2,4-Dichloropyrimidine → N-{5-[(2-Chloro-4-pyrimidinyl)ethynyl]-2-fluorophenyl}-2,2,2-trifluoroacetamide

HRID 1159986Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[CH:4][N:3]=1.[C:9]([C:11]1[CH:12]=[CH:13][C:14]([F:24])=[C:15]([NH:17][C:18](=[O:23])[C:19]([F:22])([F:21])[F:20])[CH:16]=1)#[CH:10]>C1COCC1.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.[Cu]I>[Cl:1][C:2]1[N:7]=[C:6]([C:10]#[C:9][C:11]2[CH:12]=[CH:13][C:14]([F:24])=[C:15]([NH:17][C:18](=[O:23])[C:19]([F:20])([F:21])[F:22])[CH:16]=2)[CH:5]=[CH:4][N:3]=1

Participants

Conditions

Temperature: 60 °C

Procedure

To an oven-dried flask under N2 was added 2,4-dichloropyrimidine (5.1 g, 34 mmol), anhydrous degassed THF (250 mL), dichlorobis(triphenylphosphine)-palladium(II) (595 mg, 0.85 mmol), copper(I) iodide (97 mg, 0.5 mmol), and TEA (9.5 mL, 68 mmol), and the resulting suspension was heated to 60° C. A solution of N-(5-ethynyl-2-fluorophenyl)-2,2,2-trifluoroacetamide (3.9 g, 17 mmol) in THF (100 mL) was added dropwise, and the resulting mixture stirred overnight at 60° C. After 16 h, the crude reaction mixture was filtered through celite, adsorbed to silica gel, and purified by column chromatography to afford the desired product (4.6 g, 78%) as an off white solid. 1H NMR (400 MHz, CDCl3): δ 8.65 (d, J=5.1 Hz, 1H), 8.58 (d, J=7.3 Hz, 1H), 7.49 (m, 1H), 7.41 (d, J=5.0 Hz, 1H), 7.24 (m, 1H). ES-LC/MS m/z=344 [M+H]+.

Workup

waitAfter 16 h
customthe crude reaction mixture
filtrationwas filtered through celite
custompurified by column chromatography

Sources & evidence

ORD record: ord-f6eb020a4f4f450d81d02783e977d739
Source dataset: uspto-grants-2010_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07812022B2

Reaction notes

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