Sodium hydride → (2S)-methyl 3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)propanoate

HRID 1098167Notes

Reaction equation

HRID 1098167 reaction equation
[H-].[Na+].[Si:3]([O:20][CH2:21][CH2:22][O:23][CH2:24][C@H:25]([OH:30])[C:26]([O:28][CH3:29])=[O:27])([C:16]([CH3:19])([CH3:18])[CH3:17])([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Cl[C:32]1[N:37]=[CH:36][N:35]=[C:34]2[N:38]([C:41]3[C:46]([Cl:47])=[CH:45][CH:44]=[CH:43][N:42]=3)[N:39]=[CH:40][C:33]=12>O1CCCC1>[Si:3]([O:20][CH2:21][CH2:22][O:23][CH2:24][C@H:25]([O:30][C:32]1[N:37]=[CH:36][N:35]=[C:34]2[N:38]([C:41]3[C:46]([Cl:47])=[CH:45][CH:44]=[CH:43][N:42]=3)[N:39]=[CH:40][C:33]=12)[C:26]([O:28][CH3:29])=[O:27])([C:16]([CH3:19])([CH3:18])[CH3:17])([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 575044824-Chloro-1-(3-chloropyridin-2-YL)-1H-pyrazolo[3,4-D]pyrimidineHCID 59279512(S)-methyl 3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-hydroxypropanoate

Product 1

HCID 59279503(2S)-methyl 3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)propanoateYield 53.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

60% Sodium hydride in mineral oil (1.013 g, 25.34 mmol) was added to (S)-methyl 3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-hydroxypropanoate (Intermediate AB3) (8.5 g, 21.12 mmol) in tetrahydrofuran (150 mL) cooled to 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 10 minutes. A solution of 4-chloro-1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidine (6.18 g, 23.23 mmol) in tetrahydrofuran (20 mL) was added dropwise over a period of 5 minutes. The resulting mixture was allowed to warm to ambient temperature and stirred for 2 hours. The reaction mixture was quenched with 1M citric acid and extracted with ethyl acetate. The organic layer was washed with brine, dried (MgSO4) and evaporated. The crude product was purified by flash silica chromatography, eluting with 0 to 100% ethyl acetate in isohexane to afford the product (7.15 g, 53.6%).

Workup

  1. temperatureto warm to ambient temperature
  2. stirringstirred for 2 hours
  3. customThe reaction mixture was quenched with 1M citric acid
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was washed with brine
  6. dry with materialdried (MgSO4)
  7. customevaporated
  8. customThe crude product was purified by flash silica chromatography
  9. washeluting with 0 to 100% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-28d9bf687a6b4729a7d894a7d395e706
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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