3-Chlorobenzenesulphonyl chloride → 3-Chloro-N-{2-methyl-6-(methyloxy)-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-4-yl}benzenesulfonamide

HRID 573688Notes

Reaction equation

HRID 573688 reaction equation
[CH3:1][C:2]1[S:13][C:5]2[N:6]=[C:7]([O:11][CH3:12])[CH:8]=[C:9]([NH2:10])[C:4]=2[C:3]=1[C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([O:20][CH3:21])[CH:15]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[Cl:32][C:33]1[CH:34]=[C:35]([S:39](Cl)(=[O:41])=[O:40])[CH:36]=[CH:37][CH:38]=1>C1COCC1>[Cl:32][C:33]1[CH:34]=[C:35]([S:39]([NH:10][C:9]2[CH:8]=[C:7]([O:11][CH3:12])[N:6]=[C:5]3[S:13][C:2]([CH3:1])=[C:3]([C:14]4[CH:19]=[CH:18][CH:17]=[C:16]([O:20][CH3:21])[CH:15]=4)[C:4]=23)(=[O:41])=[O:40])[CH:36]=[CH:37][CH:38]=1

Participants

5

Reactant 3

HCID 179093-Chlorobenzenesulphonyl chlorideHCID 2733832Lithium HexamethyldisilazideHCID 683241312-Methyl-6-(methyloxy)-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-4-amine

Product 1

HCID 683237633-Chloro-N-{2-methyl-6-(methyloxy)-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-4-yl}benzenesulfonamideYield 42.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-methyl-6-(methyloxy)-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-4-amine (Description 37) (16.5 mg, 0.055 mmol) in THF (0.5 mL) at −78° C. under a nitrogen atmosphere was added LiHMDS (1M solution in THF) (0.055 mL, 0.055 mmol). The solution was stirred at −78° C. for ca. 10 min before the addition of 3-chlorobenzenesulfonyl chloride (7.73 μL, 0.055 mmol). The reaction mixture was then warmed to RT under a nitrogen atmosphere overnight and was then partitioned between water and ethyl acetate (ca. 10 mL each). The aqueous layer was separated and re-extracted with ethyl acetate (ca. 10 mL). The combined organic layer was passed through phase separator and the solvent concentrated in vacuo. The residue was purified by MDAP (acidic conditions), to give the title compound (11 mg). LCMS (A) m/z: 475 [M+1]+, Rt 1.63 min (acidic).

Workup

  1. customwas then partitioned between water and ethyl acetate (ca. 10 mL each)
  2. customThe aqueous layer was separated
  3. extractionre-extracted with ethyl acetate (ca. 10 mL)
  4. concentrationthe solvent concentrated in vacuo
  5. customThe residue was purified by MDAP (acidic conditions)

Sources & evidence

ORD record
ord-349f63cb3f2746fd804b2b70ef5dda9a
Source dataset
uspto-grants-2015_05
Patent number
US09029545B2

Reaction notes

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