cis-4-amino-2-cyclopentene-1-carboxylic acid -Drug Synthesis Database

【结构式】

【分子编号】33411

【品名】cis-4-amino-2-cyclopentene-1-carboxylic acid

【CA登记号】168471-40-7

【分子式】C₆H₉NO₂

【分子量】127.143

【元素组成】C 56.68% H 7.13% N 11.02% O 25.17%

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：(II)

The hydrolysis of the chiral unsaturated bicyclic lactam (I) with aqueous refluxing HCl gives the amino acid (II), which is esterified with 2,2-dimethoxypropane, methanol and HCl to yield the methyl ester (III). The acylation of (III) with Ac2O and pyridine in dichloromethane affords the acetamide (IV), which is reduced with calcium borohydride in THF, providing the carbinol (V). The hydrolysis of the amido group of (V) with HCl in refluxing ethanol/water gives the chiral amino alcohol (VI), which is condensed with 2-amino-4,6-dichloropyrimidine (VII) by means of DIEA in refluxing butanol, yielding the adduct (VIII). The reaction of (VIII) with 4-chlorophenyldiazonium chloride (IX) by means of HOAc and NaOAc in water affords the azo compound (X), which is reduced with Zn and HOAc to provide the triaminopyrimidine (XI). The cyclization of (XI) with triethyl orthoformate gives the carbocyclic chloropurine (XII), which is finally treated with NaOH in refluxing water to yield the target carbocyclic guanine.

参考文献中间体

合成目标

【1】 Evans, C.T.; et al.; Potential use of carbocyclic nucleosides for the treatment of AIDS - Chemo-enzymatic syntheses of the enantiomers of carbovir. J Chem Soc - Perkins Trans I 1992, 5, 589.

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)	33410	cis-2-azabicyclo[2.2.1]hept-5-en-3-one		C₆H₇NO	详情	详情
(II)	33411	cis-4-amino-2-cyclopentene-1-carboxylic acid	168471-40-7	C₆H₉NO₂	详情	详情
(III)	33412	methyl cis-4-amino-2-cyclopentene-1-carboxylate		C₇H₁₁NO₂	详情	详情
(IV)	45391	methyl (1S,4R)-4-(acetamido)-2-cyclopentene-1-carboxylate		C₉H₁₃NO₃	详情	详情
(V)	45392	N-[(1R,4S)-4-(hydroxymethyl)-2-cyclopenten-1-yl]acetamide	130931-86-1	C₈H₁₃NO₂	详情	详情
(VI)	17647	[(1S,4R)-4-amino-2-cyclopenten-1-yl]methanol		C₆H₁₁NO	详情	详情
(VII)	14404	4,6-dichloro-2-pyrimidinamine; 2-Amino-4,6-dichloropyrimidine; 4,6-dichloro-2-pyrimidinylamine	56-05-3	C₄H₃Cl₂N₃	详情	详情
(VIII)	17657	[(1S,4R)-4-[(2-amino-6-chloro-4-pyrimidinyl)amino]-2-cyclopenten-1-yl]methanol		C₁₀H₁₃ClN₄O	详情	详情
(IX)	10197	4-Chlorobenzenediazonium chloride		C₆H₄Cl₂N₂	详情	详情
(X)	17659	[(1S,4R)-4-([2-amino-6-chloro-5-[(E)-2-(4-chlorophenyl)diazenyl]-4-pyrimidinyl]amino)-2-cyclopenten-1-yl]methanol		C₁₆H₁₆Cl₂N₆O	详情	详情
(XI)	17660	[(1S,4R)-4-[(2,5-diamino-6-chloro-4-pyrimidinyl)amino]-2-cyclopenten-1-yl]methanol		C₁₀H₁₄ClN₅O	详情	详情
(XII)	17650	[(1S,4R)-4-(2-amino-6-chloro-9H-purin-9-yl)-2-cyclopenten-1-yl]methanol		C₁₁H₁₂ClN₅O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

Ring opening of cis-2-azabicyclo[2.2.1]hept-5-en-3-one (I) with HCl in refluxing methanol gives cis-4-amino-2-cyclopentene-1-carboxylic acid (II), which is esterified with HCl/methanol, yielding the methyl ester (III). The protection of (III) with tert-butoxycarbonyl anhydride and triethylamine in dichloromethane affords carbamate (IV), which is cyclized with 2-ethyl-1-nitrobutane (V) by means of phenyl isocyanate in refluxing benzene to give the cyclopenta-oxazoline (VI). Ring opening of (VI) by hydrogenation with H2 over PtO2 in HCl/methanol yields amine (VII), which is acylated with acetic anhydride and triethylamine in dichloromethane to afford acetamide (VIII). The deprotection of (VIII) with HCl in ethyl ether gives the cyclopentylamine (IX), which is condensed with N,N'-bis(tert-butoxycarbonyl)-O-methylisourea (X) by means of HgCl2 in DMF to yield the protected guanidino compound (XI). Deprotection of the guanidino group of (XI) with trifluoroacetic acid in dichloromethane affords the methyl ester (XII), which is finally hydrolyzed with NaOH in THF/methanol.

参考文献中间体

合成目标

【1】 Sorbera, L.A.; Castañer, J.; Graul, A.; RWJ-270201. Drugs Fut 2000, 25, 3, 249.
【2】 Montgomery, J.A.; Babu, Y.S.; Chand, P. (BioCryst Pharmaceuticals, Inc.); Substd. cyclopentane and cyclopentene cpds. useful as neuraminidase inhibitors. WO 9933781 .

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)	33410	cis-2-azabicyclo[2.2.1]hept-5-en-3-one		C₆H₇NO	详情	详情
(II)	33411	cis-4-amino-2-cyclopentene-1-carboxylic acid	168471-40-7	C₆H₉NO₂	详情	详情
(III)	33412	methyl cis-4-amino-2-cyclopentene-1-carboxylate		C₇H₁₁NO₂	详情	详情
(IV)	33413	methyl cis-4-[(tert-butoxycarbonyl)amino]-2-cyclopentene-1-carboxylate		C₁₂H₁₉NO₄	详情	详情
(V)	33414	3-(nitromethyl)pentane		C₆H₁₃NO₂	详情	详情
(VI)	33415	methyl (3aR,4R,6S,6aS)-4-[(tert-butoxycarbonyl)amino]-3-(1-ethylpropyl)-4,5,6,6a-tetrahydro-3aH-cyclopenta[d]isoxazole-6-carboxylate		C₁₈H₃₀N₂O₅	详情	详情
(VII)	33416	methyl (1R,2R,3R,4S)-3-[(1S*)-1-amino-2-ethylbutyl]-4-[(tert-butoxycarbonyl)amino]-2-hydroxycyclopentanecarboxylate		C₁₈H₃₄N₂O₅	详情	详情
(VIII)	33417	methyl (1R,2R,3R,4S)-3-[(1S*)-1-(acetamido)-2-ethylbutyl]-4-[(tert-butoxycarbonyl)amino]-2-hydroxycyclopentanecarboxylate		C₂₀H₃₆N₂O₆	详情	详情
(IX)	33418	methyl (1R,2R,3S,4S)-3-[(1S*)-1-(acetamido)-2-ethylbutyl]-4-amino-2-hydroxycyclopentanecarboxylate		C₁₅H₂₈N₂O₄	详情	详情
(X)	33419	tert-butyl (E)-[(tert-butoxycarbonyl)amino](methoxy)methylidenecarbamate		C₁₂H₂₂N₂O₅	详情	详情
(XI)	33420	methyl (1R,2R,3S,4S)-3-[(1S*)-1-(acetamido)-2-ethylbutyl]-4-([[(tert-butoxycarbonyl)amino][(tert-butoxycarbonyl)imino]methyl]amino)-2-hydroxycyclopentanecarboxylate		C₂₆H₄₆N₄O₈	详情	详情
(XII)	33421	methyl (1R,2R,3S,4S)-3-[(1S*)-1-(acetamido)-2-ethylbutyl]-4-[[amino(imino)methyl]amino]-2-hydroxycyclopentanecarboxylate		C₁₆H₃₀N₄O₄	详情	详情

Extended Information