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

HRID 40171Notes

Reaction equation

HRID 40171 reaction equation
[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]

Participants

8

Reactant 4

HCID 1118Sulfuric AcidHCID 6362Isopropyl iodideHCID 11430Potassium CarbonateHCID 59762337HCID 59762337, compound2×

Product 1

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

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-8d5e40a4a1204307ad38981ddc8d1829
Source dataset
uspto-grants-2013_09
Patent number
US08524917B2

Reaction notes

Loading…