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

HRID 1186616Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1186616
[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]

Komponenten

6

Edukt 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

Produkt 1

HCID 86647627N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-4-nitro-2-[tetrahydro-2H-pyran-4-yl(trifluoroacetyl)amino]benzamideAusbeute 83,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 1049PyridineLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

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 acqueous 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.

Aufarbeitung

  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 acqueous NaHCO3
  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

Quellen und Nachweise

ORD-Eintrag
ord-1c4f2783d05240f5ba278218a997858f
Quelldatensatz
uspto-grants-2014_03
Patentnummer
US08673893B2

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