1. A convergent approach to the synthesis of aprepitant: a potent human NK-1 receptor antagonist
- Author
-
Vijayavitthal T. Mathad, Venkatraman Sundaram, Apurba Bhattacharya, Muttu L. Avinigiri, Subrahmanyeswararao Chalamala, Pravinchandra J. Vankawala, Rakeshwar Bandichhor, Naveenkumar Kolla, Anitha Naredla, Chandrashekar R. Elati, and Srinivas Gangula
- Subjects
Trifluoromethyl ,Stereochemistry ,medicine.drug_class ,Organic Chemistry ,Strecker amino acid synthesis ,Antagonist ,Diastereomer ,Receptor antagonist ,Biochemistry ,chemistry.chemical_compound ,chemistry ,Yield (chemistry) ,Drug Discovery ,medicine ,Receptor ,Aprepitant ,medicine.drug - Abstract
A simple and convergent approach to enantiomerically pure 5-[[2-[1-[3,5-bis(trifluoromethyl)phenyl]ethoxy-3-(4-fluorophenyl)morpholin-4-yl]methyl]-1,2-dihydro-1,2,4-triazol-3-one 1, a potent orally active antagonist of the human neurokinin-1 (NK-1) receptor, is described. The synthetic procedure starts from p-fluorobenzaldehyde to access the racemic morpholinone 2 via a modified Strecker synthesis and utilizes a diastereomeric salt resolution technique to accomplish the synthesis of 1 in enantiomerically pure form and good yield.
- Published
- 2007
- Full Text
- View/download PDF