Diisopropylethylamine → 3-(2-Chloropyrimidin-5-yl)-5,5-dimethyl-imidazolidine-2,4-dione

Temperature

0 °C

To a solution of triphosgene (1.38 g, 4.65 mmol) in ethyl acetate (20 ml) at 0° C. a solution of 2-chloro-5-aminopyrimidine (1 g, 7.75 mmol)/DIPEA (8 ml, 4.65 mmol) in ethyl acetate (40 ml) was slowly added (20 minutes) and the reaction mixture was stirred for 15 minutes at the same temperature. Maintaining the reaction mixture at 0° C., vacuum was applied (10 minutes) for removing the excess of phosgene. A solution of DMAP (0.945 g, 7.75 mmol) in ethyl acetate/dichloromethane 1:1 (8 ml) was added and the reaction mixture was stirred for 5 minutes at the same temperature. 2,2-Dimethylglycine methyl ester hydrochloride (2.37 g, 15.5 mmol) in ethyl acetate (30 ml) was slowly added (15 minutes) at 0° C. and the reaction mixture was stirred for 30 minutes at the same temperature. The reaction was quenched with aqueous buffer (pH3) while the pH was allowed to reach ˜5-6 and two phases were separated. The organic layer was washed with aqueous buffer (pH3) (2×20 ml) and then brine (20 ml), dried (Na2SO4), filtered and evaporated affording the urea intermediate as orange foam.

1. custom(10 minutes)
2. customfor removing the excess of phosgene
3. stirringthe reaction mixture was stirred for 5 minutes at the same temperature
4. stirringthe reaction mixture was stirred for 30 minutes at the same temperature
5. customThe reaction was quenched with aqueous buffer (pH3) while the pH
6. customwere separated
7. washThe organic layer was washed with aqueous buffer (pH3) (2×20 ml)
8. dry with materialbrine (20 ml), dried (Na2SO4)
9. filtrationfiltered
10. customevaporated

ORD record

ord-3bdf2b9e344f4f2ab4a0167c82d130dc

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09193704B2