2-Methyl-N-(oxetan-3-ylidene)propane-2-sulfinamide → HCID 69932998, compound

HRID 540785Notes

Reaction equation

HRID 540785 reaction equation
C([Li])CCC.Br[C:7]1[CH:8]=[N:9][CH:10]=[C:11]([C:13]2[CH:17]=[C:16]([O:18][C:19]3[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=3)[N:15]([CH2:29][CH3:30])[N:14]=2)[CH:12]=1.[CH3:31][C:32]([S:35]([N:37]=[C:38]1[CH2:41][O:40][CH2:39]1)=[O:36])([CH3:34])[CH3:33]>O1CCCC1>[CH2:29]([N:15]1[C:16]([O:18][C:19]2[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=2)=[CH:17][C:13]([C:11]2[CH:12]=[C:7]([C:38]3([NH:37][S:35]([C:32]([CH3:34])([CH3:33])[CH3:31])=[O:36])[CH2:41][O:40][CH2:39]3)[CH:8]=[N:9][CH:10]=2)=[N:14]1)[CH3:30]

Participants

5

Reactant 3

HCID 468399952-Methyl-N-(oxetan-3-ylidene)propane-2-sulfinamideHCID 67111709HCID 67111709, compoundHCID 178418339Butyllithium

Product 1

HCID 69932998HCID 69932998, compoundYield 66.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of n-butyllithium in hexanes (1.6 M, 0.35 mL, 0.56 mmol, 1.5 equiv) was added to a solution of 3-bromo-5-{1-ethyl-5-[4-(trifluoromethyl)phenoxy]-1H-pyrazol-3-yl}pyridine (152 mg, 0.37 mmol, 1.0 equiv) in tetrahydrofuran (1.5 mL) and hexanes (1.5 mL) at −78° C. The reaction mixture was stirred at −78° C. for 10 minutes, and then 2-methyl-N-oxetan-3-ylidenepropane-2-sulfinamide (Example 95, Step 4, 75 mg, 0.43 mmol, 1.15 equiv) was added neat via syringe. The reaction mixture was stirred at −78° C. for 5 minutes, then the cooling bath was removed. After 5 minutes, the mixture was quenched with water (2 mL) and extracted with EtOAc (3×5 mL). The combined organic layer was dried over MgSO4, filtered, and concentrated. The crude residue was purified by silica gel chromatography (50-100% EtOAc/hexane, then 0-5% MeOH/EtOAc) to give N-[3-(5-{1-ethyl-5-[4-(trifluoromethyl)phenoxy]-1H-pyrazol-3-yl}pyridine-3-yl)oxetan-3-yl]-2-methylpropane-2-sulfinamide (125 mg, 57%). Calc'd (M+1)+: 508.6. Found: 509.5.

Workup

  1. stirringThe reaction mixture was stirred at −78° C. for 5 minutes
  2. customthe cooling bath was removed
  3. waitAfter 5 minutes
  4. customthe mixture was quenched with water (2 mL)
  5. extractionextracted with EtOAc (3×5 mL)
  6. dry with materialThe combined organic layer was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude residue was purified by silica gel chromatography (50-100% EtOAc/hexane

Sources & evidence

ORD record
ord-d9453ca332b142c4baff065bc4b90209
Source dataset
uspto-grants-2014_10
Patent number
US08871796B2

Reaction notes

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