Rocastine fumarate, AHR-11325, -Drug Synthesis Database

【结构式】

【药物名称】Rocastine fumarate, AHR-11325

【化学名称】2-[2-(Dimethylaminoethyl)-3,4-dihydro-4-methylpyrido[3,2-f]-1,4-oxazepine-5(2H)-thione (E)-2-butenedioate

【CA登记号】91833-50-0, 91833-49-7 (free base), 91833-77-1 (free base; racemic)

【分子式】C₁₇H₂₃N₃O₅S

【分子量】381.45396

【开发单位】Wyeth Consumer Healthcare (Originator)

【药理作用】Histamine H1 Antagonists

合成路线1

The condensation of 3-hydroxy-1-methylpyrrolidine (I) with 2-chloronicotinic acid (II) by means of NaH in DMSO gives sodium 2-(1-methylpyrrolidin-3-yloxy)pyridine-3-carboxylate (III), which is then cyclized by a treatment with dry HCl in chloroform followed by a reaction with triphenylphosphine and CCl4 yielding finally 2-(2-chloroethyl)-4-methyl-3,4-dihydropyrido[3,2-f]-1,4-oxazepin-5(2H)-one (IV). The reaction of (IV) with P2S5 and K2S in refluxing toluene affords the corresponding thione (V), which is finally treated with 40% aqueous dimethylamine in ethanol at 100 C in a pressure vessel, and with fumaric acid (VI) in methanol.

参考文献中间体

【1】 Cale, A.D. Jr.; Franko, B.V.; Leonard, C.A. (A.H. Robins Co. Inc.); Fused aromatic oxazepinones and sulphur analogues thereof and their preparation and use in counteracting histamine. EP 0107930; ES 8607956; ES 8802574; US 4592866; US 4604388 .
【2】 Pento, J.T.; Castaner, R.M.; Serradell, M.N.; Castaner, J.; AHR-11325. Drugs Fut 1987, 12, 10, 924.

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)	28823	1-methyl-3-pyrrolidinol	13220-33-2	C₅H₁₁NO	详情	详情
(II)	28824	2-Chloropyridine-3-carboxylic acid; 2-Chloronicotinic acid	2942-59-8	C₆H₄ClNO₂	详情	详情
(III)	28825	sodium 2-[(1-methyl-3-pyrrolidinyl)oxy]nicotinate		C₁₁H₁₃N₂NaO₃	详情	详情
(IV)	28826	2-(2-chloroethyl)-4-methyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one		C₁₁H₁₃ClN₂O₂	详情	详情
(V)	28827	2-(2-chloroethyl)-4-methyl-3,4-dihydropyrido[3,2-f][1,4]oxazepine-5(2H)-thione		C₁₁H₁₃ClN₂OS	详情	详情
(VI)	23808	Fumaric acid; (E)-2-butenedioic acid	110-17-8	C₄H₄O₄	详情	详情

Extended Information