Dimethyl Sulfoxide → dimethyl 2-((1-(4-fluorophenyl)-1H-indazol-5-yl)(phenyl)methyl)-2-methylmalonate

HRID 563437Notes

Reaction equation

HRID 563437 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([CH:17]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)[CH:18]([C:23]([O:25][CH3:26])=[O:24])[C:19]([O:21][CH3:22])=[O:20])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1.[H-].[Na+].[CH3:35]S(C)=O.CI>C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([CH:17]([C:27]4[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=4)[C:18]([CH3:35])([C:23]([O:25][CH3:26])=[O:24])[C:19]([O:21][CH3:22])=[O:20])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 59252807dimethyl 2-((1-(4-fluorophenyl)-1H-indazol-5-yl)(phenyl)methyl)malonate

Product 1

HCID 67005816dimethyl 2-((1-(4-fluorophenyl)-1H-indazol-5-yl)(phenyl)methyl)-2-methylmalonateYield 83%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Dimethyl 2-((1-(4-fluorophenyl)-1H-indazol-5-yl)(phenyl)methyl)malonate (250 mg, 0.58 mmol) was dissolved in THF (5 mL) and 60% oil dispersion NaH was added (24 mg, 0.6 mmol). After 1 h, added DMSO (2 mL) followed by MeI (5.8 mmol). After 72 h, the reaction was quenched with MeOH then poured into brine and extracted with EtOAc×3. The organic layers were dried over MgSO4, filtered, and concentrated. The residue was purified on SiO2 by MPLC using a 1:9 to 1:3 EtOAc/hexane gradient. Obtained 215 mg (83% yield) of dimethyl 2-((1-(4-fluorophenyl)-1H-indazol-5-yl)(phenyl)methyl)-2-methylmalonate. MS found: (M+H)+=447.

Workup

  1. waitAfter 72 h
  2. customthe reaction was quenched with MeOH
  3. additionthen poured into brine
  4. extractionextracted with EtOAc×3
  5. dry with materialThe organic layers were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified on SiO2 by MPLC

Sources & evidence

ORD record
ord-2916aaac6d674617b138e5ee20fdf91c
Source dataset
uspto-grants-2011_11
Patent number
US08067447B2

Reaction notes

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