Cesium carbonate → HCID 86659379, compound

HRID 1187677Notes

Reaction equation

HRID 1187677 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C:8]2[O:12][CH:11]=[N:10][CH:9]=2)[CH:5]=[C:4]([Cl:13])[N:3]=1.[F:14][C:15]1[CH:20]=[CH:19][C:18]([C@@H:21]([NH2:23])[CH3:22])=[CH:17][CH:16]=1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[Cl:13][C:4]1[N:3]=[C:2]([NH:23][C@H:21]([C:18]2[CH:19]=[CH:20][C:15]([F:14])=[CH:16][CH:17]=2)[CH3:22])[CH:7]=[C:6]([C:8]2[O:12][CH:11]=[N:10][CH:9]=2)[CH:5]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 2779063(S)-1-(4-Fluorophenyl)-ethylamineHCID 866593785-(2,6-Dichloropyridin-4-yl)oxazole

Product 1

HCID 86659379HCID 86659379, compoundYield 64.5%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

630 mg of 5-(2,6-dichloropyridin-4-yl)oxazole obtained by Step 1, 408 mg of (S)-(−)-1-(4-fluorophenyl)ethylamine, 182 mg of 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl, 1.9 g of cesium carbonate and 66 mg of palladium acetate were added in turn to 30 ml of degassed toluene, and the mixture was stirred at 100° C. for 1.5 hours under argon atmosphere. The reaction solution was purified by silica gel column chromatography to obtain 600 mg of (S)-6-chloro-N-[1-(4-fluorophenyl)ethyl]-4-(oxazol-5-yl)pyridine-2-amine as pale yellow powder. 10 ml of degassed toluene was added to the obtained powder, and 180 mg of 2-aminopyrazine, 180 mg of 2-dicyclohexylphosphino-2′,4′,6′-triisopropyl biphenyl, 254 mg of sodium t-butoxide and 98 mg of tris(dibenzylideneacetone)dipalladium were added in turn, 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 390 mg of the objective compound as pale yellow powder.

Workup

  1. customThe reaction solution was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-517acd62e42349969a1e543ef1c0c556
Source dataset
uspto-grants-2014_03
Patent number
US08673891B2

Reaction notes

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