5-bromopyrimidine -Drug Synthesis Database

【结构式】

【分子编号】38987

【品名】5-bromopyrimidine

【CA登记号】4595-59-9

【分子式】C₄H₃BrN₂

【分子量】158.9853

【元素组成】C 30.22% H 1.9% Br 50.26% N 17.62%

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：(I)

Palladium-catalyzed coupling of 5-bromopyrimidine (I) with ethyl acrylate (II) afforded pyrimidinyl acrylate (III), which was hydrogenated over Pd/C to give (IV). Claisen condensation of (IV) with ethyl formate furnished oxoester (V). This was then cyclized with thiourea (VI) to produce the intermediate thiouracil (VII).

参考文献中间体

合成目标

【1】 Hickey, D.M.B.; Boyd, H.F.; Flynn, S.T.; et al.; 2-(Alkylthio)pyrimidin-4-ones as novel, reversible inhibitors of lipoprotein-associated phospholipase A2. Bioorg Med Chem Lett 2000, 10, 4, 395.
【2】 Pinto, I.L.; Ife, R.J.; Hickey, D.M.B.; Smith, S.A.; Leach, C.A.; Porter, R.A. (SmithKline Beecham plc); Pyrimidinone cpds. and pharmaceutical compsns. containing them. EP 1028955; WO 9924420 .

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)	38987	5-bromopyrimidine	4595-59-9	C₄H₃BrN₂	详情	详情
(II)	10164	ethyl acrylate	140-88-5	C₅H₈O₂	详情	详情
(III)	38988	ethyl (E)-3-(5-pyrimidinyl)-2-propenoate		C₉H₁₀N₂O₂	详情	详情
(IV)	38989	ethyl 3-(5-pyrimidinyl)propanoate		C₉H₁₂N₂O₂	详情	详情
(V)	38990	ethyl (Z)-3-hydroxy-2-(5-pyrimidinylmethyl)-2-propenoate		C₁₀H₁₂N₂O₃	详情	详情
(VI)	10180	Thiourea	62-56-6	CH₄N₂S	详情	详情
(VII)	38991	5-(5-pyrimidinylmethyl)-2-thioxo-2,3-dihydro-4(1H)-pyrimidinone		C₉H₈N₄OS	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 protected 4-pyrimidinylphenylalanine (III) was prepared by palladium-catalyzed coupling of the boronophenylalanine (I) with the 5-halopyrimidine (II). After acidic cleavage of the N-Boc protecting group of (III), the resultant amino ester (IV) was coupled with N-Boc-cycloleucine (V) to provide dipeptide (VI). Further acidic treatment of (VI) removed the N-Boc group to yield amine (VII). The chiral bromo acid (IX) was obtained by diazotization of D-valine (VIII) in the presence of HBr and KBr. Acylation of the racemic amine (VII) with bromo acid (IX) furnished the corresponding amide (X) as an epimeric mixture. The bromo group of (X) was finally displaced with potassium thioacetate to give the title thioacetate ester.

参考文献中间体

合成目标

【1】 Gude, C.; Chan, K.; Firooznia, F.; et al.; Synthesis and biological activity of novel potent endothelin-converting enzyme-1 inhibitors. Bioorg Med Chem Lett 2001, 11, 3, 375.

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)	47701	methyl 2-[(tert-butoxycarbonyl)amino]-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]propanoate		C₂₁H₃₂BNO₆	详情	详情
(II)	38987	5-bromopyrimidine	4595-59-9	C₄H₃BrN₂	详情	详情
(III)	47702	methyl 2-[(tert-butoxycarbonyl)amino]-3-[4-(5-pyrimidinyl)phenyl]propanoate		C₁₉H₂₃N₃O₄	详情	详情
(IV)	47703	methyl 2-amino-3-[4-(5-pyrimidinyl)phenyl]propanoate		C₁₄H₁₅N₃O₂	详情	详情
(V)	30890	1-[(tert-butoxycarbonyl)amino]cyclopentanecarboxylic acid		C₁₁H₁₉NO₄	详情	详情
(VI)	47704	methyl 2-[([1-[(tert-butoxycarbonyl)amino]cyclopentyl]carbonyl)amino]-3-[4-(5-pyrimidinyl)phenyl]propanoate		C₂₅H₃₂N₄O₅	详情	详情
(VII)	47705	methyl 2-[[(1-aminocyclopentyl)carbonyl]amino]-3-[4-(5-pyrimidinyl)phenyl]propanoate		C₂₀H₂₄N₄O₃	详情	详情
(VIII)	21056	(R)-(-)-Valine; D-Valine; (R)-alpha-Aminoisovaleric acid	640-68-6	C₅H₁₁NO₂	详情	详情
(IX)	33158	(2R)-2-bromo-3-methylbutyric acid	565-74-2	C₅H₉BrO₂	详情	详情
(X)	47706	methyl 2-[[(1-[[(2R)-2-bromo-3-methylbutanoyl]amino]cyclopentyl)carbonyl]amino]-3-[4-(5-pyrimidinyl)phenyl]propanoate		C₂₅H₃₁BrN₄O₄	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

Lithiation of 5-bromopyrimidine (I), followed by addition of CO2 produces pyrimidine-5-carboxylic acid (II). After catalytic hydrogenation of (II), the resultant tetrahydropyrimidine acid (III) is esterified with SOCl2 in MeOH to yield the corresponding methyl ester (IV). Protection of (IV) with triphenylmethyl chloride and DBU affords the N-trityl derivative (V). Then, condensation between the sodium derivative of propionamide oxime (VI) and ester (V) gives rise to the oxadiazole compound (VII). The N-trityl group of (VII) is finally removed with trifluoroacetic acid to furnish the title compound.

参考文献中间体

合成目标

【1】 Dunbar, P.G.; Durant, G.J.; Fang, Z.; Abuh, Y.F.; El-Assadi, A.A.; Ngur, D.O.; Periyasamy, S.; Hoss, W.P.; Messer, W.S. Jr.; Design, synthesis, and neurochemical evaluation of 5-(3-alkyl-1,2,4-oxadiazol-5-yl)-1,4,5,6-tetrahydropyrimidines as M1 muscarinic receptor agonists. J. Med. Chem. 1993, 36, 7, 842.

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)	38987	5-bromopyrimidine	4595-59-9	C₄H₃BrN₂	详情	详情
(II)	61334	5-pyrimidinecarboxylic acid		C₅H₄N₂O₂	详情	详情
(III)	61335	1,4,5,6-tetrahydro-5-pyrimidinecarboxylic acid		C₅H₈N₂O₂	详情	详情
(IV)	61336	methyl 1,4,5,6-tetrahydro-5-pyrimidinecarboxylate		C₆H₁₀N₂O₂	详情	详情
(V)	61337	methyl 1-trityl-1,4,5,6-tetrahydro-5-pyrimidinecarboxylate		C₂₅H₂₄N₂O₂	详情	详情
(VI)	61338	N'-hydroxypropanimidamide		C₃H₈N₂O	详情	详情
(VII)	61339	5-(3-ethyl-1,2,4-oxadiazol-5-yl)-1-trityl-1,4,5,6-tetrahydropyrimidine		C₂₇H₂₆N₄O	详情	详情

Extended Information