Triethylamine → (S)-2-(3-(4-(N-cyclohexyl-N-methylamino)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)pyrimidin-4-one

Reaction equation

[CH:1]1([N:7]([C:9]2[CH:14]=[CH:13][C:12]([C@H:15]3[CH2:20][NH:19][CH2:18][CH2:17][NH:16]3)=[CH:11][CH:10]=2)[CH3:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(CC)CC)C.Cl[C:29]1[N:34]([CH3:35])[C:33](=[O:36])[CH:32]=[C:31]([C:37]2[CH:42]=[CH:41][N:40]=[CH:39][CH:38]=2)[N:30]=1>>[CH:1]1([N:7]([C:9]2[CH:14]=[CH:13][C:12]([C@@H:15]3[NH:16][CH2:17][CH2:18][N:19]([C:29]4[N:34]([CH3:35])[C:33](=[O:36])[CH:32]=[C:31]([C:37]5[CH:38]=[CH:39][N:40]=[CH:41][CH:42]=5)[N:30]=4)[CH2:20]3)=[CH:11][CH:10]=2)[CH3:8])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

Reactant 3

HCID 8471Triethylamine

HCID 112760814(3H)-Pyrimidinone, 2-chloro-3-methyl-6-(4-pyridinyl)-

HCID 67117423(S)-2-(4-(N-cyclohexyl-N-methylamino)phenyl)piperazine

Product 1

HCID 57593972(S)-2-(3-(4-(N-cyclohexyl-N-methylamino)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)pyrimidin-4-oneYield 88%

Procedure

To a solution of (S)-2-(4-(N-cyclohexyl-N-methylamino)phenyl) piperazine (50 mg, 0.183 mmol) and triethylamine (0.077 mL, 0.55 mmol) was added 2-chloro-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one (37 mg, 0.17 mmol) at room temperature. After stirring for 4.5 h, the reaction mixture was concentrated in vacuo. The residue was partitioned between dichloromethane and saturated sodium bicarbonate aqueous solution. The organic layer was dried over anhydrous sodium sulfate and concentrated. The residue was purified by a reverse phase chromatography eluting 0.05% TFA in water-acetonitrile to afford (S)-2-(3-(4-(N-cyclohexyl-N-methylamino)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)pyrimidin-4-one (67 mg, 88%) as a oil, which was dissolved in ethyl acetate and treated with 4 N hydrogen chloride in ethyl acetate to yield its trihydrochloride.