【结 构 式】 |
【分子编号】57197 【品名】N-(5-{[(3-amino-3-iminopropyl)amino]carbonyl}-1-methyl-1H-pyrrol-3-yl)-4-({[4-(formylamino)-1-methyl-1H-pyrrol-2-yl]carbonyl}amino)-1-methyl-1H-pyrrole-2-carboxamide 【CA登记号】 |
【 分 子 式 】C22H27N9O4 【 分 子 量 】481.51464 【元素组成】C 54.88% H 5.65% N 26.18% O 13.29% |
合成路线1
该中间体在本合成路线中的序号:(I)The reaction of Distamycin A (I) with succinic anhydride and Na2CO3 in hot DMF gives the nitrile (II), which is treated with Boc2O and DMAP in dichloromethane to yield the monocarbamate (III). The reaction of (III) with Boc2O and DMAP in DMF affords the bis carbamate (IV), which is hydrolyzed with LiOH in THF/water to provide the carboxylic acid (V). The condensation of (V) with N-(2-aminoethyl)guanidine (VI) by means of by means of TBTU in DMF gives the guanidinoethyl amide (VII), which is deprotected by means of TFA in dichloromethane to yield the aminopyrrole derivative (VIII). Finally, this compound is condensed with the acid chloride (IX) by means of NaHCO3 in dioxane/water to provide the target brostallicin.
【1】 Nesi, M.; Beria, I.; Syntheses of brostallicin starting from distamycin A. Tetrahedron Lett 2002, 43, 41, 7323. |
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) | 57197 | N-(5-{[(3-amino-3-iminopropyl)amino]carbonyl}-1-methyl-1H-pyrrol-3-yl)-4-({[4-(formylamino)-1-methyl-1H-pyrrol-2-yl]carbonyl}amino)-1-methyl-1H-pyrrole-2-carboxamide | C22H27N9O4 | 详情 | 详情 | |
(II) | 57198 | N-(2-cyanoethyl)-4-({[4-({[4-(formylamino)-1-methyl-1H-pyrrol-2-yl]carbonyl}amino)-1-methyl-1H-pyrrol-2-yl]carbonyl}amino)-1-methyl-1H-pyrrole-2-carboxamide | C22H24N8O4 | 详情 | 详情 | |
(III) | 57199 | tert-butyl 5-{[(5-{[(5-{[(2-cyanoethyl)amino]carbonyl}-1-methyl-1H-pyrrol-3-yl)amino]carbonyl}-1-methyl-1H-pyrrol-3-yl)amino]carbonyl}-1-methyl-1H-pyrrol-3-yl(formyl)carbamate | C27H32N8O6 | 详情 | 详情 | |
(IV) | 57200 | tert-butyl 5-{[(5-{[(5-{[(tert-butoxycarbonyl)(2-cyanoethyl)amino]carbonyl}-1-methyl-1H-pyrrol-3-yl)amino]carbonyl}-1-methyl-1H-pyrrol-3-yl)amino]carbonyl}-1-methyl-1H-pyrrol-3-yl(formyl)carbamate | C32H40N8O8 | 详情 | 详情 | |
(V) | 53515 | 4-[({4-[({4-[(tert-butoxycarbonyl)amino]-1-methyl-1H-pyrrol-2-yl}carbonyl)amino]-1-methyl-1H-pyrrol-2-yl}carbonyl)amino]-1-methyl-1H-pyrrole-2-carboxylic acid | n/a | C23H28N6O6 | 详情 | 详情 |
(VI) | 41437 | N-(2-aminoethyl)guanidine | C3H10N4 | 详情 | 详情 | |
(VII) | 57201 | tert-butyl 5-{[(5-{[(5-{[(2-{[amino(imino)methyl]amino}ethyl)amino]carbonyl}-1-methyl-1H-pyrrol-3-yl)amino]carbonyl}-1-methyl-1H-pyrrol-3-yl)amino]carbonyl}-1-methyl-1H-pyrrol-3-ylcarbamate | C26H36N10O5 | 详情 | 详情 | |
(VIII) | 41444 | N-(2-[[amino(imino)methyl]amino]ethyl)-4-[[(4-[[(4-amino-1-methyl-1H-pyrrol-2-yl)carbonyl]amino]-1-methyl-1H-pyrrol-2-yl)carbonyl]amino]-1-methyl-1H-pyrrole-2-carboxamide | C21H28N10O3 | 详情 | 详情 | |
(IX) | 41441 | 4-[(2-bromoacryloyl)amino]-1-methyl-1H-pyrrole-2-carbonyl chloride | C9H8BrClN2O2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号:(I)The hydrolysis of Distamycin A (I) with NaOH in refluxing methanol gives the aminoacid (II), which is treated with Boc2O and TEA in DMF to yield the carbamate (III). The Curtius rearrangement of (III) by means of DPPA and TEA in hot DMF affords the imidazolidinone (IV), which is hydrolyzed with NaOH in DMF to provide the 2-aminoethyl amide (V). The reaction of (V) with the protected guanidine (VI) by means of TEA in hot DMF gives the protected 2-guanidinoethyl amide (VII), which is treated with 6N HCl in methanol to eliminate the carbamoyl and trityl protecting group and yield the precursor (VIII). Finally, this compound is condensed with the acyl chloride (IX) by means of NaHCO3 in dioxane/water to afford the target brostallicin.
【1】 Nesi, M.; Beria, I.; Syntheses of brostallicin starting from distamycin A. Tetrahedron Lett 2002, 43, 41, 7323. |
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) | 57197 | N-(5-{[(3-amino-3-iminopropyl)amino]carbonyl}-1-methyl-1H-pyrrol-3-yl)-4-({[4-(formylamino)-1-methyl-1H-pyrrol-2-yl]carbonyl}amino)-1-methyl-1H-pyrrole-2-carboxamide | C22H27N9O4 | 详情 | 详情 | |
(II) | 57202 | N-[(4-{[(4-{[(4-amino-1-methyl-1H-pyrrol-2-yl)carbonyl]amino}-1-methyl-1H-pyrrol-2-yl)carbonyl]amino}-1-methyl-1H-pyrrol-2-yl)carbonyl]-beta-alanine | C21H25N7O5 | 详情 | 详情 | |
(III) | 57203 | N-({4-[({4-[({4-[(tert-butoxycarbonyl)amino]-1-methyl-1H-pyrrol-2-yl}carbonyl)amino]-1-methyl-1H-pyrrol-2-yl}carbonyl)amino]-1-methyl-1H-pyrrol-2-yl}carbonyl)-beta-alanine | C26H33N7O7 | 详情 | 详情 | |
(IV) | 57204 | tert-butyl 1-methyl-5-[({1-methyl-5-[({1-methyl-5-[(2-oxo-1-imidazolidinyl)carbonyl]-1H-pyrrol-3-yl}amino)carbonyl]-1H-pyrrol-3-yl}amino)carbonyl]-1H-pyrrol-3-ylcarbamate | C26H32N8O6 | 详情 | 详情 | |
(V) | 57205 | tert-butyl 5-{[(5-{[(5-{[(2-aminoethyl)amino]carbonyl}-1-methyl-1H-pyrrol-3-yl)amino]carbonyl}-1-methyl-1H-pyrrol-3-yl)amino]carbonyl}-1-methyl-1H-pyrrol-3-ylcarbamate | C25H34N8O5 | 详情 | 详情 | |
(VI) | 57206 | tert-butyl [(tert-butoxycarbonyl)amino](tritylimino)methylcarbamate | C30H35N3O4 | 详情 | 详情 | |
(VII) | 57207 | tert-butyl ({2-[({4-[({4-[({4-[(tert-butoxycarbonyl)amino]-1-methyl-1H-pyrrol-2-yl}carbonyl)amino]-1-methyl-1H-pyrrol-2-yl}carbonyl)amino]-1-methyl-1H-pyrrol-2-yl}carbonyl)amino]ethyl}amino)(tritylimino)methylcarbamate | C50H58N10O7 | 详情 | 详情 | |
(VIII) | 41444 | N-(2-[[amino(imino)methyl]amino]ethyl)-4-[[(4-[[(4-amino-1-methyl-1H-pyrrol-2-yl)carbonyl]amino]-1-methyl-1H-pyrrol-2-yl)carbonyl]amino]-1-methyl-1H-pyrrole-2-carboxamide | C21H28N10O3 | 详情 | 详情 | |
(IX) | 41441 | 4-[(2-bromoacryloyl)amino]-1-methyl-1H-pyrrole-2-carbonyl chloride | C9H8BrClN2O2 | 详情 | 详情 |