ホームMCPワークベンチSkills
ホームワークベンチ通知マイページ
llms.txt · MCPガイドプライバシーポリシー · 利用規約 · サポートv1.8.0
  1. ホーム
  2. /反応

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

HRID 1098254
ノート
印刷プレビュー

反応式

HRID 1098254 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]([F: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[CH2:12][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]([F:26])=[CH:22][N:21]=2)=[O:18])[CH2:14]1)([C:6]([CH3:9])([CH3:7])[CH3:8])([CH3:5])[CH3:4]
参加物反応条件実験手順後処理出典と根拠反応ノート

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 57504700(S)-3-(3-(tert-butyldimethylsilyloxy)azetidin-1-yl)-N-(5-fluoropyridin-2-yl)-2-hydroxypropanamide

生成物 1

HCID 57504561(2S)-3-(3-(tert-butyldimethylsilyloxy)azetidin-1-yl)-2-(1-(2-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(5-fluoropyridin-2-yl)propanamide
収率 88.3%

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 (60% dispersion in mineral oil) (0.682 g, 17.05 mmol) was added to (S)-3-(3-(tert-butyldimethylsilyloxy)azetidin-1-yl)-N-(5-fluoropyridin-2-yl)-2-hydroxypropanamide (Intermediate AX2) (3.0 g, 8.12 mmol) in anhydrous THF (80 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) (2.63 g, 8.93 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 then diluted with water (50 mL) and EtOAc (100 mL). The organic layer was separated and the aqueous layer re-extracted with EtOAc (100 mL). The combined organics were washed with saturated brine (75 mL),dried (MgSO4), filtered and concentrated in vacuo. The crude product was purified by flash silica chromatography, elution gradient 30 to 70% EtOAc in isohexane to afford the product (4.29 g, 88%). 1H NMR (400 MHz, CDCl3) δ 0.04 (6H, s), 0.88 (9H, s), 3.06-3.10 (2H, m), 3.15-3.19 (1H, m), 3.27-3.31 (1H, m), 3.87-3.90 (2H, m), 4.41-4.48 (1H, m), 5.89-5.92 (1H, m), 7.40-7.55 (4H, m), 7.61-7.63 (1H, m), 8.15 (1H, d), 8.22-8.26 (1H, m), 8.36 (1H, s), 8.59 (1H, s), 9.82 (1H, s); m/z (ES+) (M+H)+=598; HPLC tR=2.82 min.

後処理

  1. temperatureto warm to room temperature
  2. stirringstirred for 3 hours
  3. customThe organic layer was separated
  4. extractionthe aqueous layer re-extracted with EtOAc (100 mL)
  5. washThe combined organics were washed with saturated brine (75 mL),dried (MgSO4),
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by flash silica chromatography, elution gradient 30 to 70% EtOAc in isohexane

出典と根拠

ORDレコード
ord-c181859aadef47bb89fb8a02a6ecc6ef
出典データセット
uspto-grants-2012_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08143263B2

反応ノート

読み込み中…

このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート