A practical procedure for preparation of N-(endo-8-(3-hydroxy)propyl-8-azabicyclo[3.2.1]oct-3-yl)-1-isoproipyl-2-oxo-1,2-dihydro-3-quinolinecarboxamide (TS-951)

Effective and convergent process for the preparation of a potent and select ive 5-HT4 receptor agonist, the title compound, by reaction of 1-isopropyl- 2-oxo-1,2-dihydro-3-quinolinecarboxylic acid (6) with endo-3-amino-8-(3-hyd roxypropyl)-8-azabicyclo[3.2.1]octane dihydrochloride (20) has been describ ed. Furthermore, this process was developed to pilot plant scale. 1-Isoprop yl-2-oxo-1,2-dihydro-3-quinolinecarboxylic acid (6) was prepared from 2-ami nobenzyl alcohol (12) in 65.6% overall yield and endo -3-amino-8-(3-hydroxy propyl)-8-azabicyclo[3.2.1]octane dihydrochloride (20) was prepared from 2, 5-dimethoxyfuran (16) in 43.4% overall yield.