Category: 179022-43-6

Some common heterocyclic compound, 179022-43-6, name is Methyl 8-azabicyclo[3.2.1]octane-3-carboxylate hydrochloride, molecular formula is C9H16ClNO2, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. COA of Formula: C9H16ClNO2

Step 1. Preparation of methyl 8-(1-(2-chloro-6-(trifluoromethyl)benzoyl)- 1H- pyrazolo [4,3-bj pyridin-3-yl)-8-aza-bicyclo [3.2.11 octane-3-carboxylate (B-2).A mixture of (3 -bromo- 1 H-pyrazolo [4,3 -b]pyridin- 1 -yl)(2-chloro-6-(trifluoromethyl)phenyl)methanone (B-i) (200mg, 0.5 Ommol), 3 -(methoxycarbonyl)-8-azonia-bicyclo[3.2.1]octane chloride 2 (0.15 g, 0.75 mmol) and Cs2CO3 (0.65g, 2.Ommol) were suspended in DMF (5mL). The reaction mixture was heated at 150C in a microwave reactor for 5h. The resulting mixture was diluted with H20 (5OmL). 2M HC1 solution was added to adjust the pH to 3 and the aqueous layer was extracted with ethyl acetate (3x2OmL). Thecombined organic layers were washed with brine (2OmL), dried over anhydrous Na2SO4 and concentrated to obtain the crude product B-2 as yellow oil. LCMS (ESI) calc?d for C23H20C1F3N403 [M+H]: 493, found: 493

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 179022-43-6, its application will become more common.

Reference:
Patent; MERCK SHARP & DOHME CORP.; BARR, Kenneth Jay; MACLEAN, John; ZHANG, Hongjun; BERESIS, Richard Thomas; WO2014/28600; (2014); A2;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Application of 179022-43-6, The chemical industry reduces the impact on the environment during synthesis 179022-43-6, name is Methyl 8-azabicyclo[3.2.1]octane-3-carboxylate hydrochloride, I believe this compound will play a more active role in future production and life.

Example 3: 8- [7-(cis-4-methyl-cyclohexyloxy)-8-trifluoromethyl-naphthalen-2-ylmethyl]-8-aza-bicyc lo[3.2.1]octane-3-carboxylic acid To a solution of methanesulfonic acid 7- (cis-4-methyl-cyclohexyloxy)-8-trifluoromethyl-naphthalen-2-ylmethyl ester (105 mg, 0.252 mmol) in N,N-dimethylformamide (2.9 mL, 38 mmol), 8- aza-bicyclo[3.2.1]octane-3-carboxylic acid methyl ester; HC1 salt (103.72 mg, 0.50426 mmol) was added, followed by cesium carbonate (246.44 mg, 0.75638 mmol). The reaction was then heated at 80 C for lh. LCMS showed no SM left, and the completion of the reaction (RT 1.56 min.; MH+ 490.3 and 1.49 min, 476.30. Cooled down, the reaction mixture was diluted with EtOAc, washed with water (2x). The organic phase was then separated, dried and concentrated. The crude was purified by HPLC, removed the solvent, the ester was then dissolved in tetrahydrofuran (1.2 mL, 14 mmol) , treated with 1.0 M of lithium hydroxide in water(1.8 mL, 1.8 mmol) at rt overnight. Acidified with conc.HCl, the organic layer was dried and concentrated. The crude was then purified by HLPC to give the title compound as a white powder (57.6 mg, 48%). LCMS: RT = 1.49 min.; MH+ 476.20; 1H NMR (400 MHz, METHANOL-d4) delta 8.36 (s, 1H), 8.15 (d, J = 9.29 Hz, 1H), 8.04 (d, J = 8.34 Hz, 1H), 7.61 (d, J = 9.54 Hz, 1H), 7.57 (d, J = 6.78 Hz, 1H), 4.96 (br. s., 1H), 4.41 (s, 2H), 4.02 (br. s., 2H), 2.81 – 3.09 (m, 2H), 1.44 – 2.63 (m, 16H), 0.98 (d, J = 5.84 Hz, 3H).

In the field of chemistry, the synthetic routes of compounds are constantly being developed and updated. I will also mention this compound in other articles, Methyl 8-azabicyclo[3.2.1]octane-3-carboxylate hydrochloride, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; BIOGEN IDEC MA INC.; GUCKIAN, Kevin; KUMARAVEL, Gnanasambandam; MA, Bin; MI, Sha; PENG, Hairuo; SHAO, Zhaohui; SUN, Lihong; TAVERAS, Arthur; WANG, Deping; XIN, Zhili; ZHANG, Lei; WO2014/18881; (2014); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 179022-43-6, name is Methyl 8-azabicyclo[3.2.1]octane-3-carboxylate hydrochloride, This compound has unique chemical properties. The synthetic route is as follows., Quality Control of Methyl 8-azabicyclo[3.2.1]octane-3-carboxylate hydrochloride

A mixture of (3-bromo-lH-pyrazolo[4,3-b]pyridin-l-yl)(2-chloro-6-(trifluoromethyl) phenyl)methanone (B-1) (200mg, 0.50mmol), 3-(methoxycarbonyl)-8-azonia- bicyclo[3.2.1]octane chloride 2 (0.15 g, 0.75 mmol) and Cs2C03 (0.65g, 2.0mmol) were suspended in DMF (5mL). The reaction mixture was heated at 150C in a microwave reactor for 5h. The result mixture was diluted with H20 (50mL). 2M HCl solution was added to adjust the pH~3 and the aqueous layer was extracted with ethyl acetate (3x20mL). The combined organic layers were washed with brine (20mL), dried over anhydrous Na2S04 and concentrated to get the crude product B-2 as yellow oil. LCMS (ESI) calc’d for C23H20ClF3N4O3 [M+H]+: 493, found: 493

According to the analysis of related databases, 179022-43-6, the application of this compound in the production field has become more and more popular.

Reference:
Patent; MERCK SHARP & DOHME CORP.; BARR, Kenneth Jay; MACLEAN, John; ZHANG, Hongjun; BERESIS, Richard Thomas; WO2014/26330; (2014); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Reference of 179022-43-6, In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 179022-43-6 as follows.

Example 27: 8-((5-((cis-4-methylcyclohexyl)oxy)naphthalen-2-yl) azabicyclo[3.2.1]octane-3-carboxylic acid To a solution of methanesulfonic acid 5-(4-methyl-cyclohexyloxy)-naphthalen-2- ylmethyl ester (177 mg, 0.508 mmol) in DMF (2 mL), 8-aza-bicyclo[3.2.1]octane-3- carboxylic acid methyl ester HCl salt (208.38 mg, 1.0131 mmol) was added, followed by cesium carbonate (495.14 mg, 1.5197 mmol). The reaction was then heated at 80 C for lh. After cooled down, the reaction mixture was diluted with EtOAc, washed with water (2x). The organic phase was then separated, dried and concentrated. The crude was purified by HPLC, removed the solvent, the ester was then dissolved in tetrahydrofuran (2.3 mL, 29 mmol) , treated with 1.0 M of lithium hydroxide in Water(3.5 mL, 3.5 mmol) at rt overnight. Acidified with 1NHC1, the organic layer was dried and concentrated. The crude was then purified by HLPC to give 8-((5-((cis-4-methylcyclohexyl)oxy)naphthalen- 2-yl)methyl)-8-azabicyclo[3.2.1]octane-3-carboxylic acid as a white powder (132.9 mg, 64% ). LCMS: RT 1.40 min.; MH+ 408.1. 1H NMR (400 MHz, METHANOL-d4) delta 8.38 (d, J = 8.72 Hz, 1H), 7.98 (s, 1H), 7.60 (d, J = 10.48 Hz, 1H), 7.46 (d, J = 4.96 Hz, 2H), 6.92 – 7.08 (m, 1H), 4.85 (br. s., 1H), 3.80 – 4.45 (m, 2H), 3.37 (s, 2H), 1.35 -2.81 (m, 18H), 1.00 (d, J = 5.65 Hz, 3H).

According to the analysis of related databases, 179022-43-6, the application of this compound in the production field has become more and more popular.

Reference:
Patent; BIOGEN IDEC MA INC.; GUCKIAN, Kevin; KUMARAVEL, Gnanasambandam; MA, Bin; SUN, Lihong; XIN, Zhili; ZHANG, Lei; WO2014/25708; (2014); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Related Products of 179022-43-6, Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 179022-43-6, name is Methyl 8-azabicyclo[3.2.1]octane-3-carboxylate hydrochloride, This compound has unique chemical properties. The synthetic route is as follows.

Example 6: 8-{l-[7-(cis-4-methyl-cyclohexyloxy)-8-trifluoromethyl-naphthalen-2-yl]-ethyl}-8-aza-bi cyclo[3.2.1]octane-3-carboxylic acid To a mixture of cesium carbonate (179 mg, 0.549 mmol) and 8-aza-bicyclo[3.2.1]octane-3-carboxylic acid methyl ester; HC1 salt (113 mg, 0.549 mmol) was added solution of 7-(l-bromo-ethyl)-2-(4-methyl-cyclohexyloxy)-l-trifluoromethyl-naphthalene (152 mg, 0.366 mmol) in N,N-dimethylformamide (4 mL, 50 mmol). The reaction mixture was stirred at rt for 30min, and heated at 50 C overnight. LCMS showed fairly clean Rt = 1.61min, m/z = 504.3. The mixture was diluted with MeOH, filtered to remove solid, and purified by HPLC (TFA method) to get the ester. The above ester was dissolved in MeOH (0.5mL) and THF (0.5 mL), added lithium hydroxide (0.0104 mL, 1.10 mmol) and water (0.5 mL) stirred at 50 C (hot plate) for lh. LC-MS shows the reaction was completed. Neutralized with concentarted HC1 solution, Prep HPLC gave product as a solid (32.7 mg, 18%). LCMS: Rt = 1.54 min, m/z = 490.3. 1H NMR (400 MHz, METHANOL-d4) delta 8.30 (s, 1H), 8.15 (d, J = 9.35 Hz, 1H), 8.08 (d, J = 8.47 Hz, 1H), 7.53 – 7.66 (m, 2H), 4.91 – 5.02 (m, 1H), 4.37 – 4.60 (m, 1H), 3.39 – 3.48 (m, 1H), 2.88 – 3.04 (m, 1H), 1.34 – 2.66 (m, 21H), 0.98 (s, 3H).

The chemical industry reduces the impact on the environment during synthesis Methyl 8-azabicyclo[3.2.1]octane-3-carboxylate hydrochloride. I believe this compound will play a more active role in future production and life.

Reference:
Patent; BIOGEN IDEC MA INC.; GUCKIAN, Kevin; KUMARAVEL, Gnanasambandam; MA, Bin; MI, Sha; PENG, Hairuo; SHAO, Zhaohui; SUN, Lihong; TAVERAS, Arthur; WANG, Deping; XIN, Zhili; ZHANG, Lei; WO2014/18881; (2014); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics