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| | 2-Azabicyclo[2.2.1]heptane-2-carboxylic acid, 3-(6-broMo-1H-benziMidazol-2-yl)-, 1,1-diMethylethyl ester,(1R,3S,4S)- Basic information | | Application |
| Product Name: | 2-Azabicyclo[2.2.1]heptane-2-carboxylic acid, 3-(6-broMo-1H-benziMidazol-2-yl)-, 1,1-diMethylethyl ester,(1R,3S,4S)- | | Synonyms: | 2-Azabicyclo[2.2.1]heptane-2-carboxylic acid, 3-(6-broMo-1H-benziMidazol-2-yl)-, 1,1-diMethylethyl ester,(1R,3S,4S)-;(1R,3S,4S)-3-(6-Bromo-1H-benzimidazol-2-yl)-2-azabicyclo[2.2.1]heptane-2-carboxylic acid 1,1-dimethylethyl ester;(1R,3S,4S)-tert-butyl 3-(6-broMo-1H-benzo[d]iMidazol-2-yl)-2-azabicyclo[2.2.1]heptane-2-carboxylate;(1R,3S,4S)-tert-butyl 3-(6-broMo-1Hbenzo[d]iMidazol-2-yl)-2-azabicyclo[2,2,1] heptanes-2-carboxylate;Ledipasvir interMediates;(1R,3S,4S)-3-(6-Bromo-1Hbenzimidazol-2-yl)-2-azabicyclo[2,2,1]heptane--2-carboxylic acid-1,1-dimethylethyleste;Ledipasvir side chain 2;Ledipasvir Intermediate 06 | | CAS: | 1256387-74-2 | | MF: | C18H22BrN3O2 | | MW: | 392.29 | | EINECS: | 800-428-5 | | Product Categories: | | | Mol File: | 1256387-74-2.mol | ![2-Azabicyclo[2.2.1]heptane-2-carboxylic acid, 3-(6-broMo-1H-benziMidazol-2-yl)-, 1,1-diMethylethyl ester,(1R,3S,4S)- Structure](CAS/20150408/GIF/1256387-74-2.gif) |
| | 2-Azabicyclo[2.2.1]heptane-2-carboxylic acid, 3-(6-broMo-1H-benziMidazol-2-yl)-, 1,1-diMethylethyl ester,(1R,3S,4S)- Chemical Properties |
| Boiling point | 554.3±30.0 °C(Predicted) | | density | 1.455±0.06 g/cm3(Predicted) | | storage temp. | 2-8°C | | pka | 10.68±0.10(Predicted) | | Appearance | White to yellow Solid | | InChI | InChI=1S/C18H22BrN3O2/c1-18(2,3)24-17(23)22-12-6-4-10(8-12)15(22)16-20-13-7-5-11(19)9-14(13)21-16/h5,7,9-10,12,15H,4,6,8H2,1-3H3,(H,20,21)/t10-,12+,15-/m0/s1 | | InChIKey | IODPTNKFQCJTSI-NVBFEUDRSA-N | | SMILES | [C@]12([H])C[C@]([H])(CC1)[C@@H](C1NC3=CC(Br)=CC=C3N=1)N2C(OC(C)(C)C)=O |
| | 2-Azabicyclo[2.2.1]heptane-2-carboxylic acid, 3-(6-broMo-1H-benziMidazol-2-yl)-, 1,1-diMethylethyl ester,(1R,3S,4S)- Usage And Synthesis |
| Application | (1R,3S,4S)-3-(6-bromo-1H-benzimidazol-2-yl)-2-azabicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester can be used as a pharmaceutical synthesis intermediate, such as Harvoni, a combination of the novel antiviral NS5A inhibitor Letipasvir (GS5885) and the NS5B blocker Sofosbuvir, which is a blockbuster hepatitis C treatment drug approved by Gilead in December 2013. | | Synthesis | General procedure for the synthesis of tert-butyl (1R,3S,4S)-3-[(2-amino-4-bromophenyl)carbamoyl]methyl-2-azabicyclo[2.2.1]heptane-2-carboxylate from (1R,3S,4S)-3-(6-bromo-1H-benzo[d]imidazol-2-yl)-2-azabicyclo[2.2.1]heptane-2-carboxylate:
1. 3-[(2-amino-4-bromophenyl)carbamoyl]-2-azabicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (617) was dissolved in ethanol, placed in a sealed tube and heated at 130 °C overnight, then warmed to 170 °C and continued to heat for 3 days. The reaction was monitored by LC-MS, showing the generation of a mixture of the target product and the Boc protecting group cleavage product (in a ratio of about 1:1).
2. Upon completion of the reaction, the reaction mixture was concentrated and then dissolved in hydrochloric acid.
3. di-tert-butyl dicarbonate (0.6 eq.) was added to the solution and the reaction mixture was stirred overnight at room temperature.
4. The reaction mixture was concentrated and purified by fast column chromatography (silica gel as stationary phase, eluent 20% to 80% ethyl acetate/hexane gradient) to afford the target product (1R,3S,4S)-tert-butyl 3-(6-bromo-1H-benzo[d]imidazol-2-yl)-2- azabicyclo[2.2.1]heptane-2- carboxylate (618, 0.383 g, yield 72%) as an orange foamy solid. | | References | [1] Patent: WO2013/40492, 2013, A2. Location in patent: Page/Page column 91
[2] Journal of Medicinal Chemistry, 2014, vol. 57, # 5, p. 2033 - 2046 |
| | 2-Azabicyclo[2.2.1]heptane-2-carboxylic acid, 3-(6-broMo-1H-benziMidazol-2-yl)-, 1,1-diMethylethyl ester,(1R,3S,4S)- Preparation Products And Raw materials |
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