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【结 构 式】 
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【分子编号】30153 【品名】(4R,5R,6S)-4-methyl-2-[2-(4-nitrobenzyloxy)acetyl]-7-oxo-6-[(1R)-1-[(triethylsilyl)oxy]ethyl]-1-azabicyclo[3.2.0]hept-2-en-3-yl trifluoromethanesulfonate 【CA登记号】 |
【 分 子 式 】C24H31F3N2O9SSi 【 分 子 量 】608.6649296 【元素组成】C 47.36% H 5.13% F 9.36% N 4.6% O 23.66% S 5.27% Si 4.61% |
合成路线1
该中间体在本合成路线中的序号：(XLI)Diazoketone (XXXIX), prepared by silyl protection of the precursor (XXXVIII), was cyclized in the presence of Rh(II) catalyst to produce oxocarbapenem (XL). Treatment of (XL) with Tf2O and 2,2,6,6-tetramethylpiperidine yielded vinyl triflate (XLI). Hydroxymethylation of (XLI) was then achieved by cross coupling with tributylstannylmethanol in the presence of Pd catalyst to furnish (XLII).
| 【1】 Yasuda, N.; et al.; Preparation of anti-MRS carbapenem L-786,392. 38th Intersci Conf Antimicrob Agents Chemother (Sept 24 1998, San Diego) 1998, Abst F-31. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXXVIII) | 30150 | (3S,4R)-3-((1R)-1-Hydroxyethyl)-4[(1R)-1-methyl-3-diazo-3-(p-nitrobenzyloxycarbonyl)-2-oxopropyl]azetidin-2-one | 137391-68-5 | C17H18N4O7 | 详情 | 详情 |
| (XXXIX) | 30151 | 2-Diazo-3-oxo-4(R)-[3(S)-[1(R)-(triethylsilyloxy)ethyl]-4-oxoazetidin-2(R)-yl]pentanoic acid 4-nitrobenzyl ester | C23H32N4O7Si | 详情 | 详情 | |
| (XL) | 30152 | (4R,5R,6S)-4-methyl-2-[2-(4-nitrobenzyloxy)acetyl]-6-[(1R)-1-[(triethylsilyl)oxy]ethyl]-1-azabicyclo[3.2.0]heptane-3,7-dione | C23H32N2O7Si | 详情 | 详情 | |
| (XLI) | 30153 | (4R,5R,6S)-4-methyl-2-[2-(4-nitrobenzyloxy)acetyl]-7-oxo-6-[(1R)-1-[(triethylsilyl)oxy]ethyl]-1-azabicyclo[3.2.0]hept-2-en-3-yl trifluoromethanesulfonate | C24H31F3N2O9SSi | 详情 | 详情 | |
| (XLII) | 30154 | (4S,5R,6S)-3-(hydroxymethyl)-4-methyl-2-[2-(4-nitrobenzyloxy)acetyl]-6-[(1R)-1-[(triethylsilyl)oxy]ethyl]-1-azabicyclo[3.2.0]hept-2-en-7-one | C24H34N2O7Si | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VIII)Several improvements is the synthesis of 258849 have been developed: The reaction of stannatrane chloride (I) with Et2Zn and CH2I2 in HF gives iodomethylstannatrane (II), which is condensed with the naphthosultam (III) (intermediate (VII) in previous synthesis of 258849, scheme 25884901a) by means of K2CO3 in DMF yielding the stannatrane derivative (IV). The reaction of (IV) with Tf2O and lutidine in dichloromethane affords the corresponding ester (V), which is condensed with 1-(carbamoylmethyl)-4-aza-1-azoniabicyclo[2.2.2]octane trifluoromethanesulfonate (VI) (intermediate (XLV) in scheme 25884901g) giving the stannatrane derivative (VII). The condensation of intermediate (VII) with carbapenem triflate (VIII) (intermediate (XLI) in scheme 25884901f) by means of a Pd catalyst in acetonitrile provides the protected carbapenem derivative (IX) (intermediate (II) in scheme 25884902a). Finally, this compound is deprotected first with HCl to eliminate the silyl group and then with H2 over Pd/C to eliminate the p-nitrobenzyl group.
| 【1】 Jensen, M.S.; et al.; Synthesis of an anti-methicillin-resistant Staphylococcus aureus (MRSA) carbapenem via stannatrane-mediated Stille coupling. Org Lett 2000, 2, 8, 1081. |
| 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) | 36871 | 5-chloro-1-aza-5-stannabicyclo[3.3.3]undecane | C9H18ClNSn | 详情 | 详情 | |
| (II) | 36872 | 5-(iodomethyl)-1-aza-5-stannabicyclo[3.3.3]undecane | C10H20INSn | 详情 | 详情 | |
| (III) | 30123 | 6-(2-hydroxyethyl)-2H-naphtho[1,8-cd]isothiazole-1,1(2H)-dione | C12H11NO3S | 详情 | 详情 | |
| (IV) | 36873 | 2-(1-aza-5-stannabicyclo[3.3.3]undec-5-ylmethyl)-6-(2-hydroxyethyl)-2H-naphtho[1,8-cd]isothiazole-1,1(2H)-dione | C22H30N2O3SSn | 详情 | 详情 | |
| (V) | 36874 | 2-[2-(1-aza-5-stannabicyclo[3.3.3]undec-5-ylmethyl)-1,1-dioxo-1,2-dihydro-2H-naphtho[1,8-cd]isothiazol-6-yl]ethyl trifluoromethanesulfonate | C23H29F3N2O5S2Sn | 详情 | 详情 | |
| (VI) | 30156 | 1-(2-amino-2-oxoethyl)-4-aza-1-azoniabicyclo[2.2.2]octane trifluoromethanesulfonate | C9H16F3N3O4S | 详情 | 详情 | |
| (VII) | 36875 | 1-(2-amino-2-oxoethyl)-4-[2-[2-(1-aza-5-stannabicyclo[3.3.3]undec-5-ylmethyl)-1,1-dioxo-1,2-dihydro-2H-naphtho[1,8-cd]isothiazol-6-yl]ethyl]-1,4-diazoniabicyclo[2.2.2]octane | C30H45N5O3SSn | 详情 | 详情 | |
| (VIII) | 30153 | (4R,5R,6S)-4-methyl-2-[2-(4-nitrobenzyloxy)acetyl]-7-oxo-6-[(1R)-1-[(triethylsilyl)oxy]ethyl]-1-azabicyclo[3.2.0]hept-2-en-3-yl trifluoromethanesulfonate | C24H31F3N2O9SSi | 详情 | 详情 | |
| (IX) | 30160 | 1-(2-amino-2-oxoethyl)-4-(2-[2-[((4S,5R,6S)-4-methyl-2-[2-(4-nitrobenzyloxy)acetyl]-7-oxo-6-[(1R)-1-[(triethylsilyl)oxy]ethyl]-1-azabicyclo[3.2.0]hept-2-en-3-yl)methyl]-1,1-dioxo-1,2-dihydro-2H-naphtho[1,8-cd]isothiazol-6-yl]ethyl)-1,4-diazonia | C46H58F6N6O15S3Si | 详情 | 详情 |