5-HYDRAZINO-2-METHOXYPYRIDINE synthesis

Yield:160664-95-9 95%

Reaction Conditions:

Stage #1: 6-methoxy-pyridin-3-ylaminewith hydrogenchloride;sodium nitrite in water at 0; for 0.5 h;
Stage #2: with hydrogenchloride;tin(II) chloride dihdyrate in water at 0; for 2.5 h;

Steps:

Synthesis of compound 9, Supp. Fig. 1B).

An aqueous solution of sodium nitrite (8.34 g, 120 mmol, 1.0 eq.) was added dropwise to a solution of 5-amino-2-methoxypyridine (Compound 1, Supp. Fig 1B, 15.0 g, 120 mmol, 1.0 eq.) in an aqueous solution of 6 M HCl (150 mL) at 0 °C. After 30 min, a solution of SnCl2.2H2O (275.29 g, 1,220 mmol, 10.12 eq.) in aqueous HCl 6 M (150 mL) was added to the above reaction mixture at 0 °C. This mixture was stirred for 2.5 h at 0 °C and then quenched with a saturated aqueous solution of KOH (40% w., until a basic pH was reached) and extracted with ethyl acetate (50 mL × 4). The organic extracts were combined, dried over anhydrous Na2SO4, and concentrated under reduced pressure, yielding the desired compound 9 (16.0 g, 95%) as a red solid. With the stability of this product being quite low, the synthesis was further processed at once. As in the previous step, the final compound was used as such in the next step without further characterization.

References:

Boutin, Jean A.;Bouillaud, Frederic;Janda, Elzbieta;Gacsalyi, István;Guillaumet, Gérald;Hirsch, Etienne C.;Kane, Daniel A.;Nepveu, Fran?oise;Reybier, Karine;Dupuis, Philippe;Bertrand, Marc;Chhour, Monivan;Le Diguarher, Thierry;Antoine, Mathias;Brebner, Karen;Da Costa, Hervé;Ducrot, Pierre;Giganti, Adeline;Goswami, Vishalgiri;Guedouari, Hala;Michel, Patrick P.;Patel, Aakash;Paysant, Jér?me;Stojko, Johann;Viaud-Massuard, Marie-Claude;Ferry, Gilles [Molecular Pharmacology,2019,vol. 95,# 3,p. 269 - 285] Location in patent:supporting information