Sodium hydride → 3-[1-(2-Fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1958433

Reaction equation

HRID 1958433 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH:10]([OH:13])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Cl[C:17]1[N:22]=[CH:21][N:20]=[C:19]2[N:23]([C:26]3[CH:31]=[CH:30][C:29]([S:32]([CH3:35])(=[O:34])=[O:33])=[CH:28][C:27]=3[F:36])[N:24]=[CH:25][C:18]=12>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH:10]([O:13][C:17]2[N:22]=[CH:21][N:20]=[C:19]3[N:23]([C:26]4[CH:31]=[CH:30][C:29]([S:32]([CH3:35])(=[O:34])=[O:33])=[CH:28][C:27]=4[F:36])[N:24]=[CH:25][C:18]=23)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 44169391-Boc-3-pyrrolidinolHCID 218976614-Chloro-1-(2-fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidine

Product 1

HCID 536304163-[1-(2-Fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-pyrrolidine-1-carboxylic acid tert-butyl esterYield 67.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 3-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester (431 mg, 2.3 mmol) and sodium hydride (92 mg, 3.82 mmol) in THF (10 mL) was stirred for 30 minutes at room temperature. Then 4-chloro-1-(2-fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidine (500 mg, 1.53 mmol) was added and stirred overnight at room temperature. The reaction mixture was quenched with water and the product extracted with ethyl acetate. The ethylacetate layer was dried over MgSO4, concentrated in vacuo, and purified by flash chromatography to afford compound A140 as a white solid (495 mg, 45%). Exact mass calculated for C21H24FN5O5S 477.15, found 478.2 (MH+).

Workup

  1. stirringstirred overnight at room temperature
  2. customThe reaction mixture was quenched with water
  3. extractionthe product extracted with ethyl acetate
  4. dry with materialThe ethylacetate layer was dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. custompurified by flash chromatography

Sources & evidence

ORD record
ord-7d469ada9f3144df87831c0277e8cc34
Source dataset
uspto-grants-2013_04
Patent number
US08410119B2

Linked notes

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