HCID 70945388, compound → VBY-825

To a stirred suspension of (3S)—N-cyclopropyl-3-((R)-3-((cyclopropylmethyl)sulfonyl)-2-(((S)-2,2,2-trifluoro-1-(4-fluorophenyl)ethyl)amino)propanamido)-2-hydroxypentanamide [63.2 g; 118 mmol] in a mixture of acetonitrile (1150 mL) and dichloromethane (1150 mL) previously cooled in a cold water bath, was added DMP (69.86 g; 164.7 mmol; 140 mol %) in portions. The resulting reaction mixture was stirred for 4 h at ambient temperature. The reaction mixture was concentrated in vacuo to distill about 1 L of solvent and the remaining solution was added to a mixture of 1M aqueous sodium thiosulfate (800 mL) and saturated aqueous sodium bicarbonate (800 mL). Ethyl acetate (1.6 L) was added and the biphasic mixture stirred for 1.5 h. The layers were separated and the organic phase was washed with water, a mixture of water and a solution of sodium chloride in water and finally a solution of sodium chloride in water. The organic phase was dried (MgSO4) and concentrated to a wet solid which was suspended in hexane. The resulting slurry was stirred overnight, filtered and the solid was washed with hexane. Drying provided 53.6 g (85%) of the title compound. Recrystallization of this material alone with 4 g of crude (S)—N-cyclopropyl-3-((R)-3-((cyclopropylmethyl)sulfonyl)-2-(((S)-2,2,2-trifluoro-1-(4-fluorophenyl)ethyl)amino)propanamido)-2-oxopentanamide from another lot (57.6 g total) using hot IPA (1700 mL) gave 52 g of a white solid after washing with cold IPA and hexane, followed by drying over P2O5 in a vacuum oven at 40° C. LC-MS, positive ion mode: m/z=536 [M+H]+ (100%); 19F-NMR (CDCl3) δ, ppm: −74.54 (s); −110.09 (s).

1. temperaturepreviously cooled in a cold water bath
2. additionwas added DMP (69.86 g; 164.7 mmol; 140 mol %) in portions
3. customThe resulting reaction mixture
4. concentrationThe reaction mixture was concentrated in vacuo
5. distillationto distill about 1 L of solvent
6. additionthe remaining solution was added to a mixture of 1M aqueous sodium thiosulfate (800 mL) and saturated aqueous sodium bicarbonate (800 mL)
7. additionEthyl acetate (1.6 L) was added
8. stirringthe biphasic mixture stirred for 1.5 h
9. customThe layers were separated
10. washthe organic phase was washed with water
11. additiona mixture of water
12. dry with materialThe organic phase was dried (MgSO4)
13. concentrationconcentrated to a wet solid which
14. stirringThe resulting slurry was stirred overnight
15. filtrationfiltered
16. washthe solid was washed with hexane
17. customDrying

ORD record

ord-9bbdf5206e8344a882e5b03c8d60cc9b

Source dataset

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08680152B2