3,4-Dichlorobenzaldehyde → 3-Phenylpropyl 4-(3,4-dichlorophenyl)-6-[(2-(N,N-diethylamino)ethoxy)methyl]-2-methylthio-1,4-dihydropyrimidine-5-carboxylate

HRID 1106632Notes

Reaction equation

HRID 1106632 reaction equation
[CH2:1]([N:3]([CH2:6][CH2:7][O:8][CH2:9][C:10](=O)[CH2:11][C:12]([O:14][CH2:15][CH2:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:13])[CH2:4][CH3:5])[CH3:2].[Cl:25][C:26]1[CH:27]=[C:28]([CH:31]=[CH:32][C:33]=1[Cl:34])[CH:29]=O.S(O)(O)(=O)=O.[CH3:40][S:41][C:42](=[NH:44])[NH2:43].C([O-])(=O)C.[Na+]>CN(C)C=O>[Cl:25][C:26]1[CH:27]=[C:28]([CH:29]2[C:11]([C:12]([O:14][CH2:15][CH2:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[O:13])=[C:10]([CH2:9][O:8][CH2:7][CH2:6][N:3]([CH2:4][CH3:5])[CH2:1][CH3:2])[NH:44][C:42]([S:41][CH3:40])=[N:43]2)[CH:31]=[CH:32][C:33]=1[Cl:34]

Participants

6

Reactant 4

HCID 227103,4-DichlorobenzaldehydeHCID 752702-Methyl-2-thiopseudourea sulfateHCID 517045Sodium AcetateHCID 220055113-phenylpropyl 4-(2-(N,N-diethylamino)ethoxy)acetoacetate

Product 1

HCID 187892393-Phenylpropyl 4-(3,4-dichlorophenyl)-6-[(2-(N,N-diethylamino)ethoxy)methyl]-2-methylthio-1,4-dihydropyrimidine-5-carboxylateYield 6.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 3-phenylpropyl 4-(2-(N,N-diethylamino)ethoxy)acetoacetate (2.0 g, 5.96 mmol), 3,4-dichlorobenzaldehyde (1.15 g, 6.56 mmol), 2-methyl-2-thiopseudourea sulfate (0.913 g, 3.28 mmol) and sodium acetate (0.27 g, 3.28 mmol) was stirred in N,N-dimethylformamide (10 mL) for 24 hours at room temperature, then heated to 60° C. for 5 days. The DMF was removed in vacuo and ethyl acetate was added to the residue. The precipitate was removed by filtration and the filtrate was washed with water, sodium hydrogen carbonate solution and brine, dried and evaporated to yield an oil. This oil was further purified by flash chromatography and RP-HPLC to give the title compound (114 mg) as an oil. The oil can be converted into a mono or dihydrochloride salt, by dissolution in ether and addition of one or two equivalents of hydrogen chloride. Electrospray MSm /z 564/566 [M+H]+.

Workup

  1. customThe DMF was removed in vacuo and ethyl acetate
  2. additionwas added to the residue
  3. customThe precipitate was removed by filtration
  4. washthe filtrate was washed with water, sodium hydrogen carbonate solution and brine
  5. customdried
  6. customevaporated
  7. customto yield an oil
  8. customThis oil was further purified by flash chromatography and RP-HPLC

Sources & evidence

ORD record
ord-7137f947c04b456b8b43546e5a3f9a03
Source dataset
uspto-grants-2000_05
Patent number
US06057332

Reaction notes

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