Water → 2-((6-chloro-3-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl)-4-Fluorobenzonitrile

Alternatively, 33 was made as follows. To a solution of 6-chloro-3-methyluracil (750 g) and N,N-diisopropylethylamine (998 mL) in NMP (3 L) was added (at <30° C. over 25 min) a solution of 32 (2963 g crude material containing 1300 g of 32 in 3 L of toluene). The mixture was then heated at 60° C. for 2 hours or until completion (as determined, for example, by HPLC). Heating was then stopped and the mixture was allowed to cool overnight. Purified water (3.8 L) was added, and the resultant slurry was stirred at ambient temperature for 1 hour and at <5° C. for one hour. The mixture was then filtered under vacuum and the wet cake was washed with IPA (2×2.25 L). The material was then dried in a vacuum oven at 40±5° C. for 16 or more hours to afford 33 as a tan solid (>85% yield; purity was >99% (AUC)).

1. customwas then heated at 60° C. for 2 hours or until completion (as determined, for example, by HPLC)
2. temperatureHeating
3. temperatureto cool overnight
4. filtrationThe mixture was then filtered under vacuum
5. washthe wet cake was washed with IPA (2×2.25 L)
6. customThe material was then dried in a vacuum oven at 40±5° C. for 16 or more hours

ORDレコード

ord-3356ef5bf01145aab104f6ad2efff00f

出典データセット

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08222411B2