SYNTHESIS METHOD AND CRYSTAL FORM OF 4-{3-[CIS-HEXAHYDROCYCLOPENTA[C]PYRROLE-2(1H)-YL]PROPOXY} BENZAMIDE HYDROCHLORIDE AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME

• Main Authors: NICOLAS ROBERT, LETELLIER PHILIPPE, GAILLARD MARINA, LECOUVE JEAN-PIERRE, BOIRET MATHIEU, MEUNIER LOIC, LERESTIF JEAN-MICHEL
• Format: Patent
• Language: English; Japanese
• Published: 12.03.2015
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

PROBLEM TO BE SOLVED: To provide an industrial synthesis method and a crystal form I of a compound represented by the formula (1), and also a crystal form I of a related free base, and a pharmaceutical formulation.SOLUTION: A crystal form I of 4-{3-[cis-hexahydrocyclopenta[c]pyrrole-2(1H)-yl]propoxy}benzamide hydrochloride represented by the formula (1) is used as a medicine for the purpose of treatment of cognitive and mental behavior disorders related to brain aging and neurodegenerative diseases and also treatment of mood disorders, attention deficit hyperactivity symptoms, obesity and pain. In a synthesis method, 1,2-dicarboxylic acid ethyl ester-cyclopentane is reacted with ammonia, followed by reduction to give bicyclic amine, with which a P-amide-phenol derivative is reacted to obtain a compound represented by the formula (1). 【課題】式（１）で示される化合物の工業合成方法、及び結晶形態Ｉ、ならびにまた、関連する遊離塩基の結晶形態Ｉおよび医薬製剤の提供。【解決手段】脳の加齢及び神経変性疾患に関連する認識及び精神行動障害の処置、ならびにまた、気分障害、注意欠陥多動性症候群、肥満及び疼痛の処置を目的とする医薬として式（１）で表される４−｛３−［cis−ヘキサヒドロシクロペンタ［ｃ］ピロール−２（１Ｈ）−イル］プロポキシ｝ベンズアミド塩酸塩の結晶形態Ｉの使用。１，２−ジカルボン酸エチルエステル−シクロペンタンをアンモニアと反応させ、還元して二環式アミンとし、Ｐ−アミド−フェノール誘導体を反応させて、式（１）で表される化合物を得る合成方法。【選択図】なし