【结 构 式】 |
【分子编号】59059 【品名】3-[chloro(methoxy)methyl]-4-methoxyphenyl methyl carbonate 【CA登记号】 |
【 分 子 式 】C11H13ClO5 【 分 子 量 】260.67392 【元素组成】C 50.68% H 5.03% Cl 13.6% O 30.69% |
合成路线1
该中间体在本合成路线中的序号:(III)Protection of 4-methoxyphenol (I) with methyl chloroformate in the presence of pyridine affords the carbonate ester (II), which is condensed with dichloromethyl methyl ether and TiCl4 to yield alpha-chloro ether (III). Acidic hydrolysis of (III) with HCl furnishes aldehyde (IV), which is converted into the sodium phenoxide (V) by methanolysis of the carbonate ester (IV). Subsequent alkylation of (V) with p-methoxybenzyl bromide (VI) produces the p-methoxybenzyl ether (VII), which is condensed with 3-morpholinopropionitrile (VIII) employing a catalytic amount of NaOMe to give the morpholino acrylonitrile (IX). After conversion of (IX) to the 3-anilino acrylonitrile (X) upon heating with aniline hydrochloride, condensation with guanidine (XI) produces the diaminopyrimidine (XII). The p-methoxybenzyl group of (XII) is then cleaved by treatment with p-toluenesulfonic acid in MeOH, producing phenol (XIII). The sodium salt generated from phenol (XIII) and NaOEt is then alkylated with ethyl 5-bromopentanoate (XIV) to furnish ether (XV). Finally, alkaline hydrolysis of the ethyl ester group of (XV) leads to the title compound.
【1】 Rosowsky, A.; Queener, S.F.; Forsch, R.A.; Inhibition of Pneumocystis carinii, Toxoplasma gondii, and Mycobacterium avium dihydrofolate reductases by 2,4-diamino-5-[2-methoxy-5-(omega-carboxyalkyloxy)benzyl]pyrimidines: Marked improvement in potency relative to trimethoprim and species selectivity. J Med Chem 2002, 45, 1, 233. |
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) | 32744 | 4-methoxyphenol | 150-76-5 | C7H8O2 | 详情 | 详情 |
(II) | 59058 | 4-methoxyphenyl methyl carbonate | C9H10O4 | 详情 | 详情 | |
(III) | 59059 | 3-[chloro(methoxy)methyl]-4-methoxyphenyl methyl carbonate | C11H13ClO5 | 详情 | 详情 | |
(IV) | 59060 | 3-formyl-4-methoxyphenyl methyl carbonate | C10H10O5 | 详情 | 详情 | |
(V) | 59061 | sodium 3-formyl-4-methoxybenzenolate | C8H7NaO3 | 详情 | 详情 | |
(VI) | 27490 | 1-(bromomethyl)-4-methoxybenzene | C8H9BrO | 详情 | 详情 | |
(VII) | 59062 | 2-methoxy-5-[(4-methoxybenzyl)oxy]benzaldehyde | C16H16O4 | 详情 | 详情 | |
(VIII) | 31933 | 3-Morpholinopropionitrile; 3-(4-Morpholinyl)propanenitrile | 4542-47-6 | C7H12N2O | 详情 | 详情 |
(IX) | 59063 | (Z)-2-{2-methoxy-5-[(4-methoxybenzyl)oxy]benzyl}-3-(4-morpholinyl)-2-propenenitrile | C23H26N2O4 | 详情 | 详情 | |
(X) | 59064 | (Z)-3-anilino-2-{2-methoxy-5-[(4-methoxybenzyl)oxy]benzyl}-2-propenenitrile | C25H24N2O3 | 详情 | 详情 | |
(XI) | 14790 | Guanidine | 113-00-8 | CH5N3 | 详情 | 详情 |
(XII) | 59065 | 2-amino-5-{2-methoxy-5-[(4-methoxybenzyl)oxy]benzyl}-4-pyrimidinylamine; 5-{2-methoxy-5-[(4-methoxybenzyl)oxy]benzyl}-2,4-pyrimidinediamine | C20H22N4O3 | 详情 | 详情 | |
(XIII) | 59066 | 3-[(2,4-diamino-5-pyrimidinyl)methyl]-4-methoxyphenol | C12H14N4O2 | 详情 | 详情 | |
(XIV) | 37151 | ethyl 5-bromopentanoate | 14660-52-7 | C7H13BrO2 | 详情 | 详情 |
(XV) | 59067 | ethyl 5-{3-[(2,4-diamino-5-pyrimidinyl)methyl]-4-methoxyphenoxy}pentanoate | C19H26N4O4 | 详情 | 详情 |