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

HRID 573605Notes

Reaction equation

HRID 573605 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.[Cl:31][C:32]1[CH:33]=[C:34]([S:38](Cl)(=[O:40])=[O:39])[CH:35]=[CH:36][CH:37]=1.C(OCC)C>C1COCC1.O.C(Cl)Cl>[Cl:31][C:32]1[CH:33]=[C:34]([S:38]([NH:10][C:9]2[CH:8]=[C:7]([CH3:11])[N:6]=[C:5]3[S:12][C:2]([CH3:1])=[C:3]([C:13]4[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH3:20])[CH:14]=4)[C:4]=23)(=[O:40])=[O:39])[CH:35]=[CH:36][CH:37]=1

Participants

8

Reactant 4

HCID 3283Diethyl EtherHCID 179093-Chlorobenzenesulphonyl chlorideHCID 2733832Lithium HexamethyldisilazideHCID 68323863HCID 68323863, compound

Product 1

HCID 683240623-Chloro-N-{2,6-dimethyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-4-yl}-benzenesulfonamideYield 55.1%

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) (100 mg, 0.352 mmol) in THF (2 mL), cooled in an ice bath, was added LiHMDS (1M solution in THF) (0.774 mL, 0.774 mmol). The reaction mixture was stirred at RT for 1 h before the addition of 3-chlorobenzenesulfonyl chloride (0.124 mL, 0.879 mmol). 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). The combined organic extracts were 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 (89 mg). LCMS (A) m/z: 459 [M+1]+, Rt 1.03 min (basic).

Workup

  1. extractionthe aqueous layer extracted with DCM (3×30 mL)
  2. customThe combined organic extracts were 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-2b17ec6c7ebb4237aac996d30365ab89
Source dataset
uspto-grants-2015_05
Patent number
US09029545B2

Reaction notes

Loading…