-Drug Synthesis Database

【结构式】

【药物名称】

【化学名称】N-(2,2-Dimethylcyclopentylmethyl)-4-[5-(3,3,3-trifluoropropyl)-1,2,4-oxadiazol-3-yl]benzamide isomer A

【CA登记号】212380-87-5 ((-)-enantiomer), 212380-88-6 ((+)-enantiomer)

【分子式】C₂₀H₂₄F₃N₃O₂

【分子量】395.42838

【开发单位】Bristol-Myers Squibb (Originator)

【药理作用】Antiarrhythmic Drugs, CARDIOVASCULAR DRUGS, Potassium Channel Blockers

合成路线1

Amine (III) was synthesized from 2,2-dimethylcyclopentanone (I) by treatment with tosylmethyl isocyanide, followed by reduction of the resultant nitrile (II) with LiAlH4. Condensation of 4-cyanobenzoic acid (IV) with amine (III) produced the corresponding amide (V). Subsequent addition of hydroxylamine to the cyano group of (V) gave rise to the hydroxyamidine (VI). The target oxadiazole derivative was then obtained by condensation of (VI) with 4,4,4-trifluorobutyric acid (VII), followed by cyclization under basic conditions. Separation of the enantiomers was carried out by chiral preparative HPLC.

参考文献中间体

【1】 LLoyd, J.; et al.; Design and synthesis of 4-substituted benzamides as potent, selective, and orally bioavailable IKS blockers. J Med Chem 2001, 44, 23, 3764.
【2】 Poss, M.A.; Lloyd, J.; Rovnyak, G.C.; Caulfield, T.J.; Atwal, K.S.; Stein, P.D.; Ahmad, S. (Bristol-Myers Squibb Co.); Benzoic acid derivs. and related cpds. as antiarrhythmic agents. WO 9837068 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	43358	2,2-dimethylcyclopentanone		C₇H₁₂O	详情	详情
(II)	43359	2,2-dimethylcyclopentanecarbonitrile		C₈H₁₃N	详情	详情
(III)	43360	(2,2-dimethylcyclopentyl)methylamine; (2,2-dimethylcyclopentyl)methanamine		C₈H₁₇N	详情	详情
(IV)	36897	4-cyanobenzoic acid；4-Carboxybenzonitrile;p-Carboxybenzonitrile	619-65-8	C₈H₅NO₂	详情	详情
(V)	52509	4-cyano-N-[(2,2-dimethylcyclopentyl)methyl]benzamide		C₁₆H₂₀N₂O	详情	详情
(VI)	52510	4-[amino(hydroxyimino)methyl]-N-[(2,2-dimethylcyclopentyl)methyl]benzamide		C₁₆H₂₃N₃O₂	详情	详情
(VII)	14781	4,4,4-Trifluorobutyric acid	406-93-9	C₄H₅F₃O₂	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)