Bromine → 4-Bromo-2-methyl-6-(4-methylpyrazol-1-yl)isoquinolin-1-one

HRID 575614Notes

Reaction equation

HRID 575614 reaction equation
[Br:1]Br.[CH3:3][N:4]1[CH:13]=[CH:12][C:11]2[C:6](=[CH:7][CH:8]=[C:9]([N:14]3[CH:18]=[C:17]([CH3:19])[CH:16]=[N:15]3)[CH:10]=2)[C:5]1=[O:20]>C(O)(=O)C>[Br:1][C:12]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([N:14]3[CH:18]=[C:17]([CH3:19])[CH:16]=[N:15]3)[CH:10]=2)[C:5](=[O:20])[N:4]([CH3:3])[CH:13]=1

Participants

4

Reactant 2

HCID 24408BromineHCID 1180214672-Methyl-6-(4-methylpyrazol-1-yl)isoquinolin-1-one

Product 1

HCID 1180215704-Bromo-2-methyl-6-(4-methylpyrazol-1-yl)isoquinolin-1-oneYield 64.7%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent2×

Procedure

Bromine (94 mg, 0.59 mmol) in acetic acid (2 mL) was added drop-wise to a solution of 2-methyl-6-(4-methylpyrazol-1-yl)isoquinolin-1-one (140.0 mg, 0.583 mmol) in acetic acid (4 mL) at 0° C. The mixture was then stirred at room temperature for 17 min and quenched with water (10 mL). The pH was adjusted to about 7-8 with aqueous 1M NaOH. Extractive work up with ethyl acetate followed by purification using silica gel chromatography (PE:EA=1:1) gave the title compound of step 2 (120.0 mg, 56%) as a light yellow solid. 1H NMR (CDCl3, 400 MHz) δ 8.51 (d, J=8.8 Hz, 1H), 8.06 (d, J=2.0 Hz, 1H), 7.89 (s, 1H), 7.87 (dd, J1=8.8 Hz, J2=2.0 Hz, 1H), 7.63 (s, 1H), 7.42 (s, 1H), 3.62 (s, 3H), 2.20 (s, 3H). LCMS: 319.8 (M+H)+.

Workup

  1. customquenched with water (10 mL)
  2. customExtractive work up with ethyl acetate followed by purification

Sources & evidence

ORD record
ord-aafe238aaa834563acc058b21ce9999c
Source dataset
uspto-grants-2015_05
Patent number
US09034900B2

Reaction notes

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