Aminopyrazine → (S)-1-{2-[1-(4-Fluorophenyl)ethylamino]-6-(pyrazin-2-ylamino)pyrimidin-4-yl}-4-(hydroxymethyl)piperidin-4-ol

HRID 2043445Notes

Reaction equation

HRID 2043445 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])[N:5]=[C:4]([N:18]2[CH2:23][CH2:22][C:21]([CH2:25][OH:26])([OH:24])[CH2:20][CH2:19]2)[CH:3]=1.[NH2:27][C:28]1[CH:33]=[N:32][CH:31]=[CH:30][N:29]=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.O1CCOCC1.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[N:5]=[C:4]([N:18]3[CH2:23][CH2:22][C:21]([CH2:25][OH:26])([OH:24])[CH2:20][CH2:19]3)[CH:3]=[C:2]([NH:27][C:28]3[CH:33]=[N:32][CH:31]=[CH:30][N:29]=3)[N:7]=2)[CH3:10])=[CH:12][CH:13]=1

Participants

8

Reactant 4

HCID 78747AminopyrazineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 86659399(S)-1-(6-chloro-2-[1-(4-fluorophenyl)ethylamino]pyrimidin-4-yl)-4-(hydroxymethyl)piperidin-4-ol

Product 1

HCID 46865461(S)-1-{2-[1-(4-Fluorophenyl)ethylamino]-6-(pyrazin-2-ylamino)pyrimidin-4-yl}-4-(hydroxymethyl)piperidin-4-olYield 69.3%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

100 mg of (S)-1-{6-chloro-2-[1-(4-fluorophenyl)ethylamino]pyrimidin-4-yl}-4-(hydroxymethyl)piperidin-4-ol, 32 mg of 2-aminopyrazine, mg of 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl, 38 mg of sodium t-butoxide and 27 mg of tris(dibenzylideneacetone)(chloroform)palladium were added in turn to a degassed mixed solution of 3 ml of toluene and 2 ml of 1,4-dioxane, and the mixture was stirred at 100° C. for 1 hour 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 80 mg of the objective compound as brown 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-2bd9c32c0a8d4023a9cbdd271cb23ea6
Source dataset
uspto-grants-2013_11
Patent number
US08586591B2

Reaction notes

Loading…