Sodium hydride → (2S)-2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-4-methoxy-N-(5-methylpyridin-2-yl)butanamide

HRID 1097989Notes

Reaction equation

HRID 1097989 reaction equation
Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C:11]3[C:16]([Cl:17])=[CH:15][CH:14]=[CH:13][N:12]=3)[N:9]=[CH:10][C:3]=12.CS([O-])=O.[Na+].[H-].[Na+].[OH:25][C@@H:26]([CH2:37][CH2:38][O:39][CH3:40])[C:27]([NH:29][C:30]1[CH:35]=[CH:34][C:33]([CH3:36])=[CH:32][N:31]=1)=[O:28]>C1COCC1.CCOC(C)=O>[Cl:17][C:16]1[C:11]([N:8]2[C:4]3=[N:5][CH:6]=[N:7][C:2]([O:25][C@@H:26]([CH2:37][CH2:38][O:39][CH3:40])[C:27]([NH:29][C:30]4[CH:35]=[CH:34][C:33]([CH3:36])=[CH:32][N:31]=4)=[O:28])=[C:3]3[CH:10]=[N:9]2)=[N:12][CH:13]=[CH:14][CH:15]=1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 2733271Sodium methanesulfinateHCID 575044824-Chloro-1-(3-chloropyridin-2-YL)-1H-pyrazolo[3,4-D]pyrimidine2×HCID 57504483(S)-2-Hydroxy-4-methoxy-N-(5-methylpyridin-2-yl)butanamide2×

Product 1

HCID 57504325(2S)-2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-4-methoxy-N-(5-methylpyridin-2-yl)butanamideYield 87.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-Chloro-1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidine (Intermediate B15) (219 mg, 0.82 mmol) was added to sodium methanesulfinate (75 mg, 0.73 mmol) and sodium hydride (38.0 mg, 0.95 mmol) in THF (5 mL) at 23° C. under nitrogen. The resulting suspension was stirred at ambient temperature for 5 minutes. (S)-2-Hydroxy-4-methoxy-N-(5-methylpyridin-2-yl)butanamide (Intermediate F1) (142 mg, 0.63 mmol) was added dropwise and the suspension was stirred at ambient temperature for a further 30 minutes. The mixture was diluted with EtOAc (50 mL), and washed sequentially with water (2×25 mL) and saturated brine (25 mL). The organic layer was dried (MgSO4) and evaporated. The residue was purified by flash silica chromatography, elution gradient 40 to 100% EtOAc in isohexane to afford (2S)-2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-4-methoxy-N-(5-methylpyridin-2-yl)butanamide (250 mg, 87%).

Workup

  1. stirringthe suspension was stirred at ambient temperature for a further 30 minutes
  2. washwashed sequentially with water (2×25 mL) and saturated brine (25 mL)
  3. dry with materialThe organic layer was dried (MgSO4)
  4. customevaporated
  5. customThe residue was purified by flash silica chromatography, elution gradient 40 to 100% EtOAc in isohexane

Sources & evidence

ORD record
ord-e9fcf38cf8fe41bba09505cae441e4ad
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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