Formic Acid → 7-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonyl-amino]-2,3,9,9a-tetrahydro-1H-pyrrolo[1,2-a]indole-8-carboxylic acid

HRID 715937Notes

Reaction equation

HRID 715937 reaction equation
[CH2:1]([N:3]([CH2:34][CH3:35])[CH2:4]/[CH:5]=[CH:6]\[C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=1[S:14]([NH:17][C:18]1[CH:26]=[CH:25][C:24]2[N:23]3[CH2:27][CH2:28][CH2:29][CH:22]3[CH2:21][C:20]=2[C:19]=1[C:30]([O:32]C)=[O:31])(=[O:16])=[O:15])[CH3:2].O.[OH-].[Li+].C(O)=O>O1CCOCC1.O.CO>[CH2:34]([N:3]([CH2:1][CH3:2])[CH2:4]/[CH:5]=[CH:6]\[C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=1[S:14]([NH:17][C:18]1[CH:26]=[CH:25][C:24]2[N:23]3[CH2:27][CH2:28][CH2:29][CH:22]3[CH2:21][C:20]=2[C:19]=1[C:30]([OH:32])=[O:31])(=[O:15])=[O:16])[CH3:35]

Participants

7

Reactant 3

HCID 284Formic AcidHCID 168937Lithium hydroxide, monohydrateHCID 86712102methyl 7-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-2,3,9,9a-tetrahydro-1H-pyrrolo[1,2-a]indole-8-carboxylate2×

Product 1

HCID 714724337-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonyl-amino]-2,3,9,9a-tetrahydro-1H-pyrrolo[1,2-a]indole-8-carboxylic acidYield 29.8%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of methyl 7-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-2,3,9,9a-tetrahydro-1H-pyrrolo[1,2-a]indole-8-carboxylate (Intermediate 27, 0.311 g) and lithium hydroxide monohydrate (0.526 g) in dioxane (10 mL) and water (2.5 mL) was irradiated in the microwave at 135° C. for 45 minutes. After cooling, the mixture was diluted with methanol and acidified with formic acid. The mixture was concentrated in vacuo and the residue was diluted with ethanol and toluene and again concentrated in vacuo. The residue was triturated with methanol in DCM (20% solution) and filtered. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of methanol and DCM with a gradient of 0-20%. The resultant solid was triturated with ethyl acetate to give a pale yellow solid which was purified by preparative HPLC (C18), eluting with a mixture of acetonitrile and water, containing 0.1% formic acid with a gradient of 5-70% to give 7-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonyl-amino]-2,3,9,9a-tetrahydro-1H-pyrrolo[1,2-a]indole-8-carboxylic acid (0.090 g).

Workup

  1. customwas irradiated in the microwave at 135° C. for 45 minutes
  2. temperatureAfter cooling
  3. concentrationThe mixture was concentrated in vacuo
  4. additionthe residue was diluted with ethanol and toluene
  5. concentrationagain concentrated in vacuo
  6. customThe residue was triturated with methanol in DCM (20% solution)
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated in vacuo
  9. customthe residue was purified by chromatography on silica
  10. washeluting with a mixture of methanol and DCM with a gradient of 0-20%
  11. customThe resultant solid was triturated with ethyl acetate
  12. customto give a pale yellow solid which
  13. customwas purified by preparative HPLC (C18)
  14. washeluting with a mixture of acetonitrile and water
  15. additioncontaining 0.1% formic acid with a gradient of 5-70%

Sources & evidence

ORD record
ord-066fd3e131ba4c15aa5de3c5a553b8e1
Source dataset
uspto-grants-2015_11
Patent number
US09187494B2

Reaction notes

Loading…