Potassium Carbonate → HCID 67376918, compound

Temperature

130 °C

In a round bottom flask equipped with reflux condenser, a mixture of 1,1-dimethylethyl 3-[2-(2-{[(4-bromophenyl)amino]carbonyl}hydrazino)-2-oxoethyl]-1-azetidinecarboxylate (5.69 mmol) and potassium carbonate (28.5 mmol) in water (110 mL) was stirred at reflux (oil bath, 130° C.) for 16 h. The reaction mixture was cooled to room temperature and concentrated in vacuo partially and then lyophilized overnight to give a white solid. The solid was treated with dichloromethane (20 mL) followed by N,N-diisopropylethylamine (11.45 mmol) and the mixture was stirred at room temperature for 10 min. The reaction mixture was cooled to 0° C. and propionyl chloride (5.76 mmol) was added. The reaction was allowed to warm to room temperature and the reaction was stirred at room temperature for 2 h. The reaction was quenched with water (100 mL) and 1N HCl solution (10 mL), stirred for 10 min, and then acidified to pH˜5 using 1N aq HCl. The layers were separated and the aqueous layer was extracted with ethyl acetate (2×50 mL). The organic layers were combined, dried over magnesium sulphate, and concentrated in vacuo. Purification of the residue by silica gel chromatography (0-7% methanol/ethyl acetate) afforded 4-(4-bromophenyl)-2-propanoyl-5-[(1-propanoyl-3-azetidinyl)methyl]-2,4-dihydro-3H-1,2,4-triazol-3-one as a pale yellow solid (660 mg) and the title compound as an ivory solid (341 mg, 60% pure, 10% yield). MS(ES)+ m/e 365.0, 366.8 [M+H]+.

1. customIn a round bottom flask equipped
2. temperaturewith reflux condenser
3. temperatureThe reaction mixture was cooled to room temperature
4. concentrationconcentrated in vacuo partially
5. customto give a white solid
6. stirringthe mixture was stirred at room temperature for 10 min
7. temperatureThe reaction mixture was cooled to 0° C.
8. temperatureto warm to room temperature
9. stirringthe reaction was stirred at room temperature for 2 h
10. customThe reaction was quenched with water (100 mL) and 1N HCl solution (10 mL)
11. stirringstirred for 10 min
12. customThe layers were separated
13. extractionthe aqueous layer was extracted with ethyl acetate (2×50 mL)
14. dry with materialdried over magnesium sulphate
15. concentrationconcentrated in vacuo
16. customPurification of the residue by silica gel chromatography (0-7% methanol/ethyl acetate)

ORD record

ord-cf00ef7995e54fe3ad4d801902001177

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08802864B2