Thionyl Chloride → methyl 4-{[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]carbamoyl}-3-nitrobenzoate

HRID 512959

反応式

HRID 512959 の反応式
[CH3:1][O:2][C:3]([C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=O)=[C:7]([N+:14]([O-:16])=[O:15])[CH:6]=1)=[O:4].S(Cl)(Cl)=O.[F:21][C:22]1[CH:23]=[C:24]([CH:36]=[C:37]([F:39])[CH:38]=1)[CH2:25][C:26]1[CH:27]=[C:28]2[C:32](=[CH:33][CH:34]=1)[NH:31][N:30]=[C:29]2[NH2:35]>C1COCC1.N1C=CC=CC=1>[F:21][C:22]1[CH:23]=[C:24]([CH:36]=[C:37]([F:39])[CH:38]=1)[CH2:25][C:26]1[CH:27]=[C:28]2[C:32](=[CH:33][CH:34]=1)[NH:31][N:30]=[C:29]2[NH:35][C:9]([C:8]1[CH:12]=[CH:13][C:5]([C:3]([O:2][CH3:1])=[O:4])=[CH:6][C:7]=1[N+:14]([O-:16])=[O:15])=[O:11]

参加物

6

反応物 3

HCID 24386Thionyl ChlorideHCID 219064744-(Methoxycarbonyl)-2-nitrobenzoic acidHCID 441342655-[(3,5-difluorophenyl)methyl]-1H-indazol-3-amine

生成物 1

HCID 68671770methyl 4-{[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]carbamoyl}-3-nitrobenzoate収率 65.2%

試薬・触媒・溶媒 2

HCID 1049Pyridine溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

4-(methoxycarbonyl)-2-nitrobenzoic acid (4.8 gr, 21.3 mmol) and thionyl chloride (15.5 mL) were stirred in THF dry (130 mL) at 70° C. for 2 hours. Volatiles were evaporated and the residue dissolved in dry pyridine (100 mL) at 0° C. A solution of 5-(3,5-difluoro-benzyl)-1H-indazol-3-ylamine (4.6 mg, 17.76 mmol) in dry pyridine (10 mL) was added to the cooled reaction mixture. Temperature was allowed to reach room temperature overnight. Reaction was quenched with NaHCO3 sat. sol and extracted with ethyl acetate. Collected organic phases were dried over Na2SO4, filtered and evaporated to dryness. Residue was purified by column chromatography over silica gel (DCM/EtOH/7N NH3 in MeOH=95/5/0.5) affording 5.4 gr (65% yield) of the title compound.

後処理

  1. customdry (130 mL) at 70° C. for 2 hours
  2. customVolatiles were evaporated
  3. dissolutionthe residue dissolved in dry pyridine (100 mL) at 0° C
  4. customReaction
  5. customwas quenched with NaHCO3 sat. sol
  6. extractionextracted with ethyl acetate
  7. dry with materialCollected organic phases were dried over Na2SO4
  8. filtrationfiltered
  9. customevaporated to dryness
  10. customResidue was purified by column chromatography over silica gel (DCM/EtOH/7N NH3 in MeOH=95/5/0.5)

出典と根拠

ORDレコード
ord-687b872099b0439085ca9c1ae037f539
出典データセット
uspto-grants-2015_08
特許番号
US09102662B2

関連ノート

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