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

HRID 1499832Notes

Reaction equation

HRID 1499832 reaction equation
[Br:1][C:2]1[C:3]([CH3:14])=[C:4]([Cl:13])[CH:5]=[C:6]([CH:10](Cl)[CH3:11])[C:7]=1[O:8][CH3:9].[CH3:15][C:16]1[C:24]2[C:19](=[N:20][CH:21]=[N:22][C:23]=2[NH2:25])[NH:18][N:17]=1.[I-].[K+].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O.C(Cl)Cl>[Br:1][C:2]1[C:7]([O:8][CH3:9])=[C:6]([CH:10]([N:18]2[C:19]3=[N:20][CH:21]=[N:22][C:23]([NH2:25])=[C:24]3[C:16]([CH3:15])=[N:17]2)[CH3:11])[CH:5]=[C:4]([Cl:13])[C:3]=1[CH3:14]

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 10796Cesium carbonateHCID 866776443-Bromo-1-chloro-5-(1-chloroethyl)-4-methoxy-2-methylbenzeneHCID 178434474HCID 178434474, compound

Product 1

HCID 866776451-[1-(3-Bromo-5-chloro-2-methoxy-4-methylphenyl)ethyl]-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amineYield 50%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
140 °C

Procedure

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, ACES Pharma Product List, item #47024), potassium iodide (9.0 mg, 0.05 mmol) and cesium carbonate (330 mg, 1.0 mmol) in N,N-dimethylformamide (4 mL) and was stirred at 140° C. for 1 h. 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, to give the desired product (103 mg, 50%). LCMS calculated for C16H18BrClN5O (M+H)+: m/z=410.0; Found: 410.2. 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. Peak 1, retention time: 12.35 min; Peak 2, retention time: 14.98 min,

Workup

  1. washwashed with sat. NaHCO3, water, brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude product was purified by silica gel chromatography
  6. washeluting with 0 to 70% EtOAc in CH2Cl2

Sources & evidence

ORD record
ord-4d6e62dee28b4eac9217c1fe257cb523
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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