2,6-Lutidine → HCID 136286726, compound

HRID 1476891Notes

Reaction equation

[F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([C:18]3[NH:22][C:21](=[O:23])[NH:20][N:19]=3)[N:8]=[C:9]2[NH:12][C@H:13]2[CH2:17][CH2:16][NH:15][CH2:14]2)=[CH:4][CH:3]=1.CC1C=CC=C(C)N=1.[C:32](Cl)(=[O:35])[CH:33]=[CH2:34]>C(Cl)Cl>[C:32]([N:15]1[CH2:16][CH2:17][C@H:13]([NH:12][C:9]2[C:10]3[C:5](=[CH:4][CH:3]=[C:2]([F:1])[CH:11]=3)[CH:6]=[C:7]([C:18]3[NH:22][C:21](=[O:23])[NH:20][N:19]=3)[N:8]=2)[CH2:14]1)(=[O:35])[CH:33]=[CH2:34]

Participants

Conditions

Temperature: -40 °C

Procedure

To a mixture of (S)-3-(7-fluoro-1-(pyrrolidin-3-ylamino)isoquinolin-3-yl)-1H-1,2,4-triazol-5(4H)-one (100 mg, 0.35 mmol) in DCM (10 mL) was added 2,6-dimethylpyridine (122 mg, 1.15 mmol). The resulting mixture was cooled to −40° C. Acryloyl chloride (45 mg, 0.49 mmol) was added dropwise and the reaction mixture was stirred at −40° C. for 30 minutes. 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 (79 mg, 75%). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.84 (s, 1H), 11.70 (s, 1H), 8.25-8.22 (d, J=10.8 Hz, 1H), 7.97-7.96 (m, 1H), 7.63-7.60 (m, 2H), 7.55-7.54 (m, 1H), 6.59-6.57 (m, 1H), 6.21-6.15 (m, 1H), 5.68-5.65 (dd, J1=10.4 Hz, J2=2.4 Hz, 1H), 5.20-5.18 (m, 1H), 4.19-4.15 (m, 0.5H), 3.70-3.67 (m, 2H), 3.69-3.45 (m, 1.5H), 3.25 (m, 0.5H), 2.26-2.24 (m, 1H), 2.08-2.03 (m, 1H).

Workup

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

Sources & evidence

ORD record: ord-36b3bbf9fcc44939b7e333805a4fe5a4
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09402841B2

Reaction notes

Loading…