(Bromomethyl)cyclobutane → N-(cyclobutylmethyl)-4-((3,5-dimethylisoxazol-4-yl)methoxy)-N-(5-isopropylpyridin-2-yl)benzenesulfonamide

HRID 594170Notes

Reaction equation

HRID 594170 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:24]=[CH:23][C:22]([CH:25]([CH3:27])[CH3:26])=[CH:21][N:20]=3)(=[O:17])=[O:16])=[CH:11][CH:10]=2)=[C:5]([CH3:28])[O:4][N:3]=1.C(N=C(N(C)C)N(C)C)(C)(C)C.Br[CH2:42][CH:43]1[CH2:46][CH2:45][CH2:44]1>C(#N)C>[CH:43]1([CH2:42][N:18]([C:19]2[CH:24]=[CH:23][C:22]([CH:25]([CH3:26])[CH3:27])=[CH:21][N:20]=2)[S:15]([C:12]2[CH:11]=[CH:10][C:9]([O:8][CH2:7][C:6]3[C:2]([CH3:1])=[N:3][O:4][C:5]=3[CH3:28])=[CH:14][CH:13]=2)(=[O:17])=[O:16])[CH2:46][CH2:45][CH2:44]1

Participants

5

Reactant 3

HCID 2734658(Bromomethyl)cyclobutaneHCID 35715812-tert-Butyl-1,1,3,3-tetramethylguanidineHCID 898760154-((3,5-dimethylisoxazol-4-yl)methoxy)-N-(5-isopropylpyridin-2-yl)benzenesulfonamide

Product 1

HCID 72194822N-(cyclobutylmethyl)-4-((3,5-dimethylisoxazol-4-yl)methoxy)-N-(5-isopropylpyridin-2-yl)benzenesulfonamideYield 23.9%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
20 °C

Procedure

To a solution of 4-((3,5-dimethylisoxazol-4-yl)methoxy)-N-(5-isopropylpyridin-2-yl)benzenesulfonamide (150 mg, 0.374 mmol) in acetonitrile (4 mL) stirred in air at 20° C., was added 2-(tert-butyl)-1,1,3,3-tetramethylguanidine (128 mg, 0.747 mmol). The reaction mixture was stirred at 20° C. for 1 hour, then (bromomethyl)cyclobutane (0.084 ml, 0.747 mmol) was added. The reaction was heated by microwaves to 150° C. for 30 minutes. After cooling the solvent was removed in vacuo and the residue was dissolved in ethyl acetate. The organic phase was washed with water (5 mL) and dried using a hydrophobic frit. The solvent was removed in vacuo to give the crude product as an orange oil. The crude product was purified by flash silica (Si) chromatography (0-25% ethyl acetate-cyclohexane gradient). The appropriate fractions were combined and evaporated in vacuo to give the title product (42 mg) as a colourless oil. LCMS (2 min, High pH) Rt 1.48 mins, m/z (ES+) 470, (M+H).

Workup

  1. temperatureThe reaction was heated by microwaves to 150° C. for 30 minutes
  2. temperatureAfter cooling the solvent
  3. customwas removed in vacuo
  4. dissolutionthe residue was dissolved in ethyl acetate
  5. washThe organic phase was washed with water (5 mL)
  6. customdried
  7. customThe solvent was removed in vacuo
  8. customto give the crude product as an orange oil
  9. customThe crude product was purified by flash silica (Si) chromatography (0-25% ethyl acetate-cyclohexane gradient)
  10. customevaporated in vacuo

Sources & evidence

ORD record
ord-97324b61a9de49769aa3252483c0df8c
Source dataset
uspto-grants-2016_01
Patent number
US09242972B2

Reaction notes

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