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【结 构 式】

【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%

与该中间体有关的原料药合成路线共 2 条

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
Extended Information