5-Bromo-4-methyl-1,3-thiazole → 7-(1-Ethyl-propyl)-2,5-dimethyl-3-(4-methyl-thiazol-5-yl)-pyrazolo[1,5-a]pyrimidine

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Reaction Steps

Add Rieke® zinc (10 g in 100 mL of THF, 13.2 mL, 18.48 mmol) to 5-bromo-4-methylthiazole (2.13 g, 18.48 mmol) and heat at reflux for 2 h. Cool the mixture to room temperature and settle the zinc down by centrifuge. Bubble nitrogen gas through 7-(1-ethyl-propyl)-3-iodo-2,5-dimethyl-pyrazolo[1,5-a]pyrimidine (900 mg, 2.62 mmol) in dry tetrahydrofuran (10 mL) and add the organozinc bromide solution followed by addition of [1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II) (106 mg, 0.13 mmol). Stir the reaction mixture under reflux overnight and cool to room temperature. Add ammonium chloride solution to the reaction mixture and extract with dichloromethane. Dry the organic portion over sodium sulfate, filter, and remove the solvent under vacuum. Purify the crude product by silica gel column chromatography, elueting with hexane/ethyl acetate (3/1) to obtain the title compound (652 mg, 79%). 1H NMR (400 MHz, CDCl3): δ 8.80 (s, 1H), 6.48 (s, 1H), 3.63 (m, 1H), 2.57 (s, 3H), 2.43 (s, 3H), 2.40 (s, 3H), 1.85 (m, 4H), 0.90 (t, 6H, J=7.3Hz). ES/MS m/z 315 (M+1)+.

Provenance & Evidence