Potassium Carbonate → HCID 57449524, compound

HRID 1897465Notes

Reaction equation

HRID 1897465 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[CH:5]2.Br[CH2:12][CH:13]1[CH2:15][CH2:14]1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:12][CH:13]1[CH2:15][CH2:14]1)[N:6]=[CH:5]2

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 81503Bromomethylcyclopropane3×HCID 7619295-bromo-1H-indazole3×

Product 1

HCID 57449524HCID 57449524, compoundYield 45.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
105 °C

Procedure

To a solution of 5-bromoindazole (15 g, 76.1 mmol) and (bromomethyl)cyclopropane (8.12 mL, 83.7 mmol) in 75 mL of DMF, K2CO3 (16 g, 114.0 mmol) was added. The mixture was heated to 105° C. After 24 hours, starting material was still observed. Additional (bromomethyl)cyclopropane (5.7 mL, 57.0 mmol) was added and reaction was heated to 105° C. for an additional 24 hours. 5-Bromoindazole was again observed so additional (bromomethyl)cyclopropane was added (4 mL, 38 mmol) and the reaction was heated at 95° C. for an additional 48 hours. After disappearance of 5-bromoindazole, the reaction mixture was poured onto DCM/brine. The two layers were separated and the aqueous layer was extracted with DCM (2×) and checked by TLC. No product was observed in aqueous layer. The combined organics were washed with H2O (2×) and brine and dried over Na2SO4. After filtration, the filtrate was concentrated and the resulting residue was purified by chromatography with 9.5:0.5 hexane/EtOAc to provide 5-bromo-1-cyclopropylmethyl-1H-indazole (8.74 g, 45% isolated yield). 1H NMR (400 MHz CDCl3) δ 7.93 (s, 1H), 7.86 (d, J=1.57 Hz, 1H), 7.43 (dd, J=8.61, 1.57 Hz, 1H), 7.31 (d, J=8.61 Hz, 1H), 4.24 (d, J=6.26 Hz, 2H), 1.37-1.26 (m, 1H), 0.62-0.55 (m, 2H), 0.43-0.37 (m, 2H); MS (APCI+) m/z 251/253 (M/M+2H, 1:1) was detected.

Workup

  1. customreaction
  2. temperaturewas heated to 105° C. for an additional 24 hours
  3. additionwas added (4 mL, 38 mmol)
  4. temperaturethe reaction was heated at 95° C. for an additional 48 hours
  5. customThe two layers were separated
  6. extractionthe aqueous layer was extracted with DCM (2×)
  7. washThe combined organics were washed with H2O (2×) and brine
  8. dry with materialdried over Na2SO4
  9. filtrationAfter filtration
  10. concentrationthe filtrate was concentrated
  11. customthe resulting residue was purified by chromatography with 9.5:0.5 hexane/EtOAc

Sources & evidence

ORD record
ord-695054e0a7aa4bb0b179771afb985dc1
Source dataset
uspto-grants-2013_08
Patent number
US08518983B2

Reaction notes

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