Diazomethane → HCID 59152919, compound

HRID 2387550Notes

Reaction equation

HRID 2387550 reaction equation
[CH2:1]([O:3][C:4](=[O:33])[CH2:5][N:6]1[C:14]2[CH2:13][CH2:12][CH2:11][C@@H:10]([N:15]([S:17]([C:20]3[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[C:22]([C:30]([CH3:32])=[CH2:31])[CH:21]=3)(=[O:19])=[O:18])[CH3:16])[C:9]=2[CH:8]=[N:7]1)[CH3:2].[N+](=[CH2:36])=[N-]>O1CCCC1.C(OCC)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:1]([O:3][C:4](=[O:33])[CH2:5][N:6]1[C:14]2[CH2:13][CH2:12][CH2:11][C@@H:10]([N:15]([CH3:16])[S:17]([C:20]3[CH:25]=[C:24]([C:26]([F:27])([F:28])[F:29])[CH:23]=[C:22]([C:30]4([CH3:36])[CH2:32][CH2:31]4)[CH:21]=3)(=[O:18])=[O:19])[C:9]=2[CH:8]=[N:7]1)[CH3:2]

Participants

6

Reactant 2

HCID 9550Diazomethane2×HCID 59152949HCID 59152949, compound

Product 1

HCID 59152919HCID 59152919, compoundYield 99%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalyst2×HCID 3283Diethyl EtherSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of {(R)-4-[(3-isopropenyl-5-trifluoromethyl-benzenesulfonyl)-methyl-amino]-4,5,6,7-tetrahydro-indazol-1-yl}-acetic acid ethyl ester (70.7 mg, 0.15 mmol) in tetrahydrofuran (2 mL) was added a solution of diazomethane in diethyl ether (1M, 8 mL) slowly at 0° C. under an argon atmosphere, and then a portion of palladium acetate (5 mg) was added. After the mixture was stirred for 10 minutes, a second portion of palladium acetate (5 mg) was added and the mixture was stirred for another 20 minutes, followed by addition of a second portion of a solution of diazomethane in diethyl ether (1M, 5 mL). After being stirred at 0° C. for 2 hours under an argon atmosphere, the reaction mixture was then quenched by the addition of a few drops of acetic acid, and then filtered through a glass funnel and concentrated in vacuo. The residue was purified by flash column (gradient elution, 0-10% methanol in dichloromethane) to afford ((R)-4-{methyl-[3-(1-methyl-cyclopropyl)-5-trifluoromethyl-benzenesulfonyl]-amino}-4,5,6,7-tetrahydro-indazol-1-yl)-acetic acid ethyl ester (74.5 mg, 99%) as a colorless semisolid. MS cald. for C23H28F3N3O4S 499, obsd. (ESI+) [(M+H)+] 500.

Workup

  1. stirringthe mixture was stirred for another 20 minutes
  2. stirringAfter being stirred at 0° C. for 2 hours under an argon atmosphere
  3. customthe reaction mixture was then quenched by the addition of a few drops of acetic acid
  4. filtrationfiltered through a glass funnel
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash column (gradient elution, 0-10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-867031929a9246358ab4e4773687707b
Source dataset
uspto-grants-2012_09
Patent number
US08268870B2

Reaction notes

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