Azetidine → 2-{4-[4-(Azetidin-1-ylacetyl)piperazin-1-yl]anilino}-4-(1-isopropyl-2-methyl-1H-imidazol-5-yl)pyrimidine hydrochloride

Participants

Reaction Steps

2-{4-[4-(Chloroacetyl)piperazin-1-yl]anilino}-4-(1-isopropyl-2-methyl-1H-imidazol-5-yl)pyrimidine (Example 24; 0.34 g, 0.75 mmol) and azetidine (2 ml) was stirred for 24 hours at ambient temperature. The solution was diluted with EtOAc (20 ml), washed with aqueous saturated sodium bicarbonate solution (10 ml) and aqueous saturated sodium chloride solution (10 ml), then dried and evaporated at reduced pressure. The residue was purified by chromatography on a 40 g silica column, eluted with a 3% MeOH-ammonia/DCM to 5% MeOH-ammonia/DCM gradient, to give the amine, which was converted to the hydrochloride salt by dissolving in EtOAc (3 ml) and treating with a 1.0 molar solution of ethereal-HCl (0.75 ml). The solid was triturated with ether (20 ml) and filtered to give the title compound (24 mg, 7%). NMR: 9.77 (s, 1H), 8.58 (d, 1H), 8.20 (s, 1H), 7.61 (d, 2H), 7.35-7.24 (m, 2H), 7.13 (d, 1H), 5.64-5.55 (m, 1H), 4.65 (brs, 1H), 4.44 (d, 2H), 4.23-4.11 (m, 2H), 4.09-3.96 (m, 2H), 3.81-3.71 (m, 2H), 3.69-3.59 (m, 2H), 3.42-3.31 (m, 2H), 3.30-3.17 (m, 2H), 2.48-2.24 (m, 2H), 2.81 (s, 3H), 1.48 (d, 6H); m/z 475.

Provenance & Evidence