Water → HCID 86723861, compound

Temperature

60 °C

To a solution of the compound prepared in Reference Example 253 (1.0 g) in acetonitrile (20 ml) was added phosphorus oxychloride (1.3 ml) and the resulting mixture was stirred at 60° C. for three hours (note: it was confirmed a formation of the above-mentioned intermediate, (R)-2-(4-methyl-2,6-dioxo-3-(3-(trifluoromethyl)phenyl)-2,3-dihydropyrimidin-1(6H)-yl)propane-1-sulfonylchloride; UPLC/MS 41.3 (M+H)/0.980 min). The reaction solution was cooled to 0° C. and thereto was added ammonia water (5.0 ml) dropwise and the resulting mixture was stirred for one hour. To the reaction mixture was added water (30 ml) and thereto was added ethyl acetate (20 ml×3) such that the intended products were extracted into an organic layer. The organic layer was washed with water (10 ml) and saturated saline (10 ml), dried on anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate) to afford the above-mentioned (R)-2-(4-methyl-2,6-dioxo-3-(3-trifluoromethylphenyl)-2,3-dihydropyrimidin-1(6H)-yl)propane-1-sulfonamide (560 mg). UPLC/MS 392 (M+H)/0.753 min. (measurement condition 9)

1. custom0.980 min
2. temperatureThe reaction solution was cooled to 0° C.
3. stirringthe resulting mixture was stirred for one hour
4. extractionwere extracted into an organic layer
5. washThe organic layer was washed with water (10 ml) and saturated saline (10 ml)
6. dry with materialdried on anhydrous sodium sulfate
7. concentrationconcentrated under reduced pressure
8. customThe residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate)

ORD record

ord-29831a69417645ec87986fc234288457

Source dataset

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09040516B2