Citric Acid → (2S)-methyl 3-((S)-1-(tert-butyldimethylsilyloxy)propan-2-yloxy)-2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)propanoate

HRID 1098219ノート

反応式

HRID 1098219 の反応式
[H-].[Na+].[Si:3]([O:10][CH2:11][C@@H:12]([O:14][CH2:15][C@H:16]([OH:21])[C:17]([O:19][CH3:20])=[O:18])[CH3:13])([C:6]([CH3:9])([CH3:8])[CH3:7])([CH3:5])[CH3:4].Cl[C:23]1[N:28]=[CH:27][N:26]=[C:25]2[N:29]([C:32]3[C:37]([Cl:38])=[CH:36][CH:35]=[CH:34][N:33]=3)[N:30]=[CH:31][C:24]=12.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1>[Si:3]([O:10][CH2:11][C@@H:12]([O:14][CH2:15][C@H:16]([O:21][C:23]1[N:28]=[CH:27][N:26]=[C:25]2[N:29]([C:32]3[C:37]([Cl:38])=[CH:36][CH:35]=[CH:34][N:33]=3)[N:30]=[CH:31][C:24]=12)[C:17]([O:19][CH3:20])=[O:18])[CH3:13])([C:6]([CH3:9])([CH3:8])[CH3:7])([CH3:5])[CH3:4]

参加物

6

反応物 4

HCID 311Citric AcidHCID 24758Sodium hydrideHCID 575044824-Chloro-1-(3-chloropyridin-2-YL)-1H-pyrazolo[3,4-D]pyrimidineHCID 86640846(S)-Methyl 3-((S)-1-(tert-butyldimethylsilyloxy)propan-2-yloxy)-2-hydroxypropanoate

生成物 1

HCID 59279482(2S)-methyl 3-((S)-1-(tert-butyldimethylsilyloxy)propan-2-yloxy)-2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)propanoate収率 69.5%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

Sodium hydride (0.219 g, 5.48 mmol) was added to (S)-methyl 3-((S)-1-(tert-butyldimethylsilyloxy)propan-2-yloxy)-2-hydroxypropanoate (Intermediate AO1) (1.336 g, 4.57 mmol) in anhydrous THF (30 mL) at 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 10 minutes and then 4-chloro-1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidine (1.216 g, 4.57 mmol) was added. The reaction mixture was allowed to warm to room temperature and stirred for 1 hour. The reaction mixture was neutralised with 1M citric acid and the majority of the THF removed in vacuo. The reaction mixture was diluted with water (20 mL) and EtOAc (50 mL). The organic layer was separated and the aqueous layer re-extracted with EtOAc (2×50 mL). The combined organics were washed with saturated brine (25 mL), dried (MgSO4) and evaporated. The crude product was purified by flash silica chromatography, eluting with 30 to 60% EtOAc in isohexane to give (2S)-methyl 3-((S)-1-(tert-butyldimethylsilyloxy)propan-2-yloxy)-2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)propanoate (1.658 g, 69.5%). m/z (ES+), (M+H)+=522.50; HPLC tR=3.35 min

後処理

  1. temperatureto warm to room temperature
  2. stirringstirred for 1 hour
  3. customthe majority of the THF removed in vacuo
  4. additionThe reaction mixture was diluted with water (20 mL) and EtOAc (50 mL)
  5. customThe organic layer was separated
  6. extractionthe aqueous layer re-extracted with EtOAc (2×50 mL)
  7. washThe combined organics were washed with saturated brine (25 mL)
  8. dry with materialdried (MgSO4)
  9. customevaporated
  10. customThe crude product was purified by flash silica chromatography
  11. washeluting with 30 to 60% EtOAc in isohexane

出典と根拠

ORDレコード
ord-d163e16003e54849a0b821d4c3a3cd3a
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…