Month: October 2020

2555-28-4, A common heterocyclic compound, 2555-28-4, name is 7-Methoxy-4-methylcoumarin, molecular formula is C11H10O3, 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.

A mixture of compound 22b (1.0 g, 5.3 mmol), NBS (1.4 g, 7.9 mmol) and BPO (20 mg) in CHCl3(30 mL) was heated to reflux at 70C for 8 hours. The reaction mixture was cooled to 0C, diluted with water, and extracted with CHCl3. The organic phase was concentrated in vacuo to afford compound 22c (1.0 g, 71 %).

The synthetic route of 2555-28-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MERCK SHARP & DOHME CORP.; KOZLOWSKI, Joseph; COBURN, Craig; YU, Wensheng; TONG, Ling; HU, Bin; ZHONG, Bin; HAO, Jinglai; WANG, Dahai; JI, Tao; WO2015/89810; (2015); A1;,
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17100-63-9, A common compound: 17100-63-9, name is Methyl 4-bromo-3-methoxybenzoate, belongs to esters-buliding-blocks compound, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below.

To a solution of methyl 4-iodo-3-methoxybenzoate (9) (0.5 g, 1.71 mmol) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-1-carboxylate(0.70 g, 2.05 mmol) in 1,4-dioxane (10.0 mL) was added 2.0 mL of water. The reaction mixture was degassed with argon for about30 min. After that Pd(dppf)Cl2.DCM (0.069 g, 0.085 mmol) andNa2CO3 (0.36 g, 3.42 mmol) were added to the reaction mixture andagain degassed with argon for another 20 min. The reactionmixturewas stirred under reflux for 3 h. After cooled down to roomtemperature, the mixture was extracted with EtOAc, washed withbrine, dried over Na2SO4, and concentrated under reduced pressure.The crude product was purified by column chromatography(Hexane/EtOAc 4:6) to afford 10 as a yellow solid (0.52 g, 79.7%).1H NMR (500 MHz, CDCl3) delta 8.15 (d, J 5.0 Hz, 1H), 7.85 (s, 1H), 7.65(d, J 10.0 Hz, 2H), 7.56 (d, J 10.0 Hz, 2H), 7.32 (d, J 10.0 Hz, 1H),7.28 (s, 1H), 3.86 (s, 3H), 3.82 (s, 3H), 1.62 (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-bromo-3-methoxybenzoate, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Naik, Ravi; Valentine, Heather; Hall, Andrew; Mathews, William B.; Harris, James C.; Carter, C. Sue; Dannals, Robert F.; Wong, Dean F.; Horti, Andrew G.; European Journal of Medicinal Chemistry; vol. 139; (2017); p. 644 – 656;,
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59247-47-1, Adding some certain compound to certain chemical reactions, such as: 59247-47-1, name is tert-Butyl 4-bromobenzoate, 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 59247-47-1.

Example 30 Preparation of 4-((S)-3-{4-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenoxy}-pyrrolidin-1-yl)-benzoic acid To a mixture of 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid [4-((S)-pyrrolidin-3-yloxy)-phenyl]-amide hydrochloride (180 mg, 0.37 mmol), 4-bromobenzoic acid tert-butyl ester (114 mg, 0.44 mmol), sodium tert-butoxide (118 mg, 1.23 mmol) and (2′,4′,6′-triisopropyl-1,1′-biphenyl-2-yl)dicyclohexylphosphine (X-PHOS, 40 mg) in dioxane (5 mL) bubbled with argon was added tris(dibenzylideneacetone)dipalladium Pd2(dba)3 (24 mg). The mixture was heated at 105¡ã C. for 2 hrs. Solvents were evaporated and the residue was extracted with ethyl acetate and 0.1N hydrochloric acid. The organic layer was dried and concentrated. The residue was purified through ISCO column chromatography (silica gel, ethyl acetate in hexane, 5percent to 60percent linear gradient) to give a white solid as 4-((S)-3-{4-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenoxy}-pyrrolidin-1-yl)-benzoic acid tert-butyl ester (150 mg, yield 69percent). The above 4-((S)-3-{4-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenoxy}-pyrrolidin-1-yl)-benzoic acid tert-butyl ester (150 mg) was dissolved in a mixture of methylene chloride (2 mL) and trifluoroacetic acid (4 mL). The mixture was stirred at room temperature for 1 hr and solvents were evaporated. The residue was extracted with ethyl acetate and water. The organic layer was dried and solvents were evaporated. The residue was triturated with ethyl acetate and hexanes to give a tan solid as 4-((S)-3-{4-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenoxy}-pyrrolidin-1-yl)-benzoic acid (75 mg). LC-MS for C28H22F3N3O5 (m/e) calcd 537, obsd 538 (M+H).

Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 59247-47-1.

Reference:
Patent; Bolin, David Robert; Cheung, Adrian Wai-Hing; Firooznia, Fariborz; Marcopulos, Nicholas; Qian, Yimin; US2010/152445; (2010); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

1559-02-0, 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 1559-02-0 as follows.

To a solution of diethyl cyclopropane-1,1-dicarboxylate (4.77 g, 25.6 mmol) in ethanol (40 mL) was added KOH (1.43 g, 25.6 mmol) in H2O (8 mL), and the reaction mixture was stirred at room temperature overnight. The ethanol was removed under reduced pressure. The residue was neutralized with HCl (6 mL, 5 mol/L), then extracted with EtOAc (100 mL*3). The combined organic phases were dried over Na2SO4, filtered and the filtrate was concentrated in vacuo to give the title compound as a white solid (3.58 g, 88.4 %). 1H NMR (400MHz, CDCl3): delta 1.27 (t, J=6.7Hz, 3H), 1.83 (m, 2H), 1.86 (m, 2H), 4.25 (m, 2H).

According to the analysis of related databases, 1559-02-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Sunshine Lake Pharma Co., Ltd.; Xi, Ning; XI, Ning; (152 pag.)EP2408300; (2016); B1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

35180-01-9,Some common heterocyclic compound, 35180-01-9, name is Chloromethyl isopropyl carbonate, molecular formula is C5H9ClO3, 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.

To a stirred suspension of PMPA (7.26 g, 0.026 mmol) in DMF (100 mL) was added Et 3 N (10.8 mL, 0.0778 mmol) at 50 C. The reaction mixture became homogeneous and chloromethyl isopropyl carbonate (12.1 g, 0.0778 mmol) was added to the reaction mixture and stirring was continued at 50 C. (oil bath temperature) for 20 h. The solvent was removed under reduced pressure and the crude product was chromatographed on a silica gel column. Elution with 10% isopropanol in CH 2 Cl 2 removed all nonpolar impurities. Further elution with the same solvent mixture yielded 1.3 g (about 10%) of the prodrug.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 35180-01-9, its application will become more common.

Reference:
Patent; GILEAD SCIENCES INCORPORATED; ARIMILLI, MURTY N; CUNDY, KENNETH C; DOUGHERTY, JOSEPH P; KIM, CHOUNG U; OLIYAI, REZA; STELLA, VALENTINO J; (59 pag.)JP2015/164934; (2015); A;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

2318-25-4, Name is Ethyl 3-ethoxy-3-iminopropionate hydrochloride, 2318-25-4, belongs to esters-buliding-blocks compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows.

.To a mixture of 281 g of Compound (I-4) suspended in 1.6 liters of acetonitrile, 210 ml of triethylamine was added while stirring at a room temperature. Following stirring for 30 minutes, 318 g of the foregoing Intermediate (I-3) and 36 ml of acetic acid were added in this order to react them. After reacting for 10 hours, 3 liters of water was added and stirring was continued. Precipitated crystals were collected by filtration. The crystals were washed with water and dried. As a result, 324 g (yield 71percent) of the objective Intermediate (I-5) was obtained, as a white crystal.

Statistics shows that Ethyl 3-ethoxy-3-iminopropionate hydrochloride is playing an increasingly important role. we look forward to future research findings about 2318-25-4.

Reference:
Patent; Fuji Photo Film Co., Ltd.; US6649771; (2003); B2;,
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. 33993-24-7, name is Cyclopropanecarboxylic anhydride, This compound has unique chemical properties. The synthetic route is as follows., 33993-24-7

EXAMPLE 37; Synthesis of cyclopropyl(2-isopropy]pyrazolo[l,5-a]pyridin-3-yl)methanone; 2-isopropyl-pyrazolo[l,5-a]pyridine (2.00 g, 12.4 mmol) was dissolved in cyclopropyl anhydride (8.00 g, 51.9 mmol). Concentrated H2SO4 (3 drops) was added at room temperature and the mixture was then heated to 140 0C for 28 hours. The mixture was then cooled to 0 0C, diluted with H2O (10 mL) and 50 % NaOH (aq) was added to achieve a solution pH of 11. This mixture was extracted with Et2O (3 x 10 mL). The combined organic layers were washed with H2O (15 mL), brine (15 mL), dried (Na2SO4), filtered and concentrated. The crude mixture was then immediately subjected to flash chromatography (90 % EtOAc/ hexane) to afford 1.02 g (4.4 mmol, 36 %) of the title compound as a white powder. This material was then recrystallized from n-heptane to afford 0.6115 g (2.7 mmol, 22 %) of SB-I1-61 was white needles, mp 72 0C (?-heptane); IR (thin film) v = 2969, 1635, 1506, 1439 1H NMR (300 MHz, CDCl3) delta = 8.42 (d, J= 6.8 Hz, IH), 8.09 (d, J= 9.0 Hz, IH), 7.33-7.27 (m, IH), 6.82 (ddd, J= 6.8, 6.8, 1.2 Hz, IH), 3.75 (sept, J = 6.9 Hz, IH), 2.47-2.39 (m, IH), 1.40 (d, J= 6.9 Hz, 6H), 1.27-1.17 (m, 2H), 0.99-0.93 (m, 2H); 13C NMR (150 MHz, CDCl3) delta = 194.8, 163.1, 141.6, 128.9, 127.4, 118.9, 113.2, 110.7, 27.8, 22.4, 20.4, 10.2; MS (EI) m/z 229 (M+ 1, 18.2), 228 (M+, 100.0), 213 (46.4), 200 (13.1), 199 (23.4), 198 (14.1), 185 (23.2), 171 (23.2), 160 (13.5), 145 (11.8), 132 (10.2), 131 (13.8), 119 (11.6), 117 (18.0), 92 (10.2 ), 91 (10.9), 90 11.0), 84 (11.2), 78 (17.6), 69 (24.6) 51 (10.9); HRMS (EI) calcd for C14H16N2O: 228.1263, found: 228.1261; Anal. Calcd for Ci4H16N2O: C, 73.66 %; H, 7.06 %; Found: C, 73.93 %; H, 7.25%. Compound 1046.

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Patent; AVIGEN, INC.; WO2007/146087; (2007); A2;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

61367-07-5, 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. 61367-07-5, name is Methyl trans-4-aminocyclohexanecarboxylate hydrochloride, This compound has unique chemical properties. The synthetic route is as follows.

EDCI (19 mg, 0.097 mmol), HOBt (13 mg, 0.097 mmol), and DIEA (0.034 mL, 0.195 mmol) were added to a solution of carboxylic acid intermediate 13 (30 mg, 0.065 mmol) dissolved in DCM. After 10 minutes, methyl trans-4-aminocyclohexanecarboxylate hydrochloride (25 mg, 0.13 mmol) and a catalytic amount of DMAP were added. After stirring overnight, the solvent was removed and the crude product was purified by column chromatography to give the 30 mg of intermediate 18 as a white solid.

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Patent; Sanofi; The Regents of the University of Michigan; US2012/289494; (2012); 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. 89-91-8, name is Methyl 2,2-dimethoxyacetate, This compound has unique chemical properties. The synthetic route is as follows., 89-91-8

General procedure: To a solution of diisopropylamine (1.5 eq.) in THF (1.5M) at ooc under N2 was added nBuli(1.4eq., 1.6M in hexane) and the mixture was stirred for 20 min. The LOA was cooled to -80C20 and TMSCI (1.4 eq.) was added followed by the methyl ester (1 eq.). The reaction was allowedto reach ooc over 3 h, brought to rt and stirred for 30 min. Pentane was added and the whiteprecipitate filtered off over celite. The solvent was removed under reduced pressure. Purificationif necessary was performed by bulb-to-bulb distillation.

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Patent; SANDOZ AG; HOEFERL-PRANTZ, Kathrin; FELZMANN, Wolfgang; WILHELM, Thorsten; BENITO-GARAGORRI, David; WO2013/189980; (2013); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

10601-80-6, 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. 10601-80-6, name is Ethyl 3,3-diethoxypropionate, This compound has unique chemical properties. The synthetic route is as follows.

Sodium hydride (2.00 g, 50.6 mmol, 60%) was added to a solution of ethyl formate (10.13 g, 168.7 mmol) in tetrahydrofuran while maintaining the internal temperature below 0 C. Then, ethyl 3,3-diethoxy propionate (5.00 g, 33.75 mmol) was added dropwise to the reaction mixture and stirred for 24 h at ambient temperature. After confirming that the reaction was complete by using TLC analysis, the reaction was quenched with 20 mL water and the tetrahydrofuran was removed under reduced pressure. The mixture was extracted with ethyl acetate and then brine. The organic phase was dried over Na2SO4 overnight and the solvent was removed in vacuo to give the title compound 14.

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Article; Zhao, Shizhen; Zhang, Xiangqian; Wei, Peng; Su, Xin; Zhao, Liyu; Wu, Mengya; Hao, Chenzhou; Liu, Chunchi; Zhao, Dongmei; Cheng, Maosheng; European Journal of Medicinal Chemistry; vol. 137; (2017); p. 96 – 107;,
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Ester – an overview | ScienceDirect Topics