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【结 构 式】 
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【分子编号】69443 【品名】tert-butyl ((1R,2S,5S)-2-azido-5-(dimethylcarbamoyl)cyclohexyl)carbamate 【CA登记号】 |
【 分 子 式 】C14H25N5O3 【 分 子 量 】311.384 【元素组成】C 54.00% H 8.09% N 22.49% O 15.41% |
合成路线1
该中间体在本合成路线中的序号：(XXVI)Alternatively, the monoprotected cyclohexanediamine (XIX) can be prepared as follows. Ring opening of N,N-dimethyl-3,4-epoxycyclohexanecarboxamide (XXII) with ammonium hydroxide at 40 °C, followed by protection of the resultant amino alcohol (XXIII) with Boc2O in aqueous NaOH provides the N-Boc-protected amino alcohol (XXIV). After conversion of alcohol (XXIV) to the corresponding mesylate (XXV) by means of methanesulfonyl chloride and Et3N in 4-methyl-2-pentanone, substitution with NaN3 in the presence of 1-dodecylpyridinium chloride in DMAc or toluene at 60 °C furnishes azide (XXVI). Finally, azide (XXVI) is reduced by transfer hydrogenation with ammonium formate and Pd/C in MeOH at 40 °C .
| 【1】 Sato, K., Kawanami, K., Yagi, T. (Daiichi Sankyo Co., Ltd.). Optically active diamine derivative and process for producing the same. EP 1925611, JP 2007106759, US 2009105491, WO 2007032498. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XIX) | 69436 | tert-butyl ((1R,2R,5S)-2-amino-5-(dimethylcarbamoyl)cyclohexyl)carbamate | C14H27N3O3 | 详情 | 详情 | |
| (XXII) | 69439 | (1R,3R,6S)-N,N-dimethyl-7-oxabicyclo[4.1.0]heptane-3-carboxamide | C9H15NO2 | 详情 | 详情 | |
| (XXIII) | 69440 | (1R,3R,4S)-3-amino-4-hydroxy-N,N-dimethylcyclohexanecarboxamide | C9H18N2O2 | 详情 | 详情 | |
| (XXIV) | 69441 | tert-butyl ((1R,2R,5S)-5-(dimethylcarbamoyl)-2-hydroxycyclohexyl)carbamate | C14H26N2O4 | 详情 | 详情 | |
| (XXV) | 69442 | (1R,2S,4S)-2-((tert-butoxycarbonyl)amino)-4-(dimethylcarbamoyl)cyclohexyl methanesulfonate | C15H28N2O6S | 详情 | 详情 | |
| (XXVI) | 69443 | tert-butyl ((1R,2S,5S)-2-azido-5-(dimethylcarbamoyl)cyclohexyl)carbamate | C14H25N5O3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXVI)Intermediate (VII) is prepared as follows. Hydrolysis of cis-azido-carbamate (XIV) using aqueous LiOH gives the corresponding carboxylic acid (XXXII), which is converted into carboxamide (XXXIII) by reaction with dimethylamine hydrochloride in the presence of EDC, HOBt and NMM in CH2Cl2. N-deprotection of carboxamide (XXXIII) with HCl in EtOH/CH2Cl2, followed by condensation of the resultant amine (XXXIV) with the lithium thiazolopyridinecarboxylate derivative (II) by means of EDC and HOBt in DMF provides amide (XXXV), which is finally reduced at the azido moiety by catalytic hydrogenation over Pd/C in MeOH .
| 【1】 Ohta, T., Komoyira, S., Yoshimo, T. et al. (Daiichi Sankyo Co., Ltd.).Diamine derivatives. CA 2451605, CA 2456841, EP 1405852, EP 1415992, JP 2008143905, US 2005020645, US 2005119486, US 2005245565, US 2008015215, US 2009270446, US 7342014, US 7365205, WO 2003000657, WO 2003000680, WO 2003016302. |
| 【2】 Ohta, T., Komoriya, S., Yoshino, T. et al. (Daiichi Sankyo Co., Ltd.). Diamine derivatives. CA 2511493, EP 1577301, JP 2007070369, JP 2008138011, US 2006252837, US 2009281074, US 7576135, WO 2004058715. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (II) | 69421 | lithium 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxylate | C8H9LiN2O2S | 详情 | 详情 | |
| (VII) | 69426 | N-((1S,2R,5S)-2-amino-5-(dimethylcarbamoyl)cyclohexyl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide | C17H27N5O2S | 详情 | 详情 | |
| (XIV) | 69431 | (1R,3R,4S)-ethyl 4-azido-3-((tert-butoxycarbonyl)amino)cyclohexanecarboxylate | C14H24N4O4 | 详情 | 详情 | |
| (XXVI) | 69443 | tert-butyl ((1R,2S,5S)-2-azido-5-(dimethylcarbamoyl)cyclohexyl)carbamate | C14H25N5O3 | 详情 | 详情 | |
| (XXXII) | 69447 | (1R,3S,4R)-4-azido-3-((tert-butoxycarbonyl)amino)cyclohexanecarboxylic acid | C12H20N4O4 | 详情 | 详情 | |
| (XXXIV) | 69448 | (1S,3R,4R)-3-amino-4-azido-N,N-dimethylcyclohexanecarboxamide | C9H17N5O | 详情 | 详情 | |
| (XXXV) | 69449 | N-((1R,2S,5S)-2-azido-5-(dimethylcarbamoyl)cyclohexyl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide | C17H25N7O2S | 详情 | 详情 |