Trifluoroacetic acid → HCID 59730223, compound

Participants

Reaction Steps

Add drop wise via an addition funnel a solution of trifluoroacetic acid (5.7 mL) in dichloromethane (25 mL) to a stirred solution of 5-(5-carbamoyl-pyridin-2-yloxy)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester (2.1 g, 5.7 mmol) in dichloromethane (75 mL) at 0° C. Warm to room temperature and stir for 18 hours. Evaporate on a rotary evaporator, dissolve the residue in methanol (50 mL) and dichloromethane (50 mL), and then add MP-carbonate resin (7.9 g @2.87 eq/g). Agitate for 2 hours, filter, concentrate on a rotary evaporator, and dry under vacuum to yield 6-(1,2,3,4-tetrahydro-isoquinolin-5-yloxy)-nicotinamide (1.5 g, 5.6 mmol): HPLC=85% (50/50 to 90/10 ACN/(0.1% TFA in water), Zorbax SB-Phenyl 4.6 mm×15 cm×5 micron, λ=254 nm). 1H NMR (DMSO-d6, 300.00 MHz): 8.55 (d, 1H), 8.23 (dd, 1H), 8.01 (s, 1H), 7.46 (s, 1H), 6.95 (m, 5H), 3.90 (s, 2H), 2.85 (m, 2H), 2.38 (m, 2H).

Provenance & Evidence