Dichloromethane → 3-chloro-N-(2,6-dimethyl-3-phenylthieno[2,3-b]pyridin-4-yl)benzenesulfonamide

HRID 573609Notes

Reaction equation

HRID 573609 reaction equation
Br[C:2]1[C:10]2[C:5](=[N:6][C:7]([CH3:22])=[CH:8][C:9]=2[NH:11][S:12]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([Cl:21])[CH:16]=2)(=[O:14])=[O:13])[S:4][C:3]=1[CH3:23].[C:24]1(B(O)O)[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C(Cl)Cl.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O.C1(C)C=CC=CC=1>[Cl:21][C:17]1[CH:16]=[C:15]([S:12]([NH:11][C:9]2[CH:8]=[C:7]([CH3:22])[N:6]=[C:5]3[S:4][C:3]([CH3:23])=[C:2]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)[C:10]=23)(=[O:14])=[O:13])[CH:20]=[CH:19][CH:18]=1

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 66827Phenylboronic AcidHCID 68324076N-(3-bromo-2,6-dimethylthieno[2,3-b]pyridin-4-yl)-3-chlorobenzenesulfonamide

Product 1

HCID 683240683-chloro-N-(2,6-dimethyl-3-phenylthieno[2,3-b]pyridin-4-yl)benzenesulfonamideYield 16.1%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

Under nitrogen, N-(3-bromo-2,6-dimethylthieno[2,3-b]pyridin-4-yl)-3-chlorobenzenesulfonamide (90 mg, 0.208 mmol) (Example 61) was dissolved in 1,4-dioxane (3 mL). Phenylboronic acid (38.1 mg, 0.313 mmol), PdCl2(dppf).DCM (17.02 mg, 0.021 mmol) and Cs2CO3 (204 mg, 0.625 mmol) were added and the mixture heated in a microwave at 120° C. for 30 min. Toluene (3 mL) was added and the mixture heated in a microwave as follows: 130° C. for 30 min, 150° C. for 30 min (×2) and finally 180° C. for 15 min (×2). Water (10 mL) was then added and the mixture extracted with ethyl acetate (3×10 mL). The organic layer was dried over MgSO4, filtered and the solvent removed in vacuo. Purification by chromatography on silica gel, eluting with a gradient of 0-30% ethyl acetate in cyclohexane was followed by further purification by MDAP (basic conditions), to afford the title compound (14.4 mg). LCMS (A) m/z: 429 [M+1]+, Rt 1.10 min (basic), Rt 1.47 min (acidic).

Workup

  1. temperaturethe mixture heated in a microwave
  2. wait150° C. for 30 min (×2) and finally 180° C. for 15 min (×2)
  3. extractionthe mixture extracted with ethyl acetate (3×10 mL)
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. customthe solvent removed in vacuo
  7. customPurification by chromatography on silica gel
  8. washeluting with a gradient of 0-30% ethyl acetate in cyclohexane
  9. customwas followed by further purification by MDAP (basic conditions)

Sources & evidence

ORD record
ord-937e7bcc767640a9bc97b4c69e32dcce
Source dataset
uspto-grants-2015_05
Patent number
US09029545B2

Reaction notes

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