【结 构 式】 |
【分子编号】14704 【品名】methyl (1R,2S,3S,4S)-3-(azidocarbonyl)bicyclo[2.2.1]heptane-2-carboxylate 【CA登记号】 |
【 分 子 式 】C10H13N3O3 【 分 子 量 】223.23164 【元素组成】C 53.81% H 5.87% N 18.82% O 21.5% |
合成路线1
该中间体在本合成路线中的序号:(XLIV)The reaction of (1R,2S,3S,4S)-bicyclo[2.2.1]heptane-2,3-dicarboxylic acid 2-monomethyl ester (XLIII) with ethylchloroformate and NaN3 gives the corresponding azide (XLIV), which is submitted to degradation in the presence of benzyl alcohol to afford (1R,2S,3S,4S)-3-(benzyloxycarbonylamino)bicyclo[2.2.1]heptane-2-carboxylic acid methyl ester (XLV). The reduction of (XLV) with NaBH4 in THF gives the hydroxymethyl derivative (XLVI), which is oxidized with oxalyl chloride as before to the corresponding aldehyde (XLVII). The Wittig condensation of (XLVII) with methoxymethyl triphenylphosphonium chloride by means of t-BuOK in THF gives the vinyl ether (XLVIII), which is hydrolyzed to the corresponding aldehyde (XLIX) with formic acid. A new Wittig condensation of (XLIX) with 4-carboxybutyl triphenylphosphonium bromide as before, followed by methylation with diazomethane yields (1R,2S,3S,4S)-7-[3-(benzyloxycarbonylamino)bicyclo[2.2.1]heptan-2-yl]-5(Z)-heptenoic acid methyl ester (L). The deprotection of (L) with trifluoroacetic acid affords the 3-amino derivative (LI), which is then condensed with [14C]- or [3H]-radiolabeled benzenesulfonyl chloride (LII) to afford the radiolabeled sulfonamide ester (LIII). Finally, this compound is hydrolyzed with NaOH to the radiolabeled free acid (XIV), already obtained, which is converted to S-1452 by treatment of the Na salt with CaCl2 in methanol-water.
【1】 Narisada, M.; Katsuyama, Y.; Watanabe, F.; Hamada, Y.; Ohtani, M.; Nagasaki, T.; Synthesis of [14C]- and [3H]-labelled (+)-[1R-[1alpha,2alpha(Z),3beta,4alpha]]-7-[3-[(phenylsulfonyl)amino] bicyclo[2.2.1]hept-2-yl]-5-heptenoic acid, ((+)-S-145) and its calcium salt (S-1452). J Label Compd Radiopharm 1992, 31, 1, 23-38. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(IL) | 14681 | benzyl N-[(1S,2S,3S,4R)-3-(2-oxoethyl)bicyclo[2.2.1]hept-2-yl]carbamate | C17H21NO3 | 详情 | 详情 | |
(XIV) | 14674 | (Z)-7-[(1R,2S,3S,4S)-3-[(phenylsulfonyl)amino]bicyclo[2.2.1]hept-2-yl]-5-heptenoic acid | C20H27NO4S | 详情 | 详情 | |
(XLIII) | 14665 | (1S,2S,3S,4R)-3-(methoxycarbonyl)bicyclo[2.2.1]heptane-2-carboxylic acid | C10H14O4 | 详情 | 详情 | |
(XLIV) | 14704 | methyl (1R,2S,3S,4S)-3-(azidocarbonyl)bicyclo[2.2.1]heptane-2-carboxylate | C10H13N3O3 | 详情 | 详情 | |
(XLV) | 14705 | methyl (1R,2S,3S,4S)-3-[[(benzyloxy)carbonyl]amino]bicyclo[2.2.1]heptane-2-carboxylate | C17H21NO4 | 详情 | 详情 | |
(XLVI) | 14706 | benzyl N-[(1S,2S,3S,4R)-3-(hydroxymethyl)bicyclo[2.2.1]hept-2-yl]carbamate | C16H21NO3 | 详情 | 详情 | |
(XLVII) | 14707 | benzyl N-[(1S,2S,3S,4R)-3-formylbicyclo[2.2.1]hept-2-yl]carbamate | C16H19NO3 | 详情 | 详情 | |
(XLVIII) | 14708 | benzyl N-[(1S,2S,3R,4R)-3-[(E)-2-methoxyethenyl]bicyclo[2.2.1]hept-2-yl]carbamate | C18H23NO3 | 详情 | 详情 | |
(L) | 14682 | methyl (Z)-7-((1R,2S,3S,4S)-3-[[(benzyloxy)carbonyl]amino]bicyclo[2.2.1]hept-2-yl)-5-heptenoate | C23H31NO4 | 详情 | 详情 | |
(LI) | 14683 | methyl (Z)-7-[(1R,2S,3S,4S)-3-aminobicyclo[2.2.1]hept-2-yl]-5-heptenoate | C15H25NO2 | 详情 | 详情 | |
(LII) | 14684 | methyl (Z)-7-[(1R,2S,3S,4S)-3-[(phenylsulfonyl)amino]bicyclo[2.2.1]hept-2-yl]-5-heptenoate | C21H29NO4S | 详情 | 详情 | |
(LIII) | 14713 | benzenesulfonyl chloride | 98-09-9 | C6H5ClO2S | 详情 | 详情 |