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

HRID 1773412ノート

反応式

HRID 1773412 の反応式
[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]

参加物

6

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 1049Pyridine溶媒HCID 6344Dichloromethane溶媒

実験手順

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.

後処理

  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
  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

出典と根拠

ORDレコード
ord-2326f1d3c89445e6a07863d8efc70c5f
出典データセット
uspto-grants-2016_02
特許番号
US09255087B2

反応ノート

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