Pyridine → 5-Chloro-N-[1-[(3-cyanophenyl)methyl]-4-(methyloxy)-1H-indazol-3-yl]-2-thiophenesulfonamide

HRID 1874654Notes

Reaction equation

HRID 1874654 reaction equation
[NH2:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[O:11][CH3:12])[N:4]([CH2:13][C:14]2[CH:15]=[C:16]([CH:19]=[CH:20][CH:21]=2)[C:17]#[N:18])[N:3]=1.[Cl:22][C:23]1[S:27][C:26]([S:28](Cl)(=[O:30])=[O:29])=[CH:25][CH:24]=1.N1C=CC=CC=1>>[Cl:22][C:23]1[S:27][C:26]([S:28]([NH:1][C:2]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][C:9]=3[O:11][CH3:12])[N:4]([CH2:13][C:14]3[CH:21]=[CH:20][CH:19]=[C:16]([C:17]#[N:18])[CH:15]=3)[N:3]=2)(=[O:30])=[O:29])=[CH:25][CH:24]=1

Participants

4

Reactant 3

HCID 1049PyridineHCID 27339255-Chlorothiophene-2-sulfonyl chlorideHCID 580544253-{[3-Amino-4-(methyloxy)-1H-indazol-1-yl]methyl}benzonitrile

Product 1

HCID 594559975-Chloro-N-[1-[(3-cyanophenyl)methyl]-4-(methyloxy)-1H-indazol-3-yl]-2-thiophenesulfonamideYield 85%

Procedure

To 3-{[3-amino-4-(methyloxy)-1H-indazol-1-yl]methyl}benzonitrile (for a preparation see Intermediate 2) (7.89 g, 28.3 mmol) was added a solution of 5-chloro-2-thiophenesulfonyl chloride (Aldrich) (6.15 g, 28.3 mmol) in pyridine (9.17 mL, 113 mmol) under nitrogen at room temperature. Reaction was exothermic and went deep red. After 40 minutes the reaction mixture was separated between ethyl acetate (500 mL) and 2N hydrochloric acid (500 mL). The aqueous phase was washed with ethyl acetate (400 mL). The combined organic solutions were dried over magnesium sulphate and evaporated in vacuo. The deep red residue was dissolved in DCM and applied to a 340 g silica cartridge. The cartridge was eluted with a gradient of 0-10% ethyl acetate in dichloromethane over 8 CV. Evaporation of the appropriate fractions gave the title compound (11.1 g, 85%) as an off-white solid. LCMS (System A) RT=1.15 min, ES+ve m/z 459/461 (M+H)+.

Workup

  1. customReaction
  2. customAfter 40 minutes the reaction mixture was separated between ethyl acetate (500 mL) and 2N hydrochloric acid (500 mL)
  3. washThe aqueous phase was washed with ethyl acetate (400 mL)
  4. dry with materialThe combined organic solutions were dried over magnesium sulphate
  5. customevaporated in vacuo
  6. dissolutionThe deep red residue was dissolved in DCM
  7. washThe cartridge was eluted with a gradient of 0-10% ethyl acetate in dichloromethane over 8 CV
  8. customEvaporation of the appropriate fractions

Sources & evidence

ORD record
ord-90ba14e721b54814a438b5a7ff0b571d
Source dataset
uspto-grants-2012_11
Patent number
US08304446B2

Reaction notes

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