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

HRID 324776Notes

Reaction equation

HRID 324776 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.[C:37]([C:40]1[S:41][CH:42]=[CH:43][CH:44]=1)(=[NH:39])[NH2:38].C(=O)([O-])O.[Na+]>CN(C)C=O>[Cl:26][C:27]1[CH:28]=[C:29]([CH:30]2[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])=[C:11]([CH2:10][O:9][CH2:8][CH2:7][N:1]3[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]3)[NH:39][C:37]([C:40]3[S:41][CH:42]=[CH:43][CH:44]=3)=[N:38]2)[CH:32]=[CH:33][C:34]=1[Cl:35]

Participants

6

Reactant 4

HCID 227103,4-DichlorobenzaldehydeHCID 516892Sodium BicarbonateHCID 2781759Thiophene-2-carboximidamide HydrochlorideHCID 220055123-Phenylpropyl 4-(2-(1-piperidinyl)ethoxy)acetoacetate

Product 1

HCID 220055453-Phenylpropyl 4-(3,4-dichlorophenyl)-6-[(2-(1-piperidinyl)ethoxy)methyl]-2-(2-thienyl)-1,4-dihydropyrimidine-5-carboxylateYield 15.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 3-phenylpropyl 4-(2-(1-piperidinyl)ethoxy)acetoacetate (2.7 g, 7.77 mmol), 3,4-dichlorobenzaldehyde (1.63 g, 9.32 mmol), 2-amidinothiophene hydrochloride (1.52 g, 9.32 mmol) and sodium hydrogen carbonate (0.79 g, 9.35 mmol) was stirred in N,N-dimethylformamide (20 mL) for 4 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 (0.73 g) as an oil. Electrospray MS m/z 612/614 [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-a9bd8567d7cd499ba949c25d9a9a3cba
Source dataset
uspto-grants-2001_04
Patent number
US06218538B1

Reaction notes

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