Trifluoroacetic acid → N-(2-Diethylamino-ethyl)-4-(3-indan-5-yl-3H-[1,2,3]triazolo[4,5-d]-pyrimidin-5-ylamino)-benzamide

Participants

Reaction Conditions

Reaction Steps

To a solution of 2,4-dichloro-5-nitropyrimidine (25.0 mg, 0.13 mmol) in THF (0.2 mL) was added a solution of 3-amino-N-methyl-benzamide (19.5 mg, 0.13 mmol) in isopropyl alcohol (0.5 mL)/dimethylformamide (0.3 mL), and CsHCO3 (25.2 mg, 0.13 mmol) in water (0.016 mL total volume). The mixture was stirred at rt for 1.5 hr at which time 4-amino-N-(2-diethylamino-ethyl)-benzamide HCl (procainamide: hydrochloride) (38.9 mg, 0.14 mmol) in isopropyl alcohol (0.5 mL)/dimethylformamide (0.3 mL) was added. The mixture was stirred at 50° C. for 20 hr. cooled to rt, and acetic acid (0.1 mL) was added. To the resulting slurry was added Zn dust (45 mg, 0.69 mmol); after stirring for 15 min at rt, the reaction solution was loaded onto a 1 g silica gel SPE cartridge and eluted with 6 mL of MeOH. The eluent was concentrated at reduced pressure, dried at approximately 1 mm Hg for 18 hr. and re-suspended in MeOH (1.0 mL). To this slurry was added HOAc (0.05 mL) and sodium nitrite (0.09 g, 1.3 mmol) in water (total volume 0.2 mL). The mixture was stirred at rt for 11 hr. loaded onto a 1 g C-18 SPE cartridge, and eluted with 6 mL of MeOH. The eluent was concentrated and the resulting residue was purified by reverse-phase liquid chromatography using a gradient of 90:10 (water:acetonitrile, with 0.1% TFA) to 10:90 (water:acetonitrile, with 0.1% TFA) to furnish (7) (0.0128 g, 0.018 mmol) as the bis TFA salt. HRMS (ES-TOF) calcd. for C25H30N9O2 m/z 488.2522 (M+H),+ found: 488.2514.

Provenance & Evidence