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【结 构 式】 
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【分子编号】39558 【品名】22,33-dimethoxy-2,5,7,20-tetraoxa-13,28-diazahexacyclo[29.2.2.2(16,19).1(3,10).1(21,25).0(4,8)]nonatriaconta-1(33),3,8,10(39),16,18,21(38),22,24,31,34,36-dodecaene-14,27-dione 【CA登记号】 |
【 分 子 式 】C35H34N2O8 【 分 子 量 】610.66364 【元素组成】C 68.84% H 5.61% N 4.59% O 20.96% |
合成路线1
该中间体在本合成路线中的序号：(V)The condensation of 3,4-methylenedioxy-5-[2-methoxy-4-(N-carbobenzoxyaminoethyl)phenoxy]phenylethylamine (I) with 4-[2-methoxy-5-(methoxycarbonylmethyl)phenoxyphenylacetic acid (II) by means of dicyclohexylcarbodiimide in methylene chloride gives the amide (III), which is hydrolyzed with aqueous Na2CO3 to the corresponding free acid (IV). The cyclization of (IV) by the p-nitrophenyl ester method yields the cyclobisamide (V), which by a Bischler-Napieralski reaction with POCl3 in chloroform is converted into the bis(3,4-dihydroisoquinoline) (VI). The hydrogenation of (VI) with H2 over Pt affords the bis(tetrahydroisoquinoline) derivative (VII), which without isolation is finally methylated with formalin and NaBH4.
| 【1】 Tomita, M.; et al.; Synthesis of di-cepharanthine. Tetrahedron Lett 1967, 1201-06. |
| 【2】 Kondo, H.; et al.; US 2206407 . |
| 【3】 Serradell, M.N.; Blancafort, P.; Mealy, N.; Castañer, J.; Cepharanthine. Drugs Fut 1979, 4, 7, 481. |
| 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) | 39554 | benzyl 4-[[6-(2-aminoethyl)-1,3-benzodioxol-4-yl]oxy]-3-methoxyphenethylcarbamate | C26H28N2O6 | 详情 | 详情 | |
| (II) | 39555 | 2-[4-[2-methoxy-5-(2-methoxy-2-oxoethyl)phenoxy]phenyl]acetic acid | C18H18O6 | 详情 | 详情 | |
| (III) | 39556 | methyl 2-[3-(4-[2-[(2-[7-[4-(2-[[(benzyloxy)carbonyl]amino]ethyl)-2-methoxyphenoxy]-1,3-benzodioxol-5-yl]ethyl)amino]-2-oxoethyl]phenoxy)-4-methoxyphenyl]acetate | C44H44N2O11 | 详情 | 详情 | |
| (IV) | 39557 | 2-[3-(4-[2-[(2-[7-[4-(2-[[(benzyloxy)carbonyl]amino]ethyl)-2-methoxyphenoxy]-1,3-benzodioxol-5-yl]ethyl)amino]-2-oxoethyl]phenoxy)-4-methoxyphenyl]acetic acid | C43H42N2O11 | 详情 | 详情 | |
| (V) | 39558 | 22,33-dimethoxy-2,5,7,20-tetraoxa-13,28-diazahexacyclo[29.2.2.2(16,19).1(3,10).1(21,25).0(4,8)]nonatriaconta-1(33),3,8,10(39),16,18,21(38),22,24,31,34,36-dodecaene-14,27-dione | C35H34N2O8 | 详情 | 详情 | |
| (VI) | 39559 | 22,33-dimethoxy-2,5,7,20-tetraoxa-13,28-diazaoctacyclo[25.6.2.2(16,19).1(3,10).1(21,25).0(4,8).0(14,39).0(31,35)]nonatriaconta-1(33),3,8,10(39),13,16,18,21(38),22,24,27,31,34,36-tetradecaene; 22-methoxy-2,5,7,20-tetraoxa-13,28-diazaoctacyclo[25.6.2.2(16,19).1(3,10).1(21,25).0(4,8).0(14,39).0(31,35)]nonatriaconta-1(33),3,8,10(39),13,16,18,21(38),22,24,27,31,34,36-tetradecaen-33-yl methyl ether | C35H30N2O6 | 详情 | 详情 | |
| (VII) | 39560 | (14S,27R)-22,33-dimethoxy-2,5,7,20-tetraoxa-13,28-diazaoctacyclo[25.6.2.2(16,19).1(3,10).1(21,25).0(4,8).0(14,39).0(31,35)]nonatriaconta-1(33),3,8,10(39),16,18,21(38),22,24,31,34,36-dodecaene; (14S,27R)-22-methoxy-2,5,7,20-tetraoxa-13,28-diazaoctacyclo[25.6.2.2(16,19).1(3,10).1(21,25).0(4,8).0(14,39).0(31,35)]nonatriaconta-1(33),3,8,10(39),16,18,21(38),22,24,31,34,36-dodecaen-33-yl methyl ether | C35H34N2O6 | 详情 | 详情 |