1H-Indazole → HCID 59375099, compound

HRID 661867Notes

Reaction equation

HRID 661867 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8]Br)[C:3]=1[CH3:10].[NH:11]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH:13]=[N:12]1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C.O>[Br:1][C:2]1[C:3]([CH3:10])=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][N:11]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH:13]=[N:12]1

Participants

6

Reactant 3

HCID 92211H-IndazoleHCID 11430Potassium CarbonateHCID 226726481-Bromo-3-(bromomethyl)-2-methylbenzene

Product 1

HCID 59375099HCID 59375099, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 1-bromo-3-(bromomethyl)-2-methylbenzene (prepared according to the procedures reported in US Pat. Appl. 2006/0173183, 250 mg, 0.947 mmol), 1H-indazole (112 mg, 0.947 mmol) and potassium carbonate (131 mg, 0.947 mmol) in acetonitrile (5 mL) was heated with stirring at 80° C. After 18.25 h, the mixture was cooled to rt, diluted with water and extracted three times with EtOAc. The combined organic layers were dried and concentrated. The residue was purified by column chromatography (eluting with a gradient from 95:5 to 65:35 hexane-EtOAc) to provide 1-(3-bromo-2-methylbenzyl)-1H-indazole as an oil which crystallized on standing (Intermediate 31-1, 74 mg, 26%). 1H NMR (400 MHz, chloroform-d) δ 8.06 (1H, d, J=0.9 Hz), 7.76 (1H, dt, J=8.1, 1.0 Hz), 7.48 (1H, d, J=7.9 Hz), 7.30-7.37 (1H, m), 7.26-7.30 (1H, m), 7.16 (1H, ddd, J=8.0, 6.8, 1.0 Hz), 6.93 (1H, t, J=7.8 Hz), 6.70 (1H, d, J=7.7 Hz), 5.61 (2H, s), 2.45 (3H, s). Mass spectrum m/z 301, 303 (M+H)+. Also obtained was 2-(3-bromo-2-methylbenzyl)-2H-indazole as a pale yellow gum (Intermediate 31-2, 164 mg, 58%). 1H NMR (400 MHz, chloroform-d) δ 7.68-7.76 (2H, m), 7.54-7.63 (2H, m), 7.28 (1H, ddd, J=8.2, 7.2, 1.1 Hz), 6.97-7.10 (3H, m), 5.63 (2H, s), 2.37 (3H, s). Mass spectrum m/z 301, 303 (M+H)+.

Workup

  1. customprepared
  2. temperaturethe mixture was cooled to rt
  3. extractionextracted three times with EtOAc
  4. customThe combined organic layers were dried
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography (
  7. washeluting with a gradient from 95:5 to 65:35 hexane-EtOAc)

Sources & evidence

ORD record
ord-db91c86ae4fc4ff1a9ed39fefbd5cb8e
Source dataset
uspto-grants-2011_12
Patent number
US08084620B2

Reaction notes

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