Asymmetric synthesis of a prostaglandin D2 receptor antagonist.
An asymmetric synthesis was developed for the production of a prostaglandin D(2) receptor antagonist for the treatment of allergic rhinitis. The stereogenic center was set using asymmetric allylic alkylation chemistry, and the core of the structure was constructed via Pd-catalyzed N-cyclization/Heck methodology. The synthesis relies on a late stage indoline oxidation which does not racemize the product.
Campos
Kevin R
KR
Department of Process Research, Merck Research Laboratories, P.O. Box 2000, RY800-B267, Rahway, New Jersey 07065-0900, USA. kevin_campos@merck.com
Journet
Michel
M
Lee
Sandra
S
Grabowski
Edward J J
EJ
Tillyer
Richard D
RD
D020650:Combinatorial Chemistry Techniques; D018360:Crystallography, X-Ray; D003500:Cyclization; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology; D008968:Molecular Conformation; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D010084:Oxidation-Reduction; D010165:Palladium / Q000737:chemistry*; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors*; D012221:Rhinitis, Allergic, Perennial / Q000188:drug therapy*
D007211:Indoles; D009942:Organometallic Compounds; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D010165:Palladium; C036293:prostaglandin D2 receptor