Trifluoroacetic acid → 2-[1-(1-Cyclopropylmethyl-cyclopropanesulfonylaminocarbonyl)-2-vinyl-cyclopropylcarbamoyl]-4-(7-methoxy-2-pyridin-2-yl-quinolin-4-yloxy)-pyrrolidine-1-carboxylic Acid Tert-Butyl Ester

Participants

Reaction Steps

Step 78e) To a mixture of the acid (0.33 g, 0.71 mmol) of the product of Step 78d (Example 78), diisopropylethylamine (0.5 mL, 3.6 mmol), TFA salt (0.205 g, 0.51 mmol) of 1-Cyclopropylmethyl-cyclopropanesulfonic acid (1-amino-2-vinyl-cyclopropanecarbonyl)-amide, and HOBt (0.1 g, 0.6 mmol) in CH2Cl2 (8 mL) was added HATU (0.35 g, 0.92 mmol). The reaction mixture was stirred at rt overnite and diluted with EtOAc, washed with pH 4.0 buffer, dried (MgSO4), removed the solvent in vacuo. The residue was purified by PTLC to provide the product in 59% (0.22 g) yield: 1H NMR (methanol-d4) □ ppm 0.64 (m, 1H), 0.96 (m, 2H), 1.33 (m, 8H), 1.39 (m, 9H), 1.90 (m, 2H), 2.18 (m, 1H), 2.54 (m, 1H), 2.81 (m, 1H), 4.01 (m, 5H), 4.44 (d, J=28.99 Hz, 1H), 5.08 (m, 1H), 5.31 (m, 1H), 5.57 (s, 1H), 6.03 (m, 1H), 6.94 (s, t H), 7.27 (d, J=8.24 Hz, 1H), 7.64 (m, 1H), 7.92 (m, 1H), 8.14 (m, 2H), 8.66 (s, 1H), 8.74 (s, 1H).

Provenance & Evidence