3-Chloro-6-phenyl-1,2,4-triazine synthesis

Yield:73214-24-1 81.1%

Reaction Conditions:

Stage #1: 6-phenyl-1,2,4-triazin-3(2H)-onewith trichlorophosphate;N,N-dimethyl-formamide in chloroform;Heating / reflux;
Stage #2: with sodium hydroxide in dichloromethane;water at 0;

Steps:

24.3

A mixture of 6-phenyl-1,2,4-triazin-3(2H)-one (2.45 g, 0.0141 mol) and DMF (0.5 mL) in phosphoryl chloride (20.0 mL, 0.214 mol) and chloroform (20.0 mL) was heated under reflux overnight. After cooling, the volatiles were removed under reduced pressure. The residue was dissolved in DCM (60 mL) and was poured into ice with stirring. The mixture was neutralized with NaOH (1N), and filtered through a pad of celite to remove a small amount of insoluble residue. The organic layer was separated. The aqueous layer was extracted with DCM (3*20 mL). The combined organic layers were dried over Na₂SO₄, filtered, and concentrated. The residue was flash chromatographed on a silica gel column to give the desired product (2.20 g, 81.1%). Analytical LCMS: (M+H)⁺=192.1/194.1.

References:

US2008/39457,2008,A1 Location in patent:Page/Page column 26-27