[(1S,4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopenten-1-yl]methyl acetate -Drug Synthesis Database

【结构式】

【分子编号】49433

【品名】[(1S,4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopenten-1-yl]methyl acetate

【CA登记号】

【分子式】C₁₆H₂₀N₆O₂

【分子量】328.37404

【元素组成】C 58.52% H 6.14% N 25.59% O 9.74%

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：(XVI)

An efficient asymmetric synthesis of abacavir has been reported: Acylation of the chiral oxazolidinone (I) with the mixed anhydride (II) by means of BuLi in THF gives the N-pentenoyloxazolidinone (III), which by condensation with acrolein (IV) catalyzed by TiCl4 and ()-spartein in dichloromethane yields the chiral adduct (V). The ring-closing metathesis of adduct (V) by means of the ruthenium catalyst (Cy3P)Cl2Ru=CHPh in dichloromethane affords the chiral cyclopentenol (VI), which is reduced to 5(R)-(hydroxymethyl)-2-cyclopenten-1(R)-ol (VII) by means of LiBH4 in THF. Reaction of diol (VII) with a) Ac2O, TEA and DMAP, b) methyl chloroformate, TEA and DMAP or c) methyl chloroformate, pyridine and DMAP gives a) the diacetate (VIII), b) the cyclic carbonate (IX) or c) the dicarbonate (X), respectively. The condensation of diacetate (VIII), cyclic carbonate (IX) or dicarbonate (X) with 2-amino-6-chloropurine (XI) by means of Pd(PPh3)4 yields the carbocyclic purines (XII), (XIII) or (XIV), respectively. Treatment of these chloro-purines (XII), (XIII) and (XIV) with cyclopropylamine (XV) in hot DMSO provides the corresponding cyclopropylaminopurine carbonate (XVI), abacavir or cyclopropylaminopurine acetate (XVII), respectively. Finally, the protecting groups of purines (XVI) and (XVII) are hydrolyzed with aqueous NaOH.

参考文献中间体

合成目标

【1】 Crimmins, M.T.; et al.; An efficient, general asymmetric synthesis of carbocyclic nucleosides: Application of an asymmetric aldol/ring-closing metathesis strategy. J Org Chem 2000, 65, 25, 8499.

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)	14694	(S)-4-Benzyl-2-oxazolidinone; (4S)-4-Benzyl-1,3-oxazolan-2-one; (S)-(-)-4-Benzyl-2-oxazolidinone	90719-32-7	C₁₀H₁₁NO₂	详情	详情
(II)	17666	1,1-dimethylpropionic 4-pentenoic anhydride		C₁₀H₁₆O₃	详情	详情
(III)	17667	(4S)-4-benzyl-3-(4-pentenoyl)-1,3-oxazolidin-2-one		C₁₅H₁₇NO₃	详情	详情
(IV)	17668	acrylaldehyde; Acrolein	107-02-8	C₃H₄O	详情	详情
(V)	17669	(4S)-3-[(2S,3R)-2-allyl-3-hydroxy-4-pentenoyl]-4-benzyl-1,3-oxazolidin-2-one		C₁₈H₂₁NO₄	详情	详情
(VI)	17670	(4S)-4-benzyl-3-[[(1S,2R)-2-hydroxy-3-cyclopenten-1-yl]carbonyl]-1,3-oxazolidin-2-one		C₁₆H₁₇NO₄	详情	详情
(VII)	17671	(1R,5R)-5-(hydroxymethyl)-2-cyclopenten-1-ol		C₆H₁₀O₂	详情	详情
(VIII)	17674	[(1R,2R)-2-(acetoxy)-3-cyclopenten-1-yl]methyl acetate		C₁₀H₁₄O₄	详情	详情
(IX)	17673	(4aR,7aR)-4,4a,5,7a-tetrahydrocyclopenta[d][1,3]dioxin-2-one		C₇H₈O₃	详情	详情
(X)	17672	[(1R,2R)-2-[(methoxycarbonyl)oxy]-3-cyclopenten-1-yl]methyl methyl carbonate		C₁₀H₁₄O₆	详情	详情
(XI)	11644	6-Chloro-9H-purin-2-amine; 6-Chloro-9H-purin-2-ylamine; 2-Amino-6-chloropurine	10310-21-1	C₅H₄ClN₅	详情	详情
(XII)	45424	[(1S,4R)-4-(2-amino-6-chloro-9H-purin-9-yl)-2-cyclopenten-1-yl]methyl acetate		C₁₃H₁₄ClN₅O₂	详情	详情
(XIII)	17650	[(1S,4R)-4-(2-amino-6-chloro-9H-purin-9-yl)-2-cyclopenten-1-yl]methanol		C₁₁H₁₂ClN₅O	详情	详情
(XIV)	45398	[(1S,4R)-4-(2-amino-6-chloro-9H-purin-9-yl)-2-cyclopenten-1-yl]methyl methyl carbonate		C₁₃H₁₄ClN₅O₃	详情	详情
(XV)	12263	Cyclopropylamine; Cyclopropanamine	765-30-0	C₃H₇N	详情	详情
(XVI)	49433	[(1S,4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopenten-1-yl]methyl acetate		C₁₆H₂₀N₆O₂	详情	详情
(XVII)	49434	[(1S,4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopenten-1-yl]methyl methyl carbonate		C₁₆H₂₀N₆O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XVI)

Alternatively, 2-amino-6-chloropurine (XI) is treated with cyclopropylamine (XV) in hot DMSO to give 2-amino-6-(cyclopropylamino)purine (XVIII), which is condensed with the chiral diacetate (VIII) by means of Pd(PPh3)4 to yield the carbocyclic purine acetate (XVI). Finally, purine (XVI) is deprotected by hydrolysis with aqueous NaOH.

参考文献中间体

合成目标

【1】 Crimmins, M.T.; et al.; An efficient, general asymmetric synthesis of carbocyclic nucleosides: Application of an asymmetric aldol/ring-closing metathesis strategy. J Org Chem 2000, 65, 25, 8499.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VIII)	17674	[(1R,2R)-2-(acetoxy)-3-cyclopenten-1-yl]methyl acetate		C₁₀H₁₄O₄	详情	详情
(XI)	11644	6-Chloro-9H-purin-2-amine; 6-Chloro-9H-purin-2-ylamine; 2-Amino-6-chloropurine	10310-21-1	C₅H₄ClN₅	详情	详情
(XV)	12263	Cyclopropylamine; Cyclopropanamine	765-30-0	C₃H₇N	详情	详情
(XVI)	49433	[(1S,4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopenten-1-yl]methyl acetate		C₁₆H₂₀N₆O₂	详情	详情
(XVIII)	41890	N-(2-amino-9H-purin-6-yl)-N-cyclopropylamine; N(6)-cyclopropyl-9H-purine-2,6-diamine		C₈H₁₀N₆	详情	详情

Extended Information