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

HRID 715935Notes

Reaction equation

HRID 715935 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][C:22]3=[CH: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.C(O)C>O1CCOCC1.O.C1(C)C=CC=CC=1>[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][C:22]3=[CH:21][C:20]=2[C:19]=1[C:30]([OH:32])=[O:31])(=[O:15])=[O:16])[CH3:35]

Participants

8

Reactant 4

HCID 284Formic AcidHCID 702EthanolHCID 168937Lithium hydroxide, monohydrateHCID 86712101methyl 7-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-2,3-dihydro-1H-pyrrolo[1,2-a]indole-8-carboxylate2×

Product 1

HCID 706735817-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-2,3-dihydro-1H-pyrrolo[1,2-a]indole-8-carboxylic acidYield 43.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent

Procedure

A suspension of methyl 7-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-2,3-dihydro-1H-pyrrolo[1,2-a]indole-8-carboxylate (Intermediate 16, 0.092 g) and lithium hydroxide monohydrate (0.077 g) in dioxane (2 mL) and water (0.5 mL) was irradiated in the microwave at 135° C. for 45 minutes. After cooling, the mixture was acidified to pH4 with formic acid. Ethanol and toluene were added and the resultant mixture was concentrated in vacuo. The residue was triturated with methanol in DCM (10% solution) and the solid was filtered off and washed with DCM. 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 0-8%. The resultant solid was triturated with ethyl acetate and dried in vacuo, at 60° C. overnight to give 7-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-2,3-dihydro-1H-pyrrolo[1,2-a]indole-8-carboxylic acid (0.039 g) as a pale yellow solid.

Workup

  1. customwas irradiated in the microwave at 135° C. for 45 minutes
  2. temperatureAfter cooling
  3. concentrationthe resultant mixture was concentrated in vacuo
  4. customThe residue was triturated with methanol in DCM (10% solution)
  5. filtrationthe solid was filtered off
  6. washwashed with DCM
  7. concentrationThe filtrate was concentrated in vacuo
  8. customthe residue was purified by chromatography on silica
  9. washeluting with a mixture of methanol and DCM with a gradient of 0-8%
  10. customThe resultant solid was triturated with ethyl acetate
  11. customdried in vacuo, at 60° C. overnight

Sources & evidence

ORD record
ord-011fc5a3954e496dbc47d1bdfb22e257
Source dataset
uspto-grants-2015_11
Patent number
US09187494B2

Reaction notes

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