Benzamidine, hydrochloride → 2-(4-Methyl-6-oxo-2-phenyl-1,6-dihydropyrimidin-5-yl)pentanoic acid

HRID 1399564Notes

Reaction equation

HRID 1399564 reaction equation
Cl.[C:2]([NH2:10])(=[NH:9])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C[O-].[Na+].[C:14]([CH:17]([CH:22]([CH2:27][CH2:28][CH3:29])[C:23]([O:25]C)=[O:24])[C:18](OC)=[O:19])(=O)[CH3:15]>CO>[CH3:15][C:14]1[N:9]=[C:2]([C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=2)[NH:10][C:18](=[O:19])[C:17]=1[CH:22]([CH2:27][CH2:28][CH3:29])[C:23]([OH:25])=[O:24]

Participants

5

Reactant 3

HCID 80289Benzamidine, hydrochlorideHCID 10942334Sodium MethoxideHCID 86665649Dimethyl 2-acetyl-3-propylsuccinate

Product 1

HCID 1363461702-(4-Methyl-6-oxo-2-phenyl-1,6-dihydropyrimidin-5-yl)pentanoic acidYield 119.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of benzamidine hydrochloride (9.2 g; 50 mmol) in methanol (46 mL) was slowly added a solution of sodium methoxide (25%) (23 mL; 100 mmol) and dimethyl 2-acetyl-3-propylsuccinate (60%) (19.2 g; 50 mmol). The reaction mixture was heated at reflux for 18 h, and after cooling, the white precipitate was filtered and washed with a small volume of methanol. The solid was dried and carefully added to a cold hydrochloric 12N solution (25 mL). The suspension was stirred for one minute at 0° C., filtered and washed with a small amount of methanol. The precipitate was dried under reduced pressure over phosphorus pentoxide to provide 17.16 g of the expected 2-(4-methyl-6-oxo-2-phenyl-1,6-dihydropyrimidin-5-yl)pentanoic acid as a white powder which was used without further purification. ESI/APCI(+): 287 (M+H); ESI/APCI(−): 285 (M−H). 1H NMR (DMSO-d6) δ 8.08 (2H, d, Harom.); 7.70 (1H, m, Harom.); 7.60 (2H, m, Harom.); 3.76 (1H, m, CHα); 2.48 (3H, s, CH3); 1.98 (1H, m, CHβ); 1.72 (1H, m, CHβ′); 1.14 (2H, m, CH2γ); 0.87 (3H, t, CH3δ).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 18 h
  3. temperatureafter cooling
  4. filtrationthe white precipitate was filtered
  5. washwashed with a small volume of methanol
  6. customThe solid was dried
  7. additioncarefully added to a cold hydrochloric 12N solution (25 mL)
  8. filtrationfiltered
  9. washwashed with a small amount of methanol
  10. dry with materialThe precipitate was dried under reduced pressure over phosphorus pentoxide

Sources & evidence

ORD record
ord-31c166f7835d4681928dbbbbd865909a
Source dataset
uspto-grants-2014_12
Patent number
US08906906B2

Reaction notes

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