Sodium hydride → (3S)-3-(1-(2-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)pyrrolidin-2-one

HRID 1098171Notes

Reaction equation

HRID 1098171 reaction equation
[H-].[Na+].[OH:3][C@H:4]1[CH2:8][CH2:7][NH:6][C:5]1=[O:9].Cl[C:11]1[N:16]=[CH:15][N:14]=[C:13]2[N:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[Cl:26])[N:18]=[CH:19][C:12]=12>C1COCC1.CN(C=O)C>[Cl:26][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=1[N:17]1[C:13]2=[N:14][CH:15]=[N:16][C:11]([O:3][C@H:4]3[CH2:8][CH2:7][NH:6][C:5]3=[O:9])=[C:12]2[CH:19]=[N:18]1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 11029774(3S)-3-hydroxypyrrolidin-2-oneHCID 112655704-Chloro-1-(2-chlorophenyl)-1H-pyrazolo[3,4-D]pyrimidine2×

Product 1

HCID 57504645(3S)-3-(1-(2-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)pyrrolidin-2-oneYield 24.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Sodium hydride (60% in oil) (0.435 g, 10.88 mmol) was added to (S)-3-hydroxypyrrolidin-2-one (CAS no. 34368-52-0) (1 g, 9.89 mmol) in THF (50 mL) at 0° C. under nitrogen. The resulting suspension was stirred at 0° C. for 10 minutes. A solution of 4-chloro-1-(2-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidine (Intermediate B15) (4.01 g, 15.13 mmol) in DMF (25 mL) was added and the resulting mixture was stirred at r.t. for 16 hours. The reaction mixture was quenched with water (20 mL) and extracted with ethyl acetate (2×50 mL). The combined organic layers were dried (MgSO4) and evaporated (3.8 g). The crude product was purified by flash silica chromatography, eluting with 0-50% MeOH in ethyl acetate to afford the product (0.810 g, 24.8%). 1H NMR (400 MHz, CDCl3) δ 2.30-2.42 (1H, m), 2.81-2.91 (1H, m), 3.45-3.64 (2H, m), 6.05 (1H, t), 6.44 (1H, s), 7.42-7.51 (2H, m), 7.51-7.56 (1H, m), 7.57-7.66 (1H, m), 8.33 (1H, s), 8.60 (1H, s); m/z (ES+) (M+H)+=330.27; HPLC tR=1.61 min.

Workup

  1. customat 0° C.
  2. stirringthe resulting mixture was stirred at r.t. for 16 hours
  3. customThe reaction mixture was quenched with water (20 mL)
  4. extractionextracted with ethyl acetate (2×50 mL)
  5. dry with materialThe combined organic layers were dried (MgSO4)
  6. customevaporated (3.8 g)
  7. customThe crude product was purified by flash silica chromatography
  8. washeluting with 0-50% MeOH in ethyl acetate

Sources & evidence

ORD record
ord-b6d0675a21304379b8a6bfd5f303524c
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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