Tag: M.W=200-300

Application of 337536-15-9,Some common heterocyclic compound, 337536-15-9, name is 4-Bromoisoindolin-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.

A suspension of Example 1C (10.6g, 50 mmol) and 4,4,5,5,4′,4′,5′,5 -octamethyl-[2,21bi[[l,3,2]dioxaborolanyl] (15.23g, 60 mmol) in DMF (390 mL) was stirred until a clearyellow solution was obtained. The solution was then treated with potassium acetate (14.72g,150 mmol), degassed with nitrogen, treated with [1.1 -bis(diphenylphosphino)-ferrocene]dichloropalladium [H]-CH2C12 (7g, 8.5 mmol) and heated to 90 C overnight. The(R)reaction was cooled to room temperature and filtered through diatomaceous earth (Celite ),and concentrated. The concentrate was partitioned between water and ethyl acetate and/?filtered through diatomaceous earth (Celite ). The organic phase was dried (Na2SO4),filtered, and concentrated. The crude product was purified by silica gel chromatographyeluting with 100% ethyl acetate and triturated from hexanes to give 4.56g (35% yield) of thedesired product

The synthetic route of 337536-15-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ABBOTT LABORATORIES; WO2004/108672; (2004); A1;,
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Adding a certain compound to certain chemical reactions, such as: 18711-13-2, name is 4,7-Dichloroindoline-2,3-dione, belongs to indolines-derivatives 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 18711-13-2, category: indolines-derivatives

4,7-Dichloro-3-(2-(4-cyclopropyl-2-fluorophenyl)-2-oxoethyl)-3-hydroxyindolin-2- one (EXAMPLE 18): To 4,7-dichloroindoline-2,3-dione (A) ( 261 mg, 1.21 mmol) in 15 mL of methanol were l-(4-cyclopropyl-2-fluorophenyl)ethanone (B) (280 mg, 1.57 mmol) and 10 drops of diethylamine (2). The reaction was stirred at 50C for 24 hours. The solvent was removed and the residue was purified with flash chromatography (0-5% Methanol/CH2C12) to get an off white solid. 4,7-Dichloro-3-(2-(4-cyclopropyl-2-fluorophenyl)-2-oxoethyl)-3- hydroxyindolin-2-one (EXAMPLE 18): off-white solid; 1H NMR (DMSO-d6, 400 MHz) delta 0.82 (m, 2H), 1.07 (m, 2H), 2.01(m, 1H), 3.66 (d, 1H, J=16 Hz), 4.26 (d, 1H, J=16Hz), 6.44(s, 1H), 6.91(d, 1H, J=8Hz), 7.01 (m, 2H), 7.31 (d, 1H, J=8Hz), 7.57(m, 1H), 10.96 (s, 1H). Chiral separation was performed by a method substantially similar to the method described above. LC screening was performed with: column: RegisCell, 250 mm x 4.6 mm, 5 mum, hexane/IPA (80/20), 1.5 ml/min, injection volume: 2.0 mu, pressure: 51.5 bar. Peak 1 : retention time: 5.16 min, width: 0.238 min, area: 3716.20, area %: 49.78. Peak 2: retention time: 6.49 min, width: 0.324 min, area: 3749.55, area %: 50.22.

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; TOKALAS, INC.; VERNIER, Jean-michael; (82 pag.)WO2016/57698; (2016); A1;,
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Synthetic Route of 1035235-27-8, In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 1035235-27-8, name is tert-Butyl 4-bromoisoindoline-2-carboxylate belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below.

A mixture of tert-butyl 4-bromoisoindoline-2-carboxylate (1.00 g, 3.37mmol), 4,4,4?,4?,5,5,5?,5?-octamethyl-2,2?-bi(1 ,3,2-dioxaborolane) (1.03 g, 4.04 mmol), AcOK (661 mg, 6.74 mmol) and Pd(dppf)C12 (50.0 mg) in dioxane (20 mL) was stirred at 90C lbr 16 h under the nitrogen atmosphere. After cooling down to 20C and LCMS showed the reaction was complete, the mixture was filtered and the filtrate was concentrated under reduced pressure to get the title compound (1.2 g, yield 103%) as a brown solid, which was directly to the next step without further purification ?HNMR(CDC13, 400 MHz) oe 7.69 (d, J 7.2 Hz, 1 H) 7.36-7.27 (m, 2 H) 4.87-4.63 (m, 4 H) 1.52 (s, 9 H) 1.31 (s, 12 H).

The synthetic route of tert-Butyl 4-bromoisoindoline-2-carboxylate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; KADMON CORPORATION, LLC; KIM, Ji-in; LIU, Kevin; POYUROVSKY, Masha; LU, Dan; ZHU, Zhenping; WO2015/54317; (2015); A1;,
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Electric Literature of 201940-08-1, 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. 201940-08-1, name is tert-Butyl 5-bromoisoindoline-2-carboxylate, This compound has unique chemical properties. The synthetic route is as follows.

To a solution of tert-butyl 5-bromoisoindoline-2-carboxylate (1.20 g, 4.02 mmol, CAS201940-08-1), 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolane (1.12 g, 4.43 mmol) in DMSO (20.0 mL) was added KOAc (1.18 g, 12.0 mmol) and Pd(PPh3)4 (139 mg, 120 umol). The mixture was stirred at 80 C. for 16 hours under N2. On completion, the mixture was diluted with H2O (50 mL), and extracted with EA (3¡Á30 mL). The organic layers were washed with brine (3¡Á30 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The mixture was purified by prep-HPLC (reserve phase (0.1% FA)) to give the title compound (500 mg, 36% yield) as yellow solid. 1H NMR (400 MHz, CDCl3) delta 7.75 (s, 1H), 7.32-7.29 (m, 1H), 7.25 (d, J=7.6 Hz, 1H), 4.74-4.66 (m, 4H), 1.54 (s, 9H), 1.37 (s, 12H).

The chemical industry reduces the impact on the environment during synthesis tert-Butyl 5-bromoisoindoline-2-carboxylate. I believe this compound will play a more active role in future production and life.

Reference:
Patent; Kymera Therapeutics, Inc.; Mainolfi, Nello; Ji, Nan; Kluge, Arthur F.; Weiss, Matthew M.; Zhang, Yi; (1443 pag.)US2019/192668; (2019); A1;,
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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. 181140-34-1, name is (R)-(-)-N-(2,3-Epoxypropyl)phthalimide, This compound has unique chemical properties. The synthetic route is as follows., HPLC of Formula: C11H9NO3

To the solution of compound A19 (500 mg, 2.46 mmol) in DMF (5 mL) was added NaN3 (319 mg, 4.92 mmol) and NH4Cl (158 mg, 2.95 mmol). The mixture was stirred at 80 C for 3 hours to give a yellow mixture. LCMS showed the reaction was completed. The mixture was partitioned between EtOAc (30 mL) and H20 (20 mL). The aqueous phase was extracted with EtOAc (30 mL x 2). The combined organic extract was dried over anhydrous Na2S04, filtered and concentrated under reduced pressure to give compound A20 (820 mg, crude) as a yellow oil.

According to the analysis of related databases, 181140-34-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; QURIENT CO., LTD.; LEAD DISCOVERY CENTER GMBH; NAM, Kiyean; KIM, Jaeseung; JEON, Yeejin; YU, Donghoon; SEO, Mooyoung; PARK, Dongsik; EICKHOFF, Jan; ZISCHINSKY, Gunther; (217 pag.)WO2019/197549; (2019); A1;,
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Adding a certain compound to certain chemical reactions, such as: 6941-75-9, name is 5-Bromoisoindoline-1,3-dione, belongs to indolines-derivatives 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 6941-75-9, Recommanded Product: 6941-75-9

Sodium borohydride (12.6 g, 330 mmol) was added to a mixed solvent of ethanol (300 mL) and water (50 mL)Add 5-bromophthalimide in 4 batches with stirring at 20-30 C(30.0 g, 132 mmol, stirred for 30 min after each addition).After the addition was complete, the reaction was incubated for 2h, hydrochloric acid solution (mass percent concentration 18%, 180g, 883.5mmol) was added dropwise at 20-30 C, heated to 75-85 C after dropping,The reaction was incubated 3h, evaporated to ethanol under reduced pressure to give an aqueous white solid.Solid plus toluene (225ml), water (300ml), 45-55 C for 30min, to clarify the upper and lower.The layers were separated and the aqueous layer was extracted with toluene (150 mL * 1).The combined toluene layers were washed with saturated brine (150 ml * 1).Divided toluene layer, add water 225ml, sodium hydroxide (6g), stirred at 80 for 3h. The hot toluene is removed by hot section and extracted with toluene (50 ml * 1).Sub-water layer was cooled to 30 C dropwise hydrochloric acid (21.0g), heated to 75-85 C, incubated for 2-3h.Drop to 50 C and extract with toluene (225 ml * 1, 150 ml * 1).Toluene was combined and washed with water (50 ml * 1).Atmospheric pressure concentrated toluene layer to 5.5X, slowly cooled to 50 precipitated white crystals, 50 stirring 1h, then slowly cooled to 0-5 incubated 1h.Filtration and crystallization from ice-toluene (60 ml) gave a white 5-bromophthalide (13.7 g, 48.5% yield) after drying in vacuo. HPLC: 98.0%.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 5-Bromoisoindoline-1,3-dione, and friends who are interested can also refer to it.

Reference:
Patent; Shanghai He Quan Pharmaceutical Research And Development Co., Ltd.; Shanghai He Quan Pharmaceutical Co., Ltd.; Changzhou Hequan Pharmaceutical Co., Ltd.; Changzhou Hequan Drug Discovery Co., Ltd.; Guo Wei; Zhang Qing; Li Yongkai; Luo Qiyu; Xie Chengfu; Shi Feng; Fu Xiaoyong; Chen Minzhang; (7 pag.)CN107082769; (2017); A;,
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Adding a certain compound to certain chemical reactions, such as: 15362-40-0, name is 1-(2,6-Dichlorophenyl)-2-indolinone, belongs to indolines-derivatives 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 15362-40-0, Recommanded Product: 1-(2,6-Dichlorophenyl)-2-indolinone

General procedure: A finely ground mixture of 5-substituted indole-3-carboxaldehyde (1 mmol) and active methylene compound (indolinone/oxindole/barbituric acid/1-(3-chlorophenyl)-3-methyl-2-pyrazolin-5-one)/2-trifluoromethylbenzaldehyde (1.2 mmol) was irradiated in microwave oven for 1-5 min. The solid product was washed with diethyl ether and purified by column chromatography to get pure products 2-5 and 11-28 except compound 3. Compound 3 was prepared by treatment of 5-substituted indole-3-carboxaldehyde with indolinone in ethanol-water in presence of NaOH (1.5 mmol).

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; Shaveta; Singh, Palwinder; European Journal of Medicinal Chemistry; vol. 74; (2014); p. 440 – 450;,
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Synthetic Route of 169037-23-4, These common heterocyclic compound, 169037-23-4, name is 5-(Trifluoromethoxy)indoline-2,3-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.

General procedure: A mixture of bisarylidenepiperidin-4-one (1.36 mmoL), isatin (2.72 mmoL) and L-phenylalanine (2.72 mmoL) were heated with stirring in [bmim]Br medium (3 mL) for 1 h at 100 C. After completion of the reaction (TLC), ethyl acetate (2 x 5 mL) was added and the reaction mixture was stirred for 10 min. The organic layer was removed under reduced pressure and the crude product was purified by column chromatography (ethyl acetate:hexane v/v 3:7). 5′-Benzyl-4′-(m-nitrophenyl)-5-(trifluoromethoxy)spiro[3,2′]oxindolopyrrolidino-4′-(m-nitrophenyl)-1?-styryl-5-benzylidene-spiro[3′.3?]piperidin-4?-one (5l): Melting point 296-298 C; white solid, 94%; 1H-NMR (CDCl3, 400 MHz): delta/ppm 5.05 (d, J = 14.64 Hz, 1H), 4.75-4.77 (m, 1H), 4.30 (d, J = 10.24 Hz, 1H), 3.86 (d, J = 13.92 Hz, 1H), 3.83 (d, J = 16.92 Hz, 1H), 3.49 (d, J = 15.4 Hz, 1H), 3.10 (d, J = 11.72 Hz, 1H), 2.73-2.77 (dd, J = 13.96, 8.08 Hz, 1H), 2.74 (d, J = 13.92 Hz, 1H), 7.01-6.68 (m, 2H), 7.18-7.82 (m, 21H,Ar); 13C-NMR (CDCl3, 100 MHz): delta/ppm 40.6, 47.4, 52.1, 53.3, 62.8, 65.6, 70.9, 98.8, 110.2, 121.9, 122.4, 122.5, 112.5, 123.6, 124.4, 124.5, 126.4, 126.5, 126.7, 128.7, 128.8, 128.9, 129.2, 129.4, 129.9, 132.4, 132.9, 135.6, 136.3, 137.7, 138.7, 139.9, 144.4, 179.8, 198.7. EI-MS: m/z 801 (M+). Anal. Calcd for C44H34F3N5O7: C, 65.91; H, 4.27; N, 8.73; Found: C, 65.99; H, 4.39; N, 8.86.

Statistics shows that 5-(Trifluoromethoxy)indoline-2,3-dione is playing an increasingly important role. we look forward to future research findings about 169037-23-4.

Reference:
Article; Arumugam, Natarajan; Almansour, Abdulrahman I.; Kumar, Raju Suresh; Govindasami, Periyasami; Al-thamili, Dhaifallah M.; Krishnamoorthy, Rajapandian; Periasamy, Vaiyapuri Subbarayan; Alshatwi, Ali A.; Mahalingam; Thangamani, Shankar; Menendez, J. Carlos; Molecules; vol. 23; 5; (2018);,
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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. 6326-79-0, name is 6-Bromoisatin, This compound has unique chemical properties. The synthetic route is as follows., Product Details of 6326-79-0

Bis(2-methoxyethyl)aminosulfur trifluoride (deoxo-fluor, 44.25 mL, 22.12 mmol, 50% solution in THF) was added dropwise over 30 min to a suspension of 6-bromoisatin (2.0 g, 8.75 mmol) in DCM (90 mL) at rt with stirring. After 24 h the reaction was cautiously quenched with saturated sodium hydrogen carbonate solution (40 mL) solution at 0 C. The layers were separated and the organics extracts dried (hydrophobic frit/phase separator) and concentrated under reduced pressure. The crude material was purified by silica gel column chromatography eluting with 20% EtOAc in iso-hexane to afford the subtitled compound as an orange solid (1.63 g, 74%). 1H NMR (400 MHz, CH3OH-d4): delta 7.50-7.46 (m, 1H), 7.36 (dd, 1H), 7.18 (d, 1H), (one exchangeable not observed).

According to the analysis of related databases, 6326-79-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; ASTRAZENECA AB; LONN, Hans Roland; CONNOLLY, Stephen; SWALLOW, Steven; KARLSSON, Staffan PO; AURELL, Carl-Johan; PONTEN, John Fritiof; DOYLE, Kevin James; VAN DE POEL, Amanda Jane; JONES, Graham Peter; WATSON, David Wyn; MACRITCHIE, Jaqueline Anne; PALMER, Nicholas John; US2015/210655; (2015); 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 104618-31-7 as follows. HPLC of Formula: C14H15NO3

EXAMPLE 1: 4- (Phthalimido) -cyclohexanone [0034] 4- (Phthalimido) -cyclohexanol (146 g) was mixed with AcOEt (1000 mL) , after which and NaBr (8 g) and TEMPO(0.5 g) was added. 1000 mL of NaClO (10 %) was added in portions and the reaction mixture was adjusted using NaHCtheta3 to pH 7- 8 to maintain the temperature between 5 and 20 0C. After the reaction was completed, the aqueous layer was separated and the organic layer was washed with brine (400 mL) and dried over Na2SO4. The solvent was removed under reduced pressure to give the product as white solid (95 % yield) .

According to the analysis of related databases, 104618-31-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; CHIRAL QUEST, INC.; WEI, Yuan; LI, Tianqiao; CHI, Yongxiang; ZHU, Jingyang; WO2010/78250; (2010); A1;,
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