Diisopropylethylamine → {1-[4-Cyclopentyl-6-(6-fluoro-1H-indol-3-yl)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carbonyl]-2,2-dimethyl-propyl}-carbamic acid tert-butyl ester

온도

0 °C

To a solution containing Boc-L-Tle-OH (160 mg, 0.7 mmol) in anhydrous NMP (4 mL) was cooled to 0° C. HATU (264 mg, 0.7 mmol) and DIPEA (148 mg, 0.7 mmol) were added followed by the addition of crude 37 (220 mg, 0.7 mmol) in anhydrous NMP (5 mL). The reaction mixture was slowly warmed to ambient temperature. After 4 h, the reaction mixture was diluted with EtOAc and washed successively with aqueous NaHCO3 and brine, dried over anhydrous Na2SO4, filtered, and concentrated. The crude product was purified by silica gel HPLC (2″ Dynamax SiO2, 20-100% EtOAc/hexanes over 30 min; Flow: 40 mL/min) to afford 280 mg (66%, 2 steps) of 38. 1H NMR (CDCl3, 300 MHz): δ8.37 (s, 1H), 7.58 (dd, J=5.7, 8.4 Hz, 1H), 7.12 (s, 1H), 6.73 (dd, J=1.8, 9.6 Hz, 1H), 6.65-6.58 (m, 1H), 5.07 (d, J=9.3 Hz, 1H), 4.76 (app t, J=8.4 Hz, 1H), 3.76 (d, J=9.3 Hz, 1H), 3.69 (app t, J=7.2 Hz, 1H), 3.41 (app t, J=8.7 Hz, 1H), 3.09 (app t, J=6.9 Hz, 1H), 3.00-2.94 (m, 2H), 2.66-2.50 (m, 2H), 1.69-1.51 (m, 5H), 1.39 (m, 3H), 1.18 (s, 9H), 0.01 (s, 9H) ppm. Mass spectrum, m/z [527.4] (M+H)+.

1. temperatureThe reaction mixture was slowly warmed to ambient temperature
2. washwashed successively with aqueous NaHCO3 and brine
3. dry with materialdried over anhydrous Na2SO4
4. filtrationfiltered
5. concentrationconcentrated
6. customThe crude product was purified by silica gel HPLC (2″ Dynamax SiO2, 20-100% EtOAc/hexanes over 30 min

ORD 기록

ord-b185a60074af454f8d96069d1f383b35

출처 데이터셋

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08399683B2