Trifluoroacetic acid → Hydrochloric Acid

Participants

Reaction Steps

To a solution of (R)-3-(3-aminopiperidin-1-yl)-5-(4-(morpholine-4-carbonyl)phenylamino)-1,2,4-triazine-6-carboxamide HCl salt (6) (90 mg, 0.19 mmol) in NMP (3 mL) was added DIEA (0.27 mL, 1.52 mmol) and then 3-bromopropanoyl chloride (108 mg, 0.58 mmol). The mixture was stirred at RT for 1 h and then at 60° C. for 1 h. The mixture was cooled to RT, diluted with EtOAc, washed with water and concentrated in vacuo to afford crude (R)-3-(3-(4-chlorobutanamido)piperidin-1-yl)-5-(4-(morpholine-4-carbonyl)phenylamino)-1,2,4-triazine-6-carboxamide. To a solution of (R)-3-(3-(4-chlorobutanamido)piperidin-1-yl)-5-(4-(morpholine-4-carbonyl)phenylamino)-1,2,4-triazine-6-carboxamide in DMF (3 mL) was added NaH (60% in mineral oil, 30 mg, 0.75 mmol). The mixture was stirred at RT for 1 h. The mixture was diluted with water, acidified with TFA, and subjected to reverse phase preparative HPLC to isolate the title compound (52) as HCl salt (31 mg). MS found for C24H30N8O4 as (M+H)+ 495.1, (M−H)− 493.2. UV: λ=275 nm.

Provenance & Evidence