1-Bromo-2-methylpropane → 4-((3,5-dimethylisoxazol-4-yl)-methoxy)-N-isobutyl-N-(6-methoxypyridazin-3-yl)benzenesulfonamide

HRID 594153Notes

Reaction equation

HRID 594153 reaction equation
[CH3:1][C:2]1[C:6]([CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12]([S:15]([NH:18][C:19]3[N:20]=[N:21][C:22]([O:25][CH3:26])=[CH:23][CH:24]=3)(=[O:17])=[O:16])=[CH:11][CH:10]=2)=[C:5]([CH3:27])[O:4][N:3]=1.[CH3:28][C:29](N=C(N(C)C)N(C)C)([CH3:31])[CH3:30].BrCC(C)C>C(#N)C.CO>[CH3:1][C:2]1[C:6]([CH2:7][O:8][C:9]2[CH:10]=[CH:11][C:12]([S:15]([N:18]([CH2:28][CH:29]([CH3:31])[CH3:30])[C:19]3[N:20]=[N:21][C:22]([O:25][CH3:26])=[CH:23][CH:24]=3)(=[O:17])=[O:16])=[CH:13][CH:14]=2)=[C:5]([CH3:27])[O:4][N:3]=1

Participants

6

Reactant 3

HCID 65551-Bromo-2-methylpropaneHCID 35715812-tert-Butyl-1,1,3,3-tetramethylguanidineHCID 1179259484-{[(3,5-dimethyl-4-isoxazolyl)methyl]oxy}-N-[6-(methyloxy)-3-pyridazinyl]benzenesulfonamide

Product 1

HCID 721942794-((3,5-dimethylisoxazol-4-yl)-methoxy)-N-isobutyl-N-(6-methoxypyridazin-3-yl)benzenesulfonamideYield 5.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
20 °C

Procedure

To a solution of 4-{[(3,5-dimethyl-4-isoxazolyl)methyl]oxy}-N-[6-(methyloxy)-3-pyridazinyl]benzenesulfonamide (16 mg, 0.041 mmol) in acetonitrile (1 mL) stirred at room temperature was added N″-(1,1-dimethylethyl)-N,N,N′,N′-tetramethylguanidine (7.02 mg, 0.041 mmol). The reaction mixture was stirred at 20° C. for 1 hour, then 1-bromo-2-methylpropane (8.91 μL, 0.082 mmol) was added. The reaction was heated by microwaves to 150° C. for 15 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 (1.0 mg). LCMS (2 min, formic) Rt 1.27 min, m/z (ES+) 447 (M+H).

Workup

  1. temperatureThe reaction was heated by microwaves to 150° C. for 15 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-25bae4f152ea428daa2e54b793570bd5
Source dataset
uspto-grants-2016_01
Patent number
US09242972B2

Reaction notes

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