Water → HCID 178489654, compound

HRID 573661Notes

Reaction equation

HRID 573661 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.[NH:31]1[CH:35]=[CH:34][C:33](B(O)O)=[N:32]1.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.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=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:35]4[CH:34]=[CH:33][NH:32][N:31]=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

8

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 53250396N-{2-Bromo-6-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-4-yl}-3-chlorobenzenesulfonamideHCID 178514837HCID 178514837, compound

Product 1

HCID 178489654HCID 178489654, compoundYield 10.3%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 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) (160 mg, 0.305 mmol) in 1,4-dioxane (2.5 mL) was added 1H-pyrazol-3-ylboronic acid (51.3 mg, 0.458 mmol), bis(triphenylphosphine)palladium(II) chloride (21.44 mg, 0.031 mmol) and potassium carbonate (127 mg, 0.916 mmol). Then, water (1 mL) was added to the mixture. The reaction mixture was then heated at 100° C. in a microwave for 15 min (×2). Extra tetrakis(triphenylphosphine)palladium(0) (35.3 mg, 0.031 mmol) was added and the mixture heated at 100° C. for another 15 min. The solvent from 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 (20 mL×2). All organic phase were combined, dried over MgSO4, filtered and the solvent removed in vacuo. The residue was purified on silica, eluting with a gradient of 0-50% ethyl acetate in cyclohexane and further purified using MDAP (acidic conditions), to give the title compound (16 mg). LCMS (A) m/z: 509 [M−1]−, Rt 1.23 min (acidic).

Workup

  1. temperaturethe mixture heated at 100° C. for another 15 min
  2. customThe solvent from was then removed in vacuo
  3. dissolutionthe residue dissolved in ethyl acetate (20 mL)
  4. washwashed with water (20 mL)
  5. extractionThe aqueous phase was re-extracted with ethyl acetate (20 mL×2)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customthe solvent removed in vacuo
  9. customThe residue was purified on silica
  10. washeluting with a gradient of 0-50% ethyl acetate in cyclohexane
  11. customfurther purified

Sources & evidence

ORD record
ord-a14cb5f6d90e4148bbdc429050b84f67
Source dataset
uspto-grants-2015_05
Patent number
US09029545B2

Reaction notes

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