2,6-Lutidine → HCID 136286739, compound

HRID 1476910Notes

Reaction equation

Cl.[CH3:2][O:3][C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:13]=1[C:12]([NH:14][C@H:15]1[CH2:19][CH2:18][NH:17][CH2:16]1)=[N:11][C:10]([C:20]1[NH:24][C:23](=[O:25])[NH:22][N:21]=1)=[CH:9]2.CC1C=CC=C(C)N=1.[C:34](Cl)(=[O:37])[CH:35]=[CH2:36]>C(Cl)Cl>[C:34]([N:17]1[CH2:18][CH2:19][C@H:15]([NH:14][C:12]2[C:13]3[C:8](=[CH:7][CH:6]=[CH:5][C:4]=3[O:3][CH3:2])[CH:9]=[C:10]([C:20]3[NH:24][C:23](=[O:25])[NH:22][N:21]=3)[N:11]=2)[CH2:16]1)(=[O:37])[CH:35]=[CH2:36]

Participants

Conditions

Temperature: -78 °C

Procedure

To a mixture of (S)-3-(8-methoxy-1-(pyrrolidin-3-ylamino)isoquinolin-3-yl)-1H-1,2,4-triazol-5(4H)-one hydrochloride (120 mg, 0.33 mmol) in DCM (8 mL) was added 2,6-dimethylpyridine (106 mg, 0.99 mmol). The resulting mixture was cooled to −78° C. Acryloyl chloride (120 mg, 1.20 mmol, 10 mg/mL in dry DCM) was added dropwise and the reaction mixture was stirred at −78° C. for 1.5 hours. 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 (34 mg, 27%). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.81 (s, 1H), 11.69 (s, 1H), 7.85 (dd, J=7.1, 14.5 Hz, 1H), 7.57-7.51 (m, 1H), 7.43 (d, J=3.3 Hz, 1H), 7.36 (d, J=8.0 Hz, 1H), 7.02 (d, J=8.0 Hz, 1H), 6.72-6.54 (m, 1H), 6.16 (m, 1H), 5.73-5.61 (m, 1H), 5.21-5.03 (m, 1H), 4.16 (m, 1H), 4.04-3.89 (m, 3H), 3.79 (m, 1H), 3.71-3.61 (m, 1H), 3.44 (m, 1H), 3.24 (m, 1H), 2.42-2.21 (m, 1H), 2.09-1.90 (m, 1H); ESI-MS m/z [M+H]+ 381.

Workup

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-48b32ab685e14020abf19b217cdd02f4
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09402841B2

Reaction notes

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