Sulfur Dioxide → 5-Cyano-2-{(4S)-5-cyano-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidin-4-yl}benzenesulfonyl chloride

Temperature

0 °C

Under argon, (4R)-4-(2-amino-4-cyanophenyl)-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carbonitrile (2.1 g, 5.1 mmol) was initially charged in a 2:1:1 mixture of acetic acid/conc. hydrochloric acid/water (50 ml in total) at −10° C. A solution of sodium nitrate (371 mg, 5.38 mmol) in water (2 ml) was then slowly added dropwise, and the mixture was stirred at from −10° C. to −5° C. for 40 min. This solution was then added to 45 ml of a sulfur dioxide-saturated suspension, cooled to −10° C., of copper(I) chloride (101.4 mg, 1.0 mmol) in glacial acetic acid (44 ml). The mixture was stirred at 0° C. for about 30 min and then at +15° C. for 1 h (reaction monitored by HPLC and LC-MS). The reaction mixture was then cooled to 0° C. and subsequently added to about 300 ml of ice-cold water using a pipette. The precipitate was filtered off and taken up in ethyl acetate (150 ml). The solution was washed twice with saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated under reduced pressure. The title compound was obtained as a solid (2.13 g, 77% of theory, purity 92%) which was used without further purification in the subsequent reaction.

1. customat −10° C
2. stirringThe mixture was stirred at 0° C. for about 30 min
3. customat +15° C. for 1 h (reaction monitored by HPLC and LC-MS)
4. filtrationThe precipitate was filtered off
5. washThe solution was washed twice with saturated sodium chloride solution
6. dry with materialdried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure

ORD record

ord-11e88af698f24055a1757b6bf76c87f6

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08288402B2