3-Chlorobenzenesulphonyl chloride → N-[2-bromo-6-methyl-3-(3-methylphenyl)thieno[2,3-b]pyridin-4-yl]-3-chlorobenzenesulfonamide

HRID 573579Notes

Reaction equation

HRID 573579 reaction equation
[Br: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]([CH3:19])[CH:14]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[Cl:30][C:31]1[CH:32]=[C:33]([S:37](Cl)(=[O:39])=[O:38])[CH:34]=[CH:35][CH:36]=1>C1COCC1>[Br:1][C:2]1[S:12][C:5]2=[N:6][C:7]([CH3:11])=[CH:8][C:9]([NH:10][S:37]([C:33]3[CH:34]=[CH:35][CH:36]=[C:31]([Cl:30])[CH:32]=3)(=[O:39])=[O:38])=[C:4]2[C:3]=1[C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([CH3:19])[CH:14]=1

Participants

5

Reactant 3

HCID 179093-Chlorobenzenesulphonyl chlorideHCID 2733832Lithium HexamethyldisilazideHCID 683240302-Bromo-6-methyl-3-(3-methylphenyl)thieno[2,3-b]pyridin-4-amine

Product 1

HCID 68323728N-[2-bromo-6-methyl-3-(3-methylphenyl)thieno[2,3-b]pyridin-4-yl]-3-chlorobenzenesulfonamideYield 43.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 2-bromo-6-methyl-3-(3-methylphenyl)thieno[2,3-b]pyridin-4-amine (Description 59) (487 mg, 1.461 mmol) in THF (10 mL) at −78° C. under nitrogen atmosphere was added LiHMDS (1M solution in THF) (1.608 mL, 1.608 mmol) and 3-chlorobenzenesulfonyl chloride (0.226 mL, 1.608 mmol). The reaction mixture was warmed to RT under a nitrogen atmosphere for ca. 1 h and was then partitioned between ethyl acetate and water (ca. 30 mL each). The aqueous layer was separated and re-extracted with ethyl acetate (ca. 30 mL) and the combined organic layer passed through a phase separator and the solvent removed in vacuo. Purification by chromatography on silica, eluting with a gradient of 0-50% ethyl acetate in cyclohexane afforded the title compound (320 mg). LCMS (A) m/z: 508/510 [M+1]+, Rt 1.60 min (acidic).

Workup

  1. customwas then partitioned between ethyl acetate and water (ca. 30 mL each)
  2. customThe aqueous layer was separated
  3. extractionre-extracted with ethyl acetate (ca. 30 mL)
  4. customthe solvent removed in vacuo
  5. customPurification by chromatography on silica
  6. washeluting with a gradient of 0-50% ethyl acetate in cyclohexane

Sources & evidence

ORD record
ord-eb804c37f0d34ff08dd56b5bca84b116
Source dataset
uspto-grants-2015_05
Patent number
US09029545B2

Reaction notes

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