Pyridine → HCID 59456027, compound

HRID 1892922Notes

Reaction equation

HRID 1892922 reaction equation
[NH2:1][C:2]1[C:10]2[C:5](=[C:6]([F:13])[CH:7]=[CH:8][C:9]=2[O:11][CH3:12])[N:4]([CH2:14][C:15]2[CH:16]=[C:17]([CH:20]=[CH:21][CH:22]=2)[C:18]#[N:19])[N:3]=1.[Cl:23][C:24]1[S:28][C:27]([S:29](Cl)(=[O:31])=[O:30])=[CH:26][CH:25]=1.N1C=CC=CC=1>C(Cl)Cl>[Cl:23][C:24]1[S:28][C:27]([S:29]([NH:1][C:2]2[C:10]3[C:5](=[C:6]([F:13])[CH:7]=[CH:8][C:9]=3[O:11][CH3:12])[N:4]([CH2:14][C:15]3[CH:22]=[CH:21][CH:20]=[C:17]([C:18]#[N:19])[CH:16]=3)[N:3]=2)(=[O:31])=[O:30])=[CH:26][CH:25]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 27339255-Chlorothiophene-2-sulfonyl chloride2×HCID 58054476HCID 58054476, compound

Product 1

HCID 59456027HCID 59456027, compoundYield 30%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 3-{[3-amino-7-fluoro-4-(methyloxy)-1H-indazol-1-yl]methyl}benzonitrile (for a preparation see Intermediate 44) (665 mg, 2.24 mmol) in dry DCM (10 mL) was added 5-chloro-2-thiophenesulfonyl chloride (0.300 mL, 2.24 mmol), followed with pyridine (2 mL). The resultant dark yellow solution was stirred at room temperature overnight. More 5-chloro-2-thiophenesulfonyl chloride was added (0.100 mL) and the reaction stirred for a further 1 h. The reaction mixture was partitioned between ethyl acetate and 2N hydrochloric acid. The aqueous phase was extracted with ethyl acetate (×2). The combined organic solutions were washed with water and brine, dried (Na2SO4) and concentrated in vacuo to leave a deep red oil. This residue was loaded in dichloromethane to a silica 100 g cartridge and purified by chromatography on Flashmaster eluting with a 0-100% ethyl acetate-dichloromethane over 40 min. The appropriate fractions were combined and evaporated in vacuo to give the title compound (323 mg, 30%) as a pale yellow powder. LCMS (System A) RT=1.2 min, ES+ve m/z 476/478 (M+H)+.

Workup

  1. stirringthe reaction stirred for a further 1 h
  2. customThe reaction mixture was partitioned between ethyl acetate and 2N hydrochloric acid
  3. extractionThe aqueous phase was extracted with ethyl acetate (×2)
  4. washThe combined organic solutions were washed with water and brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customto leave a deep red oil
  8. custompurified by chromatography on Flashmaster
  9. washeluting with a 0-100% ethyl acetate-dichloromethane over 40 min
  10. customevaporated in vacuo

Sources & evidence

ORD record
ord-f37ce2d0ece5453f8203d09ac47f6940
Source dataset
uspto-grants-2013_08
Patent number
US08507543B2

Reaction notes

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