Methyl acetoacetate → Methyl 2-(thien-2-yl)-4-(2-chloro-4-fluorophenyl)-6-methyl-1,4-dihyropyrimidin-5-carboxylate

HRID 425250Notes

Reaction equation

HRID 425250 reaction equation
Cl.[S:2]1[CH:6]=[CH:5][CH:4]=[C:3]1[C:7]([NH2:9])=[NH:8].[Cl:10][C:11]1[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:12]=1[CH:13]=O.[C:20]([O:26][CH3:27])(=[O:25])[CH2:21][C:22]([CH3:24])=O.C([O-])(=O)C.[Na+]>C(O)C>[S:2]1[CH:6]=[CH:5][CH:4]=[C:3]1[C:7]1[NH:9][C:22]([CH3:24])=[C:21]([C:20]([O:26][CH3:27])=[O:25])[CH:13]([C:12]2[CH:15]=[CH:16][C:17]([F:19])=[CH:18][C:11]=2[Cl:10])[N:8]=1

Participants

6

Reactant 4

HCID 7757Methyl acetoacetateHCID 1450242-Chloro-4-fluorobenzaldehydeHCID 517045Sodium AcetateHCID 2781759Thiophene-2-carboximidamide Hydrochloride

Product 1

HCID 25001238Methyl 2-(thien-2-yl)-4-(2-chloro-4-fluorophenyl)-6-methyl-1,4-dihyropyrimidin-5-carboxylateYield 30%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

2.164 mmol of 2-thienylformamidine hydrochloride (Schaefer F. C., Peters G. A., et al, J. Org. Chem.; 1961, 26(2): 412-418), 2.164 mmol of 2-chloro-4-fluorobenzaldehyde, 2.164 mmol of methyl acetoacetate and 2.2 mmol of sodium acetate in 10 ml of anhydrous ethanol was reacted under reflux for 20 hours and concentrated. Ethyl acetate and water were added to the reaction, and the phases were separated. The ethyl acetate layer was dried over anhydrous sodium sulfate and separated by a column chromatography to give 0.22 g of a yellow crystal (yield: 30%); 1H-NMR (400 MHz, CDCl3) δ 2.55 (3H, s, CH3); 3.62 (3H, s, CH3); 6.00 (1H, s, CH); 6.89-6.94 (1H, m, ArH); 7.03-7.05 (1H, dd, J1=4.80 Hz, J2=3.60 Hz, ArH); 7.11-7.14 (1H, m, ArH); 7.26-7.30 (1H, m, ArH); 7.33-7.34 (1H, d, J2=3.60 Hz, ArH); 7.44-7.45 (1H, d, J1=4.80 Hz ArH); MS (HREI) 344.0448 (M+).

Workup

  1. temperatureunder reflux for 20 hours
  2. concentrationconcentrated
  3. additionEthyl acetate and water were added to the reaction
  4. customthe phases were separated
  5. dry with materialThe ethyl acetate layer was dried over anhydrous sodium sulfate
  6. customseparated by a column chromatography

Sources & evidence

ORD record
ord-5af85200ea7c4f7b9c883564a93cab19
Source dataset
uspto-grants-2012_01
Patent number
US08106196B2

Reaction notes

Loading…