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【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%

与该中间体有关的原料药合成路线共 1 条

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
Extended Information