Guanidine Hydrochloride → HCID 58235128, compound

Participants

Reaction Steps

4-(4-Phenyl-1-piperidin-4-yl-1H-imidazol-5-yl)pyrimidin-2-amine [C27, prepared from tert-butyl 4-(5-acetyl-4-phenyl-1H-imidazol-1-yl)piperidine-1-carboxylate (C24) in a manner similar to the synthesis of N-methyl-4-(4-phenyl-1-piperidin-4-yl-1H-imidazol-5-yl)pyrimidin-2-amine (C26) described in Example 12, but using guanidine hydrochloride in place of N-methylguanidine hydrochloride] was reacted with isoxazole-3-carbaldehyde according to the general procedure for the synthesis of 4-{4-(4-fluorophenyl)-1-[1-(isoxazol-3-ylmethyl)piperidin-4-yl]-1H-imidazol-5-yl}-N-methylpyrimidin-2-amine (5) in Example 5. 4-{1-[1-(Isoxazol-3-ylmethyl)piperidin-4-yl]-4-phenyl-1H-imidazol-5-yl}pyrimidin-2-amine (free base of 13) was obtained as a yellow solid. Yield: 101 mg, 0.252 mmol, 29%. 1H NMR (400 MHz, CDCl3) δ 1.97-2.08 (m, 2H), 2.12-2.24 (m, 4H), 3.03 (br d, J=12 Hz, 2H), 3.69 (s, 2H), 4.59 (tt, J=11.8, 4.0 Hz, 1H), 5.07 (br s, 2H), 6.41 (d, J=1.7 Hz, 1H), 6.54 (d, J=5.2 Hz, 1H), 7.27-7.34 (m, 3H), 7.46-7.50 (m, 2H), 7.78 (s, 1H), 8.17 (d, J=5.2 Hz, 1H), 8.40 (br d, J=1.5 Hz, 1H). This solid was dissolved in ethyl acetate, treated with a solution of hydrogen chloride in diethyl ether (2 N, 1 equivalent) and allowed to stir for 18 hours. The resulting solid was collected by filtration to provide the title product as a light yellow solid. Yield: 70 mg, 0.16 mmol, 19%.

Provenance & Evidence