1-Bromo-2-methylpropane → 4-((3,5-dimethylisoxazol-4-yl)methoxy)-N-isobutyl-N-(5-methylpyridin-2-yl)benzenesulfonamide

HRID 594154Notes

Reaction equation

HRID 594154 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]([NH:9][S:10]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH2:20][C:21]3[C:22]([CH3:27])=[N:23][O:24][C:25]=3[CH3:26])=[CH:15][CH:14]=2)(=[O:12])=[O:11])=[N:7][CH:8]=1)#N.[CH3:28][C:29](N=C(N(C)C)N(C)C)([CH3:31])[CH3:30].BrCC(C)C>C(#N)C.CO>[CH3:27][C:22]1[C:21]([CH2:20][O:19][C:16]2[CH:17]=[CH:18][C:13]([S:10]([N:9]([CH2:28][CH:29]([CH3:31])[CH3:30])[C:6]3[CH:5]=[CH:4][C:3]([CH3:1])=[CH:8][N:7]=3)(=[O:12])=[O:11])=[CH:14][CH:15]=2)=[C:25]([CH3:26])[O:24][N:23]=1

Participants

6

Reactant 3

HCID 65551-Bromo-2-methylpropaneHCID 35715812-tert-Butyl-1,1,3,3-tetramethylguanidineHCID 89876006N-(5-cyanopyridin-2-yl)-4-((3,5-dimethylisoxazol-4-yl)methoxy)benzenesulfonamide

Product 1

HCID 721960224-((3,5-dimethylisoxazol-4-yl)methoxy)-N-isobutyl-N-(5-methylpyridin-2-yl)benzenesulfonamideYield 7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
20 °C

Procedure

To a solution of N-(5-cyano-2-pyridinyl)-4-{[(3,5-dimethyl-4-isoxazolyl)methyl]oxy}benzenesulfonamide (23 mg, 0.060 mmol) in acetonitrile (0.5 mL) at room temperature was added N″-(1,1-dimethylethyl)-N,N,N′,N′-tetramethylguanidine (0.024 mL, 0.120 mmol). The reaction mixture was stirred at 20° C. for 1 hour, then 1-bromo-2-methylpropane (0.013 mL, 0.120 mmol) was added. The reaction was heated by microwaves to 150° C. for 30 minutes. After cooling, the reaction mixture was diluted with methanol and passed through an aminopropyl (NH2) solid phase extraction (SPE) cartridge followed by a sulphonic acid (SCX) SPE cartridge, eluting with methanol. The appropriate fractions were combined and evaporated under a stream of nitrogen to give the crude product. The crude was purified by mass directed autoprep (formic acid modifier), to provide the title compound (1.8 mg). LCMS (2 min, formic) Rt 1.25 min, m/z (ES+) 441 (M+H).

Workup

  1. temperatureThe reaction was heated by microwaves to 150° C. for 30 minutes
  2. temperatureAfter cooling
  3. extractionpassed through an aminopropyl (NH2) solid phase extraction (SPE) cartridge
  4. washeluting with methanol
  5. customevaporated under a stream of nitrogen
  6. customto give the crude product
  7. customThe crude was purified by mass

Sources & evidence

ORD record
ord-687abf9daf0b4bdbbdca6154e94da99a
Source dataset
uspto-grants-2016_01
Patent number
US09242972B2

Reaction notes

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