【结 构 式】 |
【分子编号】19520 【品名】4-[(E)-1-ethyl-4-methoxy-3-butenyl]benzoate 【CA登记号】 |
【 分 子 式 】C14H17O3 【 分 子 量 】233.28718 【元素组成】C 72.08% H 7.35% O 20.57% |
合成路线1
该中间体在本合成路线中的序号:(III)The synthesis of 10-EDAM is as follows: 3-Methoxyallyl chloride (II) is prepared in situ by treatment of 1-methoxyallene (I) with an equivalent of HCl in ether at low temperature. The dianion of p-n-propylbenzoic acid is generated in THF at 0-5 C by lithium diisopropyl amide and subsequently alkylated with (II). The resulting 4-(p-carboxyphenyl)-1-methoxy-1-hexene (III) is brominated at pH 7-8 to give the alpha-bromoaldehyde acid (IV). Condensation with tetraaminopyrimidine in aqueous AcOH and subsequent in situ oxidation of the resultant dihydropteridine affords crystalline 10-ethyl-10-deaza-4-amino-4-desoxypteroic acid (V). Coupling of (V) with diethyl L-glutamate via the mixed anhydride method using isobutyl chloroformate affords the diethyl ester of 10-EDAM (VI). Following chromatographic purification on silica gel, the diester is saponified with 1N NaOH in methoxyethanol at room temperature to yield 10-EDAM.
【1】 DeGraw, J.I.; EDATREXATE. Drugs Fut 1989, 14, 9, 849. |
【2】 Hoff, S.; Brandsma, L.; Acid catalyzed ring closure of 1-methoxy or 1-(methylthio)-1-(alpha or beta-hydroxyalkyl)allenes. Recl Trav Chim Pays-Bas 1969, 88, 845. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(Va) | 11012 | 4-[1-[(2,4-Diamino-6-pteridinyl)methyl]propyl]benzoic acid | C17H18N6O2 | 详情 | 详情 | |
(Vb) | 13423 | 1-[(Chlorocarbonyl)oxy]-2-methylpropane; Isobutyl chloroformate;isobutyl carbonochloridate | 543-27-1 | C5H9ClO2 | 详情 | 详情 |
(IIa) | 19518 | (E)-3-chloro-1-propenyl methyl ether; (E)-3-chloro-1-methoxy-1-propene | C4H7ClO | 详情 | 详情 | |
(IIb) | 19519 | 4-propylbenzoic acid | 2438-05-3 | C10H12O2 | 详情 | 详情 |
(IVa) | 19521 | 4-(3-bromo-1-ethyl-4-oxobutyl)benzoic acid | C13H15BrO3 | 详情 | 详情 | |
(IVb) | 19522 | 2,4,6-triamino-5-pyrimidinylamine; 2,4,5,6-pyrimidinetetramine | 1004-74-6 | C4H8N6 | 详情 | 详情 |
(Vc) | 19525 | diethyl 2-aminopentanedioate | C9H17NO4 | 详情 | 详情 | |
(I) | 19517 | methyl 1,2-propadienyl ether; 1-methoxyallene | C4H6O | 详情 | 详情 | |
(III) | 19520 | 4-[(E)-1-ethyl-4-methoxy-3-butenyl]benzoate | C14H17O3 | 详情 | 详情 | |
(VI) | 19526 | diethyl 2-[(4-[1-[(2,4-diamino-6-pteridinyl)methyl]propyl]benzoyl)amino]pentanedioate | C26H33N7O5 | 详情 | 详情 |