-药物合成数据库

【药物名称】

化学结构式(Chemical Structure):

参考文献No.	23810
标题:	4-Arylmethyloxymethyl piperidines as tachykinin antagonists
作者:	Harrison, T.; Mcleod, A.M.; Stevenson, G.I.; Williams, B.J. (Merck Sharp & Dohme Ltd.)
来源:	EP 0666856; JP 1996502510; US 5620989; WO 9410165

合成路线图解说明: This compound can be obtained by two related ways: 1.- The reduction of 4-phenylpiperidine-4-carboxylic acid (I) with LiAlH4 in THF gives the corresponding methanol derivative (II), which is treated with tert-butoxycarbonyl anhydride in THF to yield the N-protected piperidine (III). The acylation of (III) with 3,5-bis(trifluoromethyl)benzyl bromide (IV) by means of NaH in DMF affords the corresponding ether (V), which is deprotected with HCl in ethyl ether to afford the free piperidine (VI) (1,2). Finally, (VI) is reductocondensed with 2-methylthiazole-5-carbaldehyde (VII) by means of sodium cyanoborohydride in methanol/acetic acid. 2.- The piperidine derivative (VI) can also be condensed with 5-(bromomethyl)-2-methylthiazole (VIII) by means of K2CO3 in DMF.

参考文献No.	478943
标题:	4,4-Disubstituted piperidine high-affinity NK1 antagonists: Structure-activity relationships and in vivo activity
作者:	Stevenson, G.I.; Huscroft, I.; Macleod, A.M.; Swain, C.J.; Cascieri, M.A.; Chicchi, G.G.; Graham, M.I.; Harrison, T.; Kelleher, F.J.; Kurtz, M.; Ladduwahetty, T.; Merchant, K.J.; Metzger, J.M.; MacIntyre, D.E.; Sadowski, S.; Sohal, B.; Owens, A.P.
来源:	J Med Chem 1998,41(23),4623

合成路线图解说明: This compound can be obtained by two related ways: 1.- The reduction of 4-phenylpiperidine-4-carboxylic acid (I) with LiAlH4 in THF gives the corresponding methanol derivative (II), which is treated with tert-butoxycarbonyl anhydride in THF to yield the N-protected piperidine (III). The acylation of (III) with 3,5-bis(trifluoromethyl)benzyl bromide (IV) by means of NaH in DMF affords the corresponding ether (V), which is deprotected with HCl in ethyl ether to afford the free piperidine (VI) (1,2). Finally, (VI) is reductocondensed with 2-methylthiazole-5-carbaldehyde (VII) by means of sodium cyanoborohydride in methanol/acetic acid. 2.- The piperidine derivative (VI) can also be condensed with 5-(bromomethyl)-2-methylthiazole (VIII) by means of K2CO3 in DMF.