【结 构 式】 |
【分子编号】38369 【品名】methyl (8S)-8-(bromomethyl)-6-[(E)-3-(4-methoxy-2-thienyl)-2-propenoyl]-2-methyl-4-[[(4-nitrophenoxy)carbonyl]oxy]-3,6,7,8-tetrahydropyrrolo[3,2-e]indole-1-carboxylate 【CA登记号】 |
【 分 子 式 】C29H24BrN3O9S 【 分 子 量 】670.49438 【元素组成】C 51.95% H 3.61% Br 11.92% N 6.27% O 21.48% S 4.78% |
合成路线1
该中间体在本合成路线中的序号:(XIV)The reaction of 4-bromothiophene-2-carbaldehyde (I) with triethyl orthoformate gives the corresponding acetal (II), which is treated with NaOMe, CuO and KI in hot methanol yielding 5-methoxythiophene-2-carbaldehyde diethylacetal (III). The hydrolysis of (III) with HCl in methanol affords the carbaldehyde (IV), which is condensed with the phosphonate (V) by means of NaH in THF to provide the ethyl acrylate (VI). The hydrolysis of (VI) with KOH in methanol gives the acrylic acid (VII), which is esterified with 4-nitrophenol, TEA and 2-chloro-1-methylpyridinium iodide in dichloromethane yielding the activate ester (VIII). The condensation of (VIII) with the tetracyclic ketone (IX) (obtained by treatment of the dimeric ketonic compound (X) with NaOMe in methanol) affords the adduct (XI), which is treated with HBr in acetonitrile to open the cyclopropane ring and provide the bromomethyl compound (XII). The aromatization of (XII) with p-nitrophenyl chloroformate (XIII) and TEA in dichloromethane affords the activated carbonate ester (XIV), which is finally treated with 1-methylpiperazine (XV) to furnish the target carbamate.
【1】 Saito, H.; Kobayashi, E.; Gomi, K.; Okamoto, A.; Nagamura, S.; Amishiro, N.; Synthesis and antitumor activity of duocarmycin derivatives: A-ring pyrrole compounds bearing 5-membered heteroarylacryloyl groups. Chem Pharm Bull 1999, 47, 10, 1393. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
11236 | 4-Nitrophenol; p-Nitrophenol | 100-02-7 | C6H5NO3 | 详情 | 详情 | |
(I) | 24142 | 4-bromo-2-thiophenecarbaldehyde | 18791-75-8 | C5H3BrOS | 详情 | 详情 |
(II) | 38358 | (4-bromo-2-thienyl)(ethoxy)methyl ethyl ether; 4-bromo-2-(diethoxymethyl)thiophene | C9H13BrO2S | 详情 | 详情 | |
(III) | 38359 | 5-(diethoxymethyl)-3-thienyl methyl ether; 2-(diethoxymethyl)-4-methoxythiophene | C10H16O3S | 详情 | 详情 | |
(IV) | 35360 | C47H75N3O14 | 详情 | 详情 | ||
(V) | 38361 | ethyl 2-(dimethoxyphosphoryl)acetate | C6H13O5P | 详情 | 详情 | |
(VI) | 38362 | ethyl (E)-3-(4-methoxy-2-thienyl)-2-propenoate | C10H12O3S | 详情 | 详情 | |
(VII) | 38363 | (E)-3-(4-methoxy-2-thienyl)-2-propenoic acid | C8H8O3S | 详情 | 详情 | |
(VIII) | 38364 | 4-nitrophenyl (E)-3-(4-methoxy-2-thienyl)-2-propenoate | C14H11NO5S | 详情 | 详情 | |
(IX) | 38365 | methyl (3bR,4aS)-2-methyl-8-oxo-1,4,4a,5,6,8-hexahydrocyclopropa[c]pyrrolo[3,2-e]indole-3-carboxylate | C14H14N2O3 | 详情 | 详情 | |
(X) | 38366 | methyl (2R,3bR,4aS)-2-methyl-3,8-dioxo-6-[(5,6,7-trimethoxy-1H-indol-2-yl)carbonyl]-1,2,3,4,4a,5,6,8-octahydrocyclopropa[c]pyrrolo[3,2-e]indole-2-carboxylate | C26H25N3O8 | 详情 | 详情 | |
(XI) | 38367 | methyl (3bR,4aS)-6-[(E)-3-(4-methoxy-2-thienyl)-2-propenoyl]-2-methyl-8-oxo-1,4,4a,5,6,8-hexahydrocyclopropa[c]pyrrolo[3,2-e]indole-3-carboxylate | C22H20N2O5S | 详情 | 详情 | |
(XII) | 38368 | methyl (8S)-8-(bromomethyl)-6-[(E)-3-(4-methoxy-2-thienyl)-2-propenoyl]-2-methyl-4-oxo-3,4,6,7,8,8a-hexahydropyrrolo[3,2-e]indole-1-carboxylate | C22H21BrN2O5S | 详情 | 详情 | |
(XIII) | 16605 | 4-Nitrophenyl chloroformate; 1-[(Chlorocarbonyl)oxy]-4-nitrobenzene | 7693-46-1 | C7H4ClNO4 | 详情 | 详情 |
(XIV) | 38369 | methyl (8S)-8-(bromomethyl)-6-[(E)-3-(4-methoxy-2-thienyl)-2-propenoyl]-2-methyl-4-[[(4-nitrophenoxy)carbonyl]oxy]-3,6,7,8-tetrahydropyrrolo[3,2-e]indole-1-carboxylate | C29H24BrN3O9S | 详情 | 详情 | |
(XV) | 10061 | 1-Methylpiperazine; 1-Methyl piperazine; N-Methylpiperazine | 109-01-3 | C5H12N2 | 详情 | 详情 |