Trifluoroacetic acid → HCID 73442528, 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-(3,5-difluorophenyl)urea (0.112 g, 0.185 mmol) and anisole (0.202 mL, 1.849 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-(3,5-difluorophenyl)-3-(5-(1-ethyl-7-(methylamino)-2-oxo-1,2,4a,8a-tetrahydro-1,6-naphthyridin-3-yl)-2,4-difluorophenyl)urea (57 mg, 64% yield). The material was dissolved in MeCN (2 mL), treated with 0.1N HCl (1.17 mL, 0.117 mmol), diluted with water (3 mL), frozen, lyophilized, triturated with Et2O and the resulting solid was collected via filtration and dried to yield 1-(3,5-difluorophenyl)-3-(5-(1-ethyl-7-(methylamino)-2-oxo-1,2,4a,8a-tetrahydro-1,6-naphthyridin-3-yl)-2,4-difluorophenyl)urea hydrochloride (57 mg, 96% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.95 (s, 1H), 8.80 (s, 1H), 8.51 (s, 1H), 8.07 (t, 1H), 7.92 (s, 1H), 7.70 (br s, 1H), 7.40 (t, 1H), 7.15 (d, 2H), 6.82-6.77 (m, 1H), 6.43 (s, 1H), 4.15 (q, 2H), 2.91 (s, 3H), 1.21 (t, 3H); MS (ESI) m/z: 486.2 [M+H]+.

Provenance & Evidence