Improved synthesis of 3-substituted-4-amino-[3,2-c]-thienopyridines.
Two syntheses of 3-substituted-4-amino-[3,2-c]thienopyridines have been developed to replace the standard literature route to these compounds, which uses unattractive conditions involving azide and high temperatures. The first synthesis utilizes a Friedel-Crafts reaction as its key ring-forming step, whereas the second route relies on an unprecedented intramolecular reductive cyclization between a nitroolefin and a nitrile as its key ring-forming step. The development and optimization of each 3-substituted-4-amino-[3,2-c]thienopyridine synthesis is discussed and a comparison of the routes is presented.
Engstrom
Kenneth M
KM
Global Pharmaceutical R&D, Process Research & Development, Abbott Laboratories, 1401 Sheridan Road, North Chicago, Illinois 60064-6290, USA. kenneth.engstrom@abbott.com
Baize
Amanda L
AL
Franczyk
Thaddeus S
TS
Kallemeyn
Jeffrey M
JM
Mulhern
Mathew M
MM
Rickert
Robert C
RC
Wagaw
Seble
S
D002245:Carbon Dioxide / Q000737:chemistry; D003500:Cyclization; D006219:Halogens / Q000737:chemistry; D008670:Metals / Q000737:chemistry; D010084:Oxidation-Reduction; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry; D013876:Thiophenes / Q000737:chemistry
D006219:Halogens; D008670:Metals; D011725:Pyridines; D013876:Thiophenes; C446540:thienopyridine; D002245:Carbon Dioxide