Formic Acid → 7-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-4H-5-oxa-3,9b-diazacyclopenta[a]naphthalene-6-carboxylic acid

HRID 595098Notes

Reaction equation

HRID 595098 reaction equation
[CH2:1]([N:3]([CH2:35][CH3:36])[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:27]=[CH:26][C:25]2[N:24]3[CH:28]=[CH:29][N:30]=[C:23]3[CH2:22][O:21][C:20]=2[C:19]=1[C:31]([O:33]C)=[O:32])(=[O:16])=[O:15])[CH3:2].O.[OH-].[Li+].C(O)=O>O1CCOCC1.O.CO>[CH2:35]([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:27]=[CH:26][C:25]2[N:24]3[CH:28]=[CH:29][N:30]=[C:23]3[CH2:22][O:21][C:20]=2[C:19]=1[C:31]([OH:33])=[O:32])(=[O:15])=[O:16])[CH3:36]

Participants

7

Reactant 3

HCID 284Formic AcidHCID 168937Lithium hydroxide, monohydrateHCID 86712815methyl 7-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-4H-5-oxa-3,9b-diazacyclopenta[a]naphthalene-6-carboxylate2×

Product 1

HCID 714724977-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-4H-5-oxa-3,9b-diazacyclopenta[a]naphthalene-6-carboxylic acidYield 67.8%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of methyl 7-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-4H-5-oxa-3,9b-diazacyclopenta[a]naphthalene-6-carboxylate (Intermediate 24, 0.138 g) and lithium hydroxide monohydrate (0.421 g) in dioxane (8 mL) and water (2 mL) was irradiated in the microwave at 135° C. for 45 minutes. After cooling, the mixture was diluted with methanol, acidified with formic acid and concentrated in vacuo. The residue was triturated with a solution of methanol in DCM (15%) and the solid was removed by filtration. 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 0-30%. The resultant gum was triturated with ethyl acetate and the solid was collected by filtration to give 7-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-4H-5-oxa-3,9b-diazacyclopenta[a]naphthalene-6-carboxylic acid (0.091 g) as a white solid.

Workup

  1. customwas irradiated in the microwave at 135° C. for 45 minutes
  2. temperatureAfter cooling
  3. concentrationconcentrated in vacuo
  4. customThe residue was triturated with a solution of methanol in DCM (15%)
  5. customthe solid was removed by filtration
  6. concentrationThe filtrate was concentrated in vacuo
  7. customthe residue was purified by chromatography on silica
  8. washeluting with a mixture of methanol and DCM with a gradient of 0-30%
  9. customThe resultant gum was triturated with ethyl acetate
  10. filtrationthe solid was collected by filtration

Sources & evidence

ORD record
ord-7d50d1a0edd545dd8c2cb09608c6ea1c
Source dataset
uspto-grants-2016_01
Patent number
US09242997B2

Reaction notes

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