p-Toluenesulfonic acid → N-[2-(5,6-dimethoxy-1-methyl-1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyrid-4-ylmethyl]-4-trifluoromethoxybenzenesulfonamide

HRID 490539Notes

Reaction equation

HRID 490539 reaction equation
C1(C)C=CC(S(O)(=O)=O)=CC=1.COC1C=C(OC)C=CC=1C[N:17]([CH2:32][C:33]1[CH:38]=[CH:37][N:36]=[C:35]2[NH:39][C:40]([C:42]3[C:50]4[C:45](=[CH:46][C:47]([O:53][CH3:54])=[C:48]([O:51][CH3:52])[CH:49]=4)[N:44]([CH3:55])[CH:43]=3)=[CH:41][C:34]=12)[S:18]([C:21]1[CH:26]=[CH:25][C:24]([O:27][C:28]([F:31])([F:30])[F:29])=[CH:23][CH:22]=1)(=[O:20])=[O:19].[OH-].[Na+]>ClCCl.C1(C)C=CC=CC=1.O>[CH3:52][O:51][C:48]1[CH:49]=[C:50]2[C:45](=[CH:46][C:47]=1[O:53][CH3:54])[N:44]([CH3:55])[CH:43]=[C:42]2[C:40]1[NH:39][C:35]2=[N:36][CH:37]=[CH:38][C:33]([CH2:32][NH:17][S:18]([C:21]3[CH:22]=[CH:23][C:24]([O:27][C:28]([F:29])([F:30])[F:31])=[CH:25][CH:26]=3)(=[O:19])=[O:20])=[C:34]2[CH:41]=1

Participants

7

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 14798Sodium HydroxideHCID 67147761HCID 67147761, compound

Product 1

HCID 67147792N-[2-(5,6-dimethoxy-1-methyl-1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyrid-4-ylmethyl]-4-trifluoromethoxybenzenesulfonamideYield 20.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent2×

Procedure

0.053 g of para-toluenesulfonic acid is added to a solution of 0.050 g of N-(2,4-dimethoxybenzyl)-N-[2-(5,6-dimethoxy-1-methyl-1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyrid-4-ylmethyl]-4-trifluoromethoxybenzenesulfonamide in 2 cm3 of dichloromethane and 5 cm3 of toluene, at a temperature in the region of 20° C. The reaction medium is stirred at this same temperature for 24 hours, at room temperature, and then heated at a temperature in the region of 60° C. for 24 hours. After cooling, the reaction medium is concentrated under reduced pressure. 5 cm3 of water and 10 cm3 of dichloromethane are added. The reaction medium is basified to pH 9 with 1N sodium hydroxide. After separation of the phases by settling, the organic phase is dried over magnesium sulfate, filtered and then concentrated under reduced pressure. The residue obtained is purified on preparative LC/MS (water/acetonitrile/TFA). The solid obtained is taken up in 5 cm3 of dichloromethane and 2 cm3 of water, and then basified with 1N sodium hydroxide to pH 9. 0.008 g of N-[2-(5,6-dimethoxy-1-methyl-1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyrid-4-ylmethyl]-4-trifluoromethoxybenzenesulfonamide is obtained, the characteristics of which are as follows:

Workup

  1. temperatureheated at a temperature in the region of 60° C. for 24 hours
  2. temperatureAfter cooling
  3. concentrationthe reaction medium is concentrated under reduced pressure
  4. addition5 cm3 of water and 10 cm3 of dichloromethane are added
  5. customAfter separation of the phases
  6. dry with materialthe organic phase is dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue obtained
  10. customis purified on preparative LC/MS (water/acetonitrile/TFA)
  11. customThe solid obtained

Sources & evidence

ORD record
ord-af0404a02e7a45f0b16e391e8bf42b08
Source dataset
uspto-grants-2009_05
Patent number
US07528147B2

Reaction notes

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