Sodium hydride → tert-Butyl 3-{3-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-6-fluoro-2-methoxyphenyl}azetidine-1-carboxylate

HRID 1499689Notes

Reaction equation

HRID 1499689 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+].[Cl:14][C:15]1[C:16]([F:37])=[C:17]([CH:26]2[CH2:29][N:28]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:27]2)[C:18]([O:24][CH3:25])=[C:19]([CH:21](Cl)[CH3:22])[CH:20]=1>CN(C)C=O>[NH2:11][C:9]1[N:8]=[CH:7][N:6]=[C:5]2[N:4]([CH:21]([C:19]3[C:18]([O:24][CH3:25])=[C:17]([CH:26]4[CH2:27][N:28]([C:30]([O:32][C:33]([CH3:35])([CH3:34])[CH3:36])=[O:31])[CH2:29]4)[C:16]([F:37])=[C:15]([Cl:14])[CH:20]=3)[CH3:22])[N:3]=[C:2]([CH3:1])[C:10]=12

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 86666861Tert-butyl 3-(3-chloro-5-(1-chloroethyl)-2-fluoro-6-methoxyphenyl)azetidine-1-carboxylateHCID 178434474HCID 178434474, compound

Product 1

HCID 86677634tert-Butyl 3-{3-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-6-fluoro-2-methoxyphenyl}azetidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (7.9 mg, 0.053 mmol) in N,N-dimethylformamide (0.6 mL) was added sodium hydride (60%, 2.5 mg, 0.11 mmol) at 0° C. and the mixture was stirred at room temperature for 10 minutes. To the mixture was added a solution of tert-butyl 3-[3-chloro-5-(1-chloroethyl)-2-fluoro-6-methoxyphenyl]azetidine-1-carboxylate (20 mg, 0.053 mmol) in N,N-dimethylformamide (0.3 mL). The reaction mixture was stirred at 35° C. overnight, then quenched with water, extracted with ether. The combined organic layers were dried over MgSO4 and concentrated to afford the desired product which was used in next step directly. LCMS calculated for C23H29ClFN6O3 (M+H)+: m/z=491.2; Found: 491.1.

Workup

  1. stirringThe reaction mixture was stirred at 35° C. overnight
  2. customquenched with water
  3. extractionextracted with ether
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-6646b41b903f45b8b193d669eaaef8b6
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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