Synthesis of a TRPV1 receptor antagonist.
A five-step synthesis of a TRPV1 receptor antagonist 1 is described. The key step involves a novel palladium-catalyzed amidation reaction of 4-chloro-1-methylindazole 8 with the benzyl urea 9 to form the unsymmetrically substituted urea 1.
Yu
Su
S
Abbott Laboratories, GPRD Process Research and Development, Dept. R450, Bldg. R8, 1401 Sheridan Road, North Chicago, Illinois 60064, USA. su.yu@abbott.com
Haight
Anthony
A
Kotecki
Brian
B
Wang
Lei
L
Lukin
Kirill
K
Hill
David R
DR
D000577:Amides / Q000737:chemistry; D000700:Analgesics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001593:Benzyl Compounds / Q000737:chemistry; D002384:Catalysis; D007191:Indazoles / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D010165:Palladium / Q000737:chemistry*; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors*; D014508:Urea / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000577:Amides; D000700:Analgesics; D001593:Benzyl Compounds; D007191:Indazoles; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D010165:Palladium; D014508:Urea