Iodoethane → 5-Bromo-3-cyclobutyl-1-ethyl-1H-indazole

HRID 1423082Notes

Reaction equation

HRID 1423082 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[C:5]2[CH:11]1[CH2:14][CH2:13][CH2:12]1.[H-].[Na+].I[CH2:18][CH3:19]>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:18][CH3:19])[N:6]=[C:5]2[CH:11]1[CH2:14][CH2:13][CH2:12]1

Participants

5

Reactant 3

HCID 6340IodoethaneHCID 24758Sodium hydrideHCID 178419332HCID 178419332, compound

Product 1

HCID 581889605-Bromo-3-cyclobutyl-1-ethyl-1H-indazoleYield 68.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

The 5-bromo-3-cyclobutyl-1H-indazole intermediate (1.501 g, 5.97 mmol) was dissolved in anhydrous DMF (25 mL), cooled to 0° C. and treated with a 60% dispersion of sodium hydride in mineral oil (330 mg, 8.26 mmol). The cold bath was removed and the reaction mixture was stirred at room temperature for 2 h after which time iodoethane (1.034 g, 6.62 mmol) was added and the reaction mixture was stirred 8 h. The reaction mixture was then cooled and quenched by addition of a saturated aqueous solution of NH4Cl (10 mL) then extracted with EtOAc (20 mL). The organic extract was dried over MgSO4, filtered, and evaporated to an oil, which was purified by silica gel flash chromatography with a 0-10% EtOAc/hexanes gradient to afford titled compound as a light yellow oil (1.14 g, 68%). 1H NMR (DMSO-d6) 7.90 (s, 1H), 7.58 (d, J=8.5, 1H), 7.44 (d, J=8.5, 1H), 4.35 (q, J=7.2, 2H), 3.85 (pent, J=7.6, 1H), 2.35-2.31 (m, 4H), 2.31-2.02 (m, 1H), 1.99 (m, 1H), 1.35 (t, J=7.6, 3H). LC/MS (Method B) 4.27 min, [M+1]+ 279/281.

Workup

  1. customThe cold bath was removed
  2. additionwas added
  3. temperatureThe reaction mixture was then cooled
  4. customquenched by addition of a saturated aqueous solution of NH4Cl (10 mL)
  5. extractionthen extracted with EtOAc (20 mL)
  6. extractionThe organic extract
  7. dry with materialwas dried over MgSO4
  8. filtrationfiltered
  9. customevaporated to an oil, which
  10. customwas purified by silica gel flash chromatography with a 0-10% EtOAc/hexanes gradient

Sources & evidence

ORD record
ord-dbff410119f145388045c7c317dedea8
Source dataset
uspto-grants-2015_01
Patent number
US08927546B2

Reaction notes

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