Thionyl Chloride → 2,6-dichloro-N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]pyridine-3-carboxamide

HRID 1526050Notes

Reaction equation

HRID 1526050 reaction equation
[Cl:1][C:2]1[C:7]([C:8]([OH:10])=O)=[CH:6][CH:5]=[C:4]([Cl:11])[N:3]=1.S(Cl)(Cl)=O.[F:16][C:17]1[CH:18]=[C:19]([CH:31]=[C:32]([F:34])[CH:33]=1)[CH2:20][C:21]1[CH:22]=[C:23]2[C:27](=[CH:28][CH:29]=1)[NH:26][N:25]=[C:24]2[NH2:30]>C1(C)C=CC=CC=1.N1C=CC=CC=1>[Cl:1][C:2]1[C:7]([C:8]([NH:30][C:24]2[C:23]3[C:27](=[CH:28][CH:29]=[C:21]([CH2:20][C:19]4[CH:31]=[C:32]([F:34])[CH:33]=[C:17]([F:16])[CH:18]=4)[CH:22]=3)[NH:26][N:25]=2)=[O:10])=[CH:6][CH:5]=[C:4]([Cl:11])[N:3]=1

Participants

6

Reactant 3

HCID 24386Thionyl ChlorideHCID 8540472,6-Dichloronicotinic acidHCID 441342655-[(3,5-difluorophenyl)methyl]-1H-indazol-3-amine

Product 1

HCID 866476302,6-dichloro-N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]pyridine-3-carboxamideYield 34.6%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 1140TolueneSolvent

Procedure

2,6-dichloropyridine-3-carboxylic acid (480 mg, 2.5 mmol) and thionyl chloride (0.28 mL, 3.75 mmol) were heated in toluene dry (120 mL) and a few drops of dry DMF at 90° C. for 2 hours Volatiles were evaporated and the residue dissolved in dry pyridine (15 mL) at 0° C. under nitrogen atmosphere. A solution of 5-(3,5-difluoro-benzyl)-1H-indazol-3-ylamine (518 mg, 2 mmol) in dry pyridine (7 mL) was added to the cooled reaction mixture. The resulting mixture was allowed to react overnight at room temperature, then the solvent removed under reduced pressure. The residue was taken-up with EtOAc and washed with aqueous NaHCO3 sat. sol., water and brine. Organic phase was dried over sodium sulfate and evaporated to dryness. The crude was purified by flash chromatography on silica gel using DCM/EtOH 100:4 as the eluant, affording 300 mg of the title compound.

Workup

  1. dry with materialdry (120 mL) and a few drops of dry DMF at 90° C. for 2 hours Volatiles
  2. customwere evaporated
  3. dissolutionthe residue dissolved in dry pyridine (15 mL) at 0° C. under nitrogen atmosphere
  4. customto react overnight at room temperature
  5. customthe solvent removed under reduced pressure
  6. washwashed with aqueous NaHCO3 sat. sol., water and brine
  7. dry with materialOrganic phase was dried over sodium sulfate
  8. customevaporated to dryness
  9. customThe crude was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-3087dfb976084439b2cc7588c21a9955
Source dataset
uspto-grants-2015_07
Patent number
US09085558B2

Reaction notes

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