Acetic Acid → HCID 131729411, compound

Participants

Reaction Conditions

Reaction Steps

Combine 2-(4-chloro-phenyl)-6-[6-(piperidin-4-yloxy)-pyridin-3-yl]-6H-thieno[2,3-c]pyridin-7-one (500 mg, 1.14 mmol) with acetic acid (0.33 mL, 5.71 mmol) in methanol (40 mL). Cool to 0° C., add formaldehyde (0.25 mL, 3.42 mmol, 37% aqueous solution) and stir for 5 min. Then add sodium cyanoborohydride (179 mg, 2.85 mmol) and warm the reaction to RT with stirring overnight. Concentrate the solution in vacuo and dilute with dichloromethane, saturated aqueous NaHCO3, and water. Separate the organic layer and extract the aqueous layer with dichloromethane. Combine the organic extracts, dry over MgSO4, filter, and concentrate in vacuo. Chromatograph the residue (silica gel, eluting with 0-10% MeOH (2N NH3)/CH2Cl2 to yield the free base. Add 1 equivalent of ammonium chloride to a solution of the free base in 1:1 methanol/CH2Cl2 and sonicate the solution until complete dissolution of NH4Cl. Concentrate in vacuo to yield 523 mg (99%) of the title compound. MS/ES m/z (35Cl) 452.0 [M+H+].

Provenance & Evidence