Sulfuric Acid → Methyl 3-(3,4-Difluorobenzylcarbamoyl)-6-isopropoxy-1-(pyridin-2-ylmethyl)-1H-indole-2-carboxylate

HRID 40171ノート

反応式

HRID 40171 の反応式
[F:1][C:2]1[CH:3]=[C:4]([CH:29]=[CH:30][C:31]=1[F:32])[CH2:5][NH:6][C:7]([C:9]1[C:17]2[C:12](=[CH:13][C:14]([OH:18])=[CH:15][CH:16]=2)[N:11]([CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=2)[C:10]=1[C:26]([OH:28])=[O:27])=[O:8].OS(O)(=O)=O.I[CH:39]([CH3:41])[CH3:40].[C:42]([O-])([O-])=O.[K+].[K+]>CO.CN(C=O)C.CCOC(C)=O>[F:1][C:2]1[CH:3]=[C:4]([CH:29]=[CH:30][C:31]=1[F:32])[CH2:5][NH:6][C:7]([C:9]1[C:17]2[C:12](=[CH:13][C:14]([O:18][CH:39]([CH3:41])[CH3:40])=[CH:15][CH:16]=2)[N:11]([CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=2)[C:10]=1[C:26]([O:28][CH3:42])=[O:27])=[O:8]

参加物

8

反応物 4

HCID 1118Sulfuric AcidHCID 6362Isopropyl iodideHCID 11430Potassium CarbonateHCID 597623373-(3,4-Difluorobenzylcarbamoyl)-6-hydroxy-1-(pyridin-2-ylmethyl)-1H-indole-2-carboxylic Acid2 回

生成物 1

HCID 59762389Methyl 3-(3,4-Difluorobenzylcarbamoyl)-6-isopropoxy-1-(pyridin-2-ylmethyl)-1H-indole-2-carboxylate

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

A solution of 3-(3,4-difluorobenzylcarbamoyl)-6-hydroxy-1-(pyridin-2-ylmethyl)-1H-indole-2-carboxylic acid (Compound 225, crude 6.5 g) and concentrated H2SO4 (0.1 ml, catalytic amount) in MeOH (100 ml) was heated to 90° C. for 16 h. The mixture was cooled and the suspension was filtered. The filtrate was concentrated, diluted with EtOAc, washed with H2O and brine, dried over Na2SO4, and concentrated in vacuo to give a pale brown solid as the crude product. General Procedure N. To a solution of the crude product in DMF (10 ml) was added 2-iodopropane (2.2 ml, 22 mmol) and K2CO3 (1.8 g, 13.2 mmol). The reaction was stirred at room temperature for 16 h and was diluted with EtOAc, washed with H2O and brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by chromatography on silica gel (0→100% EtOAc-hexanes) to yield the title compound as a white solid.

後処理

  1. temperatureThe mixture was cooled
  2. filtrationthe suspension was filtered
  3. concentrationThe filtrate was concentrated
  4. additiondiluted with EtOAc
  5. washwashed with H2O and brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customto give a pale brown solid as the crude product
  9. washwashed with H2O and brine
  10. dry with materialdried over Na2SO4
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by chromatography on silica gel (0→100% EtOAc-hexanes)

出典と根拠

ORDレコード
ord-8d5e40a4a1204307ad38981ddc8d1829
出典データセット
uspto-grants-2013_09
特許番号
US08524917B2

反応ノート

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