2,6-Lutidine → HCID 136286729, compound

HRID 1476896Notes

Reaction equation

HRID 1476896 reaction equation
Cl.[Cl:2][C:3]1[CH:12]=[C:11]2[C:6]([CH:7]=[C:8]([C:19]3[NH:23][C:22](=[O:24])[NH:21][N:20]=3)[N:9]=[C:10]2[NH:13][C@H:14]2[CH2:18][CH2:17][NH:16][CH2:15]2)=[CH:5][CH:4]=1.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]([NH:13][C:10]2[C:11]3[C:6](=[CH:5][CH:4]=[C:3]([Cl:2])[CH:12]=3)[CH:7]=[C:8]([C:19]3[NH:23][C:22](=[O:24])[NH:21][N:20]=3)[N:9]=2)[CH2:15]1)(=[O:36])[CH:34]=[CH2:35]

Participants

5

Reactant 3

HCID 79372,6-LutidineHCID 13140Acryloyl chlorideHCID 136597031HCID 136597031, compound

Product 1

HCID 136286729HCID 136286729, compoundYield 18%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a mixture of (S)-3-(7-chloro-1-(pyrrolidin-3-ylamino)isoquinolin-3-yl)-1H-1,2,4-triazol-5(4H)-one hydrochloride (120 mg) in DCM (8 mL) was added 2,6-dimethylpyridine (105 mg, 0.978 mmol). The resulting mixture was cooled to −78° C. and acryloyl chloride (48 mg, 0.530 mmol, 10 mg/mL in dry DCM) was added dropwise. The reaction mixture was stirred at −78° 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 mg, 18% over 2 steps). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.87 (s, 1H), 11.72 (s, 1H), 8.51 (S, 1H), 7.88 (m, 1H), 7.60-7.70 (m, 2H), 7.56 (d, 1H, J=4.0 Hz), 6.55-6.57 (m, 1H), 6.13-6.19 (m, 1H), 5.63-5.70 (m, 1H), 5.17-5.18 (m, 1H), 3.65-4.17 (m, 4H), 2.01-2.37 (m, 2H); ESI-MS m/z [M+H]+ 385.

Workup

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

Sources & evidence

ORD record
ord-d612dec811e84367b8a68420b4fbcfbb
Source dataset
uspto-grants-2016_08
Patent number
US09402841B2

Reaction notes

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