Roflumilast, APTA-2217, BY-217, Daxas
罗氟司特Chemical Name: 3-(Cyclopropylmethoxy)-N-(3,5-dichloropyridin-4-yl)-4-(difluoromethoxy)benzamide
CAS No. 162401-32-3
项目整合开发状态: Pre-Registered
项目研究机构: Altana (Originator), Tanabe Seiyaku (Licensee), Pfizer (Codevelopment)
合成路线:Condensation of the benzaldehyde derivative (I) with chlorodifluoromethane (II) by means of NaOH and benzyltrimethylammonium chloride (BTMA) in dioxane/water gives 3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzaldehyde (III),which is oxidized with NaClO2 and sulfamic acid in acetic acid to yield the corresponding benzoic acid derivative (IV).The reaction of (IV) with SOCl2 in refluxing toluene affords the acyl chloride (V),which is finally condensed with 3,5-dichloropyridin-4-amine (VI) by means of NaH in THF.
📌 参考资料/链接：
参考文献标题:Fluoroalkoxy-substd.benzamides and their use as cyclic nucleotide phosphodiesterase inhibitors
文献作者:Flockerzi,D.; Gutterer,B.; Hatzelmann,A.; Schudt,C.; Beume,R.; Kilian,U.; Wolf,H.P.O.(Byk Gulden Lomberg Chemische Fabrik GmbH)
参考来源:EP 0706513; JP 1996512041; US 5712298; WO 9501338
📄 详细内容
合成路线:Condensation of the benzaldehyde derivative (I) with chlorodifluoromethane (II) by means of NaOH and benzyltrimethylammonium chloride (BTMA) in dioxane/water gives 3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzaldehyde (III),which is oxidized with NaClO2 and sulfamic acid in acetic acid to yield the corresponding benzoic acid derivative (IV).The reaction of (IV) with SOCl2 in refluxing toluene affords the acyl chloride (V),which is finally condensed with 3,5-dichloropyridin-4-amine (VI) by means of NaH in THF.
参考文献标题:Roflumilast
文献作者:Castar,J.; Leeson,P.A.; Sorbera,L.A.
参考来源:Drugs Fut 2000,25(12),1261
产品链接: CAS No. 162401-32-3››