Dichloromethane → (1-{4-[8-Chloro-2-(2,2-dimethoxy-ethoxy)-quinolin-4-yloxy]-2-[2-ethyl-1-(1-methyl-cyclopropoxysulfonylaminocarbonyl)-cyclopropylcarbamoyl]-pyrrolidine-1-carbonyl}-2,2-dimethyl-propyl)-carbamic acid 2,2,2-trifluoro-1,1-dimethyl-ethyl ester

Participants

Reaction Steps

(1-{4-[8-chloro-2-(2,2-dimethoxy-ethoxy)-quinolin-4-yloxy]-2-[2-ethyl-1-(1-methyl-cyclopropoxysulfonylaminocarbonyl)-cyclopropylcarbamoyl]-pyrrolidine-1-carbonyl}-2,2-dimethyl-propyl)-carbamic acid tert-butyl ester (444 mg, 0.520 mmol) was dissolved in CH2Cl2 (2.6 mL) and MeOH (0.21 mL, 5.20 mmol), and treated with TFA (2.6 mL). After stirring for 25 min at room temperature, MeOH (7 mL) was added and the solvents were removed in vacuo. The crude mixture was partitioned with saturated NaHCO3 and DCM. The layers were separated and the organic layer was dried over Na2SO4 and concentrated. The resultant residue was dissolved in DCM (5.2 mL) to which carbonic acid 4-nitro-phenyl ester 2,2,2-trifluoro-1,1-dimethyl-ethyl ester (183 mg, 0.624 mmol) and diisopropylethylamine (362 μL, 2.08 mmol) were added sequentially. After stirring for 24 h at 35° C., the reaction was purified by column chromatography on silica (3-7% MeOH/DCM) to provide (1-{4-[8-chloro-2-(2,2-dimethoxy-ethoxy)-quinolin-4-yloxy]-2-[2-ethyl-1-(1-methyl-cyclopropoxysulfonylaminocarbonyl)-cyclopropylcarbamoyl]-pyrrolidine-1-carbonyl}-2,2-dimethyl-propyl)-carbamic acid 2,2,2-trifluoro-1,1-dimethyl-ethyl ester (222 mg, 47% yield). LCMS found 908.0 [M+H]+.

Provenance & Evidence