Hydrochloric Acid → 1-{4-[3-(ethoxycarbonyl)-1-(4-methoxyphenyl)-7-oxo-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-c]pyridin-6-yl]phenyl}cyclopropanecarboxylic acid

HRID 971137Notes

Reaction equation

HRID 971137 reaction equation
I[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH:12]2[CH2:14]C2)[C:9]([OH:11])=[O:10])=[CH:4][CH:3]=1.[CH3:15][O:16][C:17]1[CH:22]=[CH:21][C:20]([N:23]2[C:27]3[C:28](=[O:32])[NH:29][CH2:30][CH2:31][C:26]=3[C:25]([C:33]([O:35][CH2:36][CH3:37])=[O:34])=[N:24]2)=[CH:19][CH:18]=1.C([O-])([O-])=O.[K+].[K+].N1C2C(=CC=C3C=2N=CC=C3)C=CC=1.Cl>CS(C)=O.[Cu]I.CCOC(C)=O>[CH2:36]([O:35][C:33]([C:25]1[C:26]2[CH2:31][CH2:30][N:29]([C:2]3[CH:3]=[CH:4][C:5]([C:8]4([C:9]([OH:11])=[O:10])[CH2:12][CH2:14]4)=[CH:6][CH:7]=3)[C:28](=[O:32])[C:27]=2[N:23]([C:20]2[CH:19]=[CH:18][C:17]([O:16][CH3:15])=[CH:22][CH:21]=2)[N:24]=1)=[O:34])[CH3:37]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 13181,10-PhenanthrolineHCID 11430Potassium CarbonateHCID 22240468Ethyl 1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo(3,4-c)pyridine-3-carboxylateHCID 695169744-Iodophenylcyclopropyl acetic acid

Product 1

HCID 695164601-{4-[3-(ethoxycarbonyl)-1-(4-methoxyphenyl)-7-oxo-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-c]pyridin-6-yl]phenyl}cyclopropanecarboxylic acidYield 72.6%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

Part A. 4-Iodophenylcyclopropyl acetic acid (1.93 g, 6.70 mmol) and 1-(4-methoxyphenyl)-3-(ethoxycarbonyl)-1,4,5,6-tetrahydro-7H-pyrazolo[3,4-c]pyridin-7-one (1.41 g, 4.46 mmol) were stirred in DMSO (4 mL) under N2. K2CO3 (1.84 g, 13.33 mmol, 3.0 eq) was added followed by the addition of 1,10-phenanthroline (0.15 g, 20 mol %) and CuI (0.16 g, 20 mol %). The resulting mixture was stirred at 110° C. overnight. LC-MS showed completion of the reaction. EtOAc was added to the cooled solution. It was acidified with 1N HCl, and the organic layer was washed with H2O, and brine, dried over MgSO4, filtered, and concentrated to afford 1-{4-[3-(ethoxycarbonyl)-1-(4-methoxyphenyl)-7-oxo-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-c]pyridin-6-yl]phenyl}cyclopropanecarboxylic acid (1.54 g, yield: 72.6%). LC/MS (ESI+) 476.4 (M+H)+, tR=2.58 min (10–90% CH3CN/H2O in a 4-min run).

Workup

  1. customcompletion of the reaction
  2. washthe organic layer was washed with H2O, and brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-c25e834455b14700a0e4141103f0d2e8
Source dataset
uspto-grants-2007_12
Patent number
US07312214B2

Reaction notes

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