2,6-Lutidine → HCID 136286730, compound

HRID 1476901Notes

Reaction equation

Cl.[Cl:2][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:12]=1[C:11]([O:13][C@H:14]1[CH2:18][CH2:17][NH:16][CH2:15]1)=[N:10][C:9]([C:19]1[NH:23][C:22](=[O:24])[NH:21][N:20]=1)=[CH:8]2.CC1C=CC=C(C)N=1.[C:33](Cl)(=[O:36])[CH:34]=[CH2:35]>C(Cl)Cl>[C:33]([N:16]1[CH2:17][CH2:18][C@H:14]([O:13][C:11]2[C:12]3[C:7](=[CH:6][CH:5]=[CH:4][C:3]=3[Cl:2])[CH:8]=[C:9]([C:19]3[NH:23][C:22](=[O:24])[NH:21][N:20]=3)[N:10]=2)[CH2:15]1)(=[O:36])[CH:34]=[CH2:35]

Participants

Conditions

Temperature: -20 °C

Procedure

To (S)-3-(8-chloro-1-(pyrrolidin-3-yloxy)isoquinolin-3-yl)-1H-1,2,4-triazol-5(4H)-one hydrochloride (42.6 mg, 0.116 mmol) in DCM (25 mL) was added 2,6-dimethylpyridine (37.24 mg, 0.35 mmol). The resulting mixture was cooled to −20° C. Acryloyl chloride (26.1 mg, 0.29 mmol, 10 mg/mL in dry DCM) was added dropwise and the reaction mixture was warmed to 0° C. for 30 minutes. The reaction was 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 (22.02 mg, 49.25%). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.09 (s, 1H), 11.87 (s, 1H), 8.01-7.98 (m, 2H), 7.71-7.70 (d, J=4.0 Hz, 2H), 6.67-6.57 (m, 1H), 6.26-6.14 (m, 2H), 5.72-5.63 (m, 1H), 4.01-3.71 (m, 4H), 2.33-2.24 (m, 2H); ESI-MS m/z [M+H]+ 386.1.

Workup

temperaturethe reaction mixture was warmed to 0° C. for 30 minutes
customThe reaction was quenched with MeOH (5 mL)
concentrationthe mixture was concentrated in vacuo
customThe crude product was purified by preparative HPLC

Sources & evidence

ORD record: ord-6940338c2ab845f4a318cb767fa37a61
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09402841B2

Reaction notes

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