Oxalyl chloride → N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-4-nitro-2-[tetrahydro-2H-pyran-4-yl(trifluoroacetyl)amino]benzamide

HRID 512977Notes

Reaction equation

HRID 512977 reaction equation
[N+:1]([C:4]1[CH:12]=[CH:11][C:7]([C:8](O)=[O:9])=[C:6]([N:13]([CH:20]2[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)[C:14](=[O:19])[C:15]([F:18])([F:17])[F:16])[CH:5]=1)([O-:3])=[O:2].C(Cl)(=O)C(Cl)=O.[F:32][C:33]1[CH:34]=[C:35]([CH:47]=[C:48]([F:50])[CH:49]=1)[CH2:36][C:37]1[CH:38]=[C:39]2[C:43](=[CH:44][CH:45]=1)[NH:42][N:41]=[C:40]2[NH2:46]>C(Cl)Cl.N1C=CC=CC=1>[F:32][C:33]1[CH:34]=[C:35]([CH:47]=[C:48]([F:50])[CH:49]=1)[CH2:36][C:37]1[CH:38]=[C:39]2[C:43](=[CH:44][CH:45]=1)[NH:42][N:41]=[C:40]2[NH:46][C:8](=[O:9])[C:7]1[CH:11]=[CH:12][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][C:6]=1[N:13]([CH:20]1[CH2:21][CH2:22][O:23][CH2:24][CH2:25]1)[C:14](=[O:19])[C:15]([F:16])([F:17])[F:18]

Participants

6

Reactant 3

HCID 65578Oxalyl chlorideHCID 441342655-[(3,5-difluorophenyl)methyl]-1H-indazol-3-amineHCID 866438374-Nitro-2-[(tetrahydro-pyran-4-yl)-(2,2,2-trifluoro-acetyl)-amino]-benzoic acid

Product 1

HCID 86647627N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-4-nitro-2-[tetrahydro-2H-pyran-4-yl(trifluoroacetyl)amino]benzamideYield 83.7%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

4-nitro-2-[(tetrahydro-pyran-4-yl)-(2,2,2-trifluoro-acetyl)-amino]-benzoic acid (3.62 g, 10 mmol) and oxalyl chloride (3.8 mL, 30 mmol) were stirred in DCM dry (120 mL) and a few drops of dry DMF at room temperature for 2 hours Volatiles were evaporated and the residue dissolved in dry pyridine (50 mL) at 0° C. A solution of 5-(3,5-difluoro-benzyl)-1H-indazol-3-ylamine (2 gr, 7.72 mmol) in dry pyridine (20 mL) was added to the cooled reaction mixture under nitrogen atmosphere. 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 AcOEt/Hexane 7:3 as the eluant, affording 3.9 g of the title compound.

Workup

  1. dry with materialdry (120 mL) and a few drops of dry DMF at room temperature for 2 hours Volatiles
  2. customwere evaporated
  3. dissolutionthe residue dissolved in dry pyridine (50 mL) at 0° C
  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-1b3372b9da7d4af088e7f84935aa4975
Source dataset
uspto-grants-2015_08
Patent number
US09102662B2

Reaction notes

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