2,6-Lutidine → 3-[8-chloro-1-[[(3S)-1-prop-2-enoylpyrrolidin-3-yl]amino]isoquinolin-3-yl]-1,4-dihydro-1,2,4-triazol-5-one

온도

-40 °C

To a mixture of (S)-3-(8-chloro-1-(pyrrolidin-3-ylamino)isoquinolin-3-yl)-1H-1,2,4-triazol-5(4H)-one hydrochloride (100 mg, 0.3 mmol) in DCM (20 mL) was added 2,6-dimethylpyridine (97 mg, 0.91 mmol). The resulting mixture was cooled to −40° C. Acryloyl chloride (51 mg, 0.6 mmol, 10 mg/mL in dry DCM) was added dropwise and the mixture was stirred at −40° C. for 30 minutes. The reaction was subsequently quenched with MeOH (5 mL) and the mixture was concentrated in vacuo. The crude product was purified by preparative HPLC to give the title compound (57 mg, 52%). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.91 (s, 1H), 11.80 (s, 1H), 7.85-7.83 (m, 1H), 7.61-7.59 (m, 3H), 7.49-7.47 (m, 1H), 6.6-6.5 (m, 1H), 6.17-6.13 (m, 1H), 5.67-5.63 (m, 1H), 5.18-5.16 (m, 1H), 4.18-4.17 (m, 0.5H), 3.69-3.65 (m, 0.5H), 3.42 (m, 0.5H), 3.32-3.31 (m, 1.5H), 2.31-2.29 (m, 1H), 2.04-2.01 (m, 1H); ESI-MS m/z [M+H]+ 385.1.

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

ORD 기록

ord-88b9a72357b8415d92a756ca2ec6116c

출처 데이터셋

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09402841B2