Methyl iodide → (4r,7s)-2-(2,4-Difluoro-phenyl)-1,7,8,8-tetramethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one

HRID 1437997Notes

Reaction equation

HRID 1437997 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:17](=[O:18])[C:16]2[C@H:15]3[C:19]([CH3:21])([CH3:20])[C@:12]([CH3:22])([CH2:13][CH2:14]3)[C:11]=2[NH:10]1.I[CH3:24]>CN1CCCC1.C(OCC)(=O)C>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:17](=[O:18])[C:16]2[C@H:15]3[C:19]([CH3:21])([CH3:20])[C@:12]([CH3:22])([CH2:13][CH2:14]3)[C:11]=2[N:10]1[CH3:24]

Participants

5

Reactant 2

HCID 6328Methyl iodideHCID 57941350(4r,7s)-2-(2,4-Difluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one2×

Product 1

HCID 57941483(4r,7s)-2-(2,4-Difluoro-phenyl)-1,7,8,8-tetramethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-oneYield 65.3%

Reagents, catalysts & solvents 2

HCID 84541-MethylpyrrolidineSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of (4R,7S)-2-(2,4-difluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 42; 153 mg, 0.5 mmol) and iodomethane (0.16 mL, 2.55 mmol) in N-methylpyrrolidine (1 mL) was heated at 100° C. in a sealed tube overnight. The reaction mixture was purified by preparative HPLC to give a brown semi-solid which was dissolved in ethyl acetate. The solution was washed with 10% aqueous sodium thiosulfate (three times) and brine, dried (sodium sulfate), filtered, and evaporated to give (4R,7S)-2-(2,4-difluoro-phenyl)-1,7,8,8-tetramethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (104 mg, 65%) as an off-white solid. ES(+)-MS (M+H) 319.

Workup

  1. customThe reaction mixture was purified by preparative HPLC
  2. customto give a brown semi-solid which
  3. washThe solution was washed with 10% aqueous sodium thiosulfate (three times) and brine
  4. dry with materialdried (sodium sulfate)
  5. filtrationfiltered
  6. customevaporated

Sources & evidence

ORD record
ord-0e4dc7c1b1864e85ae34e2c0cea9dec2
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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