tert-butyl 4-([[(4-nitrobenzyl)oxy]carbonyl]amino)-1-piperidinecarboxylate -Drug Synthesis Database

【结构式】

【分子编号】43906

【品名】tert-butyl 4-([[(4-nitrobenzyl)oxy]carbonyl]amino)-1-piperidinecarboxylate

【CA登记号】

【分子式】C₁₈H₂₅N₃O₆

【分子量】379.41312

【元素组成】C 56.98% H 6.64% N 11.08% O 25.3%

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：(VIII)

Reductive amination of N-Boc-4-piperidone (I) with allyl amine (II) in the presence of sodium triacetoxyborohydride gave aminopiperidine (III), which was condensed with 4-nitrobenzyl chloroformate (IV) to afford carbamate (V). The Boc group of (V) was then cleaved by treatment with methanolic HCl to produce intermediate piperidine (VI). Alternatively, the condensation of 1-Boc-piperidine-4-amine (VII) with chloroformate (IV) gives carbamate (VIII), which is allylated with allyl chloride (IX) and NaH in THF, yielding the already reported carbamate (V).

参考文献中间体

合成目标

【1】 Chen, P.; Dorn, C.P. Jr.; Caldwell, C.G.; et al.; Synthesis and evaluation of CCR5 antagonists having potent in vitro antiviral activity. 220th ACS Natl Meet (Aug 20 2000, Washington DC) 2000, Abst MEDI 85.
【2】 Finke, P.E.; Mills, S.G.; Caldwell, C.G.; MacCoss, M.; Wang, L.; Kothandaraman, S.; Kim, D.; Oates, B. (Merck & Co., Inc.); Cyclic amine modulators of chemokine receptor activity. EP 1052992; US 6140349; WO 9938514 .

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)	18620	tert-butyl 4-oxo-1-piperidinecarboxylate;BOC-Piperidone;N-(tert-Butoxycarbonyl)-4-piperidone; N-Boc-4-piperidone	79099-07-3	C₁₀H₁₇NO₃	详情	详情
(II)	13672	Allylamine; 2-Propen-1-amine	107-11-9	C₃H₇N	详情	详情
(III)	43903	tert-butyl 4-(allylamino)-1-piperidinecarboxylate		C₁₃H₂₄N₂O₂	详情	详情
(IV)	33055	1-[[(chlorocarbonyl)oxy]methyl]-4-nitrobenzene	4457-32-3	C₈H₆ClNO₄	详情	详情
(V)	43904	tert-butyl 4-(allyl[[(4-nitrobenzyl)oxy]carbonyl]amino)-1-piperidinecarboxylate		C₂₁H₂₉N₃O₆	详情	详情
(VI)	43905	4-nitrobenzyl allyl(4-piperidinyl)carbamate		C₁₆H₂₁N₃O₄	详情	详情
(VII)	28414	4-Amino-1-N-Boc-piperidine; tert-butyl 4-amino-1-piperidinecarboxylate; N-Boc-4-aminopiperidine	87120-72-7	C₁₀H₂₀N₂O₂	详情	详情
(VIII)	43906	tert-butyl 4-([[(4-nitrobenzyl)oxy]carbonyl]amino)-1-piperidinecarboxylate		C₁₈H₂₅N₃O₆	详情	详情
(IX)	13235	Allyl chloride; 3-Chloro-1-propene	107-05-1	C₃H₅Cl	详情	详情

合成路线2

该中间体在本合成路线中的序号：(X)

Reductive amination of 2,5-dimethyl-2-phenylhex-4-enal (X) with methylamine and NaBH3 gives the expected secondary amine as a racemic mixture that is separated by means of mandelic acid, yielding the desired isomer (XI). The sulfonylation of the resulting amine (XI) with benzenesulfonyl chloride (XII) provided sulfonamide (XIII). Dihydroxylation with N-methylmorpholine-N-oxide in the presence of a catalytic amount of osmium tetroxide gave rise to diol (XIV), which was oxidatively cleaved to aldehyde (XV) by means of sodium periodate. Finally, reductive condensation between aldehyde (XV) and piperidine (VI) furnished the title compound.

参考文献中间体

合成目标

【1】 Chen, P.; Dorn, C.P. Jr.; Caldwell, C.G.; et al.; Synthesis and evaluation of CCR5 antagonists having potent in vitro antiviral activity. 220th ACS Natl Meet (Aug 20 2000, Washington DC) 2000, Abst MEDI 85.
【2】 Finke, P.E.; Mills, S.G.; Caldwell, C.G.; MacCoss, M.; Wang, L.; Kothandaraman, S.; Kim, D.; Oates, B. (Merck & Co., Inc.); Cyclic amine modulators of chemokine receptor activity. EP 1052992; US 6140349; WO 9938514 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VI)	43905	4-nitrobenzyl allyl(4-piperidinyl)carbamate		C₁₆H₂₁N₃O₄	详情	详情
(X)	43906	tert-butyl 4-([[(4-nitrobenzyl)oxy]carbonyl]amino)-1-piperidinecarboxylate		C₁₈H₂₅N₃O₆	详情	详情
(XI)	43907	2,5-dimethyl-2-phenyl-4-hexenal		C₁₄H₁₈O	详情	详情
(XII)	14713	benzenesulfonyl chloride	98-09-9	C₆H₅ClO₂S	详情	详情
(XIII)	43908	(2S)-N,2,5-trimethyl-2-phenyl-4-hexen-1-amine; N-[(2S)-2,5-dimethyl-2-phenyl-4-hexenyl]-N-methylamine		C₁₅H₂₃N	详情	详情
(XIV)	43909	N-[(2S)-2,5-dimethyl-2-phenyl-4-hexenyl]-N-methylbenzenesulfonamide		C₂₁H₂₇NO₂S	详情	详情
(XV)	43910	N-[(2S)-4,5-dihydroxy-2,5-dimethyl-2-phenylhexyl]-N-methylbenzenesulfonamide		C₂₁H₂₉NO₄S	详情	详情

Extended Information