Water → 3-Chloro-N-{2-(4-isoxazolyl)-6-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-4-yl}benzenesulfonamide

HRID 573662Notes

Reaction equation

HRID 573662 reaction equation
Br[C:2]1[S:22][C:5]2=[N:6][C:7]([CH3:21])=[CH:8][C:9]([NH:10][S:11]([C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[CH:15]=3)(=[O:13])=[O:12])=[C:4]2[C:3]=1[C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([O:29][CH3:30])[CH:24]=1.CC1(C)C(C)(C)OB([C:39]2[CH:40]=[N:41][O:42][CH:43]=2)O1.C(=O)([O-])[O-].[K+].[K+].O>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:20][C:16]1[CH:15]=[C:14]([S:11]([NH:10][C:9]2[CH:8]=[C:7]([CH3:21])[N:6]=[C:5]3[S:22][C:2]([C:39]4[CH:40]=[N:41][O:42][CH:43]=4)=[C:3]([C:23]4[CH:28]=[CH:27][CH:26]=[C:25]([O:29][CH3:30])[CH:24]=4)[C:4]=23)(=[O:13])=[O:12])[CH:19]=[CH:18][CH:17]=1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 164141804-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2-oxazoleHCID 53250396N-{2-Bromo-6-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-4-yl}-3-chlorobenzenesulfonamide

Product 1

HCID 683237603-Chloro-N-{2-(4-isoxazolyl)-6-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-4-yl}benzenesulfonamideYield 22.5%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of N-{2-bromo-6-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-4-yl}-3-chlorobenzenesulfonamide (Example 33) (100 mg, 0.191 mmol) in 1,4-dioxane (2 mL) was added 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoxazole (55.8 mg, 0.286 mmol), potassium carbonate (79 mg, 0.573 mmol) and bis(triphenylphosphine)palladium(II) chloride (13.40 mg, 0.019 mmol). Water (0.5 mL) was then added and the mixture heated at 100° C. in a microwave for 15 min. The solvent was then removed in vacuo and the residue dissolved in ethyl acetate (20 mL) and washed with water (20 mL). The aqueous phase was re-extracted with ethyl acetate (2×20 mL). All organic phases were combined, dried over MgSO4, filtered and concentrated. The residue was purified on silica, eluting with a gradient of 0-40% ethyl acetate in cyclohexane, to give the title compound (22 mg). LCMS (A) m/z: 512 [M+1]+, Rt 1.36 min (acidic).

Workup

  1. customThe solvent was then removed in vacuo
  2. dissolutionthe residue dissolved in ethyl acetate (20 mL)
  3. washwashed with water (20 mL)
  4. extractionThe aqueous phase was re-extracted with ethyl acetate (2×20 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified on silica
  9. washeluting with a gradient of 0-40% ethyl acetate in cyclohexane

Sources & evidence

ORD record
ord-de8b6bc2696148eeae53334a1ad763e3
Source dataset
uspto-grants-2015_05
Patent number
US09029545B2

Reaction notes

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