Hydrochloric Acid → 7-(2,4-Dimethoxybenzyl)-2-thioxo-3-[4-(2,2,2-trifluoroethoxy)phenyl]-1,2,3,5,6,7-hexahydropyrido[3,4-d]pyrimidine-4,8-dione

HRID 570727Notes

Reaction equation

HRID 570727 reaction equation
[N:1]([C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][C:12]([F:15])([F:14])[F:13])=[CH:6][CH:5]=1)=[C:2]=[S:3].[H-].[Na+].[NH2:18][C:19]1[C:24](=[O:25])[N:23]([CH2:26][C:27]2[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][C:28]=2[O:35][CH3:36])[CH2:22][CH2:21][C:20]=1[C:37](OCC)=[O:38].Cl>CN(C)C=O>[CH3:36][O:35][C:28]1[CH:29]=[C:30]([O:33][CH3:34])[CH:31]=[CH:32][C:27]=1[CH2:26][N:23]1[CH2:22][CH2:21][C:20]2[C:37](=[O:38])[N:1]([C:4]3[CH:5]=[CH:6][C:7]([O:10][CH2:11][C:12]([F:13])([F:15])[F:14])=[CH:8][CH:9]=3)[C:2](=[S:3])[NH:18][C:19]=2[C:24]1=[O:25]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 866436111-Isothiocyanato-4-(2,2,2-trifluoroethoxy)benzeneHCID 86685387Ethyl 5-amino-1-(2,4-dimethoxybenzyl)-6-oxo-1,2,3,6-tetrahydropyridine-4-carboxylate

Product 1

HCID 866853867-(2,4-Dimethoxybenzyl)-2-thioxo-3-[4-(2,2,2-trifluoroethoxy)phenyl]-1,2,3,5,6,7-hexahydropyrido[3,4-d]pyrimidine-4,8-dioneYield 29.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 1-isothiocyanato-4-(2,2,2-trifluoroethoxy)benzene (115 mg) in N,N-dimethylformamide (2 ml) was added sodium hydride (60% in oil, 45 mg), and a solution of ethyl 5-amino-1-(2,4-dimethoxybenzyl)-6-oxo-1,2,3,6-tetrahydropyridine-4-carboxylate (150 mg) in N,N-dimethylformamide (2 ml) was added dropwise thereto over 5 min under ice-cooling. The mixture was stirred for 10 min, allowed to be warmed to room temperature, and stirred for 30 min. The reaction mixture was poured into 0.5M hydrochloric acid (4 ml) under ice-cooling, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained yellow solid was washed with diethyl ether to give the title compound (70 mg) as beige fine needle crystals.

Workup

  1. temperatureover 5 min under ice-cooling
  2. stirringstirred for 30 min
  3. temperaturecooling
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe extract was washed with water and saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. washThe obtained yellow solid was washed with diethyl ether

Sources & evidence

ORD record
ord-839e6c6e8d47465b890f150551a7ec24
Source dataset
uspto-grants-2015_05
Patent number
US09023858B2

Reaction notes

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