An improved synthesis of butyl 4-[(4-amino-5-chloro-2-methoxybenzoyl)amino]-1-piperidineacetate (AU-224).
A new and facile route for the synthesis of the novel gastrointestinal prokinetic butyl 4-[(4-amino-5-chloro-2-methoxybenzoyl)amino]-1-piperidineacetate (1b), which exhibited potent gastro- and colon-prokinetic activities by oral administration without significant side effects, was established. The key intermediate, butyl 4-amino-1-piperidineacetate (16), was prepared from commercially available 4-amino-1-benzylpiperidine (2) in a high yield with four steps. Compound 1b was prepared by condensation of commercially available 4-amino-5-choloro-2-methoxybenzoic acid (7) with 16 in 84% yield. This improved synthetic route was appropriate for large-scale synthesis of 1b.
Sakaguchi
J
J
Research Division, Hokuriku Seiyaku Co., Ltd., Katsuyama, Fukui, Japan. jun.sakaguchi@hokuriku-seiyaku.co.jp
Higashi
T
T
Azuma
T
T
Suzuki
T
T
Iwasaki
N
N
Kondo
N
N
Nagata
O
O
Kato
H
H
Hanaoka
M
M
D005765:Gastrointestinal Agents / Q000138:chemical synthesis* / Q000737:chemistry; D010880:Piperidines; D013057:Spectrum Analysis
D005765:Gastrointestinal Agents; D010880:Piperidines; C440056:butyl 4-((4-amino-5-chloro-2-methoxybenzoyl)amino)-1-piperidineacetate