1-Bromo-2-methylpropane → N-(5-chloro-3-methylpyridin-2-yl)-4-fluoro-N-isobutylbenzenesulfonamide

HRID 594116Notes

Reaction equation

HRID 594116 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH3:19])[C:5]([NH:8][S:9]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)(=[O:11])=[O:10])=[N:6][CH:7]=1.[C:20](N=C(N(C)C)N(C)C)([CH3:23])([CH3:22])[CH3:21].BrCC(C)C>C(#N)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH3:19])[C:5]([N:8]([CH2:21][CH:20]([CH3:23])[CH3:22])[S:9]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)(=[O:10])=[O:11])=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 65551-Bromo-2-methylpropane2×HCID 35715812-tert-Butyl-1,1,3,3-tetramethylguanidine2×HCID 89876053N-(5-chloro-3-methylpyridin-2-yl)-4-fluorobenzenesulfonamide

Product 1

HCID 89875794N-(5-chloro-3-methylpyridin-2-yl)-4-fluoro-N-isobutylbenzenesulfonamideYield 66.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
150 °C

Procedure

N-(5-chloro-3-methylpyridin-2-yl)-4-fluorobenzenesulfonamide (502 mg, 1.67 mmol) was dissolved in acetonitrile (3.5 mL) and to this solution was added 2-(tert-butyl)-1,1,3,3-tetramethylguanidine (350 μL, 1.67 mmol). The solution was left to stir for 15 minutes then 1-bromo-2-methylpropane (363 μL, 3.34 mmol) was added. The reaction vessel was sealed and heated by microwaves to 150° C. for 1 hour. After cooling, additional 0.5 eq of 2-(tert-butyl)-1,1,3,3-tetramethylguanidine was added, along with 1 eq of 1-bromo-2-methylpropane. The reaction vessel was sealed and heated by microwaves to 150° C. for an additional 1 hour. The solution was concentrated in vacuo and the crude product extracted to the organic phase of an aqueous workup between ethyl acetate and water. The organic phase was passed through a hydrophobic frit, concentrated in vacuo and purified by flash silica (Si) chromatography (0-25% ethyl acetate-cyclohexane gradient). The relevant fractions were combined and evaporated to give the title compound (396 mg). LCMS (2 min, formic) Rt 1.38 min, m/z (ES+) 357 (M+H).

Workup

  1. waitThe solution was left
  2. customThe reaction vessel was sealed
  3. temperatureAfter cooling
  4. customThe reaction vessel was sealed
  5. temperatureheated by microwaves to 150° C. for an additional 1 hour
  6. concentrationThe solution was concentrated in vacuo
  7. extractionthe crude product extracted to the organic phase of an aqueous workup between ethyl acetate and water
  8. concentrationconcentrated in vacuo
  9. custompurified by flash silica (Si) chromatography (0-25% ethyl acetate-cyclohexane gradient)
  10. customevaporated

Sources & evidence

ORD record
ord-ea7f512797104517b89b6d16266b1abc
Source dataset
uspto-grants-2016_01
Patent number
US09242972B2

Reaction notes

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