1-(ethoxymethyl)-5-isopropyl-2-thioxo-2,3-dihydro-4(1H)-pyrimidinone -Drug Synthesis Database

【结构式】

【分子编号】27026

【品名】1-(ethoxymethyl)-5-isopropyl-2-thioxo-2,3-dihydro-4(1H)-pyrimidinone

【CA登记号】

【分子式】C₁₀H₁₆N₂O₂S

【分子量】228.31532

【元素组成】C 52.61% H 7.06% N 12.27% O 14.02% S 14.04%

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：(III)

The reaction of the silylated 5-isopropylpyrimidine (I) with chloromethyl ethyl ether (II) by means of KI in dichloromethane gives 1-(ethoxymethyl)-5-isopropyl-2-thiouracil (III), which is condensed with benzaldehyde (IV) by means of lithium diisopropylamide (LDA) in THF, and desulfurized by reaction with H2O2 and NaOH in water to afford 1-(ethoxymethyl)-5-isopropyl-6-(alpha-hydroxybenzyl)uracil (V). The reaction of (V) with acetic anhydride and pyridine gives the acetate (VI), which is finally submitted to hydrogenolysis with H2 over Pd/C in acetic acid/water/dioxane.

参考文献中间体

合成目标

【1】 Walker, R.T.; Baba, M.; De Clerq, E.; Takashima, H.; Inouye, N.; Ubasawa, M.; Miyasaka, T.; Sekiya, K.; Shigeta, S.; Tanaka, H.; Synthesis and antiviral activity of 6-benzyl analogs of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) as potent and selective anti-HIV-1 agents. J Med Chem 1995, 38, 15, 2860.
【2】 Ubasawa, M.; Tanaka, H.; Walker, R.T.; Yuasa, S.; Miyasaka, T.; De Clerq, E.; Baba, M.; HEPT derivatives: 6-benzyl-1-ethoxymethyl-5-isopropyluracil (MKC-442). Nucleosides Nucleotides 1995, 14, 3-5, 575.

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)	27025	5-isopropyl-4-[(trimethylsilyl)methyl]-2-[(trimethylsilyl)sulfanyl]pyrimidine		C₁₄H₂₈N₂SSi₂	详情	详情
(II)	13149	1-(Chloromethoxy)ethane; Chloromethyl ethyl ether	3188-13-4	C₃H₇ClO	详情	详情
(III)	27026	1-(ethoxymethyl)-5-isopropyl-2-thioxo-2,3-dihydro-4(1H)-pyrimidinone		C₁₀H₁₆N₂O₂S	详情	详情
(IV)	10498	Benzaldehyde;Benzoic aldehyde;Phenylmethanal	100-52-7	C₇H₆O	详情	详情
(V)	27027	1-(ethoxymethyl)-6-[hydroxy(phenyl)methyl]-5-isopropyl-2,4(1H,3H)-pyrimidinedione		C₁₇H₂₂N₂O₄	详情	详情
(VI)	27028	[3-(ethoxymethyl)-5-isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-4-pyrimidinyl](phenyl)methyl acetate		C₁₉H₂₄N₂O₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Lithiation of 1-(ethoxymethyl)-5-isopropyl-2-thiouracil (I) by means of LDA in cold THF, followed by condensation with 3,5-dimethylbenzaldehyde (II) gave the 6-(alpha-hydroxybenzyl) derivative (III). Oxidative hydrolysis of the thione function of (III) with H2O2 afforded the corresponding uracil (IV). Acetylation of (IV) with Ac2O in pyridine provided acetate ester (V), which was subjected to hydrogenolysis in the presence of Pd/C to furnish the title benzyl derivative.

参考文献中间体

合成目标

【1】 Walker, R.T.; Baba, M.; De Clerq, E.; Takashima, H.; Inouye, N.; Ubasawa, M.; Miyasaka, T.; Sekiya, K.; Shigeta, S.; Tanaka, H.; Synthesis and antiviral activity of 6-benzyl analogs of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) as potent and selective anti-HIV-1 agents. J Med Chem 1995, 38, 15, 2860.

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)	27026	1-(ethoxymethyl)-5-isopropyl-2-thioxo-2,3-dihydro-4(1H)-pyrimidinone		C₁₀H₁₆N₂O₂S	详情	详情
(II)	32915	3,5-dimethylbenzaldehyde	5779-95-3	C₉H₁₀O	详情	详情
(III)	38765	6-[(3,5-dimethylphenyl)(hydroxy)methyl]-1-(ethoxymethyl)-5-isopropyl-2-thioxo-2,3-dihydro-4(1H)-pyrimidinone		C₁₉H₂₆N₂O₃S	详情	详情
(IV)	38766	6-[(3,5-dimethylphenyl)(hydroxy)methyl]-1-(ethoxymethyl)-5-isopropyl-2,4(1H,3H)-pyrimidinedione		C₁₉H₂₆N₂O₄	详情	详情
(V)	38767	(3,5-dimethylphenyl)[3-(ethoxymethyl)-5-isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-4-pyrimidinyl]methyl acetate		C₂₁H₂₈N₂O₅	详情	详情

Extended Information