Dimethylformamide → 4-Chloro-8-(2,4-dimethoxybenzyl)-5-(trifluoromethyl)-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-one

HRID 2088873Notes

Reaction equation

HRID 2088873 reaction equation
ClC1C(C(C(F)(F)F)CC(OC)=O)=C(Cl)N=CN=1.COC1C=C(OC)C=CC=1CN.CN(C)C=O.[Cl:36][C:37]1[C:42]([CH:43]([C:49]([F:52])([F:51])[F:50])[CH2:44][C:45]([O:47]C)=O)=[C:41]([NH:53][CH2:54][C:55]2[CH:60]=[CH:59][C:58]([O:61][CH3:62])=[CH:57][C:56]=2[O:63][CH3:64])[N:40]=[CH:39][N:38]=1>O>[Cl:36][C:37]1[C:42]2[CH:43]([C:49]([F:51])([F:52])[F:50])[CH2:44][C:45](=[O:47])[N:53]([CH2:54][C:55]3[CH:60]=[CH:59][C:58]([O:61][CH3:62])=[CH:57][C:56]=3[O:63][CH3:64])[C:41]=2[N:40]=[CH:39][N:38]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 5972502,4-DimethoxybenzylamineHCID 86666569Methyl 3-(4,6-dichloropyrimidin-5-yl)-4,4,4-trifluorobutanoateHCID 86666570Methyl 3-(4-chloro-6-(2,4-dimethoxybenzylamino)pyrimidin-5-yl)-4,4,4-trifluorobutanoate

Product 1

HCID 866665684-Chloro-8-(2,4-dimethoxybenzyl)-5-(trifluoromethyl)-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-one

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

Combine methyl 3-(4,6-dichloropyrimidin-5-yl)-4,4,4-trifluorobutanoate (0.71 g, 1.98 mmol) diisopropylethylamine (0.38 mL, 1.1 eq), 2,4-dimethoxybenzylamine (0.32 mL, 1.05 eq), and dimethylformamide (6 mL). Heat at 50° C. overnight. Allow to cool to room temperature. Dilute with water and extract with methyl tert-butyl ether. Wash the organic layer with saturated aqueous sodium chloride. Dry the organics over anhydrous magnesium sulfate, filter, and concentrate in vacuo to give a mixture of the title compound and methyl 3-(4-chloro-6-(2,4-dimethoxybenzylamino)pyrimidin-5-yl)-4,4,4-trifluorobutanoate as an oil. Combine the crude mixture (0.78 g), diisopropylethylamine (0.63 mL), and ethanol (7.8 mL). Heat at reflux for four hours. Allow to cool to room temperature. Filter and rinse with ethanol to obtain the title compound as a white solid (0.43 g, 55%).

Workup

  1. temperatureto cool to room temperature
  2. extractionextract with methyl tert-butyl ether
  3. washWash the organic layer with saturated aqueous sodium chloride
  4. dry with materialDry the organics over anhydrous magnesium sulfate
  5. filtrationfilter
  6. concentrationconcentrate in vacuo
  7. customto give

Sources & evidence

ORD record
ord-2d743b2d976e4d20b4d9c9fc447adb5c
Source dataset
uspto-grants-2013_05
Patent number
US08436002B2

Reaction notes

Loading…