p-Bromobenzenesulfonyl chloride → 4-Bromo-N-{2,6-dimethyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-4-yl}benzenesulfonamide

HRID 573693Notes

Reaction equation

HRID 573693 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.[Br:31][C:32]1[CH:37]=[CH:36][C:35]([S:38](Cl)(=[O:40])=[O:39])=[CH:34][CH:33]=1>C1COCC1.O>[Br:31][C:32]1[CH:37]=[CH:36][C:35]([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:34][CH:33]=1

Participants

6

Reactant 3

HCID 7396p-Bromobenzenesulfonyl chlorideHCID 2733832Lithium HexamethyldisilazideHCID 68323863HCID 68323863, compound

Product 1

HCID 683239144-Bromo-N-{2,6-dimethyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-4-yl}benzenesulfonamideYield 58.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a 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 resulting reaction mixture was stirred for 45 min before addition of 4-bromobenzenesulfonyl chloride (225 mg, 0.879 mmol). The reaction mixture was then stirred at RT for a further 12 h. The reaction mixture was diluted with water (15 mL) and the aqueous layer re-extracted with DCM (30 mL×3). The organics were combined, dried over a phase separating column and concentrated. To the residue was added MeOH (ca. 0.5 mL) and a solid crashed-out which was collected by filtration and rinsed with MeOH (ca. 2 mL). The solid was then dried, to afford the title compound (104 mg). LCMS (A) m/z: 503/505 [M+1]+, Rt 1.11 min (basic).

Workup

  1. customThe resulting reaction mixture
  2. extractionthe aqueous layer re-extracted with DCM (30 mL×3)
  3. customdried over a phase
  4. customseparating column
  5. concentrationconcentrated
  6. additionTo the residue was added MeOH (ca. 0.5 mL)
  7. filtrationwas collected by filtration
  8. washrinsed with MeOH (ca. 2 mL)
  9. customThe solid was then dried

Sources & evidence

ORD record
ord-1237ba360c714e5e95efa2d6e860796c
Source dataset
uspto-grants-2015_05
Patent number
US09029545B2

Reaction notes

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