Month: August 2021

Application of 239463-85-5, A common heterocyclic compound, 239463-85-5, name is (R)-3-(5-(2-Aminopropyl)-7-cyanoindolin-1-yl)propyl benzoate (2R,3R)-2,3-dihydroxysuccinate, molecular formula is C26H31N3O8, 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.

in a container having an inner volume of 5 E and equipped with a reflux condenser, a thermometer, and a stirrer, 317 g (0.62 moles) of 3-{5-[(2R)-2-aminopropyl]-7- cyano-2,3-dihydro-1H-indol-l-yl}propio benzoate.mono(2R,3R)-tartrate, 1.8 E of ethyl acetate, and 1280 g (1.83moles) of a 20% aqueous potassium carbonate solution were mixed and stirred at room temperature for 1 hout10108] After completion of the stirring, an organic phase was separated from the reaction liquid, and the obtained organic phase was concentrated under reduced pressure. The concentrate, 1.8 E of acetonitrile, 69 g (0.65 moles) of sodium carbonate, 10 g (0.03 moles) of tetrabutylammonium bromide, and 233 g (0.74 moles) of 2-[2-(2,2,2-trifluoroeth- oxy)phenoxy]ethyl methanesulfonate were mixed and subjected to reaction under stirring at 75 to 85 C. for 30 hours. 10109] After completion of the reaction, the reaction liquid was cooled to room temperature and then filtered, with the result that 2.2 kg of an acetonitrile solution of 3-(7-cyano- 5-[(2R)-2-({2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl}amino)propyl] -2,3-dihydro-l H-indol-l -yl}propylbenzoate (content: 14.2 mass %, 0.53 moles) was obtained (yield: 85%).

The synthetic route of 239463-85-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; UBE INDUSTRIES, LTD.; MOTOYAMA, Takahiro; TAKATA, Katsunori; FUKUHARA, Yasuaki; UEMURA, Masato; SADO, Tatsunori; KASAI, Atsuyuki; (20 pag.)US2017/8842; (2017); A1;,
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Reference of 356068-93-4,Some common heterocyclic compound, 356068-93-4, name is (Z)-5-((5-Fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid, molecular formula is C16H13FN2O3, 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 solution of compound 109 (0.5 g, 1.67 mmol) in THF(150 mL) at00C was added HOBt (0.34 g, 2.8 mmol), triethylamine (0.6 mL, 4.18 mmol),ECDI HCl (0.48 g, 2.8 mmol) and compound 202 (0.6 g, 3.33 mmol) successively. The mixture was stirred overnight at room temperature, evaporated to remove solvent, diluted with water (50 mL), brine (50 mL) and saturated sodium bicarbonate solution (50 mL). The pH of solution was adjusted to 11-12 with 1OM NaOH. The mixture was filtered, washed with water, dried to obtain crude yellow solid 203 (550 mg, 69%). LCMS: 478 [M+l]+, 1H NMR (DMSO-J6): delta 2.40 (s, 3H), 2.43 (s, 3H), 3.63 (m, 2H),3.82 (s, 3H), 4.20 (t,2H), 6.92 (m, 2H), 7.07 (d, 2H), 7.70 (m, 2H), 7.84(s, 1H),7 .91 (d, 2H), 10.88 (s, IH), 13.68 (s, IH).

The synthetic route of 356068-93-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; CURIS, INC.; WO2008/33747; (2008); A2;,
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Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 102359-00-2, name is 2-Oxoindoline-5-carboxylic Acid, A new synthetic method of this compound is introduced below., Computed Properties of C9H7NO3

General procedure: A solution of 9a-d (2 mmol), EDCI (3 mmol) and HOBt (3 mmol) in dry DCM (20 mL) was stirred at 0C for 3.5 h. Then different substituted amines (2.2 mmol) and DIPEA (4 mmol) were added and the reaction was stirred at r.t. for another 1.5 h. The organic layer was washed with water and brine and dried over Na2SO4. Removal of the solvent gave a residue that was purified by column chromatography (silica gel, CH2Cl2-MeOH 100: 1 as an eluent) to furnish 10a-n as white solids.

The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.

Reference:
Article; Guo, Jing; Zhu, Mingyue; Wu, Tianxiao; Hao, Chenzhou; Wang, Kai; Yan, Zizheng; Huang, Wanxu; Wang, Jian; Zhao, Dongmei; Cheng, Maosheng; Bioorganic and Medicinal Chemistry; vol. 25; 13; (2017); p. 3500 – 3511;,
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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 1201923-48-9 as follows. Safety of (S)-tert-Butyl (1-(1,3-dioxoisoindolin-2-yl)-3-(3-fluorophenyl)propan-2-yl)carbamate

Step B 2-[(2S)-2-amino-3-(3-fluorophenyl)propyl]-1H-isoindole-1,3(2H)-dione [1.0]-hydrogen chloride To a solution of tert-butyl[(1S)-1-(3-fluorobenzyl)-2-hydroxyethyl]carbamate (9.40 g, 34.9 mmol), triphenylphosphine (9.15 g, 34.9 mmol), and phthalimide (5.14 g, 34.9 mmol) in tetrahydrofuran (100 mL, 1000 mmol) at room temperature was added diethyl azodicarboxylate (17.9 mL, 45.4 mmol). The reaction was stirred at room temperature for 2 hr and then concentrated under reduced pressure. The residue was purified by combi-flash chromatography eluted with EtOAc/hexane (0-40%) to give the desired intermediate. LCMS found: 399.0 (M+1). To the solution of the purified intermediate in methanol (20 mL, 400 mmol) was added 4.0 M hydrogen chloride in dioxane (30 mL, 100 mmol). The mixture was stirred at room temperature for 2 h and then concentrated under reduced pressure to give 3.1 g (26% total yield for the two steps) of the final product, 2-[(2S)-2-amino-3-(3-fluorophenyl)propyl]-1H-isoindole-1,3(2H)-dione [1.0]-Hydrogen chloride, as white solid. LC/MS found: 299.0 (M+H)+.

According to the analysis of related databases, 1201923-48-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Incyte Corporation; Huang, Taisheng; Feng, Hao; Kong, Lingquan; Wang, Anlai; Ye, Hai Fen; US2013/96144; (2013); A1;,
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Application of 65435-04-3, A common heterocyclic compound, 65435-04-3, name is 5-(2-Chloroacetyl)indolin-2-one, molecular formula is C10H8ClNO2, 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 suspension of 9.3 g of 5-chloroacetyl-2-oxindole was stirred in 90 mL of pyridine at 80-90 C. for 3 hours then cooled to room temperature. The precipitate was collected by vacuum filtration and washed with 20 mL of ethanol. The solid was dissolved in 90 mL of 2.5 N sodium hydroxide and stirred at 70-80 C. for 3 hours. The mixture was cooled to room temperature and acidified to pH 2 with 0.5 N hydrochloric acid. The precipitate was collected by vacuum filtration and washed thoroughly with water to give crude 5-carboxy-2-oxindole as a dark brown solid.

The synthetic route of 65435-04-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SUGEN, Inc.; US2002/183364; (2002); A1;,
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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 496-12-8 as follows. name: Isoindoline

Example 12; 2-(1,3-Dihydroisoindol-2-yl)-1-(4-dimethylamino-4-phenylcyclohexyl)ethanol; Stage 1; 2-(1,3-Dihydroisoindol-2-yl)-1-(1,4-dioxaspiro[4.5]dec-8-yl)ethanol; A solution of 8-oxiranyl-1,4-dioxaspiro[4.5]decane (1.41 g, 7.66 mmol), isoindoline (1.00 g, 8.43 mmol) and calcium trifluoromethanesulfonate (1.29 g, 3.8 mmol) in anhydrous acetonitrile (60 ml) was stirred at room temperature overnight. The solvent was then concentrated in vacuo. The residue was taken up in ethyl acetate (50 ml) and the solution was washed with 25% potassium carbonate solution (3×50 ml). The aqueous phase was extracted with ethyl acetate (3×40 ml) and the combined organic phases were dried with sodium sulfate and concentrated in vacuo.Yield: 2.04 g (88%), beige-coloured solid1H-NMR (DMSO-d6): 1.24-1.48 (m, 5H); 1.59 (br s, 1H); 1.64-1.74 (m, 3H); 2.56 (dd, 1H, J=7.4, 12.2 Hz); 2.70 (dd, 1H, J=4.7, 12.2 Hz); (m, 2H); 3.44 (m, 1H); 3.83 (s, 4H); 3.83-3.94 (m, 4H); 4.30 (d, 1H, J=4.4 Hz); 7.15-7.26 (m, 4H).

According to the analysis of related databases, 496-12-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; GRUeNENTHAL GMBH; US2011/59999; (2011); A1;,
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Related Products of 200049-46-3,Some common heterocyclic compound, 200049-46-3, name is 7-Bromo-2,3-dihydro-isoindol-1-one, molecular formula is C8H6BrNO, 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.

7-bromo-2,3-dihydro-lH-isoindol-l-one (5.7 g, 26.88 mmol) was added to sulfuric acid (60 ml) at 0C. The resulting mixture was stirred at 0C for 30 minutes. Then N-iodosuccinimide (9.07 g, 40.32 mmol) was added in one portion and the resulting suspension stirred at 0C for 2 hours. The reaction mixture was poured into ice water, causing a precipitate to form. The precipitate was extracted with ethyl acetate (3 x 200 ml). Both organic and aqueous phases contained precipitates. The organic phase was washed with 10% Na S C (200 ml) to remove excess iodine. The organic layer was dried with sodium sulphate, filtered and evaporated to afford 7-bromo-6-iodo-2,3-dihydro-lH-isoindol-l-one (7.2 g, 79%) as a white solid. 1H NMR (400 MHz, DMSO, 30C) 4.11 (2H, s), 7.43 (1H, d), 7.83 (1H, d), 8.90 (1H, s). m/z: ES+ [M+H]+ = 338.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 7-Bromo-2,3-dihydro-isoindol-1-one, its application will become more common.

Reference:
Patent; ASTRAZENECA AB; KETTLE, Jason, Grant; BAGAL, Sharanjeet, Kaur; EATHERTON, Andrew, John; FILLERY, Shaun, Michael; ROBB, Graeme, Richard; LAMONT, Scott, Gibson; KEMMITT, Paul, David; GOLDBERG, Frederick, Woolf; (158 pag.)WO2019/215203; (2019); A1;,
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Application of 22190-33-6,Some common heterocyclic compound, 22190-33-6, name is 5-Bromoindoline, molecular formula is C8H8BrN, 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.

Procedure A: To a mixture of 5-bromoindoline (10.0 g, 50.8 mmol) in DCM (80 mL), was added a solution of di-tert-butyl dicarbonate (11.2 g, 51.3mmol) in DCM (20 mL). The reaction mixture was stirred at RT for 2 h and concentrated in vacuo to give tert-butyl 5- bromoindoline-1-carboxylate as a yellow oil (18.0 g, quantitative yield). LC-MS (ESI): m/z (M)+ = 297.12 / 299.33

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5-Bromoindoline, its application will become more common.

Reference:
Patent; REMEDY PLAN, INC.; CRIMMINS, Gregory, Thomas; DE JESUS DIAZ, Dennise, Alexandra; BHURRUTH-ALCOR, Yushma; (483 pag.)WO2019/213570; (2019); A1;,
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Synthetic Route of 5428-09-1, 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 5428-09-1 as follows.

Example 7-2 Preparation of 2-(4-(trimethylsilyl)but-2-en-1-yl)isoindoline-1,3-dione 12 To a solution of 2-allylisoindoline-1,3-dione 11 (13.0 g, 69.4 mmol) in CH2Cl2 (500 mL) was added AllylTMS (79.0 g, 110 mL, 694 mmol) and Grubbs I generation catalyst. The reaction was heated to 60 °C and stirred under reflux for 4 h. Tris(hydrodxymethyl)phosphine (1 M solution in i-PrOH, 58 mL) was added and stirred under reflux for 12 h, while the color of the reaction turned from black to orange. Sat. aq. NaCl solution (100 mL) was added to the reaction and the organic phase was separated. The aqueous phase was extracted with CH2Cl2 (3 * 200 mL). The combined organic layers were dried over MgSO4 and the solvent was removed under reduced pressure. Column chromatography over SiO2 (Cyclohexane/ EtOAc = 85:15) afforded the title compound (15.0 g, 54.9 mmol, 78.9 percent) as a yellow resin. Rf: 0.57 (Cyclohexane/EtOAc = 85:15) 1H NMR (300 MHz, CDCl3) delta = -0.10 – 0.09 (m, 9H), 1.44 (d, J = 8.2 Hz, 1.6 H), 1.72 (d, J = 8.8 Hz, 0.4 H), 4.21 (d, J = 6.5 Hz, 1.6 H), 4.29 (dd, J = 14.5, 5.9 Hz, 0.4 H), 5.26 – 5.47 (m, 0.8 H), 5.56 – 5.70 (m, 0.2 H), 5.70 – 5.87 (m, 0.8 H), 5.94 – 6.09 (m, 0.2 H), 7.65 – 7.74 (m, 2H), 7.79 – 7.88 (m, 2H). 13C NMR (75 MHz, cdcl3) delta = -2.05, -1.83, -1.43, 18.92, 22.73, 34.72, 39.87, 120.51, 121.30, 123.12, 130.78, 132.24, 133.76, 133.90, 167.99.

According to the analysis of related databases, 5428-09-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Max-Planck-Gesellschaft zur Foerderung der Wissenschaften e.V.; The designation of the inventor has not yet been filed; EP2899192; (2015); A1;,
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These common heterocyclic compound, 104618-32-8, name is 2-(4-Oxocyclohexyl)isoindoline-1,3-dione, 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. Formula: C14H13NO3

Preparation of 2-amino-6-phthalimido-4,5,6,7-tetrahydrobenzothiazole via 4-(phthalimido)-cyclohexanone; 1.0 Kg of 4-(phthalimido)-cyclohexanol was added in 20.0 L of acetone at 250C to 350C. The reaction mixture was cooled to 50C to 100C and treated with chromic acid solution. 0.2 L of isopropanol was added and stirred for 30 min. The reaction mixture was filtered and washed with acetone (1.0 L). The filtrate was treated with 0.4 kg sodium bicarbonate at 250C to 350C and stirred for 1 h. The reaction mass was again filtered, washed with acetone (1.0 L). Excess of acetone was distilled under vacuum. The residue was treated with 0.5 L ethanol followed by distillation of ethanol under vacuum. The reaction mass was cooled and treated with 3.36 L ethanol at 450C to 250C while gradual cooling. The reaction mixture was further cooled to 150C to 200C and treated with 0.22 L of bromine and 0.43 Kg of thiourea under stirring for 1 h. The reaction mixture was heated to reflux at 750C to 780C for 6 hrs. The reaction mixture was cooled and stirred for 1 hr at 50C to 100C. The product was isolated by centrifuge, washing with ethanol 0.66 L and drying under vacuum at 500C to 550C. (yield: 0.70 Kg).

The synthetic route of 2-(4-Oxocyclohexyl)isoindoline-1,3-dione has been constantly updated, and we look forward to future research findings.

Reference:
Patent; CADILA HEALTHCARE LIMITED; WO2008/41240; (2008); A1;,
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