Methyl Acetate → HCID 59334646, compound

HRID 1639871Notes

Reaction equation

HRID 1639871 reaction equation
Br[C:2]1[CH:10]=[CH:9][C:8]2[C:4](=[CH:5][N:6]([CH3:11])[N:7]=2)[C:3]=1[CH:12]1[CH2:14][CH:13]1[CH2:15][NH:16][C:17](=[O:19])[CH3:18].[C:20](OC)(=[O:22])C>CO.C[O-].[Na+].Cl.[Cu]Br>[CH3:20][O:22][C:2]1[CH:10]=[CH:9][C:8]2[C:4](=[CH:5][N:6]([CH3:11])[N:7]=2)[C:3]=1[CH:12]1[CH2:14][CH:13]1[CH2:15][NH:16][C:17](=[O:19])[CH3:18]

Participants

6

Reactant 2

HCID 6584Methyl AcetateHCID 59334491HCID 59334491, compound

Product 1

HCID 59334646HCID 59334646, compoundYield 16%

Reagents, catalysts & solvents 3

HCID 24593copper(I) bromideCatalystHCID 313Hydrochloric AcidSolventHCID 23694274Sodium methanolate methanolSolvent

Procedure

N-{[2-(5-Bromo-2-methyl-2H-indazol-4-yl)cyclopropyl]methyl}acetamide (200 mg, 0.621 mmol) obtained in Example 29, copper(I) bromide (89.0 mg, 0.621 mmol) and methyl acetate (148 μL, 1.863 mmol) were dissolved in 28% sodium methoxide methanol solution (8 mL), and the mixture was heated under reflux for 1.5 hr. The reaction mixture was diluted with aqueous hydrochloric acid solution, and the aqueous layer was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (methanol/ethyl acetate=3/97→10/90), HPLC and recrystallization (ethyl acetate/hexane) to give the title compound (27.1 mg, yield 16%).

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 1.5 hr
  3. extractionthe aqueous layer was extracted with ethyl acetate
  4. washThe extract was washed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customthe solvent was evaporated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (methanol/ethyl acetate=3/97→10/90), HPLC and recrystallization (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-eab46b53312f471382a6a836ba68154f
Source dataset
uspto-grants-2012_02
Patent number
US08110585B2

Reaction notes

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