|
【结 构 式】 
|
【分子编号】24535 【品名】benzhydryl (2S,3S)-3-(azidomethyl)-3-methyl-4,4,7-trioxo-4lambda(6)-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate 【CA登记号】 |
【 分 子 式 】C21H20N4O5S 【 分 子 量 】440.47976 【元素组成】C 57.26% H 4.58% N 12.72% O 18.16% S 7.28% |
合成路线1
该中间体在本合成路线中的序号：(III)1) The reaction of benzhydryl 2alpha-methyl-2beta-(chloromethyl)penam-3alpha-carboxylate (I) with sodium azide in DMF gives the corresponding azidomethyl derivative (II), which is oxidized with KMnO4 in aqueous acetic acid to the dioxide (III). The cyclization of (III) with trimethylsilylacetylene (IV) at 95 C yields benzhydryl 2a-methyl-2B-(4 trimethylsilyl-1,2,3-triazol-1 ylmethyl)penam 3a-carboxylate-1,1-dioxide (V), which is desilylated with KF and 18-crown-6 in hot DMF affording the benzhydryl ester of YTR-830 (VI). Then this compound is submitted to hydrogenolysis with H2 over Pd/C in ethyl / acetate / water.
| 【1】 Micetich, R.G.; et al. (Taiho Pharmaceutical Co., Ltd.); Penicillin derivatives and process for preparation of the same. EP 0097446; ES 523701; ES 538020 . |
| 【2】 Cai, S.X.; Drewe, J.A. (Cytovia, Inc.); Substd. nicotinamides and analogs as activators of caspases and inducers of apoptosis and the use thereof. WO 0155115 . |
| 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) | 24533 | benzhydryl (2S,3R)-3-(chloromethyl)-3-methyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate | C21H20ClNO3S | 详情 | 详情 | |
| (II) | 24534 | benzhydryl (2S,3S)-3-(azidomethyl)-3-methyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate | C21H20N4O3S | 详情 | 详情 | |
| (III) | 24535 | benzhydryl (2S,3S)-3-(azidomethyl)-3-methyl-4,4,7-trioxo-4lambda(6)-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate | C21H20N4O5S | 详情 | 详情 | |
| (IV) | 23897 | ethynyl(trimethyl)silane；trimethylsilyl acetylene | 1066-54-2 | C5H10Si | 详情 | 详情 |
| (V) | 24538 | benzhydryl (2S,3S)-3-methyl-4,4,7-trioxo-3-[[4-(trimethylsilyl)-1H-1,2,3-triazol-1-yl]methyl]-4lambda(6)-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate | C26H30N4O5SSi | 详情 | 详情 | |
| (VI) | 24539 | benzhydryl (2S,3S)-3-methyl-4,4,7-trioxo-3-(1H-1,2,3-triazol-1-ylmethyl)-4lambda(6)-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate | C23H22N4O5S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(III)2) The ester (VI) can also be obtained by cyclization of (III) with vinyl acetate (VII) at 110 C.
| 【1】 Micetich, R.G.; et al. (Taiho Pharmaceutical Co., Ltd.); Penicillin derivatives and process for preparation of the same. EP 0097446; ES 523701; ES 538020 . |
| 【2】 Cai, S.X.; Drewe, J.A. (Cytovia, Inc.); Substd. nicotinamides and analogs as activators of caspases and inducers of apoptosis and the use thereof. WO 0155115 . |
| 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) | 24533 | benzhydryl (2S,3R)-3-(chloromethyl)-3-methyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate | C21H20ClNO3S | 详情 | 详情 | |
| (II) | 24534 | benzhydryl (2S,3S)-3-(azidomethyl)-3-methyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate | C21H20N4O3S | 详情 | 详情 | |
| (III) | 24535 | benzhydryl (2S,3S)-3-(azidomethyl)-3-methyl-4,4,7-trioxo-4lambda(6)-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate | C21H20N4O5S | 详情 | 详情 | |
| (VI) | 24539 | benzhydryl (2S,3S)-3-methyl-4,4,7-trioxo-3-(1H-1,2,3-triazol-1-ylmethyl)-4lambda(6)-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate | C23H22N4O5S | 详情 | 详情 | |
| (VII) | 24543 | vinyl acetate | 108-05-4 | C4H6O2 | 详情 | 详情 |