Diethyl Ether → N-{2,6-Dimethyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-4-yl}-3-(methyloxy)benzenesulfonamide

HRID 573608Notes

Reaction equation

HRID 573608 reaction equation
[CH3:1][C:2]1[S:12][C:5]2[N:6]=[C:7]([CH3:11])[CH:8]=[C:9]([NH2:10])[C:4]=2[C:3]=1[C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH3:20])[CH:14]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH3:31][O:32][C:33]1[CH:34]=[C:35]([S:39](Cl)(=[O:41])=[O:40])[CH:36]=[CH:37][CH:38]=1.C(OCC)C>C1COCC1.O.C(Cl)Cl>[CH3:1][C:2]1[S:12][C:5]2=[N:6][C:7]([CH3:11])=[CH:8][C:9]([NH:10][S:39]([C:35]3[CH:36]=[CH:37][CH:38]=[C:33]([O:32][CH3:31])[CH:34]=3)(=[O:41])=[O:40])=[C:4]2[C:3]=1[C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH3:20])[CH:14]=1

Participants

8

Reactant 4

HCID 3283Diethyl EtherHCID 2733832Lithium HexamethyldisilazideHCID 27375043-Methoxybenzenesulfonyl chlorideHCID 68323863HCID 68323863, compound

Product 1

HCID 68323815N-{2,6-Dimethyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-4-yl}-3-(methyloxy)benzenesulfonamideYield 69.9%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 2,6-dimethyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-4-amine (Description 4) (120 mg, 0.422 mmol) in THF (2 mL), cooled in an ice bath, was added LiHMDS (1M solution in THF) (0.928 mL, 0.928 mmol). The reaction mixture was stirred at RT for 45 min before the addition of 3-(methyloxy)benzenesulfonyl chloride (218 mg, 1.055 mmol) and the reaction mixture was then stirred at RT for a further 12 h. The reaction mixture was then diluted with water (15 mL) and the aqueous layer extracted with DCM (3×30 mL) and the combined organic extracts dried over a phase separating column and concentrated. Purification by chromatography on silica gel, eluting with a gradient of 0-20% ethyl acetate in cyclohexane, afforded a solid which was dissolved in the minimum amount of DCM. Upon addition of diethyl ether, a solid precipitated out which was collected by filtration, washed with diethyl ether and dried, to afford the title compound (134 mg). LCMS (A) m/z: 455 [M+1]+, Rt 1.12 min (basic).

Workup

  1. extractionthe aqueous layer extracted with DCM (3×30 mL)
  2. customthe combined organic extracts dried over a phase
  3. customseparating column
  4. concentrationconcentrated
  5. customPurification by chromatography on silica gel
  6. washeluting with a gradient of 0-20% ethyl acetate in cyclohexane
  7. customafforded a solid which
  8. customa solid precipitated out which
  9. filtrationwas collected by filtration
  10. washwashed with diethyl ether
  11. customdried

Sources & evidence

ORD record
ord-50b937d3539841a78616bb9c49a81094
Source dataset
uspto-grants-2015_05
Patent number
US09029545B2

Reaction notes

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