Water → 4-[[2-[5-[[Boc(2-methoxyethyl)amino]methyl]-2-pyridyl]-7-thieno[3,2-b]pyridyl]oxy]-3-fluoroaniline

Participants

Reaction Steps

To a solution of 4-amino-2-fluorophenol (4, scheme 1) (14.29 g, 112 mmol 1.2 eq.) in DMSO (117 mL) was added potassium tert-butoxide (13.66 g, 122 mmol, 1.3 eq.) over 5 min. The reaction mixture was stirred at r.t. for 30 minutes. tert-Butyl(6-(7-chlorothieno[3,2-b]pyridin-2-yl)pyridin-3-yl)methyl(2-methoxyethyl)carbamate (11) (40.65 g, 94 mmol, 1 eq) was added and the reaction mixture was heated at 100° C. for 1.5 h. Additional amounts of the phenol 4 (0.83 g, 6.53 mmol, 0.07 eq.) in DMSO (5 mL) and potassium tert-butoxide (1.05 g, 9.38 mmol, 0.1 eq.) were added to the reaction mixture which was heated at 100° C. for an additional 30 min. After cooling down to r.t., the reaction mixture was poured into water (900 mL) at 40° C. over 15 min. After stirring for 15 min at 40° C., the mixture was cooled to r.t. over 1 h. The solid was collected by filtration and the cake was washed with water (2×115 mL). The product was dried in vacuum for 16 h then triturated with MTBE (115 mL) for 1 h, collected by filtration and the cake was washed with MTBE (2×20 mL). The product was dried in a vacuum oven (45° C.) to afford title compound 13 as a beige solid (44.02 g, 84 mmol, 90% yield).

Provenance & Evidence