Sodium Bicarbonate → HCID 22055246, compound

Participants

Reaction Steps

A solution of 5-bromomethyl-4-chloro-pyrrolo[2,1-f][1,2,4]triazine (100 mg, 0.408 mmole), 4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (1.56 gm, 7.76 mmole) and NaHCO3 (131 mg, 1.56 mmol) in dry acetonitrile (5 mL) was stirred at RT for 3 days. 3-chloro-4-(3-fluoro-benzyloxy)-phenylamine 3A (92 mg, 0.367 mmole) and additional NaHCO3 (131 mg, 1.56 mmol) were added and the reaction was left stirring overnight. The solvent was removed and the residue was partitioned between DCM and water. The organic phase was separated, dried (Na2SO4), and the solvent removed. The residue was treated with a mixture of TFA:DCM (1:1) at 0° C. for 80 min and the solvents were removed. The residue was taken up in DCM, washed with a sat. aq. NaHCO3 solution and then dried (Na2SO4). Removal of the solvent followed by radial chromatography (2 mm silica gel plate eluted with DCM containing 5% of a 2 M solution of NH3 in MeOH) afforded the titled product as an oil (85 mg, 43%). Analytical HPLC retention time=1.60 min. (YMC Xterra S7 C18, 3.0×50 mm column, 10–90% aqueous methanol over 2 minutes containing 0.1% TFA, 5 mL/min, monitoring at 220 nm) and a LC/MS M++1=482.

Provenance & Evidence