Hydrochloric Acid → Methyl 4-(2-oxo-5,6-diphenyl-1,2,3,4-tetrahydropyrimidin-4-yl)-2-(trifluoromethyl)benzoate

HRID 401115Notes

Reaction equation

HRID 401115 reaction equation
[CH:1]([C:3]1[CH:12]=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[C:5]([C:13]([F:16])([F:15])[F:14])[CH:4]=1)=O.[C:17]1([C:23](=O)[CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[NH2:32][C:33]([NH2:35])=[O:34].Cl>C(O)C>[O:34]=[C:33]1[NH:35][CH:1]([C:3]2[CH:12]=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[C:5]([C:13]([F:16])([F:15])[F:14])[CH:4]=2)[C:24]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[C:23]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[NH:32]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 1176UreaHCID 99482-PhenylacetophenoneHCID 57443312Methyl 4-formyl-2-(trifluoromethyl)benzoate2×

Product 1

HCID 67061100Methyl 4-(2-oxo-5,6-diphenyl-1,2,3,4-tetrahydropyrimidin-4-yl)-2-(trifluoromethyl)benzoate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of methyl 4-formyl-2-(trifluoromethyl)benzoate (Intermediate 82) (180 mg, 0.80 mmol), 1,2-diphenyl-ethanone (222 mg, 0.80 mmol) and urea (145 mg, 2.4 mmol) in ethanol (3 mL) was added conc. HCl (0.2 mL), then the resulting mixture was refluxed for 2 days. The mixture was concentrated in vacuo to give methyl 4-(2-oxo-5,6-diphenyl-1,2,3,4-tetrahydropyrimidin-4-yl)-2-(trifluoromethyl)benzoate, which was used crude. This was taken up in MeOH (3 mL) and 2 N aq. NaOH (3 mL) was added; then the resulting mixture was stirred at 40° C. for 3 hours. The mixture was acidified with aqueous HCl till pH=5 and then followed a standard aqueous/EtOAc workup. Purified by prep-HPLC (0.1% TFA as additive) to give Compound 157 (34 mg, two steps yield 10%) as white solid. 1H NMR (MeOD 400 MHz) δ 7.82 (d, J=8.0 Hz, 1H), 7.72-7.67 (m, 2H), 7.36-7.20 (m, 5H), 7.10-7.05 (m, 3H), 6.88-6.85 (m, 2H), 5.30 (s, 1H). MS (ESI): m/z 439.2 [M+1]+.

Workup

  1. temperaturethe resulting mixture was refluxed for 2 days
  2. concentrationThe mixture was concentrated in vacuo

Sources & evidence

ORD record
ord-3b78c7120e19446eaba65a984a43f6ec
Source dataset
uspto-grants-2014_06
Patent number
US08741915B2

Reaction notes

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