Potassium Iodide → HCID 86677776, compound

HRID 1499852Notes

Reaction equation

HRID 1499852 reaction equation
[Br:1][C:2]1[C:3]([CH3:15])=[C:4]([Cl:14])[CH:5]=[C:6]([CH:11](Cl)[CH3:12])[C:7]=1[O:8][CH2:9][CH3:10].[CH3:16][C:17]1[C:25]2[C:20](=[N:21][CH:22]=[N:23][C:24]=2[NH2:26])[NH:19][N:18]=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][CH2:9][CH3:10])=[C:6]([CH:11]([N:19]2[C:20]3=[N:21][CH:22]=[N:23][C:24]([NH2:26])=[C:25]3[C:17]([CH3:16])=[N:18]2)[CH3:12])[CH:5]=[C:4]([Cl:14])[C:3]=1[CH3:15]

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 10796Cesium carbonateHCID 86677775HCID 86677775, compoundHCID 178434474HCID 178434474, compound

Product 1

HCID 86677776HCID 86677776, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 3-bromo-1-chloro-5-(1-chloroethyl)-4-ethoxy-2-methylbenzene (150 mg, 0.50 mmol), 3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (110 mg, 0.76 mmol), potassium iodide (9 mg, 0.05 mmol) and cesium carbonate (330 mg, 1.0 mmol) in N,N-dimethylformamide (4 mL) 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 (103 mg, 50%). LCMS calculated for C17H20BrClN5O (M+H)+: m/z=423.1; Found: 423.0. The racemic products were applied on a Phenomenex Lux-Cellulose 1 column (21.1×250 mm, 5 micron particle size), eluting with 4% ethanol in hexanes at a flow rate of 18 mL/min, ˜13 mg/injection, to provide two enantiomers. Peak 1, retention time: 8.64 min; Peak 2, retention time: 10.64 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 (103 mg, 50%)
  7. washeluting with 4% ethanol in hexanes at a flow rate of 18 mL/min, ˜13 mg/injection
  8. customto provide two enantiomers

Sources & evidence

ORD record
ord-8888f5b2d17444b2a9d3778e02ecdd77
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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