Aminopyrazine → HCID 86659401, compound

HRID 1187727Notes

Reaction equation

HRID 1187727 reaction equation
Cl[C:2]1[CH:7]=[C:6]([N:8]2[CH:12]=[C:11]([CH3:13])[N:10]=[CH:9]2)[N:5]=[C:4]([NH:14][C@H:15]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)[CH3:16])[N:3]=1.[NH2:24][C:25]1[CH:30]=[N:29][CH:28]=[CH:27][N:26]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.CC(C)([O-])C.[Na+]>C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[F:23][C:20]1[CH:21]=[CH:22][C:17]([C@@H:15]([NH:14][C:4]2[N:3]=[C:2]([NH:24][C:25]3[CH:30]=[N:29][CH:28]=[CH:27][N:26]=3)[CH:7]=[C:6]([N:8]3[CH:12]=[C:11]([CH3:13])[N:10]=[CH:9]3)[N:5]=2)[CH3:16])=[CH:18][CH:19]=1

Participants

8

Reactant 4

HCID 78747AminopyrazineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 86659400HCID 86659400, compound

Product 1

HCID 86659401HCID 86659401, compoundYield 97.7%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

60 mg of (S)-4-chloro-N-[1-(4-fluorophenyl)ethyl]-6-(4-methyl-1H-imidazol-1-yl)pyrimidine-2-amine, 19 mg of 2-aminopyrazine, 17 mg of 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl, 35 mg of sodium t-butoxide and 9 mg of tris(dibenzylideneacetone)dipalladium were added in turn to 2 ml of degassed toluene, and the mixture was stirred at 100° C. for 2 hours under argon atmosphere. The reaction solution was diluted with ethyl acetate. The solution was washed in turn with water and brine and then dried over magnesium sulfate. The solvent was distilled off under reduced pressure, and then the obtained residue was purified by silica gel column chromatography to obtain 69 mg of (S)—N2-[1-(4-fluorophenyl)ethyl]-6-(4-methyl-1H-imidazol-1-yl)-N4-(pyrazin-2-yl)pyrimidine-2,4-diamine. Furthermore, the obtained compound was subjected to hydrochlorination using a conventional method to obtain 48 mg of the objective compound as pale yellow powder.

Workup

  1. washThe solution was washed in turn with water and brine
  2. dry with materialdried over magnesium sulfate
  3. distillationThe solvent was distilled off under reduced pressure
  4. customthe obtained residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-5bea801fbe604f998ff860869c3fea5b
Source dataset
uspto-grants-2014_03
Patent number
US08673891B2

Reaction notes

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