4-Methylpyrazole → 2-Methyl-6-(4-methylpyrazol-1-yl)isoquinolin-1-one

HRID 575613Notes

Reaction equation

HRID 575613 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[N:7]([CH3:13])[CH:6]=[CH:5]2.[CH3:14][C:15]1[CH:16]=[N:17][NH:18][CH:19]=1.C([O-])([O-])=O.[K+].[K+].C(OCC)(=O)C>CN1C(=O)CCC1.[Cu]I>[CH3:13][N:7]1[CH:6]=[CH:5][C:4]2[C:9](=[CH:10][CH:11]=[C:2]([N:17]3[CH:16]=[C:15]([CH3:14])[CH:19]=[N:18]3)[CH:3]=2)[C:8]1=[O:12]

Participants

7

Reactant 4

HCID 34064-MethylpyrazoleHCID 8857Ethyl Acetate2×HCID 11430Potassium CarbonateHCID 231581786-Bromo-2-methyl-1,2-dihydroisoquinolin-1-one

Product 1

HCID 1180214672-Methyl-6-(4-methylpyrazol-1-yl)isoquinolin-1-oneYield 52.7%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

6-Bromo-2-methylisoquinolin-1-one (300.0 mg, 1.27 mmol), 4-methyl-1H-pyrazole (210.0 mg, 2.54 mmol), CuI (30.0 mg, 0.127 mmol) and K2CO3 (360.0 mg, 2.54 mmol) in NMP (3.0 mL) were microwaved at 195° C. for 5 h. Extractive work up with ethyl acetate followed by silica gel chromatography (PE:EA=5:1) gave the title compound of step 1 (160.0 mg, 52%) as a light yellow solid. 1H NMR (CDCl3, 400 MHz) δ 8.49 (d, J=8.8 Hz, 1H), 7.84 (s, 1H), 7.83 (d, J=2.0 Hz, 1H), 7.74 (dd, J1=8.8 Hz, J2=2.0 Hz, 1H), 7.59 (s, 1H), 7.10 (d, J=7.6 Hz, 1H), 6.52 (d, J=7.6 Hz, 1H), 3.62 (s, 3H), 2.19 (s, 3H). LCMS: 240.0 (M+H)+.

Sources & evidence

ORD record
ord-b467a2ab24d34beb97d29fb3e87b7454
Source dataset
uspto-grants-2015_05
Patent number
US09034900B2

Reaction notes

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