2,5-Disubstituted Pyrazolo[4,3-c]cinnolin-3-ones
Corresponding Author
Douglas C. Beshore
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA, 19486 USA
E-mail: [email protected]Search for more papers by this authorAdam W. Johnson
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA, 19486 USA
Search for more papers by this authorRobert M. DiPardo
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA, 19486 USA
Search for more papers by this authorDaniel R. Pitts
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA, 19486 USA
Search for more papers by this authorVictoria Cofre
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA, 19486 USA
Search for more papers by this authorScott D. Kuduk
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA, 19486 USA
Search for more papers by this authorCorresponding Author
Douglas C. Beshore
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA, 19486 USA
E-mail: [email protected]Search for more papers by this authorAdam W. Johnson
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA, 19486 USA
Search for more papers by this authorRobert M. DiPardo
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA, 19486 USA
Search for more papers by this authorDaniel R. Pitts
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA, 19486 USA
Search for more papers by this authorVictoria Cofre
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA, 19486 USA
Search for more papers by this authorScott D. Kuduk
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA, 19486 USA
Search for more papers by this authorAbstract
Complementary strategies to 2,5-disubstituted pyrazolo[4,3-c]cinnolin-3-ones are reported herein, providing late stage substituent introduction at either the 2- or the 5-position. Treating a readily prepared 4-thiocinnoline ester with substituted hydrazines afforded late stage access to the 2-position, while late stage substituent introduction at the 5-position was achieved via two different strategies: alkylation of 4-hydrazonopyrazol-3-ones, followed by a ring-closing intramolecular SNAr tactic and direct reaction of 5-(2-fluorophenyl)-2,4-dihydro-3H-pyrazol-3-ones with aryl diazonium salts, followed by cyclization. The strategies described herein provide practical and general methods to prepare 2,5-disubstituted pyrazolo[4,3-c]cinnolin-3-ones.
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References and Notes
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