Cesium carbonate → 3-Chloro-N-{2-(3,5-dimethyl-4-isoxazolyl)-6-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-4-yl}benzenesulfonamide

HRID 573624Notes

Reaction equation

HRID 573624 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.[CH3:31][C:32]1[C:36](B(O)O)=[C:35]([CH3:40])[O:34][N:33]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=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:36]4[C:32]([CH3:31])=[N:33][O:34][C:35]=4[CH3:40])=[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 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 27343463,5-Dimethylisoxazole-4-boronic acidHCID 53250396N-{2-Bromo-6-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-4-yl}-3-chlorobenzenesulfonamide

Product 1

HCID 683241553-Chloro-N-{2-(3,5-dimethyl-4-isoxazolyl)-6-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-4-yl}benzenesulfonamideYield 18.4%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

N-{2-Bromo-6-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-4-yl}-3-chlorobenzenesulfonamide (100 mg, 0.191 mmol) (Example 33), (3,5-dimethyl-4-isoxazolyl)boronic acid (40.4 mg, 0.286 mmol), palladium(II) acetate (4.29 mg, 0.019 mmol), xantphos (22.09 mg, 0.038 mmol) and Cs2CO3 (187 mg, 0.573 mmol) were weighed into a round bottom flask. Degassed toluene (2 mL) was added to the mixture which was then heated at 110° C. for 19 h. After cooling to RT, the mixture was filtered through celite and rinsed with ethyl acetate (30 mL) and the combined filtrate concentrated. Purification by chromatography on silica gel, eluting with a gradient of 0-50% ethyl acetate in isohexane, afforded the title compound (19 mg). LCMS (A) m/z: 540 [M+1]+, Rt 1.40 min (acidic), Rt 0.94 min (basic).

Workup

  1. temperatureAfter cooling to RT
  2. filtrationthe mixture was filtered through celite
  3. washrinsed with ethyl acetate (30 mL)
  4. concentrationthe combined filtrate concentrated
  5. customPurification by chromatography on silica gel
  6. washeluting with a gradient of 0-50% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-307b0fbb5c4f4a6cafdc4454a9350d70
Source dataset
uspto-grants-2015_05
Patent number
US09029545B2

Reaction notes

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