(1S,2S)-2-amino-3-cyclopenten-1-ol -Drug Synthesis Database

【结构式】

【分子编号】38017

【品名】(1S,2S)-2-amino-3-cyclopenten-1-ol

【CA登记号】

【分子式】C₅H₉NO

【分子量】99.1326

【元素组成】C 60.58% H 9.15% N 14.13% O 16.14%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(IX)

The cyclization of the imidazolyl riboside (I) with [13C]-formic acid ethyl ester (II) by means of sodium ethoxide in refluxing ethanol gives labeled inosine (III), which is acetylated with Ac2O and pyridine yielding the triacetate (IV). The nitration of (IV) with ammonium nitrate and trifluoroacetic anhydride affords the 1-nitroinosine (V), which is rearranged with 15NH4Cl in acetonitrile/water to provide the doubly labeled inosine (VI). The reaction of (VI) with SOCl2 gives the chloropurine (VII), which is condensed with the dideuterated 2-aminocyclopentanol (rac-trans)-(VIII) (obtained by hydrogenation of the unsaturated analogue (rac-trans)-(IX)) by means of NaHCO3 in isopropanol providing a diastereomeric mixture (X). The deacetylation of (X) with tert-butylamine in methanol furnishes a mixture of the target compound along with its diastereomer, which is separated by preparative HPLC.

参考文献中间体

合成目标

【1】 Wadsworth, A.H.; et al.; Synthesis of isotopically labelled versions of adenosine agonist GR79236. J Label Compd Radiopharm 2000, 43, 1, 11.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IV),(VI)	38014	(2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydro-3-furanyl acetate		C₁₆H₁₈N₄O₈	详情	详情
(I)	37427	5-amino-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-1H-imidazole-4-carboxamide		C₉H₁₄N₄O₅	详情	详情
(II)	16602	ethyl formate	109-94-4	C₃H₆O₂	详情	详情
(II)	45175	ethyl formate		C₃H₆O₂	详情	详情
(III)	38013	9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-1,9-dihydro-6H-purin-6-one		C₁₀H₁₂N₄O₅	详情	详情
(III)	45176	9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-1,9-dihydro-6H-purin-6-one		C₁₀H₁₂N₄O₅	详情	详情
(IV)	45177	(2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydro-3-furanyl acetate		C₁₆H₁₈N₄O₈	详情	详情
(V)	38015	(2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(1-nitro-6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydro-3-furanyl acetate		C₁₆H₁₇N₅O₁₀	详情	详情
(V)	45178	(2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(1-nitro-6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydro-3-furanyl acetate		C₁₆H₁₇N₅O₁₀	详情	详情
(VI)	45179	(2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydro-3-furanyl acetate		C₁₆H₁₈N₄O₈	详情	详情
(VII)	38016	(2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(6-chloro-9H-purin-9-yl)tetrahydro-3-furanyl acetate		C₁₆H₁₇ClN₄O₇	详情	详情
(VII)	45180	(2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(6-chloro-9H-purin-9-yl)tetrahydro-3-furanyl acetate		C₁₆H₁₇ClN₄O₇	详情	详情
(VIII)	38010	(1S,2S)-2-aminocyclopentanol		C₅H₁₁NO	详情	详情
(VIII)	45181	(1S,2S)-2-aminocyclopentanol		C₅H₁₁NO	详情	详情
(IX)	38017	(1S,2S)-2-amino-3-cyclopenten-1-ol		C₅H₉NO	详情	详情
(X)	38018	(2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(6-[[(1S,2S)-2-hydroxycyclopentyl]amino]-9H-purin-9-yl)tetrahydro-3-furanyl acetate		C₂₁H₂₇N₅O₈	详情	详情
(X)	45182	(2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(6-[[(1S,2S)-2-hydroxycyclopentyl]amino]-9H-purin-9-yl)tetrahydro-3-furanyl acetate		C₂₁H₂₇N₅O₈	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

The commercially available 8-[14C]-inosine (I) with Ac2O in hot pyridine gives the triacetate (II), which is treated with SOCl2 and DMF in dichloromethane yielding the chloropurine (III). The condensation of (III) with (1S-trans)-2-aminocyclopentanol by means of NaHCO3 in hot isopropanol affords the acetylated target compound (V), which is finally deacetylated with t-Bu-NH2 in methanol.

参考文献中间体

合成目标

【1】 Wadsworth, A.H.; et al.; Synthesis of isotopically labelled versions of adenosine agonist GR79236. J Label Compd Radiopharm 2000, 43, 1, 11.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	38013	9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-1,9-dihydro-6H-purin-6-one	C₁₀H₁₂N₄O₅	详情	详情
(I)	63751	9-[3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-1,9-dihydro-6H-purin-6-one	C₁₀H₁₂N₄O₅	详情	详情
(II)	38014	(2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydro-3-furanyl acetate	C₁₆H₁₈N₄O₈	详情	详情
(II)	63752	4-(acetyloxy)-2-[(acetyloxy)methyl]-5-(6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydro-3-furanyl acetate	C₁₆H₁₈N₄O₈	详情	详情
(III)	38015	(2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(1-nitro-6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydro-3-furanyl acetate	C₁₆H₁₇N₅O₁₀	详情	详情
(III)	63753	4-(acetyloxy)-2-[(acetyloxy)methyl]-5-(6-chloro-9H-purin-9-yl)tetrahydro-3-furanyl acetate	C₁₆H₁₇ClN₄O₇	详情	详情
(IV)	38017	(1S,2S)-2-amino-3-cyclopenten-1-ol	C₅H₉NO	详情	详情
(V)	38018	(2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(6-[[(1S,2S)-2-hydroxycyclopentyl]amino]-9H-purin-9-yl)tetrahydro-3-furanyl acetate	C₂₁H₂₇N₅O₈	详情	详情
(V)	63754	4-(acetyloxy)-2-[(acetyloxy)methyl]-5-{6-[(2-hydroxycyclopentyl)amino]-9H-purin-9-yl}tetrahydro-3-furanyl acetate	C₂₁H₂₇N₅O₈	详情	详情

合成路线3

该中间体在本合成路线中的序号：(II)

The condensation of the ribosyl chloropurine (I) with (rac-trans)-2-amino-3-cyclopentenol (II) by means of NaHCO3 in isopropanol gives a diastereomeric mixture of adenosine derivatives (III) + (IV) that is separated by HPLC. The desired isomer (III) is acetylated with Ac2O and pyridine yielding the tetraacetate (V), which is hydrogenated with tritium over Pt in THF to afford the tetraacetate (VI) of the target compound. Finally, (VI) is deacetylated by means of t-BuNH2 in methanol.

参考文献中间体

合成目标

【1】 Wadsworth, A.H.; et al.; Synthesis of isotopically labelled versions of adenosine agonist GR79236. J Label Compd Radiopharm 2000, 43, 1, 11.

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)	18716	6-chloropurine riboside; (2R,3R,4S,5R)-2-(6-chloro-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydro-3,4-furandiol	2004-06-0	C₁₀H₁₁ClN₄O₄	详情	详情
(II)	38017	(1S,2S)-2-amino-3-cyclopenten-1-ol		C₅H₉NO	详情	详情
(III)	38019	(2R,3R,4S,5R)-2-(6-[[(1S,5S)-5-hydroxy-2-cyclopenten-1-yl]amino]-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydro-3,4-furandiol		C₁₅H₁₉N₅O₅	详情	详情
(IV)	38020	(2R,3R,4S,5R)-2-(6-[[(1R,5R)-5-hydroxy-2-cyclopenten-1-yl]amino]-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydro-3,4-furandiol		C₁₅H₁₉N₅O₅	详情	详情
(V)	38021	(2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(6-[[(1S,5S)-5-hydroxy-2-cyclopenten-1-yl]amino]-9H-purin-9-yl)tetrahydro-3-furanyl acetate		C₂₁H₂₅N₅O₈	详情	详情
(VI)	38018	(2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(6-[[(1S,2S)-2-hydroxycyclopentyl]amino]-9H-purin-9-yl)tetrahydro-3-furanyl acetate		C₂₁H₂₇N₅O₈	详情	详情

Extended Information