Hydrochloric Acid → 4-Chloro-2,3-dihydro-indole-1-carboxylic Acid [4-(2-amino-ethoxy)-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-amide

関与物質

反応手順

A 1 mL aliquot of tert-butyl {2-[4-({[(2,5-dioxopyrrolidin-1-yl)oxy]carbonyl}amino)-2-(1-methyl-1H-pyrazol-5-yl)phenoxy]ethyl}carbamate in dimethylformamide (78.8 μmol) was added to 4-chloroindoline (14.52 mg, 1.2 eq) and stirred at room temperature for 18 hr. To this was added 2.0M hydrochloric acid in ether (197 μL, 5 eq) and the reaction was stirred at room temperature for 24 hr (2-3 drops of concentrated hydrochloric acid was added if the deprotection was incomplete and the resulting mixture was stirred for another 24 hr). The ether and hydrochloric acid were evaporated under a stream of nitrogen and the resulting material was purified by HPLC. The proper fractions were collected and lyophilized to afford the title compound as a white solid in 43.5% yield. LCMS m/z (%)=412 (M+H 35Cl, 100), 414 (M+H 37Cl, 36). 1H NMR (400 MHz, DMSO-d6) δ ppm 3.10-3.24 (m, 4H), 3.71 (s, 3H), 4.13-4.21 (m, 4H), 6.34 (d, J=2.02 Hz, 1H), 6.96 (d, J=8.08 Hz, 1H), 7.13-7.21 (m, 2H), 7.48-7.50 (m, 2H), 7.64 (dd, J=8.84, 2.78 Hz, 1H), 7.81 (d, J=7.58 Hz, 1H), 7.92 (s, 2H), 8.63 (s, 1H).

情報源と証拠