2-Bromoisovalerianic acid ethyl ester; ethyl 2-bromo-3-methylbutanoate -Drug Synthesis Database

【结构式】

【分子编号】27032

【品名】2-Bromoisovalerianic acid ethyl ester; ethyl 2-bromo-3-methylbutanoate

【CA登记号】609-12-1

【分子式】C₇H₁₃BrO₂

【分子量】209.08302

【元素组成】C 40.21% H 6.27% Br 38.22% O 15.3%

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 condensation of ethyl 2-bromo-3-methylbutyrate (IX) with phenylacetonitrile (X) by means of activated Zn in THF gives the ethyl 2-isopropyl-3-oxo-4-phenylbutyrate (XI), which is cyclized with thiourea (XII) by means of sodium ethoxide in refluxing ethanol yielding 6-benzyl-5-isopropyl-2-thioracil (XIII). The desulfurization of (XIII) with a refluxing solution of 10% chloroacetic acid in water affords the corresponding uracil (XIV), which is finally alkylated with chloromethyl ethyl ether (II) and BSA in chloroform.

参考文献中间体

合成目标

【1】 Larsen, D.K.; et al.; Synthesis and potent anti-HIV-1 activity of novel 6-benzyluracil analogues of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine. J Med Chem 1996, 39, 12, 2427.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(II)	13149	1-(Chloromethoxy)ethane; Chloromethyl ethyl ether	3188-13-4	C₃H₇ClO	详情	详情
(IX)	27032	2-Bromoisovalerianic acid ethyl ester; ethyl 2-bromo-3-methylbutanoate	609-12-1	C₇H₁₃BrO₂	详情	详情
(X)	17046	Phenylacetonitrile; 2-phenylacetonitrile; Benzyl cyanide	140-29-4	C₈H₇N	详情	详情
(XI)	27033	ethyl 2-isopropyl-3-oxo-4-phenylbutanoate		C₁₅H₂₀O₃	详情	详情
(XII)	10180	Thiourea	62-56-6	CH₄N₂S	详情	详情
(XIII)	27034	6-benzyl-5-isopropyl-2-thioxo-2,3-dihydro-4(1H)-pyrimidinone		C₁₄H₁₆N₂OS	详情	详情
(XIV)	27035	6-benzyl-5-isopropyl-2,4(1H,3H)-pyrimidinedione		C₁₄H₁₆N₂O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

The reaction of 2-phenylacetonitrile (I) with 2-bromo-3-methylbutyric acid ethyl ester (II) by means of Zn in THF gives the ketoester (III), which is cyclized with thiourea (IV) by means of sodium ethoxide in ethanol yielding 6-benzyl-5-isopropyl-2-thioxo-1,2,3,4-tetrahydropyrimidin-4-one (V). Finally, this compound is treated with chloromethyl methyl sulfide (VI) and K2CO3 in DMF.

参考文献中间体

合成目标

【1】 Vig, R.; Mao, C.; Venkatachalam, T.K.; Tuel-Ahlgren, L.; Sudbeck, E.A.; Uckun, F.M.; 5-Alkyl-2-[(methylthiomethyl)thio]-6-(benzyl)-pyrimidin-4-(1H)-ones as potent non-nucleoside reverse transcriptase inhibitors of S-DABO series. Bioorg Med Chem Lett 1998, 8, 12, 1461.
【2】 Sudbeck, E.A.; Mao, C.; Vig, R.; Venkatachalam, T.K.; Tuel-Ahlgren, L.; Uckun, F.M.; Structure-based design of novel dihydroalkoxybenzyloxopyrimidine derivatives as potent nonnucleoside inhibitors of the human immunodeficiency virus reverse transcriptase. Antimicrob Agents Chemother 1998, 42, 12, 3225.

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)	17046	Phenylacetonitrile; 2-phenylacetonitrile; Benzyl cyanide	140-29-4	C₈H₇N	详情	详情
(II)	27032	2-Bromoisovalerianic acid ethyl ester; ethyl 2-bromo-3-methylbutanoate	609-12-1	C₇H₁₃BrO₂	详情	详情
(III)	27033	ethyl 2-isopropyl-3-oxo-4-phenylbutanoate		C₁₅H₂₀O₃	详情	详情
(IV)	10180	Thiourea	62-56-6	CH₄N₂S	详情	详情
(V)	27034	6-benzyl-5-isopropyl-2-thioxo-2,3-dihydro-4(1H)-pyrimidinone		C₁₄H₁₆N₂OS	详情	详情
(VI)	27701	chloro(methylsulfanyl)methane	2373-51-5	C₂H₅ClS	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 2-(3,5-dimethylphenyl)acetonitrile (I) with ethyl 2-bromo-3-methylbutyrate (II) by means of Zn in THF gives the beta-ketoester (III), which is cyclized with thiourea (IV) by means of sodium ethoxide in ethanol yielding the thioxopyrimidinone (V). Finally, this compound is condensed with choromethyl methyl sulfide by means of K2CO3 in DMF.

参考文献中间体

合成目标

【1】 Vig, R.; Mao, C.; Venkatachalam, T.K.; Tuel-Ahlgren, L.; Sudbeck, E.A.; Uckun, F.M.; 5-Alkyl-2-[(methylthiomethyl)thio]-6-(benzyl)-pyrimidin-4-(1H)-ones as potent non-nucleoside reverse transcriptase inhibitors of S-DABO series. Bioorg Med Chem Lett 1998, 8, 12, 1461.
【2】 Sudbeck, E.A.; Mao, C.; Vig, R.; Venkatachalam, T.K.; Tuel-Ahlgren, L.; Uckun, F.M.; Structure-based design of novel dihydroalkoxybenzyloxopyrimidine derivatives as potent nonnucleoside inhibitors of the human immunodeficiency virus reverse transcriptase. Antimicrob Agents Chemother 1998, 42, 12, 3225.

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)	30213	2-(3,5-dimethylphenyl)acetonitrile	39101-54-7	C₁₀H₁₁N	详情	详情
(II)	27032	2-Bromoisovalerianic acid ethyl ester; ethyl 2-bromo-3-methylbutanoate	609-12-1	C₇H₁₃BrO₂	详情	详情
(III)	30214	ethyl 4-(3,5-dimethylphenyl)-2-isopropyl-3-oxobutanoate		C₁₇H₂₄O₃	详情	详情
(IV)	10180	Thiourea	62-56-6	CH₄N₂S	详情	详情
(V)	30215	6-(3,5-dimethylbenzyl)-5-isopropyl-2-thioxo-2,3-dihydro-4(1H)-pyrimidinone		C₁₆H₂₀N₂OS	详情	详情
(VI)	27701	chloro(methylsulfanyl)methane	2373-51-5	C₂H₅ClS	详情	详情

Extended Information