1-Boc-piperidin-4-ylpropionic acid; 3-[1-(tert-butoxycarbonyl)-4-piperidinyl]propionic acid -Drug Synthesis Database

【结构式】

【分子编号】27476

【品名】1-Boc-piperidin-4-ylpropionic acid; 3-[1-(tert-butoxycarbonyl)-4-piperidinyl]propionic acid

【CA登记号】

【分子式】C₁₃H₂₃NO₄

【分子量】257.32996

【元素组成】C 60.68% H 9.01% N 5.44% O 24.87%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(XII)

Compound (XI) was coupled with N-Boc-3-(4-piperidinyl)propionic acid (XII) to produce diamide (XIII). Finally, hydrolysis of the methyl ester of (XIII) with LiOH, followed by acid removal of the Boc group yielded the title compound.

参考文献中间体

合成目标

【1】 Hoekstra, W.J.; Damiano, B.P.; Maryanoff, B.E.; et al.; Potent orally active GPIIb/IIIa antagonists containing a nipecotic acid subunit. Structure - Activity studies leading to the discovery of RWJ-53308. J Med Chem 1999, 42, 25, 5254.
【2】 Costanzo, M.J.; Hoekstra, W.J.; Maryanoff, B.E. (Ortho-McNeil Pharmaceutical, Inc.); Carboxamide derivs. of pyrrolidine, piperidine and hexahydroazepine for the treatment of thrombosis disorders. EP 0923555; JP 2000510111; US 6069254; WO 9741102 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XI)	27475	methyl (3S)-3-[[(3R)piperidinylcarbonyl]amino]-3-(3-pyridinyl)propanoate	C₁₅H₂₁N₃O₃	详情	详情
(XII)	27476	1-Boc-piperidin-4-ylpropionic acid; 3-[1-(tert-butoxycarbonyl)-4-piperidinyl]propionic acid	C₁₃H₂₃NO₄	详情	详情
(XIII)	27477	tert-butyl 4-[3-[(3R)-3-([[(1S)-3-methoxy-3-oxo-1-(3-pyridinyl)propyl]amino]carbonyl)piperidinyl]-3-oxopropyl]-1-piperidinecarboxylate	C₂₈H₄₂N₄O₆	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XXX)

The intermediate piperidine (XXIX) has been prepared by an alternative procedure. N-Boc-3-(4-Piperidinyl)propionic acid (XXX) is converted to the mixed anhydride (XXXI), which is further reacted with N,O-dimethylhydroxylamine producing the Weinreb amide (XXXII). Condensation of (XXXII) with 4-fluorophenylmagnesium bromide (XXII) leads to ketone (XXXIII). Acidic cleavage of the N-Boc group of (XXXIII), followed by treatment of the resultant piperidine (XXXIV) with benzyl chloroformate leads to the Cbz-protected analogue (XXXV). Difluorination of ketone (XXXV) is carried out by the method of Katzenellenbogen, consisting of formation of dithioketal (XXXVI), which is then reacted with 1,3-dibromo-5,5-dimethylhydantoin (DBDMH) in the presence of HF-pyridine to afford the gem-difluoro compound (XXXVII), accompanied by an unseparable by-product. A new protecting group switch is required in order to achieve complete purification of (XXXVII), which is thus converted into the N-Boc derivative (XXVIII). Acidic cleavage of (XXVIII) as above leads to the piperidine (XXIX).

参考文献中间体

合成目标

【1】 1,3,4-Trisubstituted pyrrolidine CCR5 receptor antagonists: Modifications of the arylpropylpiperidine side chains. Bioorg Med Chem Lett 2003, 13, 1, 119.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XXII)	13643	4-fluorophenyl magnesium bromide;Bromo(4-fluorophenyl)magnesium;bromo(p-fluorophenyl)Magnesium;p-Fluorophenylmagnesium bromide	352-13-6	C₆H₄BrFMg	详情	详情
(XXVIII)	65139	tert-butyl 4-[3,3-difluoro-3-(4-fluorophenyl)propyl]-1-piperidinecarboxylate		C₁₉H₂₆F₃NO₂	详情	详情
(XXIX)	65144	4-[3,3-difluoro-3-(4-fluorophenyl)propyl]piperidine		C₁₄H₁₈F₃N	详情	详情
(XXX)	27476	1-Boc-piperidin-4-ylpropionic acid; 3-[1-(tert-butoxycarbonyl)-4-piperidinyl]propionic acid		C₁₃H₂₃NO₄	详情	详情
(XXXI)	65145			C₁₈H₃₁NO₆	详情	详情
(XXXII)	65146	tert-butyl 4-{3-[methoxy(methyl)amino]-3-oxopropyl}-1-piperidinecarboxylate		C₁₅H₂₈N₂O₄	详情	详情
(XXXIII)	65147	tert-butyl 4-[3-(4-fluorophenyl)-3-oxopropyl]-1-piperidinecarboxylate		C₁₉H₂₆FNO₃	详情	详情
(XXXIV)	65149	1-(4-fluorophenyl)-3-(4-piperidinyl)-1-propanone	25872-68-8	C₁₄H₁₈FNO	详情	详情
(XXXV)	65148	benzyl 4-[3-(4-fluorophenyl)-3-oxopropyl]-1-piperidinecarboxylate		C₂₂H₂₄FNO₃	详情	详情
(XXXVI)	65150	benzyl 4-{2-[2-(4-fluorophenyl)-1,3-dithiolan-2-yl]ethyl}-1-piperidinecarboxylate		C₂₄H₂₈FNO₂S₂	详情	详情
(XXXVII)	65151	benzyl 4-[3,3-difluoro-3-(4-fluorophenyl)propyl]-1-piperidinecarboxylate		C₂₂H₂₄F₃NO₂	详情	详情

Extended Information