2,4-Diamino-6-hydroxypyrimidine; 2,6-diamino-4-pyrimidinol -Drug Synthesis Database

【结构式】

【分子编号】14811

【品名】2,4-Diamino-6-hydroxypyrimidine; 2,6-diamino-4-pyrimidinol

【CA登记号】56-06-4

【分子式】C₄H₆N₄O

【分子量】126.118

【元素组成】C 38.09% H 4.8% N 44.42% O 12.69%

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：(XXVI)

3) The silylation of 4-(3-formylpropyl)benzoic acid methyl ester (XXIII) with hexamethyldisilazane (HMSAZ) and trimethylsilyl iodide in dichloromethane gives the 4-(trimethylsilyloxy)-3-butenyl derivative (XXIV), which is brominated with Br2 in CCl4 yielding the 2-bromo-3-formylpropyl derivative (XXV). The cyclization of (XXV) with 2,4-diamino-6-hydroxypyrimidine (XXVI) by means of sodium acetate in methanol/water affords the 4-[2-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl] benzoic acid methyl ester (XXVII), which is saponified with NaOH to the corresponding free acid (XX) already obtained. The synthesis is then continued as in scheme 1735602a. 4) The benzoic ester (XXVII) can also be obtained by condensation of 4-(2-formylethyl)benzoic acid methyl ester (XIV) with methoxymethyltriphenylphosphonium bromide by means of potassium tert-butoxide in toluene giving 4-(4-methoxy-3-butenyl)benzoic acid methyl ester (XXVIII), which is then cyclized with 2,4-diamino-6-hydroxypyrimidine (XXVI) by means of Br2 in acetonitrile.

参考文献中间体

合成目标

【1】 Castaner, J.; Graul, A.; Tracy, M.; Penetrexed Disodium. Drugs Fut 1998, 23, 5, 498.
【2】 Barnett, C.J.; Wilson, T.M. (Eli Lilly and Company); Process for preparing 5-substd. pyrrolo[2,3-d]pyrimidines. EP 0589720; US 5416211 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XIV)	63842	methyl 4-(3-oxopropyl)benzoate		C₁₁H₁₂O₃	详情	详情
(XX)	14805	4-[2-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoic acid		C₁₅H₁₄N₄O₃	详情	详情
(XXIII)	14808	methyl 4-(4-oxobutyl)benzoate		C₁₂H₁₄O₃	详情	详情
(XXIV)	14809	methyl 4-[(E)-4-[(trimethylsilyl)oxy]-3-butenyl]benzoate		C₁₅H₂₂O₃Si	详情	详情
(XXV)	14810	methyl 4-(2-bromo-4-oxobutyl)benzoate		C₁₂H₁₃BrO₃	详情	详情
(XXVI)	14811	2,4-Diamino-6-hydroxypyrimidine; 2,6-diamino-4-pyrimidinol	56-06-4	C₄H₆N₄O	详情	详情
(XXVII)	14812	methyl 4-[2-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoate		C₁₆H₁₆N₄O₃	详情	详情
(XXVIII)	14813	methyl 4-[(E)-4-methoxy-3-butenyl]benzoate		C₁₃H₁₆O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

2,6-Diamino-4-hydroxypyrimidine (I) was cyclized with 1,3-dichloroacetone (II) in DMF at room temperature, and the resulting unstable furopyrimidine (III) was rapidly purified by a short column of silica gel and stored at -20 C. Then, the nucleophilic displacement reaction of chloride (III) with 2-naphthalenethiol (IV) in the presence of potassium carbonate in DMSO yielded the desired thioether.

参考文献中间体

合成目标

【1】 Gangjee, A.; et al.; Selective Pneumocystis carinii dihydrofolate reductase inhibitors: Design, synthesis, and biological evaluation of new 2,4-diamino-5-substituted-furo[2, 3-d]pyrimidines. J Med Chem 1998, 41, 8, 1263.

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)	14811	2,4-Diamino-6-hydroxypyrimidine; 2,6-diamino-4-pyrimidinol	56-06-4	C₄H₆N₄O	详情	详情
(II)	63907	1,3-dichloroacetone		C₃H₄Cl₂O	详情	详情
(III)	18884	5-(chloromethyl)furo[2,3-d]pyrimidine-2,4-diamine; 2-amino-5-(chloromethyl)furo[2,3-d]pyrimidin-4-ylamine		C₇H₇ClN₄O	详情	详情
(IV)	15234	2-Naphthalenethiol; 2-Naphthylhydrosulfide	91-60-1	C₁₀H₈S	详情	详情

Extended Information