Cyclohexanesulfonyl chloride → N-{2,6-Dimethyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-4-yl}-cyclohexanesulfonamide

HRID 573607Notes

Reaction equation

HRID 573607 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.[CH:31]1([S:37](Cl)(=[O:39])=[O:38])[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]1>C1COCC1.O>[CH3:1][C:2]1[S:12][C:5]2=[N:6][C:7]([CH3:11])=[CH:8][C:9]([NH:10][S:37]([CH:31]3[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]3)(=[O:39])=[O:38])=[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

6

Reactant 3

HCID 237554Cyclohexanesulfonyl chloride2×HCID 2733832Lithium Hexamethyldisilazide2×HCID 68323863HCID 68323863, compound

Product 1

HCID 53250393N-{2,6-Dimethyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-4-yl}-cyclohexanesulfonamideYield 14.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 2,6-dimethyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-4-amine (100 mg, 0.352 mmol) (Description 4) 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 45 min before the addition of cyclohexanesulfonyl chloride (0.161 g, 0.879 mmol). The reaction mixture was then stirred at RT for a further 12 h. The reaction mixture was then re-cooled in an ice bath before the addition of LiHMDS (1M solution in THF) (0.352 mL, 0.352 mmol). The reaction mixture was then stirred at RT for 45 min before the addition of cyclohexanesulfonyl chloride (0.064 g, 0.352 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) and the combined organic extracts dried over a phase separating column and concentrated. The residue was then purified by MDAP (basic conditions), to afford the title compound (22 mg). LCMS (A) m/z: 431 [M+1]+, Rt 1.16 min (basic).

Workup

  1. stirringThe reaction mixture was then stirred at RT for a further 12 h
  2. extractionthe aqueous layer extracted with DCM (3×30 mL)
  3. customthe combined organic extracts dried over a phase
  4. customseparating column
  5. concentrationconcentrated
  6. customThe residue was then purified by MDAP (basic conditions)

Sources & evidence

ORD record
ord-ca494326b9a24145b492cadc78e92d0c
Source dataset
uspto-grants-2015_05
Patent number
US09029545B2

Reaction notes

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