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【结 构 式】 
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【分子编号】22346 【品名】tert-butyl (Z)-[(6-aminohexyl)amino][(tert-butoxycarbonyl)amino]methylidenecarbamate 【CA登记号】 |
【 分 子 式 】C17H34N4O4 【 分 子 量 】358.48152 【元素组成】C 56.96% H 9.56% N 15.63% O 17.85% |
合成路线1
该中间体在本合成路线中的序号：(XII)Monoalkylation of 1,3-propanediamine (I) with 4-chlorobutanol (II) in refluxing n-BuOH afforded diaminoalcohol (III), which was protected as the bis-carbamate (IV) upon treatment with Boc2O. Subsequent reaction of (IV) with methanesulfonyl chloride and Et3N provided mesylate (V), and this was further treated with ethanolic ammonia to yield primary amine (VI). Condensation of amine (VI) with (methoxycarbonylmethyl) phenyl carbonate (VII) in refluxing toluene gave carbamate (VIII). Saponification of the methyl ester function of (VIII) then furnished carboxylic acid (IX). 1,6-Hexanediamine (X) was condensed with N,N'-bis(tert-butoxycarbonyl)-S-methylisothiourea (XI) to produce the (6-aminohexyl)guanidine derivative (XII). This was then coupled with carboxylic acid (IX) using DCC and HOBt. Finally, the N-Boc groups were deprotected with trifluoroacetic acid in CH2Cl2.
| 【1】 Lebreton, L.; Annat, J.; Derrepas, P.; Dutartre, P.; Renaut, P.; Structure-immunosuppressive activity relationships of new analogues of 15-deoxyspergualin. 1. Structural modifications of the hydroxyglycine moiety. J Med Chem 1999, 42, 2, 277. |
| 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) | 19331 | 3-aminopropylamine; 1,3-propanediamine | 109-76-2 | C3H10N2 | 详情 | 详情 |
| (II) | 22336 | 4-chloro-1-butanol | 928-51-8 | C4H9ClO | 详情 | 详情 |
| (III) | 22337 | 4-[(3-aminopropyl)amino]-1-butanol | C7H18N2O | 详情 | 详情 | |
| (IV) | 22338 | tert-butyl 3-[(tert-butoxycarbonyl)amino]propyl(4-hydroxybutyl)carbamate | C17H34N2O5 | 详情 | 详情 | |
| (V) | 22339 | 4-((tert-butoxycarbonyl)[3-[(tert-butoxycarbonyl)amino]propyl]amino)butyl methanesulfonate | C18H36N2O7S | 详情 | 详情 | |
| (VI) | 22340 | tert-butyl 4-aminobutyl[3-[(tert-butoxycarbonyl)amino]propyl]carbamate | C17H35N3O4 | 详情 | 详情 | |
| (VII) | 22341 | methyl 2-[(phenoxycarbonyl)oxy]acetate | C10H10O5 | 详情 | 详情 | |
| (VIII) | 22342 | methyl 9-(tert-butoxycarbonyl)-2,2-dimethyl-4,15-dioxo-3,16-dioxa-5,9,14-triazaoctadecan-18-oate | C21H39N3O8 | 详情 | 详情 | |
| (IX) | 22343 | 9-(tert-butoxycarbonyl)-2,2-dimethyl-4,15-dioxo-3,16-dioxa-5,9,14-triazaoctadecan-18-oic acid | C20H37N3O8 | 详情 | 详情 | |
| (X) | 22344 | 1,6-hexanediamine; 6-aminohexylamine | 124-09-4 | C6H16N2 | 详情 | 详情 |
| (XI) | 22345 | tert-butyl (E)-[(tert-butoxycarbonyl)amino](methylsulfanyl)methylidenecarbamate | C12H22N2O4S | 详情 | 详情 | |
| (XII) | 22346 | tert-butyl (Z)-[(6-aminohexyl)amino][(tert-butoxycarbonyl)amino]methylidenecarbamate | C17H34N4O4 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XV)The resulting carboxylic acid (XIV) was coupled with the Boc-protected guanidinohexylamine (XV) using DCC and HOBt to produce amide (XVI). Finally, sequential deprotection of the N-benzyl group of (XVI) by hydrogenolysis, and then cleavage of the Boc groups by means of trifluoroacetic acid yielded the target compound.
| 【1】 Lebreton, L.; et al.; Structure - Immunosuppressive activity relationships of new analogues of 15-deoxyspergualin. 2. Structural modifications of the spermidine moiety. J Med Chem 1999, 42, 23, 4749. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XIV) | 31811 | (6R)-9-benzyl-2,2,6-trimethyl-4,15-dioxo-3,16-dioxa-5,9,14-triazaoctadecan-18-oic acid | C23H37N3O6 | 详情 | 详情 | |
| (XV) | 22346 | tert-butyl (Z)-[(6-aminohexyl)amino][(tert-butoxycarbonyl)amino]methylidenecarbamate | C17H34N4O4 | 详情 | 详情 | |
| (XVI) | 31812 | (E)-11-[(tert-butoxycarbonyl)amino]-15,15-dimethyl-2,13-dioxo-14-oxa-3,10,12-triaza-11-hexadecen-1-yl 4-(benzyl[(3R)-3-[(tert-butoxycarbonyl)amino]butyl]amino)butylcarbamate | C40H69N7O9 | 详情 | 详情 | |
| (XVII) | 31813 | (E)-11-[(tert-butoxycarbonyl)amino]-15,15-dimethyl-2,13-dioxo-14-oxa-3,10,12-triaza-11-hexadecen-1-yl 4-([(3R)-3-[(tert-butoxycarbonyl)amino]butyl]amino)butylcarbamate | C33H63N7O9 | 详情 | 详情 |