Pyrazole → HCID 86730153, compound

HRID 1850123Notes

Reaction equation

HRID 1850123 reaction equation
[CH3:1][C:2]([S@:5]([NH:7][C@H:8]([C:10]1[C:11]([CH3:15])=[N:12][NH:13][CH:14]=1)[CH3:9])=[O:6])([CH3:4])[CH3:3].C([O-])([O-])=O.[Cs+].[Cs+].[CH2:22](Br)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.N1C=CC=N1>CN(C=O)C.CCOC(C)=O.CCOC(C)=O.CCCCCCC>[CH2:22]([N:13]1[CH:14]=[C:10]([C@@H:8]([NH:7][S@@:5]([C:2]([CH3:3])([CH3:4])[CH3:1])=[O:6])[CH3:9])[C:11]([CH3:15])=[N:12]1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

8

Reactant 4

HCID 1048PyrazoleHCID 7498Benzyl Bromide2×HCID 10796Cesium carbonate2×HCID 178434542HCID 178434542, compound

Product 1

HCID 86730153HCID 86730153, compoundYield 37.3%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolventHCID 21899848Ethylacetate heptaneSolvent

Procedure

(R)-2-methyl-N—((S)-1-(3-methyl-1H-pyrazol-4-yl)ethyl)propane-2-sulfinamide (290 mg, 1.26 mmol) was dissolved in DMF (5 ml) and added dropwise to a solution of Cs2CO3 (458 mg, 1.41 mmol) in DMF (4 ml). The resulting reaction mixture was stirred at room temperature for 15 min. benzylbromide (216 mg, 1.26 mmol) was added and the reaction was stirred at room temperature for 2 h. LCMS shows mostly product with some starting pyrazole. Added another 0.1 ml of BnBr and 135 mg of Cs2CO3. Stirred another 24H at 50° C. The reaction mixture was diluted with EtOAc (300 mL), washed with 4% aqueous NaCl (2×150, 2×50 mL). The combined aq. layers were back extracted with EtOAc (100 ml). The combined organic layers were washed with brine (100 ml), dried over Na2SO4, filtered and concentrated. Silica gel chromatography, EtOAc/heptane 20-80% to give title compound (mix of regioisomers, 150 mg, 0.470 mmol).

Workup

  1. customThe resulting reaction mixture
  2. additionwas added
  3. stirringStirred another 24H at 50° C
  4. washwashed with 4% aqueous NaCl (2×150, 2×50 mL)
  5. extractionThe combined aq. layers were back extracted with EtOAc (100 ml)
  6. washThe combined organic layers were washed with brine (100 ml)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-93b280f89cee4b66bd8b56dbdc559e3d
Source dataset
uspto-grants-2015_02
Patent number
US08957068B2

Reaction notes

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