2,6-Lutidine → 3-[7-chloro-1-[(3S)-1-prop-2-enoylpyrrolidin-3-yl]oxyisoquinolin-3-yl]-1,4-dihydro-1,2,4-triazol-5-one

온도

0 °C

To a mixture of (S)-3-(7-chloro-1-(pyrrolidin-3-yloxy)isoquinolin-3-yl)-1H-1,2,4-triazol-5(4H)-one (180 mg, 0.489 mmol) in DCM (10 mL) was added 2,6-dimethylpyridine (157 mg, 1.467 mmol) at −20° C. followed by the dropwise addition of acryloyl chloride (88 mg, 0.978 mmol, 10 mg/mL in dry DCM). The reaction mixture was warmed to 0° C. over a 30 minute period. The reaction was quenched with MeOH (5 mL) and the mixture concentrated in vacuo. The crude product was purified by preparative HPLC to give the title compound (35 mg, 18%). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.06 (br, 1H), 11.84 (s, 1H), 8.16 (s, 1H), 8.09 (dd, J=1.8 Hz and 8.9 Hz, 1H), 8.03 (s, 1H), 7.83-7.86 (m, 1H), 6.55-6.72 (m, 1H), 6.12-6.19 (m, 2H), 5.63-5.72 (m, 1H), 4.65-4.12 (m, 4H), 2.25-2.42 (m, 2H).

1. customThe reaction was quenched with MeOH (5 mL)
2. concentrationthe mixture concentrated in vacuo
3. customThe crude product was purified by preparative HPLC

ORD 기록

ord-e148cc3f82bf4568be73c0b6570942dd

출처 데이터셋

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09402841B2