Pyrimidine, 2,4-dichloro-5-methyl- → 2-(2-((2-Chloro-5-methylpyrimidin-4-yl)ethynyl)phenyl)propanamide

HRID 592445Notes

Reaction equation

[C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH:9]([CH3:13])[C:10]([NH2:12])=[O:11])#[CH:2].[Cl:14][C:15]1[N:20]=[C:19](Cl)[C:18]([CH3:22])=[CH:17][N:16]=1.F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C>CN(C=O)C.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:14][C:15]1[N:20]=[C:19]([C:2]#[C:1][C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[CH:9]([CH3:13])[C:10]([NH2:12])=[O:11])[C:18]([CH3:22])=[CH:17][N:16]=1

Participants

Conditions

Temperature: 60 °C

Procedure

A suspension of 2-(2-ethynylphenyl)propanamide K7 (2.00 g, 11.5 mmol), 2,4,-dichloro-5-methylpyrimidine (2.45 g, 15.0 mmol), CuI (0.044 g, 0.33 mmol), PdCl2(PPh3)2 (0.162 g, 0.231 mmol) and tri-t-butylphosphonium tetrafluoroborate (0.067 g, 0.23 mmol) in DMF (15 mL) was bubbled with N2 for 10 minutes. Et3N (10 mL) was added and the reaction mixture was stirred under N2 at 60° C. for 2.5 hours. The mixture was cooled, diluted with Et2O and the precipitate was isolated by filtration and washed with Et2O then water to give the title compound A48 as a white solid (2.08 g, 60%). LCMS-A: rt 5.86 min; m/z 300 [M+H]+.

Workup

customwas bubbled with N2 for 10 minutes
additionEt3N (10 mL) was added
temperatureThe mixture was cooled
additiondiluted with Et2O
customthe precipitate was isolated by filtration
washwashed with Et2O

Sources & evidence

ORD record: ord-921fcdb4d7d946208855864493c2290b
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09238644B2

Reaction notes

Loading…