Yield:-

Reaction Conditions:

Stage #1: [1,2,4]triazolo[4,3-b]pyridazin-3-olwith phosphorus trichloride for 3.5 h;Reflux;
Stage #2: with sodium hydroxide in water;

Steps:

10.b

b) The 3-chloro-1,2,4-triazolo[4,3-b]pyridazine can be prepared in the following way:A mixture of 436 mg of [1,2,4]triazolo[4,3-b]pyridazin-3-ol in 6 cm³ of phosphoric trichloride is stirred at reflux for 3 h 30. The reaction mixture is run into a 4N aqueous solution of sodium hydroxide and the mixture obtained is extracted with a 90/10 mixture of ethyl acetate/methanol. The aqueous phase, which is still acidic (pH 1), is brought to pH 11 by adding concentrated sodium hydroxide, and then extracted again with a 90/10 mixture of ethyl acetate/methanol. The organic phases are combined and then dried over magnesium sulphate, filtered, then evaporated under vacuum. 808 mg of a whitish gum are thus obtained. 640 mg of this gum are taken up in ethyl acetate and the resulting solution is washed with water. The organic phase is dried over magnesium sulphate, filtered and then evaporated under vacuum, to give 281 mg of 3-chloro-1,2,4-triazolo[4,3-b]pyridazine, in the form of a white powder, the characteristics of which are as follows:MASS SPECTRUM: UPLC-MS-DAD-ELSD: 155(+)/=(M+H)(+)/(1 Cl present).

References:

US2010/298315,2010,A1 Location in patent:Page/Page column 26