Tag: M.W=200-300

These common heterocyclic compound, 3339-73-9, name is 3-(1,3-Dioxoisoindolin-2-yl)propanoic acid, 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 3-(1,3-Dioxoisoindolin-2-yl)propanoic acid

Step-1: 3-(1,3-dioxoisoindolin-2-yl)-N’-(2-methoxyacetyl)propanehydrazide Oxalyl chloride (27.47 g, 0.216 mol) was added slowly to an ice-cooled solution of 3-(1,3-dioxoisoindolin-2-yl)propanoic acid (15.80 g, 0.072 mol) in DCM (250 mL) followed by catalytic DMF (0.5 mL). The reaction mixture was stirred at room temperature for 1 h and volatiles were removed completely under vacuum to obtain the intermediate acid chloride as a yellow solid. A solution of 2-methoxyacetohydrazide (2, 9.01 g, 0.086 mol) in DCM (50 mL) was added to a solution of this acid chloride in DCM (200 mL) at 0 C. followed by triethylamine (60.5 g, 0.597 mol). The resultant reaction mixture was stirred at room temperature for 1 h. The resulting yellow suspension was quenched onto crushed ice (200 mL). Separated organic layer was washed with water (2×200 mL), brine (150 mL) and concentrated under vacuum to afford crude product (5 g). The aqueous layer which also contains desired product was concentrated under reduced pressure to afford a solid residue. The crude residue was dried and extracted sequentially with THF (1000 mL), acetone (300 mL) and acetonitrile (400 mL). The combined organic layer was concentrated to obtain yellow semisolid (37 g) which was combined with solid residue (5 g) from organic layer and was used in the next reaction without purification. LC-MS [M+H]+ 306.1 m/z.

The synthetic route of 3-(1,3-Dioxoisoindolin-2-yl)propanoic acid has been constantly updated, and we look forward to future research findings.

Reference:
Patent; PROTEOSTASIS TEHRAPEUTICS, INC.; Bastos, Cecilia M.; Munoz, Benito; Tait, Bradley; (48 pag.)US2017/1993; (2017); A1;,
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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. 552330-86-6, name is 5-Bromoisoindolin-1-one, A new synthetic method of this compound is introduced below., Recommanded Product: 552330-86-6

5-Bromoisoindolin-1-one (10 g, 47.16 mmol) and sodium ethanethiolate (9.92 g, 117.90mmol) were mixed together in DMF (100 mL) and the reaction heated to 100 C for 20mm. The reaction was cooled to rt, poured into water (100 mL) and the product extractedwith EtOAc (3 x 200 mL). The combined organic extracts were washed with brine (4 x 50mL). LCMS indicated product in the aqueous washings, and consequently they werecombined and extracted with EtOAc (4 x 50 mL). The organic extracts were combined, dried using a phase separator cartridge and concentrated in vacuo. The solid obtained was dried under high vacuum overnight. 5-(Ethylthio)isoindolin-1-one (8.68 g, 95%) was obtained as a yellow solid. The material was used in the next step without furtherpurification.LC/MS: m/zrr 194 [M+H]. ?H NMR (500 MHz, DMSO-d6) i5 1.27 (t, 3H), 3.06 (q, 2H), 4.33 (s, 2H), 7.36 (dd, 1H), 7.47 – 7.48 (m, 1H), 7.57 (d, 1H), 8.45 (s, 1H).

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:
Patent; ASTRAZENECA AB; LEVER, Sarah; NARJES, Frank; OLSSON, Roine, Ingemar; VON BERG, Stefan; (124 pag.)WO2018/229155; (2018); A1;,
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Reference of 5181-35-1, 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 5181-35-1 as follows.

To a solution of 2-(2-bromoethoxy)isoindoline- l,3-dione (20 g, 7.4 mmol prepared according to the procedure described in step 1 of preparation 10) and 5-methyl- lH-tetrazole (6.22 g, 7.4 mmol) in dimethylformamide (100 ml) was added cesium carbonate (24.13 g, 7.4 mmol) in a lot wise under stirring at 25-30 C. After 16 hours, completion of the reaction was confirmed by performing the thin layer chromatography using mixture of chloroform and methanol as solvent. The resulted reaction mixture was filtered and the filtrate was slowly poured into chilled water (700 ml) under stirring. After 30 minutes of stirring, the reaction mixture was extracted with ethyl acetate (200 ml and 100 ml). The combined organic layer was washed with brine (100 ml). The organic layer was dried on sodium sulfate and concentrated on rota vapour to provide 18 g of the crude product. The two regio isomers were separated by using column chromatography using mixture of acetone and hexane as an eluent. The upper spot isolated at 15-25% concentration of acetone in hexane yielded 7.0 g of non-polar isomer 2-[2-(5-methyl-2H-tetrazol-2-yl)ethoxy]-lH-isoindole-l,3(2H)-dione. The lower spot isolated at 25-40% concentration of acetone in hexane yielded 3.8 g of polar isomer 2-[2-(5-methyl-lH-tetrazol-l-yl)ethoxy]-lH-isoindole-l,3(2H)-dione. (10.8 g, 53 % yield). Analysis: Mass: 274.2 (M+l); for Molecular weight: 273 and Molecular formula: C12H11N5O3.

According to the analysis of related databases, 5181-35-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; WOCKHARDT LIMITED; TADIPARTHI, Ravikumar; PATIL, Vijaykumar Jagdishwar; DEKHANE, Deepak; SHAIKH, Mohammad Usman; BIRAJDAR, Satish; DOND, Bharat; PATEL, Mahesh Vithalbhai; (100 pag.)WO2017/81615; (2017); A1;,
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897957-06-1, name is 6-Bromo-1-methylindolin-2-one, belongs to indolines-derivatives compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. Computed Properties of C9H8BrNO

Step 3: Synthesis of Intermediate R7 [0295] To I-4.2 (32.0 g, 142 mmol) in anhydrous dioxane (400 mL) is added R3 (54.4 g, 241 mmol) and potassium acetate (41.6 g, 424 mmol). The mixture is purged with Argon, [1,1?-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) as a comple× with dichloromethane (11.2 g, 14 mmol) is added and the mixture is heated to 90 C. for 2 h. The reaction mixture is diluted with ethyl acetate and water, the organic layer is washed with water, dried over MgSO4 and concentrated. The residue is purified via flash chromatography (cyclohexane/EA=70:30). Yield 72%, m/z 274 [M+H]+, rt 0.67 min, LC-MS Method V011_S01

The synthetic route of 897957-06-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; ANDERSKEWITZ, Ralf; GRUNDL, Marc; MORSCHHAEUSER, Gerd; OOST, Thorsten; PAUTSCH, Alexander; US2014/275114; (2014); A1;,
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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. 5394-18-3, name is 2-(4-Bromobutyl)isoindoline-1,3-dione, A new synthetic method of this compound is introduced below., Computed Properties of C12H12BrNO2

a) A solution of imidazole (13.6 g) in dry DMF (50 ml) was added dropwise to a stirred suspension of sodium hydride (8.0 g, 60% dispersion in oil) in dry DMF (250 ml) at ambient temperature under nitrogen for 2.5 hours. A slurry of N-(4-bromobutyl)phthalimide (53.6 g) in dry DMF (80 ml) was added and the mixture heated at 95 C. for 16 hours. The solvent was evaporated off under vacuum and the residue was extracted with hot toluene. The combined toluene extracts were evaporated to dryness and the residue triturated with ether and dried to give N-[4-(imidazol-1-yl)butyl]phthalimide, m.p. 76-79 C.

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:
Patent; The Boots Company PLC; US5547972; (1996); A;,
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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. 1336963-95-1, name is 6-Bromo-7-fluoroindoline-2,3-dione, A new synthetic method of this compound is introduced below., Product Details of 1336963-95-1

To a solution of 6-bromo-7-fluoroindoline-2,3-dione (1.41 g, 5.80 mmol) in 2 N NaOH (15 mL) was added H202 (30%, 3 mL) at 0C, the mixture was stirred at 0C for 30 mm. After stirring at rt for 16 h, the mixture was poured into ice water, the solution was acidified with Conc. HC1, the precipitate was filtered and dried in the air to afford the desired product as a white solid (1.2 g, 89% yield)

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:
Patent; ARAXES PHARMA LLC; LI, Liansheng; FENG, Jun; LONG, Yun Oliver; LIU, Yuan; WU, Tao; REN, Pingda; LIU, Yi; (246 pag.)WO2017/87528; (2017); A1;,
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Reference of 18711-15-4,Some common heterocyclic compound, 18711-15-4, name is 4,6-Dichloroisatin, molecular formula is C8H3Cl2NO2, 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.

(i) 3-Hydroxy-4,6-dichloro-1,3-dihydro-3-(benzofuran-5-yl)indole-2-one 2.25 g of magnesium for a Grignard reaction in 15 ml of anhydrous THF are placed in a round-bottomed flask equipped with a mechanical stirrer, and under a stream of nitrogen. A mixture of 13.6 g of 5-bromobenzofuran in 35 ml of anhydrous THF is then added. The mixture is stirred for one hour, followed by addition of a solution of 5 g of 4,6-dichloro-1H-indole-2,3-dione in 50 ml of anhydrous THF. The mixture is stirred at room temperature for 4 hours 30 minutes. Water is added and the resulting mixture is extracted with ethyl acetate. The organic phase is separated out, dried over Na2SO4, filtered and evaporated under vacuum. The residue is taken up in ethyl acetate and washed with 1N sodium hydroxide solution. The organic phase is dried over Na2SO4, filtered and evaporated under vacuum. The solid is taken up in ethyl ether and filtered off. 4.2 g of expected product are obtained.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 4,6-Dichloroisatin, its application will become more common.

Reference:
Patent; SANOFI; US2011/312972; (2011); A1;,
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These common heterocyclic compound, 3335-98-6, name is 1-Phenyloxindole, 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. Computed Properties of C14H11NO

General procedure: The appropriate compound 2 (10 mmol) was dissolved inmethanol (100 mL) and treated with the equivalent of the appropriatealdehyde 1 and piperidine (1 mL). For compounds 39, 41 and42 the yield was much lower (5%), and an improvement (15-20%)was obtained by replacing piperidine with 33% NH4OHThe reaction mixture was refluxed for 5-10 h, except for compounds39-42 which required a longer reflux time (16-24 h; theprogress of the reaction was followed by TLC). The precipitate,formed on cooling, was collected by filtration.Compounds 39e41 were purified by column chromatographywith petroleum ether/acetone as the eluent. Most of the crudeproducts were crystallized from methanol, except 27 (acetone/petroleumether), 34, 43-48, 50-52 (ethanol) and 42, 49 (toluene). Inthe case of compound 10, the two E/Z isomers were isolated byfractional crystallization from methanol.

The synthetic route of 1-Phenyloxindole has been constantly updated, and we look forward to future research findings.

Reference:
Article; Morigi, Rita; Locatelli, Alessandra; Leoni, Alberto; Rambaldi, Mirella; Bortolozzi, Roberta; Mattiuzzo, Elena; Ronca, Roberto; Maccarinelli, Federica; Hamel, Ernest; Bai, Ruoli; Brancale, Andrea; Viola, Giampietro; European Journal of Medicinal Chemistry; vol. 166; (2019); p. 514 – 530;,
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Adding a certain compound to certain chemical reactions, such as: 18711-15-4, name is 4,6-Dichloroisatin, 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 18711-15-4, COA of Formula: C8H3Cl2NO2

(1) 1-Methyl-4,6-dichloroisatin A mixture of 60% NaH (20.5 mg), 4,6-dichloroisatin (947 mg), and iodomethane (0.328 mL) in THF (20 mL) were stirred overnight at room temperature, poured into 1 N hydrochloric acid, and extracted with ethyl acetate. The extracts were washed with sat. aqueous NaCl, dried over MgSO4, and concentrated. The residue was washed with hexane to give the title compound (849 mg, 84%). 1H-NMR (DMSO-d6, 300 MHz) delta 3.12-3.11 (3H, m), 7.33-7.30 (2H, m).

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; Sumitomo Pharmaceuticals Co., Ltd.; US6576656; (2003); B1;,
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Some common heterocyclic compound, 3339-73-9, name is 3-(1,3-Dioxoisoindolin-2-yl)propanoic acid, molecular formula is C11H9NO4, 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. Computed Properties of C11H9NO4

General procedure: The DCC (1.2 equiv) was added to the solution of 1 (0.2 mmol), DMAP (0.2 equiv), and appropriate carboxylic acid (1.2 equiv) in anhydrous CH2Cl2 (8 mL) at 0 C. The resulting mixture was stirred at room temperature until the starting material was not observed by TLC. The reaction mixture was filtered, and the residue was washed with CH2Cl2 (2 × 10 mL). Then, the CH2Cl2 solution was washed with 5% HCl (3 × 30 mL), saturated NaHCO3 (3 × 30 mL) and saturated NaCl (3 × 30 mL), respectively. Subsequently, the organic layer was dried over anhydrous Na2SO4 and concentrated to dryness under reduced pressure. At last, the residue was purified by column chromatography over the silica gel to yield the pure target compounds.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3339-73-9, its application will become more common.

Reference:
Article; Wang, Li-Jun; Geng, Chang-An; Ma, Yun-Bao; Huang, Xiao-Yan; Luo, Jie; Chen, Hao; Guo, Rui-Hua; Zhang, Xue-Mei; Chen, Ji-Jun; Bioorganic and Medicinal Chemistry; vol. 20; 9; (2012); p. 2877 – 2888;,
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