Potassium Phosphate, Tribasic → 2-(6-(7-(Trifluoromethyl)imidazo[1,2-a]pyrimidin-3-yl)pyridin-2-yl)benzonitrile

HRID 1796008Notes

Reaction equation

Br[C:2]1[N:7]=[C:6]([C:8]2[N:12]3[CH:13]=[CH:14][C:15]([C:17]([F:20])([F:19])[F:18])=[N:16][C:11]3=[N:10][CH:9]=2)[CH:5]=[CH:4][CH:3]=1.[C:21]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1B(O)O)#[N:22].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C)C(=O)C>[F:18][C:17]([F:20])([F:19])[C:15]1[CH:14]=[CH:13][N:12]2[C:8]([C:6]3[N:7]=[C:2]([C:24]4[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=4[C:21]#[N:22])[CH:3]=[CH:4][CH:5]=3)=[CH:9][N:10]=[C:11]2[N:16]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a degassed solution of 3-(6-bromopyridin-2-yl)-7-trifluoromethyl-imidazo[1,2-α]pyrimidine (200 mg, 0.58 mmol), 2-cyanophenylboronic acid (172 mg, 1.16 mmol) and potassium phosphate (370 mg, 1.75 mmol) in N,N-dimethylacetamide (4 ml) was added tetrakis(triphenylphosphine)paladium(0) (33.8 mg, 29.2 μmol) and the reaction heated at 80° C. for 18 h. After cooling to ambient temperature the reaction was poured onto a cartridge of strong cation-exchange resin and non-basic impurities removed by elution with methanol. The product was then eluted with a 2M solution of ammonia in methanol and evaporated to give an orange oil. This residue was purified by silica gel chromatography eluting with isohexane on a gradient of ethyl acetate (20-60%) to give a solid. Crystallisation from ethyl acetate-dichloromethane gave 2-[6-(7-trifluoromethylimidazo[1,2-α]pyrimidin-3-yl)pyridin-2-yl]benzonitrile (26 mg) as a white solid: δH (400 MHz, CDCl3) 7.38 (1H, d, J 7),7.61 (2H, m), 7.78 (2H, m), 7.91 (2H, m), 7.99 (1H, dd, J 9 and 9), 8.58 (1H, s), 10.62 (1H, d, J 9); m/z (ES+) 366 (M++H).

Workup

temperatureAfter cooling to ambient temperature the reaction
additionwas poured onto a cartridge of strong cation-exchange resin and non-basic impurities
customremoved by elution with methanol
washThe product was then eluted with a 2M solution of ammonia in methanol
customevaporated
customto give an orange oil
customThis residue was purified by silica gel chromatography
washeluting with isohexane on a gradient of ethyl acetate (20-60%)
customto give a solid
customCrystallisation from ethyl acetate-dichloromethane

Sources & evidence

ORD record: ord-a9f79d43cf41417cbb2879c46b85f589
Source dataset: uspto-grants-2006_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07030128B2

Reaction notes

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