Trifluoroacetic acid → HCID 73442527, compound

Participants

Reaction Steps

A solution of 1-(5-(7-((4-methoxybenzyl)(methyl)amino)-1-ethyl-2-oxo-1,2,4a,8a-tetrahydro-1,6-naphthyridin-3-yl)-2,4-difluorophenyl)-3-(2,5-difluorophenyl)urea (0.129 g, 0.213 mmol) and anisole (0.233 mL, 2.130 mmol) in DCM (2 mL) was treated with TFA (2 mL, 26.0 mmol) and stirred at RT overnight. The mixture was concentrated to dryness, treated with EtOAc and satd. NaHCO3, stirred for 1 h and the resulting solid collected via filtration and dried to afford 1-(2,5-difluorophenyl)-3-(5-(1-ethyl-7-(methylamino)-2-oxo-1,2,4a,8a-tetrahydro-1,6-naphthyridin-3-yl)-2,4-difluorophenyl)urea (84 mg, 81% yield). The material was suspended in MeCN (2 mL), treated with 0.5 N HCl (2.076 mL, 0.208 mmol), diluted with water (2 mL), frozen, lyophilized, triturated with Et2O and the resulting solid was collected via filtration and dried to yield 1-(2,5-difluorophenyl)-3-(5-(1-ethyl-7-(methylamino)-2-oxo-1,2,4a,8a-tetrahydro-1,6-naphthyridin-3-yl)-2,4-difluorophenyl)urea hydrochloride (85 mg, 94% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.24 (s, 1H), 9.18 (s, 1H), 8.53 (s, 1H), 8.18 (t, 1H), 8.02-7.97 (m, 1H), 7.94 (s, 1H), 7.90 (br s, 1H), 7.42 (t, 1H), 7.32-7.26 (m, 1H), 6.84-6.80 (m, 1H), 6.48 (s, 1H), 4.19 (q, 2H), 2.94 (s, 3H), 1.21 (t, 3H); MS (ESI) m/z: 486.2 [M+H]+.

Provenance & Evidence