Ethylmorpholine → N-{[2-fluoro-3-(trifluoromethyl)phenyl]methyl}-3-methyl-2-oxo-4-imidazolidinecarboxamide

A mixture of 3-methyl-2-oxo-4-imidazolidinecarboxylic acid (86 mg, 0.6 mmol) (prepared as described in Example 28 from 1,1-dimethylethyl 3-methyl-2-oxo-4-imidazolidinecarboxylate, itself prepared as described in step (iii) of Example 13, starting originally from (4S)-2-oxo-3-{[(phenylmethyl)oxy]carbonyl}-4-imidazolidinecarboxylic acid), N-ethyl morpholine (0.380 ml, 3.00 mmol), 1-hydroxybenzotriazole hydrate (110 mg, 0.720 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (138 mg, 0.720 mmol) in dichloromethane (9 ml) was stirred at room temperature for 10 minutes, under an argon atmosphere. {[2-Fluoro-3-(trifluoromethyl)phenyl]methyl}amine (0.1 ml, 0.684 mmol) was added and the reaction was stirred overnight under an argon atmosphere. The reaction mixture was diluted with dichloromethane (10 ml) and the solution was washed with saturated sodium hydrogen carbonate solution (10 ml), water (10 ml), citric acid solution (10 ml) and brine (10 ml). The citric acid layer was re-extracted with dichloromethane and the dichloromethane extracts were combined, dried and evaporated. The residue was purified by mass-directed automated HPLC. Fractions containing product were collected and the solvent was evaporated in vacuo to give N-{[2-fluoro-3-(trifluoromethyl)phenyl]methyl}-3-methyl-2-oxo-4-imidazolidinecarboxamide (16 mg, 8% yield) as a white solid. LC/MS [M+H]+=320, retention time=1.85 minutes.

1. customprepared
2. customprepared
3. stirringthe reaction was stirred overnight under an argon atmosphere
4. washthe solution was washed with saturated sodium hydrogen carbonate solution (10 ml), water (10 ml), citric acid solution (10 ml) and brine (10 ml)
5. extractionThe citric acid layer was re-extracted with dichloromethane
6. customdried
7. customevaporated
8. customThe residue was purified
9. additionFractions containing product
10. customwere collected
11. customthe solvent was evaporated in vacuo

ORD record

ord-b93ec2642cf64618bbe3c10313a46b46

Source dataset

uspto-grants-2011_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07932282B2