【结 构 式】 |
【分子编号】58985 【品名】methyl 4-[(E)-2-(2,4-diaminofuro[2,3-d]pyrimidin-5-yl)-1-ethylethenyl]benzoate 【CA登记号】 |
【 分 子 式 】C18H18N4O3 【 分 子 量 】338.36608 【元素组成】C 63.89% H 5.36% N 16.56% O 14.19% |
合成路线1
该中间体在本合成路线中的序号:(VIIIb)Condensation of 2,6-diaminopyrimidin-4-one (I) with 1,3-dichloroacetone (II) affords the furopyrimidine (III). Subsequent reaction of (III) with tributylphosphine provides the phosphonium salt (IV). Treatment of 4-hydroxypropiophenone (V) with trifluoromethanesulfonic anhydride leads to the aryl triflate (VI). This is then subjected to palladium-catalyzed carbonylation under modified Gerlach's conditions to furnish ethyl 4-propionylbenzoate (VII). Wittig condensation between the phosphorane derived from (IV) and keto ester (VII) produces olefin (VIIIa-b) as a mixture of Z/E isomers. Subsequent hydrogenation of (VIIIa-b) over Pd/C gives (IX). The methyl ester group of (IX) is hydrolyzed under alkaline conditions to afford acid (X), which is then activated as the mixed anhydride (XI) with isobutyl chloroformate and triethylamine.
【1】 Mcguire, J.J.; Zeng, Y.; Gangjee, A.; Kisliuk, R.L.; Synthesis of N-[4-[ethyl-2-(2,4-diaminofuro[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic acid as an antifolate. J Med Chem 2002, 45, 9, 1942. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(VIIIa) | 58984 | methyl 4-[(Z)-2-(2,4-diaminofuro[2,3-d]pyrimidin-5-yl)-1-ethylethenyl]benzoate | C18H18N4O3 | 详情 | 详情 | |
(VIIIb) | 58985 | methyl 4-[(E)-2-(2,4-diaminofuro[2,3-d]pyrimidin-5-yl)-1-ethylethenyl]benzoate | C18H18N4O3 | 详情 | 详情 | |
(I) | 14277 | 2,6-Diamino-4(3H)-pyrimidinone | 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) | 58981 | tributyl[(2,4-diaminofuro[2,3-d]pyrimidin-5-yl)methyl]phosphonium chloride | C19H34ClN4OP | 详情 | 详情 | |
(V) | 58982 | 4'-Hydroxypropiophenone; 4-Hydroxypropiophenone; Ethyl 4-Hydroxyphenyl ktone; p-Hydroxypropiophenone; Paroxypropione | 70-70-2 | C9H10O2 | 详情 | 详情 |
(VI) | 58983 | 4-propionylphenyl trifluoromethanesulfonate | C10H9F3O4S | 详情 | 详情 | |
(VII) | 11008 | methyl 4-propionylbenzoate | C11H12O3 | 详情 | 详情 | |
(IX) | 58988 | methyl 4-{1-[(2,4-diaminofuro[2,3-d]pyrimidin-5-yl)methyl]propyl}benzoate | C18H20N4O3 | 详情 | 详情 | |
(X) | 58986 | 4-{1-[(2,4-diaminofuro[2,3-d]pyrimidin-5-yl)methyl]propyl}benzoic acid | C17H18N4O3 | 详情 | 详情 | |
(XI) | 58987 | C22H26N4O5 | 详情 | 详情 |