Fluorine → 1-(2-Chloro-5-fluoropyrimidin-4-yl)ethanone

Participants

Reaction Steps

Halopyridine 9, wherein L is halogen (9A) may be obtained, for example, from 2-bromo-1-(2-chloro-pyridin-4-yl)-ethanone prepared by halogenation of 1-(2-chloropyridin-4-yl)ethanone, obtainable from 2-chloro-4-cyano pyridine, as described in J. Het. Chem., 1983, 20, 533. 1-[2-(Methylthio)pyrimidin-4-yl] derivative 9, wherein L is CH3—S— (9B), obtainable from 2-bromo-1-(2-methylsulfanyl-pyrimidin-4-yl)-ethanone (described in WO03/011838), may be activated to the corresponding sulfoxide or sulfone 9, wherein L is CH3—S(O)— or CH3—S(O)2— (9D), by oxidation, for example with oxone. Halopyrimidine derivative 9, wherein L is halogen and R5 is fluorine (9C), may be instead prepared from 2-bromo-1-(2-chloro-5-fluoropyrimidin-4-yl)ethanone, obtained by halogenation of 1-(2-chloro-5-fluoropyrimidin-4-yl)ethanone, in turn prepared as described in WO04/058762.

Provenance & Evidence