Sodium hydride → 1-[1-(3-Bromo-5-chloro-2-methoxy-4-methylphenyl)ethyl]-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine

HRID 1499702Notes

Reaction equation

[H-].[Na+].[Br:3][C:4]1[C:5]([CH3:16])=[C:6]([Cl:15])[CH:7]=[C:8]([CH:12](Cl)[CH3:13])[C:9]=1[O:10][CH3:11].[CH3:17][C:18]1[C:26]2[C:21](=[N:22][CH:23]=[N:24][C:25]=2[NH2:27])[NH:20][N:19]=1>CN(C)C=O.C(Cl)Cl>[Br:3][C:4]1[C:9]([O:10][CH3:11])=[C:8]([CH:12]([N:20]2[C:21]3=[N:22][CH:23]=[N:24][C:25]([NH2:27])=[C:26]3[C:18]([CH3:17])=[N:19]2)[CH3:13])[CH:7]=[C:6]([Cl:15])[C:5]=1[CH3:16]

Participants

Conditions

Temperature: 30 °C

Procedure

Sodium hydride (36 mg, 0.91 mmol) was added to a mixture of 3-bromo-1-chloro-5-(1-chloroethyl)-4-methoxy-2-methylbenzene (150 mg, 0.503 mmol), 3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (110 mg, 0.76 mmol) in N,N-dimethylformamide (8 mL) and the reaction was stirred at 30° C. overnight. The mixture was diluted with methylene chloride, washed with sat. NaHCO3, water, brine, dried over Na2SO4, filtered and concentrated. The crude product was purified by silica gel chromatography, eluting with 0 to 70% EtOAc in CH2Cl2 (103 mg, 50%). LCMS calculated for C16H18BrClN5O (M+H)+: m/z=410.0; Found: 410. The racemic products were applied on a Phenomenex Lux-Cellulose 1 column (21.1×250 mm, 5 micron particle size), eluting with 5% ethanol in hexanes at a flow rate of 18 mL/min, ˜13 mg/injection, to provide two enantiomers.

Workup

washwashed with sat. NaHCO3, water, brine
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated
customThe crude product was purified by silica gel chromatography
washeluting with 0 to 70% EtOAc in CH2Cl2 (103 mg, 50%)
washeluting with 5% ethanol in hexanes at a flow rate of 18 mL/min, ˜13 mg/injection
customto provide two enantiomers

Sources & evidence

ORD record: ord-2472c563c2f24b0d9e939ad070f5cbee
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09199982B2

Reaction notes

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