Water → HCID 68323761, compound

HRID 573665Notes

Reaction equation

HRID 573665 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:44]=[CH:43][N:42]=[CH:41][CH:40]=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:44]=[CH:43][N:42]=[CH:41][CH:40]=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 27346484-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine2×HCID 53250396N-{2-Bromo-6-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-4-yl}-3-chlorobenzenesulfonamide

Product 1

HCID 68323761HCID 68323761, compoundYield 37.1%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalyst2×HCID 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)pyridine (58.7 mg, 0.286 mmol), bis(triphenylphosphine)palladium(II) chloride (13.40 mg, 0.019 mmol), potassium carbonate (79 mg, 0.573 mmol) and water (1 mL). The reaction mixture was heated at 100° C. in a microwave for 15 min (×2) and then for 30 min (×1). Another portion of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (58.7 mg, 0.286 mmol) and additional bis(triphenylphosphine)palladium(II) chloride (13.40 mg, 0.019 mmol) were added and heating continued, at 100° C. in a microwave, for another 15 min. The solvent was then removed in vacuo and the residue dissolved in ethyl acetate (30 mL) and washed with water (30 mL). The aqueous phase was re-extracted with ethyl acetate (30 mL×2). All organic phases were combined, dried over MgSO4, filtered and concentrated. The residue was purified on silica, eluting with a gradient of 0-50% ethyl acetate in cyclohexane and then further purified using MDAP (acidic conditions), to give the title compound (37 mg). LCMS (A) m/z: 520 [M−1]−, Rt 1.22 min (acidic).

Workup

  1. temperatureheating
  2. waitcontinued, at 100° C. in a microwave, for another 15 min
  3. customThe solvent was then removed in vacuo
  4. dissolutionthe residue dissolved in ethyl acetate (30 mL)
  5. washwashed with water (30 mL)
  6. extractionThe aqueous phase was re-extracted with ethyl acetate (30 mL×2)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified on silica
  11. washeluting with a gradient of 0-50% ethyl acetate in cyclohexane
  12. customfurther purified

Sources & evidence

ORD record
ord-2e9164842b894f549e1b6ee093cd8206
Source dataset
uspto-grants-2015_05
Patent number
US09029545B2

Reaction notes

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