Citric Acid → (2S)-3-(3-(tert-butyldimethylsilyloxy)azetidin-1-yl)-2-(1-(2-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(5-methylpyridin-2-yl)propanamide

HRID 1098175ノート

反応式

HRID 1098175 の反応式
[H-].[Na+].[Si:3]([O:10][CH:11]1[CH2:14][N:13]([CH2:15][C@H:16]([OH:27])[C:17]([NH:19][C:20]2[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][N:21]=2)=[O:18])[CH2:12]1)([C:6]([CH3:9])([CH3:8])[CH3:7])([CH3:5])[CH3:4].Cl[C:29]1[N:34]=[CH:33][N:32]=[C:31]2[N:35]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=3[Cl:44])[N:36]=[CH:37][C:30]=12.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1.O.CCOC(C)=O>[Si:3]([O:10][CH:11]1[CH2:14][N:13]([CH2:15][C@H:16]([O:27][C:29]2[N:34]=[CH:33][N:32]=[C:31]3[N:35]([C:38]4[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=4[Cl:44])[N:36]=[CH:37][C:30]=23)[C:17]([NH:19][C:20]2[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][N:21]=2)=[O:18])[CH2:12]1)([C:6]([CH3:9])([CH3:8])[CH3:7])([CH3:5])[CH3:4]

参加物

8

反応物 4

HCID 311Citric AcidHCID 24758Sodium hydrideHCID 112655704-Chloro-1-(2-chlorophenyl)-1H-pyrazolo[3,4-D]pyrimidine2 回HCID 57504650(S)-3-(3-(tert-butyldimethylsilyloxy)azetidin-1-yl)-2-hydroxy-N-(5-methylpyridin-2-yl)propanamide

生成物 1

HCID 57504553(2S)-3-(3-(tert-butyldimethylsilyloxy)azetidin-1-yl)-2-(1-(2-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(5-methylpyridin-2-yl)propanamide収率 115.8%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
0 °C

実験手順

Sodium hydride (132 mg, 3.30 mmol) was added to (S)-3-(3-(tert-butyldimethylsilyloxy)azetidin-1-yl)-2-hydroxy-N-(5-methylpyridin-2-yl)propanamide (Intermediate AD8) (482 mg, 1.32 mmol) in anhydrous THF (5 mL) at 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 10 minutes and then 4-chloro-1-(2-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidine (Intermediate B1) (385 mg, 1.45 mmol) was added. The reaction mixture was allowed to warm to room temperature and stirred for 3 hours. The reaction mixture was neutralised with 1M citric acid and diluted with water and EtOAc. The organic layer was separated and washed with saturated brine, dried (MgSO4) and evaporated to afford the product (908 mg) which was used without further purification. m/z (ES+) (M+H)+=594.52; HPLC tR=1.87 min.

後処理

  1. temperatureto warm to room temperature
  2. stirringstirred for 3 hours
  3. customThe organic layer was separated
  4. washwashed with saturated brine
  5. dry with materialdried (MgSO4)
  6. customevaporated

出典と根拠

ORDレコード
ord-f976e31330c84589ab6b92b65dddeb5e
出典データセット
uspto-grants-2012_03
特許番号
US08143263B2

反応ノート

読み込み中…