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

HRID 1157631Notes

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]([CH3:24])=[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]([CH3:24])=[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 a solution of 2,4-dichloropyrimidine (3.8 g, 25.5 mmol) in THF (175 mL) was added Pd(PPh3)2Cl2 (1.8 g, 2.6 mmol), CuI (247 mg, 1.3 mmol), and TEA (10.7 mL, 76.5 mmol) and the mixture was heated to 60° C. A solution of N-(5-ethynyl-2-methylphenyl)-2,2,2-trifluoroacetamide (6.4 g, 28 mmol) in THF (75 mL) was added through an addition funnel over 60 min. After 16 h, the dark reaction was concentrated onto silica gel and purified by column chromatography. Fractions containing product were concentrated and the impurity was triturated with DCM. The remaining liquid was purified again by column chromatography to give the desired product (2.7 g, 31%). 1H NMR (400 MHz, d6-DMSO) δ 11.09 (s, 1H), 8.83 (d, J=4.8 Hz, 1H), 7.77 (d, J=5.2 Hz, 1H), 7.62 (s, 1H), 7.58 (dd, J=8.0 and 1.6 Hz, 1H), 7.45 (d, J=8.0 Hz, 1H), 2.24 (s, 3H) ppm.

Workup

customthe dark reaction
concentrationwas concentrated onto silica gel
custompurified by column chromatography
additionFractions containing product
concentrationwere concentrated
customthe impurity was triturated with DCM
customThe remaining liquid was purified again by column chromatography

Sources & evidence

ORD record: ord-50221c909fc34bb680c281feb5ff93dd
Source dataset: uspto-grants-2010_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07807673B2

Reaction notes

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