethyl acetate/hexanes) to afford 80 mg (0.14 mmol, 26% yield) of tert-butyl (3R)-3-{[2-({3-methyl-5-[2-(3-oxo-1,4-diazepan-1-yl)-1,3-thiazol-5-yl]phenyl}amino)pyrimidin-4-yl]oxy}pyrrolidine-1-carboxylate.

後処理

  1. waitleft
  2. stirringto stir overnight
  3. temperatureThe mixture was then cooled to room temperature
  4. extractionextracted with ethyl acetate (×3)
  5. washThe combined organics were washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. custompurified by Combiflash

出典と根拠

ORDレコード
ord-8a1fca8547614f15b73376b7e56589f3
出典データセット
uspto-grants-2014_05
特許番号
US08735417B2

反応ノート

読み込み中…