Month: November 2020

496-12-8, 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.

A literature procedure1 was modified by replacing triethylamine with N,N-diisopropylethylamine. To a stirred mixture of tetrahydroisoindoline (0.11 mL, 1.0 mmol), N-Boc-(R)-phenylalanine (265 mg, 1.0 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (182 mg, 1.0 mmol) and anhydrous 1-hydroxybenzotriazole (203 mg, 1.5 mmol) in N,N-dimethylformamide (3.0 mL) was added N,N-diisopropylethylamine (1.3 mL, 7.5 mmol). The mixture was stirred at 20 for 16 h. The solvent was evaporated and the residue was dissolved in ethyl acetate (20 mL) and the solution was washed with water (2 x 20 mL). The combined aqueous fractions were re-extracted with ethyl acetate (2 x 20 mL) and all the combined organic layers were washed with saturated aqueous sodium hydrogen carbonate (2 x 20 mL) then with brine (20 mL) filtered and dried (MgSO4). Column chromatography (25:75 ethyl acetate: dichloromethane) of the residue gave 7c (175 mg, 48%) as a cream solid, m.p. 156-160 (decomp.); 1H NMR (500 MHz, CDCl3) delta 7.30-7.20 (7H, m), 7.16-7.14 (1H, m), 7.22-7.00 (1H, m), 5.36 (1H, d, J=9.0 Hz), 4.88 (1H, d, J=13.8 Hz), 4.82 (1H, d, J=15.9 Hz), 4.68-4.77 (1H, m), 4.63 (1H, d, J=15.9 Hz), 4.06 (1H, d, J=13.8 Hz), 3.10-2.98 (2H, m), 1.40 (9H, s); 13C NMR (125 MHz, CDCl3) delta 170.2, 155.1, 150.8, 136.5, 130.0, 129.3, 128.7, 127.1, 120.6, 116.7, 79.9, 51.0, 49.3, 49.1, 45.5, 41.9, 40.6, 28.4.

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:
Article; Chan, A. W. Edith; Greenwood, Simon O. R.; Hansen, D. Flemming; Marson, Charles M.; Bioorganic and medicinal chemistry letters; (2020);,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

61-70-1,Some common heterocyclic compound, 61-70-1, name is 1-Methylindolin-2-one, molecular formula is C9H9NO, 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: To a Schlenk tube were added oxindole 1 (0.3 mmol), t-BuONO (0.6 mmol), andTHF (2 mL). Then the tube was stirred at 50 C under 1 atm of O2 for the indicatedtime until complete consumption of starting material monitored by TLC analysis.After the reaction was finished, the reaction mixture was washed with brine. The aqueous phase was re-extracted with ethyl acetate. The combined organic extractswere dried over Na2SO4, removal of the solvent under vacuum afforded the crudeproduct, which was purified further by column chromatography using hexane-ethylacetate.

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

Reference:
Article; Wei, Wen-Ting; Ying, Wei-Wei; Zhu, Wen-Ming; Wu, Yi; Huang, Yi-Ling; Cao, Yi-Qi; Wang, Yi-Ning; Liang, Hongze; Synlett; vol. 28; 17; (2017); p. 2307 – 2310;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

883-44-3, The chemical industry reduces the impact on the environment during synthesis 883-44-3, name is 2-(3-Hydroxypropyl)isoindoline-1,3-dione, I believe this compound will play a more active role in future production and life.

Compound 359l-(3-((((2R^S,4R,5R)-5 6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2- yl)methyl)(isopropyl)amino)propyl)-3-(3-chlorophenyl)ureaStep 1. Preparation of 2-(3-((((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2- dimethyltetrahydrofuro[3,4-d][l,3]dioxol-4-yl)methyl)amino)propyl)isoindoline-l,3- dioneTo a solution of 2-(3-hydroxypropyl)isoindoline-l,3-dione (1.0 g, 4.88 mmol) in EA (50 mL) was added IBX (3.4 g, 12.19 mmol). The mixture was heated to reflux for 2h. After cooling, the mixture was filtered and the filtrate was concentrated to give 3-(l,3- dioxoisoindolin-2-yl)propanal crude (not weight), which was directly used for next step.To a solution of 9-((3aR,4R,6R,6aR)-6-(aminomethyl)-2,2- dimethyltetrahydrofuro[3,4-d][l,3]dioxol-4-yl)-9H-purin-6-amine (1.5 g, 4.90 mmol) and 3- (l ,3-dioxoisoindolin-2-yl)propanal (from last step) in DCE (50 mL) was added NaBH(OAc)3 (1.56 g, 7.30 mmol). The reaction mixture was stirred at rt overnight then saturated NaHC03 aqueous solution (50 mL) was added. The resulting mixture was extracted with DCM (50 mL x 2). The combined organic layers were dried over Na2S04 and concentrated. The residue was purified by SGC (DCM : MeOH = 100 : 1 to 10 : 1) to afford the title compound (1.38 g, yield: 57%) as a white solid. 1H NMR (500 MHz, MeOD): 58.30 (s, 1H), 8.23 (s, 1H), 7.85-7.79 (m, 4H), 6.17 (d, J = 2.5 Hz, 1H), 5.48 (dd, J = 2.5, 6.0 Hz, 1H), 5.03 (dd, J = 3.0, 6.5 Hz, 1H), 4.36 (t , J = 3.5 Hz, 1H), 3.67-3.65 (m, 2H), 2.94-2.89 (m, 2H), 2.62-2.60 (m, 2H), 1.82-1.79 (m, 2H), 1.60 (s, 9H), 1.39 (s, 3H) ppm; ESI-MS (m/z): 494.2 [M+l]+.

The chemical industry reduces the impact on the environment during synthesis 2-(3-Hydroxypropyl)isoindoline-1,3-dione. I believe this compound will play a more active role in future production and life.

Reference:
Patent; EPIZYME, INC.; CHESWORTH, Richard; KUNTZ, Kevin, Wayne; OLHAVA, Edward, James; PATANE, Michael, A.; WO2012/82436; (2012); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Some common heterocyclic compound, 6326-79-0, name is 6-Bromoisatin, molecular formula is C8H4BrNO2, 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. 6326-79-0

General procedure: To mixture of isatins (1 mmol), malononitrile (1 mmol), and dimedone or 4-hydroxycoumarin or barbituric acids (1 mmol) in ethanol (4 mL), 5mg of Fe3O4APTPOSS MNPs added as the catalyst, and the mixture was stirred for an appropriate time at room temperature (Table 2). The reaction was monitored by TLC. After completion of the reaction, precipitate was filtered and dried in a drying oven to furnish 2-aminopyrano-3-carbonitriles.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 6326-79-0, its application will become more common.

Reference:
Article; Safaei-Ghomi, Javad; Nazemzadeh, Seyed Hadi; Shahbazi-Alavi, Hossein; Catalysis Communications; vol. 86; (2016); p. 14 – 18;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

A common compound: 14192-26-8, name is Methyl 2-oxoindoline-6-carboxylate, belongs to indolines-derivatives 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. 14192-26-8

To a stirred solution of methyl 2-oxoindoline-6-carboxylate (1.00 g, 5.23 mmol) in acetic anhydride (10.9 mL, 1 15 mmol) was added (triethoxymethyl)benzene (3.55 mL, 15.7 mmol) and the mixture was stirred at 1 10 C for 4 h. The reaction mixture was cooled to rt and the resulting precipitate collected by filtration. The precipitate was washed with hexanes (100 mL) and dried in vacuo to afford the subtitle compound (?)-methyl 1-acetyl-3- (ethoxy(phenyl)methylene)-2-oxoindoline-6-carboxylate as a beige solid (1.66 g, 82%); Rl 2.61 min (Method 1); m/z 366 (M+H)+ (ES+).

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, 14192-26-8, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; RESPIVERT LIMITED; WALTERS, Iain; BIRCH, Louise; HILL-COUSINS, Joseph; COLLINGWOOD, Stephen, Paul; STEVENSON, Christopher, Scott; (126 pag.)WO2017/109513; (2017); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

These common heterocyclic compound, 52351-75-4, name is 6-Methoxyindoline-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. 52351-75-4

General procedure: 2-Acetoxy-4?-methoxyacetophenone(5b) (779 mg, 3.74 mmol) in EtOH (8.20 mL) was added to a solution of compound 4a (500 mg,3.40 mmol) in 10N NaOH (3.0 mL) and EtOH (800 L) at 85 C. After the mixture was stirred at 85 Cfor 1 h, H2O (10.0 mL) was added to the mixture at 0 C. The mixture was acidified to pH 1 with 1N HCl.The precipitate was collected by filtration and washed with H2O and EtOH to give the title compound 6bas a yellow solid (742 mg, 74%)

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 52351-75-4.

Reference:
Article; Yamamoto, Koki; Okazaki, Shiho; Ohno, Hiroaki; Matsuda, Fuko; Ohkura, Satoshi; Maeda, Kei-ichiro; Fujii, Nobutaka; Oishi, Shinya; Bioorganic and Medicinal Chemistry; vol. 24; 16; (2016); p. 3494 – 3500;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

These common heterocyclic compound, 1127-59-9, name is 7-Methylindoline-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. 1127-59-9

General procedure: The chemical synthesis route of the target IBT compounds is illustrated in Scheme 1. The IBTs 3 were synthesized by the reaction of isatin 1 and N-phenylhydrazinecarbothioamide 2 in an aqueous solution of ethanol and acetic acid under reflux [22,23]. Generally, equivalent 1 and 2 was dissolved in a solution of acetic acid/water/alcohol solution, and then the mixture was refluxed for approximate 5-6 h. The reaction mixture was subsequently cooled to room temperature and in most cases a yellow or orange solid precipitated out. This precipitate was filtered, washed with water, and then dried to give a crude product. Recrystallization from ethanol gave pure solid in high yields. 4.2.17 (Z)-2-(7-Methyl-2-oxoindolin-3-ylidene)-N-(p-tolyl)hydrazinecarbothioamide (3-17) Yield 73percent; m.p.: 247-249 ¡ãC; yellow solid; 1H NMR (DMSO-d6, 400 MHz), delta 12.82 (s, 1H, NNH), 11.32 (s, 1H, NH), 10.74 (s, 1H, SCNH), 7.63 (d, 1H, J = 7.2 Hz, Ar1-H4), 7.50-7.48 (d, 2H, J = 8.0 Hz, Ar2-H3 and Ar2-H5), 7.25-7.19 (m, 3H, J = 7.6 Hz, Ar1-H6, Ar2-H2 and Ar2-H6), 7.03 (t, 1H, J = 7.6 Hz, Ar1-H5), 2.34 (s, 3H, Ar2-CH3), 2.248 (s, 3H, Ar1-CH3); 13C NMR (DMSO-d6, 101 MHz), delta 176.2, 163.1, 141.0, 135.9, 135.3, 132.5, 132.5, 128.8, 125.5, 122.3, 120.4, 119.6, 118.8, 20.6, 15.9; IR: (KBr, nu/cm-1), 3302 (NN-H), 3164 (CON-H), 3063 (Ar-H), 1693 (-CONH-), 1626 (C=N), 1585 and 1478 (Ar-C=C), 1211 (C=S), 1135 (N-N); Elemental analysis calculated for C17H16N4OS, C: 62.94, H: 4.97, N: 17.27, found C: 62.70, H: 5.15, N: 17.28; ESI-MS m/z: 323.1, [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 1127-59-9.

Reference:
Article; Zhang, Xu-Meng; Guo, Hui; Li, Zai-Shun; Song, Fu-Hang; Wang, Wei-Min; Dai, Huan-Qin; Zhang, Li-Xin; Wang, Jian-Guo; European Journal of Medicinal Chemistry; vol. 101; (2015); p. 419 – 430;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

118289-55-7, 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. 118289-55-7 name is 6-Chloro-5-(2-chloroethyl)indolin-2-one, 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.

General procedure: Equimolar mixture of 6-chloro-5-(2-chloroethyl)-1,3-dihydro-2H-indol-2-one 1 (1.00mol) and the carbonyl compound (4i-x) (1.00mol) was stirred at RT in methanol (10mL) for 2h in presence of potassium carbonate (1.20mol). After completion, the reaction mass was filtered to remove inorganic salt, added methanol (10-20mL) and activated charcoal to the filtrate and stirred for 1hr. The crude product was filtered to remove charcoal, methanol was evaporated and cooled to 0-5C to get crude solid. Recrystallized using aqueous ethanol or methanol (Yield 60-70%).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 6-Chloro-5-(2-chloroethyl)indolin-2-one, and friends who are interested can also refer to it.

Reference:
Article; Meti, Gangadhar Y.; Kamble, Atulkumar A.; Kamble, Ravindra R.; Somagond, Shilpa M.; Devarajegowda; Kumari, Sandhya; Kalthur, Guruprasad; Adiga, Satish K.; European Journal of Medicinal Chemistry; vol. 121; (2016); p. 221 – 231;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

2913-97-5,Some common heterocyclic compound, 2913-97-5, name is N-(2-Oxoethyl)phthalimide, molecular formula is C10H7NO3, 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 mixture of phthalimidoacetaldehyde (64 g, 0.34 mol) and trans-1-methoxy-3-(trimethylsilyloxy)-1,3-butadiene (81.5 g, 0.38 mol) in benzene (600 ml) stirred for 15 min. under nitrogen was added dropwise a 45 percent solution of zinc chloride diethyl ether complex in dichloromethane (55.5 ml, 0.17 mol) at 0 ¡ãC. The reaction was allowed warm up to room temperature overnight. To the reaction mixture was added water (500 ml) and the resulting mixture was extracted with ethyl acetate (200 ml). The organic extract was washed successively with 1.0 N hydrochloric acid (2 x 200 ml) and brine (200 ml). The organic phase was dried (Na2SO4), filtered and the solvent evaporated invacuo which afforded a slowly crystallising oil (98 g). To the solid was added a mixture of ethyl acetate and diethyl ether (400 ml, 1:1) and the resulting precipitate was filtered off, washed with a small portion of diethyl ether and dried at 50 ¡ãC for 1 hour affording 59.8 g (69 percent) of 2-(4-oxo-3,4-dihydro-2H-pyran-2-ylmethyl)-isoindote-1,3-dione as a solid. The filtrate was evaporated invacuo and the residue purified by column chromatography on silica gel (1 L) using a mixture of ethyl acetate and heptane (1:2) as eluent. Pure fractions were collected and the solvent evaporated invacuo to almost dryness, the solid was filtered off and dried invacuo at 50 ¡ãC for 16 h affording an additional 15 g (17 percent) of 2-(4-oxo-3,4-dihydro-2H-pyran-2-ylmethyl)-isoindole-1,3-dione as a solid.1H-NMR (300 MHz, CDCl3) delta 2.61 (d, 2H), 3.85 (dd, 1H), 4.18 (dd, 1H), 4.76 (m, 1H), 5.43 (d, 1H), 7.28 (d, 1H), 7.69 – 7.77 (m, 2H), 7.84 – 7.88 (m, 2H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route N-(2-Oxoethyl)phthalimide, its application will become more common.

Reference:
Patent; NOVO NORDISK A/S; Ontogen Corporation; EP1214325; (2005); B1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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. 1074-82-4, name is Potassium 1,3-dioxoisoindolin-2-ide, A new synthetic method of this compound is introduced below., 1074-82-4

General procedure: The appropriate dibromoalkane derivative 2a-2e (11.9 mmol) was added slowly to a mixture of the starting material phthalimide potassium salt (1) (1g, 5.4 mmol) and anhydrous K2CO3 (0.82 g, 5.94 mmol) in acetone (15 mL). The reaction mixture was heated to 60-65 C and stirred for 6-10 h under an argon atmosphere. After complete reaction, the solvent was evaporated under reduced pressure. Water (50 mL) was added to the residue and the mixture was extracted with dichloromethane (30 mL ¡Á 3). The combined organic phases were washed with saturated aqueous NaCl, dried over Na2SO4, and filtered. The solvent was evaporated to dryness under reduced pressure. The crude product was purified on a silica gel chromatography using dichloromethane/acetone (50:1) as eluent to give the intermediates 3a-3e.

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; Sang, Zhipei; Wang, Keren; Wang, Huifang; Yu, Lintao; Wang, Huijuan; Ma, Qianwen; Ye, Mengyao; Han, Xue; Liu, Wenmin; Bioorganic and Medicinal Chemistry Letters; vol. 27; 22; (2017); p. 5053 – 5059;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem