Aminopyrazine → N2-((1S)-1-(4-Fluorophenyl)ethyl)-4-(1-methyl-1H-pyrazol-4-yl)-N6-2-pyrazinyl-2,6-pyridinediamine

HRID 2043395Notes

Reaction equation

HRID 2043395 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C@H:9]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)[CH3:10])[CH:5]=[C:4]([C:18]2[CH:19]=[N:20][N:21]([CH3:23])[CH:22]=2)[CH: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.C1(C)C=CC=CC=1>[F:17][C:14]1[CH:15]=[CH:16][C:11]([C@@H:9]([NH:8][C:6]2[CH:5]=[C:4]([C:18]3[CH:19]=[N:20][N:21]([CH3:23])[CH:22]=3)[CH:3]=[C:2]([NH:24][C:25]3[CH:30]=[N:29][CH:28]=[CH:27][N:26]=3)[N:7]=2)[CH3:10])=[CH:12][CH:13]=1

Participants

7

Reactant 4

HCID 78747AminopyrazineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 86659376HCID 86659376, compound

Product 1

HCID 46866319N2-((1S)-1-(4-Fluorophenyl)ethyl)-4-(1-methyl-1H-pyrazol-4-yl)-N6-2-pyrazinyl-2,6-pyridinediamineYield 73.7%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

235 mg of (S)-6-chloro-N-[1-(4-fluorophenyl)ethyl]-4-(1-methyl-1H-pyrazol-4-yl)pyridine-2-amine, 74 mg of 2-aminopyrazine, 68 mg of 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl, 95 mg of sodium t-butoxide and 37 mg of tris(dibenzylideneacetone)(chloroform)dipalladium were added in turn to 6 ml of degassed toluene, and the mixture was stirred at 100° C. for 1.5 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 204 mg of (S)—N2-[1-(4-fluorophenyl)ethyl]-4-(1-methyl-1H-pyrazol-4-yl)-N6-(pyrazin-2-yl)pyridine-2,6-diamine as pale yellow powder. The obtained compound was dissolved in ethanol, and an equivalent of 1N hydrochloric acid was added thereto, and then the solvent was removed to obtain 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-4b06030d9c834070b19ca8eb1c2fefc9
Source dataset
uspto-grants-2013_11
Patent number
US08586591B2

Reaction notes

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