The synthesis of S 18986, a chiral AMPA receptor modulator, via catalytic asymmetric hydrogenation

The asymmetric hydrogenation of a dihydropyrrolo-benzothiadiazine dioxide 1 with a diphosphine ruthenium diamine catalyst has been used to synthesize the AMPA receptor positive modulator tetrahydropyrrolo-benzothiadiazine dioxide 2 (S 18986) in high enantiomeric excess. The use of factorial experimental design led to significant improvements in the process parameters and improved enantioselectivity. (C) 2003 Elsevier Ltd. All rights reserved.