Month: April 2021

Reference of 6341-92-0, 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. 6341-92-0, name is 6-Chloroisatin belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below.

EXAMPLE 19a rac-6-Chloro-3-cyclohexyl-3-hydroxy-1,3-dihydro-indol-2-one A solution of cyclohexyl magnesium bromide in ether (2.0 M, 3.10 mL, 6.25 mmol) (Aldrich) was added dropwise to a suspension of 6-chloroisatin (0.45 g, 2.5 mmol) (Crescent) in tetrahydrofuran (12.5 mL) with cooling in a -25 C. bath and magnetic stirring at such a rate that reaction temperature was kept below -10 C. Cooling bath was then removed and mixture was allowed to warm to room temperature. After stirring for an additional 2 hours, 15% aqueous ammonium chloride solution (12.5 mL) was added and mixture was extracted with ethyl acetate. Ethyl acetate layers were then washed with water, brine, combined, dried (Na2SO4), filtered and concentrated. Residue was stirred in dichloromethane at room temperature for 30 minutes and filtered to give crude rac-6-chloro-3-cyclohexyl-3-hydroxy-1,3-dihydro-indol-2-one as an off-white powder. (Yield 0.28 g, 43%).

The synthetic route of 6-Chloroisatin has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Luk, Kim-Chun; So, Sung-Sau; Zhang, Jing; Zhang, Zhuming; US2006/293319; (2006); A1;,
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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. 52351-75-4, name is 6-Methoxyindoline-2,3-dione belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below. Recommanded Product: 52351-75-4

General procedure: Suitable indoline-2,3-dione 1a-c (1.0 mmol) was dissolved in methanol (5 mL) with gentle heating, then arylhydrazine (2.4 mmol) was slowly added with stirring at room temperature. After stirring overnight, the resulting precipitate was filtered and crystallized or the reaction mixture was evaporated to dryness and the residue suitably purified.

The synthetic route of 52351-75-4 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Campagna, Francesco; Catto, Marco; Purgatorio, Rosa; Altomare, Cosimo D.; Carotti, Angelo; De Stradis, Angelo; Palazzo, Gerardo; European Journal of Medicinal Chemistry; vol. 46; 1; (2011); p. 275 – 284;,
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Adding a certain compound to certain chemical reactions, such as: 13220-46-7, name is 4-Methylindolin-2-one, 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 13220-46-7, Application In Synthesis of 4-Methylindolin-2-one

A mixture of 4-methylindolin-2-one (500 mg, 3.40 mmol), l-bromo-4-iodo- benzene (1.15 g, 4.06 mmol), Cul (500 mg, 2.63 mmol), L-PROLINE (310 mg, 2.69 mmol) and CsF (1.03 g, 6.78 mmol) in EtOAc (20 mL) was stirred at 50 C for 36 hours under N2 atmosphere. A black suspension was formed. TLC (PE/EtOAc = 3/1, Rf = 0.67) showed the starting material was consumed nearly. The reaction mixture was diluted with EtOAc/EEO (2/1, 100 mL) then separated. The aqueous was extracted with EtOAc (800 mL x3). The combined organic phase was concentrated. The residue was purified by Combi Flash (15% EtOAc in PE) to give l-(4-bromophenyl)-4-methylindolin-2-one (235 mg, yield: 23%) as a light yellow solid. NMR (400 MHz, CDCb) d 2.32 (3H, s), 3.60 (2H, s), 6.62 (1H, d, J= 8.0 Hz), 6.92 (1H, d, J= 7.6 Hz), 7.13 (1H, t , J= 8.0 Hz), 7.30 (2H, d, J= 8.4 Hz), 7.65 (2H, d , J= 8.2 Hz).

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, 4-Methylindolin-2-one, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; PETRA PHARMA CORPORATION; KESICKI, Edward A.; RAVI, Kannan Karukurichi; LINDSTROeM, Johan; PERSSON, Lars Boukharta; LIVENDAHL, Madeleine; VIKLUND, Jenny; GINMAN, Tobias; FORSBLOM, Rickard; RAHM, Fredrik; HICKEY, Eugene R.; DAHLGREN, Markus K.; GERASYUTO, Aleksey I.; (478 pag.)WO2019/126733; (2019); A1;,
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Electric Literature of 667463-64-1, 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. 667463-64-1 name is 6-Bromo-1-methylindoline-2,3-dione, 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.

Step 2: Synthesis of Intermediate 1-12.2 1-12.1 (15.0 g, 63 mmol) and hydrazine hydrate (30 mL, 618 mmol) are heated to 125 C for 72 h. To the cool reaction mixture DCM is added and extracted with water and 1 M HC1. The organic layer is dried over MgSC>4 and concentrated. The crystallized residue is dissolved in DCM, methanol is added and the DCM is removed in vacuo. The crystallized product is filtered by sunction and washed with cold methanol. Yield 63%, m/z 226/228 [M+H]+, rt 1.16 min, LC-MS Method V001 003.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 6-Bromo-1-methylindoline-2,3-dione, and friends who are interested can also refer to it.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; ANDERSKEWITZ, Ralf; GRAUERT, Matthias; GRUNDL, Marc; HAEBEL, Peter, Wilhelm; OOST, Thorsten; PAUTSCH, Alexander; PETERS, Stefan; BINDER, Florian; VINTONYAK, Viktor; WO2014/140075; (2014); A1;,
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Some common heterocyclic compound, 5332-26-3, name is 2-(Bromomethyl)isoindoline-1,3-dione, molecular formula is C9H6BrNO2, 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 C9H6BrNO2

General procedure: S-alkylation of the products was achieved by following a modified method [38]. The oxadiazoles (6a, 6b, 13) (0.02, mol) and K2CO3 (0.022, mol) were stirred in 10mL of acetone for 20 mints followed by the addition of alkyl bromides 7a-c and 7d-m (0.022, mol). The reaction mixture was stirred for 4-6h at room temperature. The reaction mixture was concentrated under vacuum and crude solid gained was recrystallized from methanol to get pure products.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5332-26-3, its application will become more common.

Reference:
Article; Batool, Farwa; Hamdani, Syeda Shamila; Hameed, Shahid; Khan, Bilal Ahmad; Mughal, Ehsan Ullah; Saeed, Muhammad; Saleem, Hafiza Nosheen; Bioorganic Chemistry; vol. 96; (2020);,
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Application of 897957-06-1,Some common heterocyclic compound, 897957-06-1, name is 6-Bromo-1-methylindolin-2-one, molecular formula is C9H8BrNO, 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.

Step 3: Synthesis of Intermediate R12To 1-5.2 (32.0 g, 142 mmol) in anhydrous dioxane (400 mL) is added Ri 1 (54.4 g, 241 mmol) andpotassium acetate (41.6 g, 424 mmol). The mixture is purged with Argon, [1, 1?-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) as a complex 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 Mg504 and concentrated. The residue is purified via flash chromatography (cyclohexane / EA = 70:30). Yield72%, m/z 274 [M+H]+, rt 0.67 mi LC-MS Method VOil SOl.

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; GRAUERT, Matthias; GRUNDL, Marc; OOST, Thorsten; PAUTSCH, Alexander; PETERS, Stefan; WO2014/140091; (2014); A1;,
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These common heterocyclic compound, 3891-07-4, name is 2-(2-Hydroxyethyl)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. SDS of cas: 3891-07-4

To a solution of 4a (1.88 g, 20 mmol), N-(2-hydroxyethyl)phthalimide (3.82 g, 20 mmol) and triphenylphosphine (7.87 g, 30 mmol) in tetrahydrofuran (30 mL) was added dropwise a solution of diethyl azodicarboxylate (4.7 mL, 30 mmol) in tetrahydrofuran (10 mL) at 0C over 0.5 h. The mixture was stirred at the same temperature for 6h and concentrated under reduced pressure. The residue was diluted in diethyl ether and stirred at -5 to 0C for 30 min and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (silica gel), eluting with petroleum ether and ethyl acetate (6:1, v/v) to give 5a (5.02g, 94 %) as a off-white solid.

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

Reference:
Article; Wang, Minghua; Ye, Cheng; Liu, Mingliang; Wu, Zhaoyang; Li, Linhu; Wang, Chunlan; Liu, Xiujun; Guo, Huiyuan; Bioorganic and Medicinal Chemistry Letters; vol. 25; 14; (2015); p. 2782 – 2787;,
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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. 104618-32-8, name is 2-(4-Oxocyclohexyl)isoindoline-1,3-dione, This compound has unique chemical properties. The synthetic route is as follows., category: indolines-derivatives

A solution of N-(4-oxocyclohexyl)phthalimide (14, 3.53 g, 15 mmol, 1 eq.) and 4-(methylsulfonyl)phenylhydrazine (2.70 g, 15 mmol, 1 eq.) in glacial acetic acid (110 mL) was heated at reflux for 47 h. The mixture was concentrated in vacuo and the residue was dissolved in CH2Cl2 (200 mL). Afterwards, the organic layer was washed with water (2 * 70 mL) and brine (70 mL), dried (Na2SO4) and concentrated under reduced pressure. The residue was purified by fc with a gradient (? = 6 cm, l = 13 cm, v = 60 mL, cyclohexane/CH2Cl2 60:40, 50:50, 30:70, 0:100, CH2Cl2/methanol 100:10, Rf = 0.51 (cyclohexane/ethyl acetate/formic acid 3:7:0.2)). Pale yellow solid, mp 282-284 C, yield 4.50 g (79%). Purity (HPLC): 86.6% (tR = 19.6 min). C21H18N2O4S (394.5 g/mol). Exact mass (APCI): m/z = 395.1072 (calcd. 395.1060 for C21H19N2O4S [M + H+]). 1H NMR (600 MHz, DMSO-D6): delta (ppm) = 2.11 (d, J = 12.3 Hz, 1H, 2-H), 2.64-2.74 (m, 1H, 2-H), 2.92-3.01 (m, 3H, 1-CH2, 4-H), 3.12 (s, 3H, CH3), 3.29-3.33 (m, 1H, 4-H), 4.47-4.54 (m, 1H, 3-H), 7.49 (d, J = 8.6 Hz, 1H, 8-H), 7.56 (dd, J = 8.6/1.4 Hz, 1H, 7-H), 7.84-7.93 (m, 5H, 5-H, 4-Hphth, 5-Hphth, 6-Hphth, 7-Hphth), 11.45 (s, 1H, NH). 13C NMR (151 MHz, DMSO-D6): delta (ppm) = 22.5 (1C, C-1), 24.2 (1C, C-4), 26.2 (1C, C-2), 44.6 (1C, CH3), 47.4 (1C, C-3), 108.3 (1C, C-4a), 111.2 (1C, C-8), 117.3 (1C, C-5), 118.9 (1C, C-7), 123.0 (2C, C-4phth, C-7phth), 126.3 (1C, C-4b), 130.7 (1C, C-6), 131.5 (2C, C-3aphth, C-7aphth), 134.5 (2C, C-5phth, C-6phth), 136.8 (1C, C-9a), 138.5 (1C, C-8a), 167.9 (2C, C=O). FTIR (neat): ? (cm-1) = 3348 (m, N-H), 2939 (w, C-H, aliph), 1697 (s, C=O), 1620 (w, C-C, arom), 1130 (s, SO2).

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 104618-32-8.

Reference:
Article; Heimann, Dominik; Boergel, Frederik; de Vries, Henk; Bachmann, Kim; Rose, Victoria E.; Frehland, Bastian; Schepmann, Dirk; Heitman, Laura H.; Wuensch, Bernhard; European Journal of Medicinal Chemistry; vol. 143; (2018); p. 1436 – 1447;,
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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 141452-01-9 as follows. HPLC of Formula: C10H11NO2

1.26 g (5.8 mmoles) of di-tert-butyldicarbonate and 0.80 ml (5.8 mmoles) of Et3N are added successively at 20 C. to a solution of 0.85 g (4.8 mmoles) of methyl 5-indolinecarboxylate (J Heterocycl Chem (1993) 30 (4), 1133-1136) in 15 ml of CH2Cl2. The reaction mixture is stirred for 20 hours and concentrated to dryness under vacuum. The residue is divided between 50 ml of AcOEt and 25 ml of water. After stirring and decanting, the organic phase is washed with 25 ml of salt water, dried over MgSO4, filtered and concentrated to dryness under vacuum. The powder obtained is suspended in heptane, stirred and filtered in order to produce a white solid with a yield of 73%. Melting point=107-107.5 C.

According to the analysis of related databases, 141452-01-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Societe de Conseils de Recherches et d’Applications Scientifiques (S.C.R.A.S.); US6747024; (2004); B1;,
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Reference of 1035235-27-8, These common heterocyclic compound, 1035235-27-8, name is tert-Butyl 4-bromoisoindoline-2-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.

Step a. A suspension of 3-amino-N-methylisoquinoline-6-carboxamide TFA salt (Intermediate 6, 0.40 g, 1.262 mmol), tert-butyl 4-bromoisoindoline-2-carboxylate (Intermediate 1, 0.15 g, 0.505 mmol), and potassium tert-butoxide (0.28 g, 2.525 mmol) in toluene (10 ml) was degassed with nitrogen for 10 min at rt. BetaIotaNuAlphaRho (0.047 g, 0.050 mmol) and Pd2(dba)3 (0.032 g, 0.050 mmol) were added to the reaction mixture at rt. The reaction mixture was heated at 105C for 2 h. The resulting reaction mixture was cooled to rt, poured into water (20 ml) and extracted with EtOAc (2 x 40 ml). The combined organic phase was dried over Na2S04, filtered and concentrated under reduced pressure. The resulting residue was purified by flash chromatography (4% MeOH in DCM) yielding tert-butyl 4-((6-(methylcarbamoyl)isoquinolin-3-yl)amino)isoindoline-2-carboxylate (0.135 g, 0.322 mmol). LCMS: Method A, 2.278 min, MS: ES+ 419.5.

The synthetic route of 1035235-27-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MISSION THERAPEUTICS LIMITED; GIBSON, Karl Richard; JONES, Alison; KEMP, Mark Ian; MADIN, Andrew; STOCKLEY, Martin Lee; WHITLOCK, Gavin Alistair; WOODROW, Michael D; (241 pag.)WO2017/158388; (2017); A1;,
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