Potassium Carbonate → 3-Phenylpropyl 2-(4-chlorophenyl)-4-(3,4-dichlorophenyl)-6-[(2-(1-piperidinyl)ethoxy)methyl]-1,4-dihydropyrimidine-5-carboxylate

HRID 324785

Reaction equation

HRID 324785 reaction equation
[N:1]1([CH2:7][CH2:8][O:9][CH2:10][C:11](=O)[CH2:12][C:13]([O:15][CH2:16][CH2:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:14])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[Cl:26][C:27]1[CH:28]=[C:29]([CH:32]=[CH:33][C:34]=1[Cl:35])[CH:30]=O.Cl.[Cl:37][C:38]1[CH:46]=[CH:45][C:41]([C:42]([NH2:44])=[NH:43])=[CH:40][CH:39]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[Cl:37][C:38]1[CH:46]=[CH:45][C:41]([C:42]2[NH:44][C:11]([CH2:10][O:9][CH2:8][CH2:7][N:1]3[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]3)=[C:12]([C:13]([O:15][CH2:16][CH2:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[O:14])[CH:30]([C:29]3[CH:32]=[CH:33][C:34]([Cl:35])=[C:27]([Cl:26])[CH:28]=3)[N:43]=2)=[CH:40][CH:39]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 227103,4-DichlorobenzaldehydeHCID 2034364-Chlorobenzene-1-carboximidamide hydrochlorideHCID 220055123-Phenylpropyl 4-(2-(1-piperidinyl)ethoxy)acetoacetate

Product 1

HCID 220055203-Phenylpropyl 2-(4-chlorophenyl)-4-(3,4-dichlorophenyl)-6-[(2-(1-piperidinyl)ethoxy)methyl]-1,4-dihydropyrimidine-5-carboxylateYield 3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 3-phenylpropyl 4-(2-(1-piperidinyl)ethoxy)acetoacetate (5.46 g, 15.70 mmol), 3,4-dichlorobenzaldehyde (2.75 g, 15.70 mmol), 4-chlorobenzamidine hydrochloride (3.0 g, 15.70 mmol) and potassium carbonate (2.17 g, 15.70 mmol) was stirred in N,N-dimethylformamide (15 ml) for 5 days at room temperature and then heated to 60° C. for 3 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. The oil was further purified by flash chromatography and RP-HPLC to give the title compound (300 mg) as an oil. Electrospray MS m/z 640/642 [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. customThe oil was further purified by flash chromatography and RP-HPLC

Sources & evidence

ORD record
ord-b512d2d240a34d0e8f796183c5d0b819
Source dataset
uspto-grants-2001_04
Patent number
US06218538B1

Linked notes

Loading…