Stannane, tributyl(1-ethoxyethenyl)- → 1-(4-(5-chloro-4-(5-methyl-1H-pyrazol-3-ylamino)pyrimidin-2-ylamino)-2,5-dimethylphenyl)ethanone

HRID 2093803Notes

Reaction equation

HRID 2093803 reaction equation
Br[C:2]1[C:7]([CH3:8])=[CH:6][C:5]([NH:9][C:10]2[N:15]=[C:14]([NH:16][C:17]3[CH:21]=[C:20]([CH3:22])[N:19](C4CCCCO4)[N:18]=3)[C:13]([Cl:29])=[CH:12][N:11]=2)=[C:4]([CH3:30])[CH:3]=1.C([Sn](CCCC)(CCCC)[C:36]([O:38]CC)=[CH2:37])CCC>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:29][C:13]1[C:14]([NH:16][C:17]2[CH:21]=[C:20]([CH3:22])[NH:19][N:18]=2)=[N:15][C:10]([NH:9][C:5]2[C:4]([CH3:30])=[CH:3][C:2]([C:36](=[O:38])[CH3:37])=[C:7]([CH3:8])[CH:6]=2)=[N:11][CH:12]=1

Participants

5

Reactant 2

HCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 86653323N2-(4-bromo-2,5-dimethylphenyl)-5-chloro-N4-(5-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-3-yl)pyrimidine-2,4-diamine

Product 1

HCID 671677381-(4-(5-chloro-4-(5-methyl-1H-pyrazol-3-ylamino)pyrimidin-2-ylamino)-2,5-dimethylphenyl)ethanone

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of N2-(4-bromo-2,5-dimethylphenyl)-5-chloro-N4-(5-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-3-yl)pyrimidine-2,4-diamine (166 mg, 0.34 mmol), tributyl(1-ethoxyvinyl)stannane (146 mg, 0.41 mmol) and Pd(PPh3)4 (39 mg, 0.034 mmol) in toluene (2 mL) was degassed and heated at 100° C. under N2 for 14 h. After cooling down to room temperature, the mixture was concentrated. The resulting residue was redissolved in acetonitrile (2 mL) and treated with 1N HCl (2 mL) for 14 h. After extraction with EtOAc (3×15 mL), the combined organic layers were treated with saturated aqueous KF (10 mL). The resulted organic layer was collected and treated with brine and dried over MgSO4. After removing the drying agent by filtration, the filtrate was concentrated and purified by flash column chromatography (silica gel, 0-100% EtOAc in hexanes gradient) to provide 1-(4-(5-chloro-4-(5-methyl-1H-pyrazol-3-ylamino)pyrimidin-2-ylamino)-2,5-dimethylphenyl)ethanone as a white solid; ESMS m/z 371.1 (M+H+).

Workup

  1. customwas degassed
  2. temperatureAfter cooling down to room temperature
  3. concentrationthe mixture was concentrated
  4. dissolutionThe resulting residue was redissolved in acetonitrile (2 mL)
  5. additiontreated with 1N HCl (2 mL) for 14 h
  6. extractionAfter extraction with EtOAc (3×15 mL)
  7. additionthe combined organic layers were treated with saturated aqueous KF (10 mL)
  8. customThe resulted organic layer was collected
  9. additiontreated with brine
  10. dry with materialdried over MgSO4
  11. customAfter removing the drying agent
  12. filtrationby filtration
  13. concentrationthe filtrate was concentrated
  14. custompurified by flash column chromatography (silica gel, 0-100% EtOAc in hexanes gradient)

Sources & evidence

ORD record
ord-e0c658aea3cd47aeaa5be0acc45515b2
Source dataset
uspto-grants-2013_05
Patent number
US08445505B2

Reaction notes

Loading…