135908-33-7 Archives - Esters-buliding-blocks

Aguilar, Angelo et al. published their research in Journal of Medicinal Chemistry in 2017 | CAS: 135908-33-7

Methyl 4-aminobicyclo[2.2.2]octane-1-carboxylate (cas: 135908-33-7) belongs to esters. Esters typically have a pleasant smell; those of low molecular weight are commonly used as fragrances and are found in essential oils and pheromones. Esters contain a carbonyl center, which gives rise to 120鎺?C閳ユ弲閳ユ彊 and O閳ユ弲閳ユ彊 angles. Unlike amides, esters are structurally flexible functional groups because rotation about the C閳ユ彊閳ユ弲 bonds has a low barrier. Their flexibility and low polarity is manifested in their physical properties; they tend to be less rigid (lower melting point) and more volatile (lower boiling point) than the corresponding amides. Synthetic Route of C10H17NO2

Discovery of 4-((3’R,4’S,5’R)-6”-Chloro-4′-(3-chloro-2-fluorophenyl)-1′-ethyl-2”-oxodispiro[cyclohexane-1,2′-pyrrolidine-3′,3”-indoline]-5′-carboxamido)bicyclo[2.2.2]octane-1-carboxylic Acid (AA-115/APG-115): A Potent and Orally Active Murine Double Minute 2 (MDM2) Inhibitor in Clinical Development was written by Aguilar, Angelo;Lu, Jianfeng;Liu, Liu;Du, Ding;Bernard, Denzil;McEachern, Donna;Przybranowski, Sally;Li, Xiaoqin;Luo, Ruijuan;Wen, Bo;Sun, Duxin;Wang, Hengbang;Wen, Jianfeng;Wang, Guangfeng;Zhai, Yifan;Guo, Ming;Yang, Dajun;Wang, Shaomeng. And the article was included in Journal of Medicinal Chemistry in 2017.Synthetic Route of C10H17NO2 This article mentions the following:

The authors previously reported the design of spirooxindoles with two identical substituents at the carbon-2 of the pyrrolidine core as potent MDM2 inhibitors. In this paper the authors describe an extensive structure-activity relationship study of this class of MDM2 inhibitors, which led to the discovery of 60 (AA-115/APG-115, 4-((3R,4S,5R)-6”-chloro-4-(3-chloro-2-fluorophenyl)-1-ethyl-2”-oxodispiro[cyclohexane-1,2-pyrrolidine-3,3”-indoline]-5′-carboxamido)bicyclo[2.2.2]octane-1-carboxylic acid). Compound 60 has a very high affinity to MDM2 (K_i < 1 nM), potent cellular activity, and an excellent oral pharmacokinetic profile. Compound 60 is capable of achieving complete and long-lasting tumor regression in vivo and is currently in phase I clin. trials for cancer treatment. In the experiment, the researchers used many compounds, for example, Methyl 4-aminobicyclo[2.2.2]octane-1-carboxylate (cas: 135908-33-7Synthetic Route of C10H17NO2).

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

9/14/2021 News Simple exploration of 135908-33-7

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 135908-33-7, its application will become more common.

Some common heterocyclic compound, 135908-33-7, name is Methyl 4-aminobicyclo[2.2.2]octane-1-carboxylate, molecular formula is C10H17NO2, 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. HPLC of Formula: C10H17NO2

At RT, 258 mg (1.41 mmol) of methyl 4-aminobicyclo[2.2.2]octane-1-carboxylate, 402 mg (1.06 mmol) of HATU and 182 mg (1.41 mmol) of DIPEA were added to a solution of 210 mg (0.71 mmol) of 6-chloro-3-methyl-2-phenylquinoline-4-carboxylic acid in 5 ml of DMF. The mixture was then stirred at 60 C. for 1 h. After cooling to RT, the mixture was added to 20 ml of a 10% strength citric acid solution. The resulting precipitate was filtered off, washed with water and dried under reduced to pressure. This gave 326 mg (97% of theory, purity 98%) of the title compound. 1H-NMR (400 Mhz, DMSO-d6): delta [ppm]=8.48 (s, 1H), 8.05 (d, 1H), 7.77 (dd, 1H), 7.66 (d, 1H), 7.60-7.47 (m, 5H), 3.59 (s, 3H), 2.32 (s, 3H), 2.09-2.00 (m, 6H), 1.91-1.82 (m, 6H). LC/MS (Method 1, ESIpos): Rt=1.22 min, m/z=463 [M+H]+.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 135908-33-7, its application will become more common.

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; BECK, Hartmut; THALER, Tobias; KAST, Raimund; MEININGHAUS, Mark; TERJUNG, Carsten; MUENSTER, Uwe; OLENIK, Britta; (92 pag.)US2018/36300; (2018); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Extracurricular laboratory: Synthetic route of 135908-33-7

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Methyl 4-aminobicyclo[2.2.2]octane-1-carboxylate, and friends who are interested can also refer to it.

Electric Literature of 135908-33-7, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 135908-33-7 name is Methyl 4-aminobicyclo[2.2.2]octane-1-carboxylate, This compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.

Example 874-{[N-cyano-2-methyl-2-phenoxypropanimidoyl]amino}bicyclo[2.2.2]octane-1-carboxylic acidEthyl N-cyano-2-methyl-2-phenoxypropanimidoate (CI-1) (1 mmol) and methyl 4-aminobicyclo[2.2.2]octane-1-carboxylate (BA-2) (1 mmol) were mixed, and the neat mixture was heated to 100 C. under nitrogen and stirred for 5 hours. After cooling, the mixture was purified by column chromatography on silica gel (mobile phase:CH2Cl2/CH3OH=50/1) to give an impure ester product which was dissolved in methanol (10 mL). To the solution was added a solution of LiOH (10 mg) in methanol (40 mL) and water (1 mL). The mixture was refluxed overnight. After removal of the solvent, the residue was dissolved in water and adjusted pH=56 with HCl (1 mol/L), extracted with ethyl acetate (50 mL×3). The combined extracts were washed with brine, dried over sodium sulfate and concentrated. The residue was purified by preparative reverse phase HPLC [Waters 2767; Benetnach 10-C18 20×250 mm, 10 mum; 35-60% acetonitrile/water (0.05% trifluoroacetic acid), 30 mL/minute; detection at 214 and 254 nm] to give the titled compound.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Methyl 4-aminobicyclo[2.2.2]octane-1-carboxylate, and friends who are interested can also refer to it.

Reference:
Patent; ABBOTT LABORATORIES; US2010/267738; (2010); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Share a compound : 135908-33-7

The synthetic route of Methyl 4-aminobicyclo[2.2.2]octane-1-carboxylate has been constantly updated, and we look forward to future research findings.

These common heterocyclic compound, 135908-33-7, name is Methyl 4-aminobicyclo[2.2.2]octane-1-carboxylate, its 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. Safety of Methyl 4-aminobicyclo[2.2.2]octane-1-carboxylate

General method D, 4-(isopropoxycarbonylamino)bicyclo[2.2.2]octane-1-carboxylate.

The synthetic route of Methyl 4-aminobicyclo[2.2.2]octane-1-carboxylate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Cyteir Therapeutics, Inc.; Castro, Alfredo C.; McComas, Casey Cameron; Vacca, Joseph; Maclay, Tyler; (132 pag.)US2019/77799; (2019); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Analyzing the synthesis route of 135908-33-7

Application of 135908-33-7, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 135908-33-7 name is Methyl 4-aminobicyclo[2.2.2]octane-1-carboxylate, This compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.

A mixture containing methyl 4-aminobicyclo[2.2.2]octane-l-carboxylate (298mg, 1.63 mmol), 4′-tert-butylbiphenyl-2-carboxylic acid (414 mg, 1.63 mmol), DMAP (227 mg, 1.86 mmol) and EDC HCl (470 mg, 2.45 mmol) in CH2Cl2 (5 mL) was stirred at room temperature for 18 h. The reaction mixture was concentrated under reduced pressure and the resulting residue was purified by chromatography (elution = 16:1 petrolueum ether/EtOAc) to afford methyl 4-(4′-fcrt-butylbiphenyl-2- ylcarboxamido)bicyclo[2.2.2]octane-l -carboxylate as an off-white solid (186 mg, yield: 27%). 1H NMR (400 MHz, CDCl3): delta 7.74 (IH, d, J= 6.4 Hz), 7.48-7.39 (4H, m), 7.35- 7.31 (3H, m), 4.77 (IH, s), 3.62 (3H, s), 1.79-1.75 (6H, m), 1.62-1.58 (6H, m), 1.36 (9H, s).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Methyl 4-aminobicyclo[2.2.2]octane-1-carboxylate, and friends who are interested can also refer to it.

Reference:
Patent; SIRTRIS PHARMACEUTICALS, INC.; WO2008/100423; (2008); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Continuously updated synthesis method about C10H17NO2

Adding a certain compound to certain chemical reactions, such as: 135908-33-7, name is Methyl 4-aminobicyclo[2.2.2]octane-1-carboxylate, belongs to esters-buliding-blocks compound, can increase the reaction rate and produce products with better performance than those obtained under traditional synthetic methods. Here is a downstream synthesis route of the compound 135908-33-7, Formula: C10H17NO2

Example 8 : 4- (((2- ((trans-4- (tert-butyl)c clohexyl)oxy) -4-methylnaphthalen- l-yl)methyl)amino)bicyclo[2.2.2]octane-l-carboxylic acid To a mixture of 2-(cis-4-tert-butylcyclohexyloxy)-4-methyl-l-naphthaldehyde (lOOmg, 0.31 mmol, 1.0 eq) in toluene (1 mL) were added methyl 4- aminobicyclo[2.2.2]octane-l-carboxylate hydrochloride (81 mg, 0.37 mmol, 1.2 eq) and MgS04 (74 mg, 0.62 mmol, 2.0 eq). The resulting mixture was heated to reflux and stirred for 48 h. After being concentrated under reduced pressure, the residue was dissolved in THF (lmL). NaBH(OAc)3 (196 mg, 0.93 mmol, 3.0 eq) was added and the mixture was heated to reflux and stirred for 24 h. After cooling down to room temperature, the residue was diluted with EtOAc (5 mL). The suspension was filtered and the filtrate was concentrated under reduced pressure to give the residue, which was purified by column chromatography on silica gel (petroleum ether /EtOAc = 1/1) to yield the target ester (35 mg, 23 % yield) as a yellow oil. LCMS m/z 492.4 [M+H] +. Hydrolysis following standard condition gave the title compound as a white solid (20 mg, 69% yield). LCMS m/z 478.3 [M+H] +; 1H NMR (400 MHz, CD3OD) delta: 8.06- 8.01 (m, 2H), 7.61-7.59 (m, 1H), 7.49-7.47 (m, 1H), 7.36 (s, 1H), 4.54 (bs, 3H), 2.74 (s, 3H), 2.32-2.29 (m, 2H), 2.16 (bs, 12H), 1.99-1.94 (m, 2H), 1.54-1.51 (m, 2H), 1.34-1.24 (m, 2H), 1.20-1.14 (m, 1H), 0.91 (s, 9H).

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 4-aminobicyclo[2.2.2]octane-1-carboxylate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; BIOGEN IDEC MA INC.; GUCKIAN, Kevin; KUMARAVEL, Gnanasambandam; LIU, Xiaogao; MA, Bin; PENG, Hairuo; WO2014/120764; (2014); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Simple exploration of 135908-33-7

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 135908-33-7, its application will become more common.

Introduction of a new synthetic route about 135908-33-7

Statistics shows that Methyl 4-aminobicyclo[2.2.2]octane-1-carboxylate is playing an increasingly important role. we look forward to future research findings about 135908-33-7.

Related Products of 135908-33-7, These common heterocyclic compound, 135908-33-7, name is Methyl 4-aminobicyclo[2.2.2]octane-1-carboxylate, its 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.

General procedure: Example 69: 4-(((6-((trans-4-(tert-butyl)cyclohexyl)oxy)quinolin-2-yl)methyl)amino)bicyclo[2.2.2] octane-l-carboxylic acid Step 1: methyl 4-(((6-((trans-4-(tert-butyl cyclohexyl oxy quinolin-2-yl methyl amino bicyclor2.2.21oct ane- 1 -carboxylate 2) NaBH(OAc)3 (3 eq), it, 1 h Y: 30% The solution of 6-((trans-4-(tert-butyl)cyclohexyl)oxy)quinoline-2-carbaldehyde (200 mg, 0.6 mmol) and methyl 4-aminobicyclo[2.2.2]octane-l-carboxylate (142 mg, 0.644 mmol) in Ethanol (2 mL, 30 mmol) was heated to reflux for 2h. The yellow solution was cooled to room temperature and sodium cyanoborohydride (48.6 mg, 0.773 mmol) was added and was heated to reflux for lh. After cooled down to room temperature, citric acid was added and concentrated down. The solid was suspended in water and filtrate, and the collected solid was washed thoroughly with water. HPLC purification of the solid give the product (62.7 mg, 20%). LCMS Rt = 1.67 min, m/z = 479.30 [M+l]. Lithium hydroxide (15.7 mg, 0.655 mmol) was added to a solution of 4-{ [6-(trans-4-tert-Butyl-cyclohexyloxy)-quinolin-2-ylmethyl]-amino}-bicyclo[2.2.2]octa ne-l-carboxylic acid methyl ester (62.7 mg, 0.131 mmol) in tetrahydrofuran (0.8 mL, 10 mmol) and methanol (0.8 mL, 20 mmol). The mixture was stirred at 50 C overnight, the solvent was concentrated. The residue was taken up in DMSO and cone. HCl (200 uL) was added to solubilize. Purification by preparative HPLC gave the product as a white solid (63 mg, 20%). LCMS (100%, RT=1.57 min, m/z=465.30. 1H NMR (400 MHz, METHANOL-d4) delta ppm 0.94 (s, 9 H) 1.06 – 1.60 (m, 5 H), 1.86 – 1.99 (m, 2H), 2.00- 2.10 (m, 12 H), 2.24 – 2.37 (m, 2 H) 4.32 – 4.46 (m, 1 H) 4.49 (s, 2 H) 7.34 (d, J=2.51 Hz, 1 H) 7.42 (dd, J=9.29, 2.76 Hz, 1 H), 7.47 (d, J=8.53 Hz, 1 H) 8.01 (d, J=9.29 Hz, 1 H) 8.28 (d, J=8.28 Hz, 1 H). Step 2: 4-(((6-((trans-4-(tert-butyl)cvclohexyl)oxy)quinolin-2-yl)methyl)amino)bicyclor2.2.21oct ane-l-carboxylic acid Lithium hydroxide (15.7 mg, 0.655 mmol) was added to a solution of 4-{ [6-(trans-4-tert-butyl-cyclohexyloxy)-quinolin-2-ylmethyl]-amino}-bicyclo[2.2.2]octa ne-l-carboxylic acid methyl ester (62.7 mg, 0.131 mmol) in tetrahydrofuran (0.8 mL, 10 mmol) and methanol (0.8 mL, 20 mmol). The mixture was stirred at 50 C overnight, the solvent was concentrated. The residue was taken up in DMSO and cone. HCl (200 uL) was added to solubilize. Purification by preparative HPLC gave the product as a white solid (2.3 mg, 4%). LCMS (100%, RT=1.57 min, m/z=465.30. 1H NMR (400 MHz, METHANOL-d4) delta ppm 0.94 (s, 9 H) 1.06 – 1.60 (m, 5 H), 1.86 – 1.99 (m, 2H), 2.00- 2.10 (m, 12 H), 2.24 – 2.37 (m, 2 H) 4.32 – 4.46 (m, 1 H) 4.49 (s, 2 H) 7.34 (d, J=2.51 Hz, 1 H) 7.42 (dd, J=9.29, 2.76 Hz, 1 H), 7.47 (d, J=8.53 Hz, 1 H) 8.01 (d, J=9.29 Hz, 1 H) 8.28 (d, J=8.28 Hz, 1 H).

Statistics shows that Methyl 4-aminobicyclo[2.2.2]octane-1-carboxylate is playing an increasingly important role. we look forward to future research findings about 135908-33-7.

Reference:
Patent; BIOGEN IDEC MA INC.; GUCKIAN, Kevin; KUMARAVEL, Gnanasambandam; MA, Bin; MI, Sha; PENG, Hairuo; SHAO, Zhaohui; SUN, Lihong; TAVERAS, Arthur; XIN, Zhili; ZHANG, Lei; WO2014/18891; (2014); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics