Triethylamine → HCID 11605291, compound

Participants

Reaction Steps

(2S,4R)-4-({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}oxy)-1-methylpiperidine-2-carboxylic acid (15) (145 mg, 0.32 mmol) was dissolved in DMF (10 ml) under nitrogen. Triethylamine (0.13 ml, 0.95 mmol) was added, followed by DIPEA (0.055 ml, 0.32 mmol) and methylamine hydrochloride (0.043 g, 0.63 mmol). The mixture was cooled in an ice/water bath and HATU (180 mg, 0.47 mmol) was then added portionwise such that the temperature remained <10° C. The reaction mixture was stirred at room temperature overnight and evaporated to dryness. The residues were dissolved in EtOAc, washed with water (10 ml), brine (10 ml), dried over MgSO4, filtered and evaporated. The crudes were purified by column chromatography eluting with increasingly polar mixtures of methylene chloride/methanol (100/0-90/10). Fractions containing the desired product were combined and evaporated. The resulting solids were dissolved in methanol, loaded onto an SCX column and eluted with MeOH (20 ml) followed by 7N NH3 in MeOH. Appropriate fractions were combined and evaporated to give the title product as a white solid (69 mg, 40%): 1H NMR Spectrum: (DMSO-d6) δ1.63-1.69 (2H, m), 2.15-2.21 (6H, m), 2.55-2.62 (4H, m), 2.93-2.98 (1H, m), 3.94 (3H, s), 4.43-4.51 (1H, m), 7.23 (1H, s), 7.28-7.33 (1H, m), 7.49-7.56 (2H, m), 7.68-7.72 (1H, m), 7.86 (1H, s), 8.39 (1H, s), 9.57 (1H, s); Mass Spectrum: (M+H)+ 474.

Provenance & Evidence