2-(2-Ethynylphenyl)propanamide → 2-(2-((2-((6-Methoxypyridin-3-yl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethynyl)phenyl)propanamide

HRID 592472Notes

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[C:15]1[C:20]([C:21]([F:24])([F:23])[F:22])=[CH:19][N:18]=[C:17]([NH:25][C:26]2[CH:27]=[N:28][C:29]([O:32][CH3:33])=[CH:30][CH:31]=2)[N:16]=1>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>[CH3:33][O:32][C:29]1[N:28]=[CH:27][C:26]([NH:25][C:17]2[N:16]=[C:15]([C:2]#[C:1][C:3]3[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=3[CH:9]([CH3:13])[C:10]([NH2:12])=[O:11])[C:20]([C:21]([F:24])([F:22])[F:23])=[CH:19][N:18]=2)=[CH:31][CH:30]=1

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 2-(2-ethynylphenyl)propanamide K7 (0.120 g, 0.693 mmol), 4-chloro-N-(6-methoxypyridin-3-yl)-5-(trifluoromethyl)pyrimidin-2-amine A68 (0.211 g, 0.693 mmol), CuI (0.013 g, 0.069 mmol), t-Bu3PHBF4 (0.020 g, 0.069 mmol) and PdCl2(PPh3)2 (0.024 g, 0.035 mmol) in DMF (3 mL) was bubbled with N2 for 5 minutes. Et3N (1 mL) was added and the reaction mixture was stirred in the microwave at 120° C. for 15 minutes. The volatiles were removed in vacuo and the black residue was adsorbed onto silica. Purification by column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.) gave the title compound A69 as a yellow solid (0.198 g, 65%). LCMS-D: rt 3.43 min; m/z 442 [M+H]+.

Workup

customwas bubbled with N2 for 5 minutes
additionEt3N (1 mL) was added
customThe volatiles were removed in vacuo
customPurification by column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.)

Sources & evidence

ORD record: ord-88271574e3354da8a1c083994023d819
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09238644B2

Reaction notes

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