Triethylamine → HCID 11690038, compound

HRID 2233752Notes

Reaction equation

HRID 2233752 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][C:12]([O:14]C)=[O:13])[C:6]([CH3:16])=[C:5]2[O:17][C:18]1[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=1.C(N(CC)CC)C.[CH3:32][S:33](Cl)(=[O:35])=[O:34].[OH-].[Na+]>CC#N.C1COCC1.O>[Cl:24][C:21]1[CH:22]=[CH:23][C:18]([O:17][C:5]2[C:4]3[C:8](=[CH:9][CH:10]=[C:2]([NH:1][S:33]([CH3:32])(=[O:35])=[O:34])[CH:3]=3)[N:7]([CH2:11][C:12]([OH:14])=[O:13])[C:6]=2[CH3:16])=[CH:19][CH:20]=1

Participants

8

Reactant 4

HCID 8471Triethylamine2×HCID 14798Sodium HydroxideHCID 31297Methanesulfonyl chloride2×HCID 866092365-Amino-3-(4-chlorophenoxy)-2-methyl-1H-indole-1-acetic acid, methyl ester

Product 1

HCID 11690038HCID 11690038, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of the product from step (ii) (0.688 g) in MeCN (5 ml) was added triethylamine (1.39 ml) and methanesulfonyl chloride (0.54 ml) and the reaction stirred at rt for 5 h. Further triethylamine (0.83 ml) and methanesulfonyl chloride (0.54 ml) were added and the reaction stirred for 16 h. The residue was partitioned between ethylacetate/water, the organics were separated, washed with 2M hydrochloric acid, sodium hydrogencarbonate solution, brine, dried and evaporated under reduced pressure. The residue was purified by chromatography on silica eluting with 30-40% ethylacetate/iso-hexane to give a mixture of mono- and di-methanesulfonamides. This was dissolved in THF (2 ml) and a solution of 1 M sodium hydroxide (4 ml) was added and the reaction heated at 55° C. for 2 h. After cooling to RT, water (10 ml) was added and the solution extracted with ethylacetate. The aqueous solution was acidified with 2M hydrochloric acid and extracted with ethylacetate. These later organics were dried and evaporated under reduced pressure. Yield 302 mg

Workup

  1. stirringthe reaction stirred for 16 h
  2. customThe residue was partitioned between ethylacetate/water
  3. customthe organics were separated
  4. washwashed with 2M hydrochloric acid, sodium hydrogencarbonate solution, brine
  5. customdried
  6. customevaporated under reduced pressure
  7. customThe residue was purified by chromatography on silica eluting with 30-40% ethylacetate/iso-hexane
  8. customto give
  9. temperaturethe reaction heated at 55° C. for 2 h
  10. temperatureAfter cooling to RT
  11. extractionthe solution extracted with ethylacetate
  12. extractionextracted with ethylacetate
  13. customThese later organics were dried
  14. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-411c30627a92411abeeecc69843b78b1
Source dataset
uspto-grants-2010_05
Patent number
US07709521B2

Reaction notes

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