Tributyltin Chloride → 7-(1,1-Dimethoxyethyl)-3-[2-(pyridin-4-yl)pyrimidin-4-yl]imidazo[1,2-alpha]pyrimidine

Participants

Reaction Conditions

Reaction Steps

To a solution of 3-bromo-7-(1,1-dimethoxyethyl)imidazo[1,2-α]pyrimidine (1.0 g, 3.5 mmol) at −45° C. was added isopropylmagnesium chloride (2.6 ml of a 2M solution in THF, 5.2 mmol) dropwise. After stirring at −45° C. for 1.5 h tri-n-butylstannyl chloride (1.52 ml, 5.6 mmol) was added dropwise. The solution was stirred at −45° C. for 15 min then the cooling bath was removed and the solution stirred at room temperature for 1.5 h. After this time half of the solution was taken and degassed with N2 for 15 min. 4-Chloro-2-(pyridin-4-yl)pyrimidine (prepared according to J. Med. Chem., 1982, 25(7), 837-842) (487 mg, 2.55 mmol) and tetrakis(triphenylphosphine)palladium(0) (294 mg, 0.26 mmol) were then added and the mixture heated at reflux for 18 h. After this time the solvent was evaporated and the residue partitioned between dichloromethane (2×40 ml) and water (40 ml). The combined organic layers were washed with brine (40 ml), dried (MgSO4) and evaporated. The residue was chromatographed on silica gel, eluting with 1:1 isohexane:ethyl acetate followed by dichloromethane:MeOH (97:3), to afford 7-(1,1-dimethoxyethyl)-3-[2-(pyridin-4-yl)pyrimidin-4-yl]imidazo[1,2-α]pyrimidine (171 mg, 28%) as an off-white solid: δH (360 MHz, CDCl3) 1.76 (3H, s), 3.33 (6H, s), 7.66-7.69 (2H, m), 8.28 (2H, dd, J 4.6 and 1.5), 8.60 (1H, s), 8.80-8.90 (3H, m), 10.30 (1H, d, J 7.3); m/z (ES+) 363 (M++H).

Provenance & Evidence