1-Bromo-2-methylpropane → 4-{[(3,5-dimethyl-4-isoxazolyl)methyl]oxy}-N-(4,6-dimethyl-3-pyridinyl)-N-(2-methylpropyl)benzenesulfonamide

HRID 594157Notes

Reaction equation

HRID 594157 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[CH:20]=[N:21][C:22]([CH3:26])=[CH:23][C:24]=3[CH3:25])(=[O:17])=[O:16])=[CH:11][CH:10]=2)=[C:5]([CH3:27])[O:4][N:3]=1.[C:28](N=C(N(C)C)N(C)C)([CH3:31])([CH3:30])[CH3:29].BrCC(C)C>C(#N)C>[CH3:1][C:2]1[C:6]([CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12]([S:15]([N:18]([C:19]3[CH:20]=[N:21][C:22]([CH3:26])=[CH:23][C:24]=3[CH3:25])[CH2:29][CH:28]([CH3:31])[CH3:30])(=[O:17])=[O:16])=[CH:11][CH:10]=2)=[C:5]([CH3:27])[O:4][N:3]=1

Participants

5

Reactant 3

HCID 65551-Bromo-2-methylpropane2×HCID 35715812-tert-Butyl-1,1,3,3-tetramethylguanidine2×HCID 1179257044-{[(3,5-dimethyl-4-isoxazolyl)methyl]oxy}-N-(4,6-dimethyl-3-pyridinyl)benzenesulfonamide

Product 1

HCID 721944234-{[(3,5-dimethyl-4-isoxazolyl)methyl]oxy}-N-(4,6-dimethyl-3-pyridinyl)-N-(2-methylpropyl)benzenesulfonamideYield 14.9%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

4-{[(3,5-dimethyl-4-isoxazolyl)methyl]oxy}-N-(4,6-dimethyl-3-pyridinyl)benzenesulfonamide (100 mg, 0.258 mmol) and 2-(tert-butyl)-1,1,3,3-tetramethylguanidine (44.2 mg, 0.258 mmol) were dissolved in acetonitrile (1 mL). The mixture was stirred at room temperature for 1 hour, then 1-bromo-2-methylpropane (0.028 mL, 0.258 mmol) was added. The reaction was stirred at room temperature for 20 hours, then additional 2-(tert-butyl)-1,1,3,3-tetramethylguanidine (44.2 mg, 0.258 mmol) and 1-bromo-2-methylpropane (0.028 mL, 0.258 mmol) were added. The reaction was heated to 60° C. and stirred for a further 2 hours. The solvent was removed in vacuo and the residue was partitioned between water (5 mL) and dichloromethane (5 mL). The organic layer was separated, concentrated and purified by mass directed autoprep (formic acid modifier). The required fractions were combined and concentrated to provide the title compound (17 mg) as a colourless oil. LCMS (2 min, formic) Rt 1.04 mins, m/z (ES+) 444 (M+H).

Workup

  1. stirringThe reaction was stirred at room temperature for 20 hours
  2. temperatureThe reaction was heated to 60° C.
  3. stirringstirred for a further 2 hours
  4. customThe solvent was removed in vacuo
  5. customthe residue was partitioned between water (5 mL) and dichloromethane (5 mL)
  6. customThe organic layer was separated
  7. concentrationconcentrated
  8. custompurified by mass
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-7604837e92474205956b1ac4f90438ec
Source dataset
uspto-grants-2016_01
Patent number
US09242972B2

Reaction notes

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