Lithium hydroxide, monohydrate → 8-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-5,6-dihydropyrazolo[5,1-a]isoquinoline-7-carboxylic acid

HRID 595097Notes

Reaction equation

HRID 595097 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[C:24]3=[CH:28][CH:29]=[N:30][N:23]3[CH2:22][CH2:21][C:20]=2[C:19]=1[C:31]([O:33]C)=[O:32])(=[O:16])=[O:15])[CH3:2].O.[OH-].[Li+]>O1CCOCC1.O>[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[C:24]3=[CH:28][CH:29]=[N:30][N:23]3[CH2:22][CH2:21][C:20]=2[C:19]=1[C:31]([OH:33])=[O:32])(=[O:15])=[O:16])[CH3:36]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 86712814methyl 8-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-5,6-dihydropyrazolo[5,1-a]isoquinoline-7-carboxylate2×

Product 1

HCID 714724968-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-5,6-dihydropyrazolo[5,1-a]isoquinoline-7-carboxylic acidYield 36.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of methyl 8-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-5,6-dihydropyrazolo[5,1-a]isoquinoline-7-carboxylate (Intermediate 20, 0.057 g) and lithium hydroxide monohydrate (0.090 g) in dioxane (4 mL) and water (1 mL) was heated to 80° C. for 32 hours. The resultant mixture was concentrated in vacuo and the residue was acidified with aqueous citric acid solution (10%) and extracted into DCM, dried (MgSO4) 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 0-15% to give 8-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-5,6-dihydropyrazolo[5,1-a]isoquinoline-7-carboxylic acid (0.020 g) as a white solid.

Workup

  1. concentrationThe resultant mixture was concentrated in vacuo
  2. extractionextracted into DCM
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo
  6. customthe residue was purified by chromatography on silica
  7. washeluting with a mixture of methanol and DCM with a gradient of 0-15%

Sources & evidence

ORD record
ord-31d68ea23d1d4f6883fe63f2afe06828
Source dataset
uspto-grants-2016_01
Patent number
US09242997B2

Reaction notes

Loading…