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

HRID 1892890Notes

Reaction equation

HRID 1892890 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 8CV. 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 8CV
  8. customEvaporation of the appropriate fractions

Sources & evidence

ORD record
ord-b589e1e608754bcda21fc6c5922f3f10
Source dataset
uspto-grants-2013_08
Patent number
US08507543B2

Reaction notes

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