4-[[(2R,3R)-2-amino-3-cyclohexyl-3-hydroxypropanoyl](butyl)amino]-N,1-dibenzyl-4-piperidinecarboxamide -Drug Synthesis Database

【结构式】

【分子编号】64665

【品名】4-[[(2R,3R)-2-amino-3-cyclohexyl-3-hydroxypropanoyl](butyl)amino]-N,1-dibenzyl-4-piperidinecarboxamide

【CA登记号】

【分子式】C₃₃H₄₈N₄O₃

【分子量】548.76928

【元素组成】C 72.23% H 8.82% N 10.21% O 8.75%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(VI)

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.

参考文献中间体

合成目标

【1】 Shibayama, S.; Hamano, S.; Takaoka, Y.; Habashita, H. (Ono Pharmaceutical Co., Ltd.); Triazaspiro[5.5]undecane derivs. and drugs containing the same as the active ingredient. EP 1378510; WO 0274770 .

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)	64663	(2R,3R)-2-[(tert-butoxycarbonyl)amino]-3-cyclohexyl-3-hydroxypropanoic acid		C₁₄H₂₅NO₅	详情	详情
(II)	15720	1-benzyltetrahydro-4(1H)-pyridinone; 1-Benzyl-4-piperidone; N-Benzyl-4-piperidone; 1-(benzyl)-4-piperidinone; 1-benzylpiperidin-4-one; 1-(benzyl)piperidin-4-one	3612-20-2	C₁₂H₁₅NO	详情	详情
(III)	16730	1-(Isocyanatomethyl)benzene; Benzyl Isocyanate	3173-56-6	C₈H₇NO	详情	详情
(IV)	39041	butylamine; 1-butanamine	109-73-9	C₄H₁₁N	详情	详情
(V)	64664	tert-butyl (1R)-2-[{1-benzyl-4-[(benzylamino)carbonyl]-4-piperidinyl}(butyl)amino]-1-[(R)-cyclohexyl(hydroxy)methyl]-2-oxoethylcarbamate		C₃₈H₅₆N₄O₅	详情	详情
(VI)	64665	4-[[(2R,3R)-2-amino-3-cyclohexyl-3-hydroxypropanoyl](butyl)amino]-N,1-dibenzyl-4-piperidinecarboxamide		C₃₃H₄₈N₄O₃	详情	详情
(VII)	64666	(3R)-9-benzyl-1-butyl-3-[(R)-cyclohexyl(hydroxy)methyl]-1,4,9-triazaspiro[5.5]undecane-2,5-dione		C₂₆H₃₉N₃O₃	详情	详情
(VIII)	64667	(3R)-1-butyl-3-[(R)-cyclohexyl(hydroxy)methyl]-1,4,9-triazaspiro[5.5]undecane-2,5-dione		C₁₉H₃₃N₃O₃	详情	详情
(IX)	64668	4-(4-formylphenoxy)benzoic acid		C₁₄H₁₀O₄	详情	详情

Extended Information