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

HRID 1784687Notes

Reaction equation

HRID 1784687 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

4

Reactant 3

HCID 8471TriethylamineHCID 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.

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. customThe residue was partitioned between dichloromethane and saturated sodium bicarbonate aqueous solution
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by a reverse phase chromatography
  6. washeluting 0.05% TFA in water-acetonitrile

Sources & evidence

ORD record
ord-191ef9472c454fc186967e24cce1f2d0
Source dataset
uspto-grants-2009_03
Patent number
US07504411B2

Reaction notes

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