Sodium hydride → Methyl 6-bromo-1-cyclopentyl-1H-indazole-4-carboxylate

HRID 1476424Notes

Reaction equation

HRID 1476424 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:11]([O:13][CH3:14])=[O:12])[C:5]2[CH:6]=[N:7][NH:8][C:9]=2[CH:10]=1.[H-].[Na+].I[CH:18]1[CH2:22][CH2:21][CH2:20][CH2:19]1>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]([C:11]([O:13][CH3:14])=[O:12])[C:5]2[CH:6]=[N:7][N:8]([CH:18]3[CH2:22][CH2:21][CH2:20][CH2:19]3)[C:9]=2[CH:10]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 73784IodocyclopentaneHCID 24728062methyl 6-bromo-1H-indazole-4-carboxylate

Product 1

HCID 67468180Methyl 6-bromo-1-cyclopentyl-1H-indazole-4-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Ice-cooled methyl 6-bromo-1H-indazole-4-carboxylate (2 g, 7.84 mmol) in 30 mL of DMF was treated with NaH (60%, 345 mg, 8.63 mmol) and the mixture was stirred for 1 hr at 0° C. Iodocyclopentane (2.31 g, 11.8 mmol) was then added and the mixture was stirred at 100° C. overnight. After cooling to RT, the reaction mixture was partitioned between water and ethyl acetate. The organic phase was washed with water and brine, dried over MgSO4, filtered and evaporated. Hexanes was added to the brown oil and it was purified using silica gel chromatography (eluent: Hex/EtOAc, gradient 0 to 25%). The less polar product was evaporated to give an orange oil, and was dried on hivac overnight. The product was confirmed to be the alkylated 1-isomer as suggested by 2D H NMR, and was collected as 807 mg (32%). 1H NMR (400 MHz, DMSO-d6): δ 8.40 (s, 1H) 8.37 (s, 1H) 7.81 (d, J=1.52 Hz, 1H) 5.26 (quin, J=7.07 Hz, 1H) 3.95 (s, 3H) 2.08-2.17 (m, 2H) 1.93-2.01 (m, 2H) 1.82-1.92 (m, 2H) 1.64-1.73 (m, 2H); LCMS (ES+): m/z=323.3/325.3

Workup

  1. stirringthe mixture was stirred at 100° C. overnight
  2. temperatureAfter cooling to RT
  3. customthe reaction mixture was partitioned between water and ethyl acetate
  4. washThe organic phase was washed with water and brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. additionHexanes was added to the brown oil and it
  9. customwas purified
  10. customThe less polar product was evaporated
  11. customto give an orange oil
  12. customwas dried on hivac overnight
  13. customwas collected as 807 mg (32%)

Sources & evidence

ORD record
ord-a540b8690ad440fb8c873c08736855d8
Source dataset
uspto-grants-2015_04
Patent number
US09018382B2

Reaction notes

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