Water → 1-(4-(4-(2-tert-butyl-6-(trifluoromethyl)pyrimidin-4-yl)piperazin-1-yl)butyl)-4-methylpyridin-2(1H)-one

HRID 2194380Notes

Reaction equation

HRID 2194380 reaction equation
Cl[CH2:2][CH2:3][CH2:4][CH2:5][N:6]1[CH:11]=[CH:10][C:9]([CH3:12])=[CH:8][C:7]1=[O:13].[C:14]([C:18]1[N:23]=[C:22]([N:24]2[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]2)[CH:21]=[C:20]([C:30]([F:33])([F:32])[F:31])[N:19]=1)([CH3:17])([CH3:16])[CH3:15].C(N(CC)CC)C.O>CS(C)=O>[C:14]([C:18]1[N:23]=[C:22]([N:24]2[CH2:25][CH2:26][N:27]([CH2:2][CH2:3][CH2:4][CH2:5][N:6]3[CH:11]=[CH:10][C:9]([CH3:12])=[CH:8][C:7]3=[O:13])[CH2:28][CH2:29]2)[CH:21]=[C:20]([C:30]([F:31])([F:32])[F:33])[N:19]=1)([CH3:17])([CH3:15])[CH3:16]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 183996102-(tert-Butyl)-4-(piperazin-1-yl)-6-(trifluoromethyl)pyrimidineHCID 592346451-(4-chlorobutyl)-4-methylpyridin-2(1H)-one

Product 1

HCID 159495641-(4-(4-(2-tert-butyl-6-(trifluoromethyl)pyrimidin-4-yl)piperazin-1-yl)butyl)-4-methylpyridin-2(1H)-oneYield 60.7%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

1-(4-Chlorobutyl)-4-methylpyridin-2(1H)-one (0.99 g, 4.96 mmol) from Example 1.1, 2-tert-butyl-4-piperazin-1-yl-6-(trifluoromethyl)pyrimidine (1.36 g, 4.71 mmol; prepared as described in DE 19735410) and triethylamine (1.51 g, 14.87 mmol) in 25 ml of dimethyl sulfoxide were stirred at 100° C. for 5 hours. Water was then added to the reaction mixture, and the aqueous mixture was extracted twice with tert-butyl methyl ether. The organic phase was extracted three times with a saturated aqueous sodium chloride solution and three times with a 5% aqueous citric acid solution. The aqueous phase was then made alkaline and extracted three times with tert-butyl methyl ether. The combined organic phases were dried over Na2SO4 and, after removal of the desiccant by filtration, concentrated. The resulting oily residue (1.99 g) was purified by chromatography on silica gel (eluent: CH2Cl2/CH3OH: 96.5:3.5), resulting in 1.29 g of the title compound.

Workup

  1. extractionthe aqueous mixture was extracted twice with tert-butyl methyl ether
  2. extractionThe organic phase was extracted three times with a saturated aqueous sodium chloride solution and three times with a 5% aqueous citric acid solution
  3. extractionextracted three times with tert-butyl methyl ether
  4. dry with materialThe combined organic phases were dried over Na2SO4
  5. customafter removal of the
  6. filtrationdesiccant by filtration
  7. concentrationconcentrated
  8. customThe resulting oily residue (1.99 g) was purified by chromatography on silica gel (eluent: CH2Cl2/CH3OH: 96.5:3.5)

Sources & evidence

ORD record
ord-f121e826ba6d4f6b82659dd1abf2df96
Source dataset
uspto-grants-2012_12
Patent number
US08334289B2

Reaction notes

Loading…