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【结 构 式】 
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【药物名称】Caracasanamide 【化学名称】3-(3,4-Dimethoxyphenyl)-N-[4-[3-(3-methyl-2-butenyl)guanidino]butyl]propenamide 【CA登记号】146269-39-8 【 分 子 式 】C21H32N4O3 【 分 子 量 】388.51419 |
【开发单位】Consiglio Nazionale delle Ricerche (Originator) 【药理作用】CARDIOVASCULAR DRUGS, Hypertension, Treatment of |
合成路线1
The condensation of 3,4-dimethoxy-N-(4-aminobutyl)cinnamamide (I) with N,N'-bis(tert-butoxycarbonyl)-S-methyl-N-(3-methyl-2-butenyl)isothiourea (II) gives the protected target compound (III), which is finally deprotected by treatment with methanesulfonic acid.
| 【1】 Delle Monache, G.; et al.; Caracasanamide, a novel hypotensive agent from verbesina caracasana. Bioorg Med Chem Lett 1992, 2, 5, 415. |
| 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) | 26451 | (E)-N-(4-aminobutyl)-3-(3,4-dimethoxyphenyl)-2-propenamide | C15H22N2O3 | 详情 | 详情 | |
| (II) | 26452 | tert-butyl [(tert-butoxycarbonyl)imino](methylsulfanyl)methyl(3-methyl-2-butenyl)carbamate | C17H30N2O4S | 详情 | 详情 | |
| (III) | 26453 | tert-butyl [(tert-butoxycarbonyl)imino][(4-[[(E)-3-(3,4-dimethoxyphenyl)-2-propenoyl]amino]butyl)amino]methyl(3-methyl-2-butenyl)carbamate | C31H48N4O7 | 详情 | 详情 |
合成路线2
The reaction of S-methylisothiourea (I) with Boc2O by means of NaHCO3 gives the N-Boc protected isothiourea (II), which is condensed with 1,4-butanediamine (III) in hot THF to yield the guanidine derivative (IV). The acylation of the amino group of (IV) with 3,4-dimethoxycinnamoyl chloride (V) with THF/DMF affords the corresponding amide (VI), which is deprotected with TFA to provide N-(4-guanidinobutyl)-3,4-dimethoxycinnamamide (VII). Finally, the guanidino group of (VII) is alkylated with 3-methyl-2-butenyl bromide (VIII) catalyzed by DMAP in THF to provide the target, caracasanamide.
| 【1】 Delle Monache, G.; Delle Monache, F.; Botta, B.; Bonnevaux Castillo, S.; Espinal, R.; De Luca, C.; Carmignani, M. (Consiglio Nazionale delle Ricerche); Guanidine derivs. having hypotensive activity, compsn. containing them, and process for obtaining them. EP 0330629; JP 1990003661; US 5059624 . |
| 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) | 10272 | [[Amino(imino)methyl]sulfanyl]methane | 2986-19-8 | C2H6N2S | 详情 | 详情 |
| (II) | 22345 | tert-butyl (E)-[(tert-butoxycarbonyl)amino](methylsulfanyl)methylidenecarbamate | C12H22N2O4S | 详情 | 详情 | |
| (III) | 42070 | 1,4-butanediamine; 4-aminobutylamine | 110-60-1 | C4H12N2 | 详情 | 详情 |
| (IV) | 53109 | tert-butyl (Z)-[(4-aminobutyl)amino][(tert-butoxycarbonyl)amino]methylidenecarbamate | n/a | C15H30N4O4 | 详情 | 详情 |
| (V) | 33601 | (E)-3-(3,4-dimethoxyphenyl)-2-propenoyl chloride | C11H11ClO3 | 详情 | 详情 | |
| (VI) | 53110 | tert-butyl (Z)-[(tert-butoxycarbonyl)amino][(4-{[(E)-3-(3,4-dimethoxyphenyl)-2-propenoyl]amino}butyl)amino]methylidenecarbamate | n/a | C26H40N4O7 | 详情 | 详情 |
| (VII) | 53111 | (E)-N-(4-{[amino(imino)methyl]amino}butyl)-3-(3,4-dimethoxyphenyl)-2-propenamide | n/a | C16H24N4O3 | 详情 | 详情 |
| (VIII) | 12989 | 4-Bromo-2-methyl-2-butene; 1-Bromo-3-methyl-2-butene | 870-63-3 | C5H9Br | 详情 | 详情 |