Hydrochloric Acid → HCID 131732650, compound

Participants

Reaction Steps

tert-Butyl (1-(5-((2S,4R)-1-acetyl-4-((5-cyanopyridin-2-yl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)picolinoyl)piperidin-4-yl)carbamate (for a preparation see Intermediate 43) (0.258 ml, 0.313 mmol) was dissolved in anhydrous DCM (4 ml). TFA (1 ml, 12.98 mmol) was added and the reaction mixture which was stirred under nitrogen at r.t. for 8 h. The reaction mixture was concentrated in vacuo and loaded onto a SCX cartridge (5 g, pre-conditioned with MeOH). The cartridge was washed with MeOH (40 ml) and eluted with ammonia in MeOH (2M). The methanolic ammonia fractions were concentrated to give an orange oil. The oil was further purified by chromatography on a silica cartridge (10 g), eluting with a MeOH/DCM gradient (2-12%, over 120 mls) followed by 10% of 2M NH3 in MeOH/DCM for 120 mls to give a pale orange solid. The solid was re-dissolved in MeOH (1 ml) and 1.1 equivalents of 1M hydrogen chloride in diethyl ether were added. The mixture was triturated with diethyl ether to give 6-(((2S,4R)-1-acetyl-6-(6-(4-aminopiperidine-1-carbonyl)pyridin-3-yl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)amino)nicotinonitrile, hydrochloride (19 mg, 0.030 mmol, 8.59% yield) as an orange solid. LCMS (Formate, 2 min), Rt=0.60 min, MH+=510.

Provenance & Evidence