5-Amino-2-chloropyridine → 2-chloro-N-(6-chloropyridin-3-yl)-6-phenylpyrimidin-4-amine

Participants

Reaction Steps

Cooled a solution of 5-amino-2-chloropyridine (218.55 mg, 1.7 mmol) in dry THF (4.3 mL) in a dry-ice/acetone bath under nitrogen. The mixture was treated with a solution of nBuLi in hexanes (0.68 mL, 2.5M, 1.7 mmol) dropwise and stirred cold for 10 minutes. Allowed to warm to room temperature and ˜1.7 mL of the mixture was added dropwise to a solution of 2,4-dichloro-6-phenylpyrimidine (X) (190 mg, 0.844 mmol) in dry THF (2 mL). The mixture was stirred for 15 minutes and treated with an additional ˜0.3 mL of the lithium anilide solution and stirred for another 15 minutes. The reaction was poured into a mixture of saturated sodium bicarbonate and ethyl acetate. The layers were separated and the aqueous layer was extracted twice with ethyl acetate. The combined organics was dried over magnesium sulfate, filtered and concentrated to yield a film. The film was taken up in chloroform and loaded onto 100 g of silica gel. The silica gel was eluted with ethyl acetate/hexanes (10%, 20%, 30%, 40%). The appropriate fractions were concentrated on a rotary evaporator to yield 2-chloro-N-(6-chloropyridin-3-yl)-6-phenylpyrimidin-4-amine (XII) as a film (41.15 mg). ESI/MS 317.0756, 319.0810 (M+H).

Provenance & Evidence