3(S)-Amino-2-ethoxy-N2-nitropiperidine-1-carboxamidine -Drug Synthesis Database

【结构式】

【分子编号】29388

【品名】3(S)-Amino-2-ethoxy-N2-nitropiperidine-1-carboxamidine

【CA登记号】

【分子式】C₈H₁₇N₅O₃

【分子量】231.25488

【元素组成】C 41.55% H 7.41% N 30.28% O 20.76%

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：(XVIII)

The compound was also prepared by solution-phase synthesis. Treatment of O-tert-butyl-D-serine (XIII) with isobutyl chloroformate (XII) produced carbamate (XIV). Subsequent coupling of (XIV) with L-alanine tert-butyl ester (XV) by means of EDC and HOBt yielded the protected dipeptide (XVI). Deprotection of both tert-butyl groups of (XVI) with trifluoroacetic acid produced dipeptide (XVII), which was coupled to nitro-L-arginine ethyl aminal (XVIII) to furnish tripeptide (XIX). Hydrogenolysis of the nitro group of (XIX) over Pd/C gave (XX). The ethyl acetal of (XX) was finally hydrolyzed in 3M HCl to yield the title compound.

参考文献中间体

合成目标

【1】 Cohen, C.R.; Weinhouse, M.I.; Roberts, C.; et al.; Synthesis and biological activity of transition-state urokinase inhibitors. 217th ACS Natl Meet (March 21 1999, Anaheim) 1999, Abst MEDI 090.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XII)	13423	1-[(Chlorocarbonyl)oxy]-2-methylpropane; Isobutyl chloroformate;isobutyl carbonochloridate	543-27-1	C₅H₉ClO₂	详情	详情
(XIII)	29383	(2R)-2-amino-3-(tert-butoxy)propionic acid		C₇H₁₅NO₃	详情	详情
(XIV)	29384	(2R)-3-(tert-butoxy)-2-[(isobutoxycarbonyl)amino]propionic acid		C₁₂H₂₃NO₅	详情	详情
(XV)	29385	tert-butyl (2S)-2-aminopropanoate		C₇H₁₅NO₂	详情	详情
(XVI)	29386	tert-butyl (2S)-2-([(2R)-3-(tert-butoxy)-2-[(isobutoxycarbonyl)amino]propanoyl]amino)propanoate		C₁₉H₃₆N₂O₆	详情	详情
(XVII)	29387	(2S)-2-([(2R)-3-hydroxy-2-[(isobutoxycarbonyl)amino]propanoyl]amino)propionic acid		C₁₁H₂₀N₂O₆	详情	详情
(XVIII)	29388	3(S)-Amino-2-ethoxy-N2-nitropiperidine-1-carboxamidine		C₈H₁₇N₅O₃	详情	详情
(XIX)	29389	Isobutoxycarbinyl-D-seryl-L-alanine 1-[2-ethoxy-1-(N2-nitroamidino)piperidin-3(S)-ylamide		C₁₉H₃₅N₇O₈	详情	详情
(XX)	29390	isobutyl (1R)-2-[[(1S)-2-([(3S)-1-[amino(imino)methyl]-2-ethoxypiperidinyl]amino)-1-methyl-2-oxoethyl]amino]-1-(hydroxymethyl)-2-oxoethylcarbamate		C₁₉H₃₆N₆O₆	详情	详情

合成路线2

该中间体在本合成路线中的序号：(X)

Coupling of N-Boc-D-pyridylalanine (I) to glycine methyl ester (II) produced the protected dipeptide (III). Subsequent catalytic hydrogenation of the pyridine ring of (III) over PtO2 gave piperidine (IV), which was then treated with the guanylating reagent (V) to afford the guanidine derivative (VI). Acid cleavage of the Boc protecting group of (VI) provided amine (VII). This was condensed with benzylsulfonyl chloride to give sulfonamide (VIII). After basic hydrolysis of the methyl ester of (VIII), the resultant carboxylic acid (IX) was coupled to nitroargininal ethyl aminal (X), yielding amide (XI).

参考文献中间体

合成目标

【1】 Levy, O.E.; Uong, T.H.; Tamura, S.Y.; et al.; Guanylpiperidine peptidomimetics: Potent and selective bis-cation inhibitors of factor Xa. Bioorg Med Chem Lett 2000, 10, 8, 745.

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)	51044	Boc-D-4-Pyridylalanine; Boc-D-4-Pyridylala	37535-58-3	C₁₃H₁₈N₂O₄	详情	详情
(II)	17568	methyl 2-aminoacetate		C₃H₇NO₂	详情	详情
(III)	51045	methyl 2-[[(2R)-2-[(tert-butoxycarbonyl)amino]-3-(4-pyridinyl)propanoyl]amino]acetate		C₁₆H₂₃N₃O₅	详情	详情
(IV)	51046	methyl 2-[[(2R)-2-[(tert-butoxycarbonyl)amino]-3-(4-piperidinyl)propanoyl]amino]acetate		C₁₆H₂₉N₃O₅	详情	详情
(V)	32861	benzyl (E)-[[(benzyloxy)carbonyl]amino](methylsulfanyl)methylidenecarbamate		C₁₈H₁₈N₂O₄S	详情	详情
(VI)	51047	methyl 2-([(2R)-3-[1-([[(benzyloxy)carbonyl]amino][[(benzyloxy)carbonyl]imino]methyl)-4-piperidinyl]-2-[(tert-butoxycarbonyl)amino]propanoyl]amino)acetate		C₃₃H₄₃N₅O₉	详情	详情
(VII)	51048	methyl 2-([(2R)-2-amino-3-[1-([[(benzyloxy)carbonyl]amino][[(benzyloxy)carbonyl]imino]methyl)-4-piperidinyl]propanoyl]amino)acetate		C₂₈H₃₅N₅O₇	详情	详情
(VIII)	51049	methyl 2-([(2R)-3-[1-([[(benzyloxy)carbonyl]amino][[(benzyloxy)carbonyl]imino]methyl)-4-piperidinyl]-2-[(benzylsulfonyl)amino]propanoyl]amino)acetate		C₃₅H₄₁N₅O₉S	详情	详情
(IX)	51050	2-([(2R)-3-[1-([[(benzyloxy)carbonyl]amino][[(benzyloxy)carbonyl]imino]methyl)-4-piperidinyl]-2-[(benzylsulfonyl)amino]propanoyl]amino)acetic acid		C₃₄H₃₉N₅O₉S	详情	详情
(X)	29388	3(S)-Amino-2-ethoxy-N2-nitropiperidine-1-carboxamidine		C₈H₁₇N₅O₃	详情	详情
(XI)	51051			C₄₂H₅₄N₁₀O₁₁S	详情	详情

Extended Information