873140, GW-873140, ONO-4128, AK-602-药物合成数据库

【药物名称】873140, GW-873140, ONO-4128, AK-602

化学结构式(Chemical Structure):

参考文献No.	57915
标题:	Triazaspiro[5.5]undecane derivs. and drugs containing the same as the active ingredient
作者:	Shibayama, S.; Hamano, S.; Takaoka, Y.; Habashita, H. (Ono Pharmaceutical Co., Ltd.)
来源:	EP 1378510; WO 0274770

合成路线图解说明: The cyclization of (3R)-N-Boc-3-cyclohexyl-D-serine (I) with 1-benzylpiperidin-4-one (II), benzyl isonitrile (III) and butylamine (IV) in refluxing methanol gives the piperidine derivative (V), whose Boc group is removed by treatment with TFA in dichloromethane, yielding compound (VI). The cyclization of (VI) by means of AcOH in hot toluene affords the spiro[piperazine-2,4'-piperidine] derivative (VII), which is hydrogenated in methanol over palladium hydroxide on carbon to cleave the benzyl protecting group and provide the unprotected spiro derivative (VIII). Finally, this compound is reductocondensed with 4-(4-formylphenoxy)benzoic acid (IX) by means of sodium triacetoxyborohydride in DMF/AcOH to give the target spiro[piperazine-2,4'-piperidine] derivative.

参考文献No.	818895
标题:	GW-873140
作者:	McIntyre, J.A.; Casta馿r, J.
来源:	Drugs Fut 2004,29(7),677

合成路线图解说明: The cyclization of (3R)-N-Boc-3-cyclohexyl-D-serine (I) with 1-benzylpiperidin-4-one (II), benzyl isonitrile (III) and butylamine (IV) in refluxing methanol gives the piperidine derivative (V), whose Boc group is removed by treatment with TFA in dichloromethane, yielding compound (VI). The cyclization of (VI) by means of AcOH in hot toluene affords the spiro[piperazine-2,4'-piperidine] derivative (VII), which is hydrogenated in methanol over palladium hydroxide on carbon to cleave the benzyl protecting group and provide the unprotected spiro derivative (VIII). Finally, this compound is reductocondensed with 4-(4-formylphenoxy)benzoic acid (IX) by means of sodium triacetoxyborohydride in DMF/AcOH to give the target spiro[piperazine-2,4'-piperidine] derivative.