In a 25 mL round-bottomed flask, 6-chloro-2-methyl-4-(5-(piperidin-4-yl)pyridin-2-ylamino)pyridazin-3(2H)-one (620 mg, 1.94 mmol, Eq: 1.00) and formaldehyde (1.57 g, 1.44 ml, 19.4 mmol, Eq: 10) were combined with THF to give a light yellow solution. Acetic acid (116 mg, 111 μl, 1.94 mmol, Eq: 1.00) was added. The reaction mixture was cooled to 0° C. Sodium triacetoxyborohydride (616 mg, 2.91 mmol, Eq: 1.5) was added. The reaction mixture was stirred at room temperature 2 hr. LC/MS showed reaction was complete. The reaction mixture was poured into water. Saturated NaHCO3 was added to make it basic and the resultant mixture was extracted with EtOAc. The combined extracts were washed with water, dried over Na2SO4 and concentrated in vacuo. The resultant solid was triturated with ether to afford the desired product as an off-white solid (580 mg). (M+H)+=334 m/e. This was combined with previous batches to give 1.06 g 6-chloro-2-methyl-4-(1′-methyl-1′,2′,3′,4′,5′,6′-hexahydro-[3,4]bipyridinyl-6-ylamino)-2H-pyridazin-3-one, which was carried on as is into the next reaction.
