Sodium hydride → 6-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-4-chloro-N-ethyl-3',5'-difluoro-3-methylbiphenyl-2-carboxamide

HRID 1499727Notes

Reaction equation

HRID 1499727 reaction equation
[CH3:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[NH2:11])[NH:4][N:3]=1.[H-].[Na+].CS(O[CH:19]([C:21]1[CH:26]=[C:25]([Cl:27])[C:24]([CH3:28])=[C:23]([C:29]([NH:31][CH2:32][CH3:33])=[O:30])[C:22]=1[C:34]1[CH:39]=[C:38]([F:40])[CH:37]=[C:36]([F:41])[CH:35]=1)[CH3:20])(=O)=O>CN(C)C=O>[NH2:11][C:9]1[N:8]=[CH:7][N:6]=[C:5]2[N:4]([CH:19]([C:21]3[CH:26]=[C:25]([Cl:27])[C:24]([CH3:28])=[C:23]([C:29]([NH:31][CH2:32][CH3:33])=[O:30])[C:22]=3[C:34]3[CH:35]=[C:36]([F:41])[CH:37]=[C:38]([F:40])[CH:39]=3)[CH3:20])[N:3]=[C:2]([CH3:1])[C:10]=12

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 866776621-{4-Chloro-6-[(ethylamino)carbonyl]-3',5'-difluoro-5-methylbiphenyl-2-yl}ethyl methanesulfonateHCID 178434474HCID 178434474, compound

Product 1

HCID 715089366-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-4-chloro-N-ethyl-3',5'-difluoro-3-methylbiphenyl-2-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a mixture of 3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (from ChemBridge) (26 mg, 0.17 mmol) in N,N-dimethylformamide (0.5 mL) was added sodium hydride (14 mg, 0.35 mmol). After stirring at room temperature for 30 minutes, to the resulting mixture was added to a mixture of 1-{4-chloro-6-[(ethylamino)carbonyl]-3′,5′-difluoro-5-methylbiphenyl-2-yl}ethyl methanesulfonate (50 mg, 0.1 mmol) in N,N-dimethylformamide (0.5 mL). The reaction was stirred at room temperature overnight and then quenched with water. The resultant mixture was purified on RP-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min) to give the desired product. The product was isolated as a racemic mixture. LCMS calculated for C24H24ClF2N6O (M+H)+: m/z=485.2; Found: 485.1

Workup

  1. stirringThe reaction was stirred at room temperature overnight
  2. customquenched with water
  3. customThe resultant mixture was purified on RP-HPLC (XBridge C18 column
  4. washeluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min)

Sources & evidence

ORD record
ord-8bf4d44a34194adca1009284143d9757
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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