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【结 构 式】 
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【分子编号】11154 【品名】4-methoxybenzyl (7R)-3-[(Z)-2-(4-methyl-1,3-thiazol-5-yl)ethenyl]-8-oxo-7-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate 【CA登记号】 |
【 分 子 式 】C29H27N3O5S2 【 分 子 量 】561.6826 【元素组成】C 62.01% H 4.85% N 7.48% O 14.24% S 11.42% |
合成路线1
该中间体在本合成路线中的序号：(III)
| 【1】 Prabhat KS.Vempali A.Sundaravadivelan S.et aL2005.An imprared Wooessfortlk preparation of cefditoren and its intermediates W0 2005003141 |
| 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) | 11151 | 4-methoxybenzyl (7R)-3-(chloromethyl)-8-oxo-7-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | 104146-10-3 | C24H23ClN2O5S | 详情 | 详情 |
| (II) | 11153 | 4-Methyl-1,3-thiazole-5-carbaldehyde | 82294-70-0 | C5H5NOS | 详情 | 详情 |
| (III) | 11154 | 4-methoxybenzyl (7R)-3-[(Z)-2-(4-methyl-1,3-thiazol-5-yl)ethenyl]-8-oxo-7-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C29H27N3O5S2 | 详情 | 详情 | |
| (IV) | 66174 | (6R,7R)-7-amino-3-((Z)-2-(4-methylthiazol-5-yl)vinyl)-8-oxo-1-azabicyclo[4.2.0]octane-2-carboxylic acid | C14H17N3O3S | 详情 | 详情 | |
| (V) | 66175 | (Z)-S-benzo[d]thiazol-2-yl 2-(2-aminothiazol-4-yl)-2-(methoxyimino)ethanethioate | 94088-75-2 | C13H10N4O2S3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(III)
| 【1】 Sakagsmi K, Atsumi K, Yamamoto Y，et aL 1991. Synthesis and activity of pivaloyloxymethyl一[( Z-(2-anunothiazol-4-yD-2-methoxyiminoaceuunido]一3(Z)-(4-methylthiazol-5-yl) vinyl-3-cepllern-4-carbox)rlate (ME1207) and its related compound. Chem Pharm Bull, 39 (9): 2433^-2436 |
| 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) | 11151 | 4-methoxybenzyl (7R)-3-(chloromethyl)-8-oxo-7-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | 104146-10-3 | C24H23ClN2O5S | 详情 | 详情 |
| (II) | 11153 | 4-Methyl-1,3-thiazole-5-carbaldehyde | 82294-70-0 | C5H5NOS | 详情 | 详情 |
| (III) | 11154 | 4-methoxybenzyl (7R)-3-[(Z)-2-(4-methyl-1,3-thiazol-5-yl)ethenyl]-8-oxo-7-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C29H27N3O5S2 | 详情 | 详情 | |
| (IV) | 11155 | 4-methoxybenzyl (7R)-7-amino-3-[(Z)-2-(4-methyl-1,3-thiazol-5-yl)ethenyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C21H21N3O4S2 | 详情 | 详情 | |
| (V) | 66179 | (Z)-3-methoxy-2-(2-(tritylamino)thiazol-4-yl)acrylic acid | C26H22N2O3S | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(IV)The reaction of 3-(chloromethyl)-7-(phenylacetamido)-3-cephem-4-carboxylic acid 4-methoxybenzyl ester (I) with triphenylphosphine and NaI in acetone gives the corresponding phosphonium salt (II), which is condensed with 4-methylthiazole-5-carboxaldehyde (III) by means of NaHCO3 in dichloromethane affording 3-[2(Z)-(4-methylthiazol-5-yl)vinyl]-7-(phenylacetamido)-3-cephem-4-carboxylic acid 4-methoxybenzyl ester (IV). The cleavage of the amido group of (IV) with PCl5 and pyridine yields the 7-amino compound (V), which is condensed with 2-(methoxyimino)-2-[2-(tritylamino)thiazol-4-yl]acetic acid (VI) by means of POCl3 in dichloromethane giving 3-[2(Z)-(4-methylthiazol-5-yl)vinyl]-7-[2(Z)-methoxyimino)-2-(2-tritylamino)thiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid 4-methoxybenzyl ester (VII). The deprotection of (VII) with trifluoroacetic acid and anisole yields the free amino acid (VIII), which is finally esterified with iodomethyl pivalate (IX) in DMF.
| 【1】 Yamamoto, Y.; Yoshida, T.; Tamura, A.; Atsumi, K.; Fukatsu, S.; Sakagami, K.; Nishihata, K.; Synthesis and oral activity of pivaloyloxymethyl 7-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3(Z)--(4-methylthiazol-5-yl)vinyl-3-cephem-4-carboxylate (ME1207) and its related compound. Chem Pharm Bull 1992, 39, 9, 2433. |
| 【2】 Atsumi, K.; Sakagami, K.; Yamamoto, Y.; Yoshida, T.; Nishihata, K.; Kondo, S.; Fukatsu, S. (Meiji Seika Kaisha, Ltd.); New cephalosporin cpds. and the production thereof. EP 0175610; ES 8704955; JP 1986178991; JP 1987019593 . |
| 【3】 Castaner, J.; Prous, J.; Cefditoren Pivoxil. Drugs Fut 1992, 17, 8, 665. |
| 【4】 Sakagami, K.; Tamura, A.; Yoshida, T.; Nishihata, K.; Fukatsu, S.; Atsumi, K.; Synthesis and oral activity of ME1207, a new orally active cephalosporin. J Antibiot 1990, 43, 8, 1047. |
| 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) | 11151 | 4-methoxybenzyl (7R)-3-(chloromethyl)-8-oxo-7-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | 104146-10-3 | C24H23ClN2O5S | 详情 | 详情 |
| (II) | 11152 | 4-methoxybenzyl (7R)-8-oxo-7-[(2-phenylacetyl)amino]-3-[(triphenylphosphoranyl)methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C42H39N2O5PS | 详情 | 详情 | |
| (III) | 11153 | 4-Methyl-1,3-thiazole-5-carbaldehyde | 82294-70-0 | C5H5NOS | 详情 | 详情 |
| (IV) | 11154 | 4-methoxybenzyl (7R)-3-[(Z)-2-(4-methyl-1,3-thiazol-5-yl)ethenyl]-8-oxo-7-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C29H27N3O5S2 | 详情 | 详情 | |
| (V) | 11155 | 4-methoxybenzyl (7R)-7-amino-3-[(Z)-2-(4-methyl-1,3-thiazol-5-yl)ethenyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C21H21N3O4S2 | 详情 | 详情 | |
| (VI) | 11156 | 2-(Methoxyimino)-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetamide | C25H22N4O2S | 详情 | 详情 | |
| (VII) | 11157 | 4-methoxybenzyl (7R)-7-[[2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetyl]amino]-3-[(Z)-2-(4-methyl-1,3-thiazol-5-yl)ethenyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C27H26N6O6S3 | 详情 | 详情 | |
| (VIII) | 11158 | (7R)-7-[[2-(2-Amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetyl]amino]-3-[(Z)-2-(4-methyl-1,3-thiazol-5-yl)ethenyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid | C19H18N6O5S3 | 详情 | 详情 | |
| (IX) | 11159 | iodomethyl pivalate | C6H11IO2 | 详情 | 详情 |