【结 构 式】 |
【分子编号】42926 【品名】1-chloroethane 【CA登记号】75-00-3 |
【 分 子 式 】C2H5Cl 【 分 子 量 】64.5144 【元素组成】C 37.24% H 7.81% Cl 54.95% |
合成路线1
该中间体在本合成路线中的序号:(II)The alkylation of pilosine (I) with ethyl chloride (II) by means of LDA in THF gives trans-pilocarpine (III), which is isomerized with LDA in THF, yielding a mixture of cis- and trans-pilocarpine (IV). Finally, this mixture is resolved by crystallization with di-p-toluoyl tartaric acid.
【1】 Shapiro, G.; Enz, A.; Pilocarpine analogs as muscarinic agonists. Drugs Fut 1992, 17, 6, 489. |
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) | 42933 | (4R)-4-[(1-methyl-1H-imidazol-5-yl)methyl]dihydro-2(3H)-furanone | C9H12N2O2 | 详情 | 详情 | |
(II) | 42926 | 1-chloroethane | 75-00-3 | C2H5Cl | 详情 | 详情 |
(III) | 42934 | (3R,4R)-3-ethyl-4-[(1-methyl-1H-imidazol-5-yl)methyl]dihydro-2(3H)-furanone | C11H16N2O2 | 详情 | 详情 | |
(IV) | 42935 | (4R)-3-ethyl-4-[(1-methyl-1H-imidazol-5-yl)methyl]dihydro-2(3H)-furanone | C11H16N2O2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号:(VI)This compound has been obtained by two different ways: 1. The reaction of 2,3-dihydro-1H-benzimidazol-2-one (I) with trichloromethyl chloroformate (II) in THF gives 2-oxo-2,3-dihydro-1H-benzimidazol-2-ylcarbonyl chloride (III), which is condensed with endo-8-methyl-8-azabicyclo[3,2,1]octan-3-amine (IV) in THF, yielding the corresponding amide (V). Finally, this compound is alkylated with ethyl chloride (VI) and NaH in DMF. 2. The condensation of 2-nitrophenyl isocyanate (VII) with endo-8-methyl-8-azabicyclo[3,2,1]octan-3-amine (IV) in THF/cyclohexane gives the corresponding 2-nitrophenylurea (VIII), which is reduced with H2 over Pd/C in ethanol to yield the 2-aminophenylurea (IX). The acylation of (IX) with phenyl chloroformate (X) in toluene affords the carbamate (XI), which is cyclized by means of NaOH in ethanol to afford the amide (V). Finally, this compound is alkylated with ethyl chloride (VI) and NaH in DMF.
【1】 Turconi, M.; Schiantarelli, P.; Borsini, F.; Rizzi, C.A.; Ladinsky, H.; Donetti, A.; Azabicycloalkyl benzimidazolones: Interaction with serotonergic 5-HT3 and 5-HT4 receptors and potential therapeutic implications. Drugs Fut 1991, 16, 11, 1011. |
【2】 Turconi, M.; et al.; Azabicycloalkyl benzimidazolone derivatives: A novel class of 5-HT3 receptor antagonists. 199th ACS Natl Meet (April 22 1990, Boston) 1990, Abst MEDI 103. |
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) | 42923 | 1,3-dihydro-2H-benzimidazol-2-one | 615-16-7 | C7H6N2O | 详情 | 详情 |
(II) | 42918 | Chloroformic acid trichloromethyl ester; di-Phosgene; Chloroformic Acid, Trichloromethyl Ester; Trichloromethyl chloroformate; Diphosgene | 503-38-8 | C2Cl4O2 | 详情 | 详情 |
(III) | 42924 | 2-oxo-2,3-dihydro-1H-benzimidazole-1-carbonyl chloride | C8H5ClN2O2 | 详情 | 详情 | |
(IV) | 19105 | (1R,5S)-8-methyl-8-azabicyclo[3.2.1]oct-3-ylamine; (1R,5S)-8-methyl-8-azabicyclo[3.2.1]octan-3-amine | C8H16N2 | 详情 | 详情 | |
(V) | 42925 | N-[(1R,5S)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl]-2-oxo-2,3-dihydro-1H-benzimidazole-1-carboxamide | C16H20N4O2 | 详情 | 详情 | |
(VI) | 42926 | 1-chloroethane | 75-00-3 | C2H5Cl | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号:(VI)The condensation of 2-nitrophenyl isocyanate (VII) with endo-8-methyl-8-azabicyclo[3,2,1]octan-3-amine (IV) in THF/cyclohexane gives the corresponding 2-nitrophenylurea (VIII), which is reduced with H2 over Pd/C in ethanol to yield the 2-aminophenylurea (IX). The acylation of (IX) with phenyl chloroformate (X) in toluene affords the carbamate (XI), which is cyclized by means of NaOH in ethanol to afford the amide (V). Finally, this compound is alkylated with ethyl chloride (VI) and NaH in DMF.
【1】 Turconi, M.; et al.; Synthesis of a new class of 2,3-dihydro-2-oxo-1H-benzimidazole-1-carboxylic acid derivatives as highly potent 5-HT3 receptor antagonists. J Med Chem 1990, 33, 8, 2101. |
【2】 Turconi, M.; et al.; Azabicycloalkyl benzimidazolone derivatives: A novel class of 5-HT3 receptor antagonists. 199th ACS Natl Meet (April 22 1990, Boston) 1990, Abst MEDI 103. |
【3】 Turconi, M.; Schiantarelli, P.; Borsini, F.; Rizzi, C.A.; Ladinsky, H.; Donetti, A.; Azabicycloalkyl benzimidazolones: Interaction with serotonergic 5-HT3 and 5-HT4 receptors and potential therapeutic implications. Drugs Fut 1991, 16, 11, 1011. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(IV) | 19105 | (1R,5S)-8-methyl-8-azabicyclo[3.2.1]oct-3-ylamine; (1R,5S)-8-methyl-8-azabicyclo[3.2.1]octan-3-amine | C8H16N2 | 详情 | 详情 | |
(V) | 42925 | N-[(1R,5S)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl]-2-oxo-2,3-dihydro-1H-benzimidazole-1-carboxamide | C16H20N4O2 | 详情 | 详情 | |
(VI) | 42926 | 1-chloroethane | 75-00-3 | C2H5Cl | 详情 | 详情 |
(VII) | 32771 | 1-isocyanato-2-nitrobenzene; 2-nitrophenyl isocyanate | 3320-86-3 | C7H4N2O3 | 详情 | 详情 |
(VIII) | 42927 | N-[(1R,5S)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl]-N'-(2-nitrophenyl)urea | C15H20N4O3 | 详情 | 详情 | |
(IX) | 42928 | N-(2-aminophenyl)-N'-[(1R,5S)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl]urea | C15H22N4O | 详情 | 详情 | |
(X) | 13580 | 1-[(Chlorocarbonyl)oxy]benzene; phenyl chloroformate | 1885-14-9 | C7H5ClO2 | 详情 | 详情 |
(XI) | 42929 | phenyl 2-[([[(1R,5S)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl]amino]carbonyl)amino]phenylcarbamate | C22H26N4O3 | 详情 | 详情 |