Potassium Carbonate → Methyl 2-{[6-(4-cyanophenyl)-5-(cyclopropylcarbonyl)-4-methyl-2-oxo-3-[3-(trifluoromethyl)phenyl]-3,6-dihydropyrimidin-1(2H)-yl]methyl}-1,3-oxazole-4-carboxylate

HRID 421801Notes

Reaction equation

HRID 421801 reaction equation
[CH:1]1([C:4]([C:6]2[CH:7]([C:24]3[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[CH:26][CH:25]=3)[NH:8][C:9](=[O:23])[N:10]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[CH:14]=3)[C:11]=2[CH3:12])=[O:5])[CH2:3][CH2:2]1.C(=O)([O-])[O-].[K+].[K+].Cl[CH2:39][C:40]1[O:41][CH:42]=[C:43]([C:45]([O:47][CH3:48])=[O:46])[N:44]=1>CN(C)C=O>[C:28]([C:27]1[CH:26]=[CH:25][C:24]([CH:7]2[N:8]([CH2:39][C:40]3[O:41][CH:42]=[C:43]([C:45]([O:47][CH3:48])=[O:46])[N:44]=3)[C:9](=[O:23])[N:10]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:20])[F:21])[CH:14]=3)[C:11]([CH3:12])=[C:6]2[C:4]([CH:1]2[CH2:3][CH2:2]2)=[O:5])=[CH:31][CH:30]=1)#[N:29]

Participants

5

Reactant 3

HCID 11430Potassium Carbonate2×HCID 2763199Methyl 2-(chloromethyl)oxazole-4-carboxylate2×HCID 596848504-{5-(Cyclopropylcarbonyl)-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidin-4-yl}benzonitrile

Product 1

HCID 59684873Methyl 2-{[6-(4-cyanophenyl)-5-(cyclopropylcarbonyl)-4-methyl-2-oxo-3-[3-(trifluoromethyl)phenyl]-3,6-dihydropyrimidin-1(2H)-yl]methyl}-1,3-oxazole-4-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred suspension of 4-{5-(cyclopropylcarbonyl)-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidin-4-yl}benzonitrile (Example 22) (150 mg, 0.35 mmol) and potassium carbonate (98 mg, 0.71 mmol) in dimethylformamide (3 ml) is added methyl 2-(chloromethyl)-1,3-oxazole-4-carboxylate (93 mg, 0.53 mmol). The reaction mixture is stirred at room temperature overnight, then an additional equivalent of potassium carbonate (0.35 mmol) and methyl 2-(chloromethyl)-1,3-oxazole-4-carboxylate (0.35 mmol) are added, and the solution is stirred an additional 72 hours. The reaction mixture is quenched with water (20 ml) and extracted with ethyl acetate (3×50 ml). The combined organic phases are washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated. The residue is purified by HPLC (RP18 column; eluent: acetonitrile/water 30:70→90:10).

Workup

  1. stirringthe solution is stirred an additional 72 hours
  2. customThe reaction mixture is quenched with water (20 ml)
  3. extractionextracted with ethyl acetate (3×50 ml)
  4. washThe combined organic phases are washed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue is purified by HPLC (RP18 column; eluent: acetonitrile/water 30:70→90:10)

Sources & evidence

ORD record
ord-c3d59d852e4947c1804db63af35bd04c
Source dataset
uspto-grants-2012_01
Patent number
US08101615B2

Reaction notes

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