5-methyl-1-[(1R)-1-({(1S)-1-[(trityloxy)methyl]-2-propenyl}oxy)-2-propenyl]-2,4(1H,3H)-pyrimidinedione -Drug Synthesis Database

【结构式】

【分子编号】62191

【品名】5-methyl-1-[(1R)-1-({(1S)-1-[(trityloxy)methyl]-2-propenyl}oxy)-2-propenyl]-2,4(1H,3H)-pyrimidinedione

【CA登记号】

【分子式】C₃₁H₃₀N₂O₄

【分子量】494.59028

【元素组成】C 75.28% H 6.11% N 5.66% O 12.94%

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：(V)

The reaction of 5-methyluridine (I) with TrCl and pyridine gives the 5'-O-trityl derivative (II), which is oxidized with NaIO4 in ethanol/water to yield the dialdehyde (III). The Wittig reaction of (III) with methyltriphenylphosphonium bromide (IV) and t-BuOK in toluene to afford the bis vinyl compound (V), which is submitted to a ring closing metathesis reaction catalyzed by a Ru catalyst in dichloromethane to provide the unsaturated nucleoside (VI). Finally, this compound is deprotected by means of AcOH in water to furnish the target Stavudine.

参考文献中间体

合成目标

【1】 Ewing, D.F.; et al.; Synthesis of acyclic bis-vinyl pyrimidines: A general route to d4T via metathesis. Tetrahedron 2003, 59, 7, 941.

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)	12206	1-[(2R,3R,4S,5R)-3,4-Dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-5-methyl-2,4(1H,3H)-pyrimidinedione; 5-Methyluridine	1463-10-1	C₁₀H₁₄N₂O₆	详情	详情
(II)	41905	1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(trityloxy)methyl]tetrahydro-2-furanyl]-5-methyl-2,4(1H,3H)-pyrimidinedione		C₂₉H₂₈N₂O₆	详情	详情
(III)	62190	(2R)-2-({(1R)-1-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]-2-oxoethyl}oxy)-3-(trityloxy)propanal		C₂₉H₂₆N₂O₆	详情	详情
(IV)	30484	Methyl(triphenyl)phosphonium bromide	1779-49-3	C₁₉H₁₈BrP	详情	详情
(V)	62191	5-methyl-1-[(1R)-1-({(1S)-1-[(trityloxy)methyl]-2-propenyl}oxy)-2-propenyl]-2,4(1H,3H)-pyrimidinedione		C₃₁H₃₀N₂O₄	详情	详情
(VI)	12199	5-Methyl-1-[(2R,5S)-5-[(trityloxy)methyl]-2,5-dihydro-2-furanyl]-2,4(1H,3H)-pyrimidinedione		C₂₉H₂₆N₂O₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

The reaction of 5-methyluridine (I) with trityl chloride (II) and pyridine gives the 5'-O-trityl analogue (III), which is submitted to an oxidative cleavage of the vicinal dihydroxy group by means of NaIO4 in EtOH/water to yield the dialdehyde (IV). The double Wittig olefination of (IV) by means of methyltriphenylphosphonium bromide (V) and t-BuOK in toluene affords the bis alkene (VI), which is submitted to a ring closing metathesis by means of the Grubb's catalyst in dichloromethane to provide the unsaturated nucleoside (VII). Finally, this compound was deprotected by means of 80% AcOH to furnish the target Stavudine.

参考文献中间体

合成目标

【1】 Ewing, D.; Glacon, V.; Mackenzie, G.; Postel, D.; Len, C.; A novel approach to unsaturated acyclic nucleoside analogues and the first synthesis of d4T by ring closure metathesis. Tetrahedron Lett 2002, 43, 19, 3503.

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)	12206	1-[(2R,3R,4S,5R)-3,4-Dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-5-methyl-2,4(1H,3H)-pyrimidinedione; 5-Methyluridine	1463-10-1	C₁₀H₁₄N₂O₆	详情	详情
(II)	28630	Triphenylchloromethane; 1-[Chloro(diphenyl)methyl]benzene; Trityl chloride	76-83-5	C₁₉H₁₅Cl	详情	详情
(III)	41905	1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(trityloxy)methyl]tetrahydro-2-furanyl]-5-methyl-2,4(1H,3H)-pyrimidinedione		C₂₉H₂₈N₂O₆	详情	详情
(IV)	62190	(2R)-2-({(1R)-1-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]-2-oxoethyl}oxy)-3-(trityloxy)propanal		C₂₉H₂₆N₂O₆	详情	详情
(V)	30484	Methyl(triphenyl)phosphonium bromide	1779-49-3	C₁₉H₁₈BrP	详情	详情
(VI)	62191	5-methyl-1-[(1R)-1-({(1S)-1-[(trityloxy)methyl]-2-propenyl}oxy)-2-propenyl]-2,4(1H,3H)-pyrimidinedione		C₃₁H₃₀N₂O₄	详情	详情
(VII)	12199	5-Methyl-1-[(2R,5S)-5-[(trityloxy)methyl]-2,5-dihydro-2-furanyl]-2,4(1H,3H)-pyrimidinedione		C₂₉H₂₆N₂O₄	详情	详情

Extended Information