825-70-7 Archives - Indolines-derivatives

The important role of 825-70-7

Electric Literature of 825-70-7, 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 825-70-7 as follows.

General procedure: to a suspension of iv (1mmol) in acetonitrile (10ml) was added 5-fluoroindoline (1.2mmol). The reaction mixture was stirred at 40C for 16h and then evaporated to dryness under reduced pressure. Water (10mL) and diethylether (15mL) were added and the resulting mixture was stirred for 5min. The precipitate formed was filtered off and dried to give 7 (86%) as a white solid.

According to the analysis of related databases, 825-70-7, the application of this compound in the production field has become more and more popular.

Reference:
Article; Certal, Victor; Halley, Frank; Virone-Oddos, Angela; Filoche-Romme, Bruno; Carry, Jean-Christophe; Gruss-Leleu, Florence; Bertin, Luc; Guizani, Houlfa; Pilorge, Fabienne; Richepin, Patrick; Karlsson, Andreas; Charrier, Veronique; Abecassis, Pierre-Yves; Vincent, Loic; Nicolas, Jean-Paul; Lengauer, Christoph; Garcia-Echeverria, Carlos; Schio, Laurent; Bioorganic and Medicinal Chemistry Letters; vol. 24; 6; (2014); p. 1506 – 1510;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Discovery of C9H10FN

Adding a certain compound to certain chemical reactions, such as: 825-70-7, name is 5-Fluoro-2-methylindoline, 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 825-70-7, Computed Properties of C9H10FN

Example 13c and Example 14c Synthesis of (+)-2-{2-[5-fluoro-2-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-6-(morpholin-4-yl)pyrimidin-4(3H)-one and of (-)-2-{2-[5-fluoro-2-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-6-(morpholin-4-yl)pyrimidin-4(3H)-one 430 mg of 5-fluoro-2-methyl-2,3-dihydro-1H-indole (reference example 4c, step 1c) and 872 mg of N-[3-(dimethylamino)propyl]-N?-ethylcarbodiimide hydrochloride are added to a solution of 743 mg of sodium [4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate (obtained in step 2c of example 1c) in 25 ml of N,N-dimethylformamide and 25 ml of pyridine. The reaction mixture is stirred at ambient temperature for 48 hours and then 100 ml of water are added and the mixture is extracted with ethyl acetate. The organic phase is washed successively with a 0.1N hydrochloric acid solution, water and a saturated sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue is purified by silica column chromatography, elution being carried out with a mixture of dichloromethane and methanol (95/05: v/v), so as to give 580 mg of 2-{2-[5-fluoro-2-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-6-(morpholin-4-yl)pyrimidin-4(3H)-one.The enantiomers are separated by chiral chromatography on a Whelk 01 SS, 10 mum column (10 mum, 80×350 mm), elution being carried out with a mixture of: heptane/dichloromethane/ethanol/methanol: 70/20/5/5; flow rate: 200 ml/min.252 mg of (+)-2-{2-[5-fluoro-2-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-6-(morpholin-4-yl)pyrimidin-4(3H)-one are obtained, as first enantiomer, in the form of a white solid, the characteristics of which are the following:1H NMR spectrum (400 MHz): 1.26 (d, J=6.4 Hz, 3H); 2.70 (m, 1H); 3.34 to 3.48 (m, 5H); 3.60 (m, 4H); 3.71 (d, J=15.9 Hz, 1H); 3.91 (d, J=15.9 Hz, 1H); 4.73 (m, 1H); 5.20 (s, 1H); 7.00 (dt, J=3.0 and 9.1 Hz, 1H); 7.15 (dd, J=3.0 and 9.1 Hz, 1H); 7.95 (dd, J=5.0 and 9.1 Hz, 1H); 11.65 (broad m, 1H)Mass spectrometry: method ARetention time Tr (min)=0.72;[M+H]+: m/z 373; [M-H]-: m/z 371;Optical rotation: alphaD=+60.4 (c=1.939 mg/0.5 ml CH3OH)Then the second enantiomer, 246 mg of (-)-2-{2-[5-fluoro-2-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-6-(morpholin-4-yl)pyrimidin-4(3H)-one, is obtained in the form of a white solid, the characteristics of which are the following:1H NMR spectrum (400 MHz): 1.26 (d, J=6.5 Hz, 3H); 2.69 (m, 1H); 3.35 to 3.47 (m, 5H); 3.60 (m, 4H); 3.71 (d, J=15.9 Hz, 1H); 3.91 (d, J=15.9 Hz, 1H); 4.72 (m, 1H); 5.20 (s, 1H); 7.00 (td, J=3.0 and 9.1 Hz, 1H); 7.15 (dd, J=3.0 and 9.1 Hz, 1H); 7.95 (dd, J=5.0 and 9.1 Hz, 1H); 11.66 (broad m, 1H)Mass spectrometry: method ARetention time Tr (min)=0.72;[M+H]+: m/z 373; [M-H]-: m/z 371;Optical rotation: alphaD=-57.9+/-1.1 (c=1.833 mg/0.5 ml CH3OH)

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Reference:
Patent; SANOFI; Brollo, Maurice; Carry, Jean-Christophe; Certal, Victor; Didier, Eric; Doerflinger, Gilles; EL Ahmad, Youssef; Filoche-Romme, Bruno; Halley, Frank; Karlsson, Karl Andreas; Schio, Laurent; Thompson, Fabienne; US2013/274253; (2013); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

New learning discoveries about C9H10FN

Some common heterocyclic compound, 825-70-7, name is 5-Fluoro-2-methylindoline, molecular formula is C9H10FN, 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. COA of Formula: C9H10FN

Under argon atmosphere conditions, add 0.0151g (0.10mmol) of 5-fluoro-2-methylindolinoline (1d), 0.0013g (0.002mmol) of acid eosinY, 0.150g of Antarctic lipase CAL- A, 0.0146 g (0.10 mmol) of n-octyl mercaptan, 0.104 g (0.50 mmol) of allyl-3-methoxyphenyl carbonate (2b), methyl tert-butyl ether (TBME) 2.0 mL;The reaction was stirred at 45 C for 6 hours under a 6w white light. After the reaction, the insoluble enzyme was removed by suction filtration, the solvent was distilled off under reduced pressure, and the solvent was separated by column chromatography. The eluent: (V) petroleum ether / (V) Ethyl acetate = 30/1. 0.0190 g of a yellow liquid product (3db) was obtained with a product yield of 81%.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 825-70-7, its application will become more common.

Reference:
Patent; Central China Normal University; Zhou Shaolin; Shi Weimin; (16 pag.)CN110437123; (2019); A;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Introduction of a new synthetic route about 825-70-7

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.

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. 825-70-7, name is 5-Fluoro-2-methylindoline, A new synthetic method of this compound is introduced below., Formula: C9H10FN

5-Fluoro-2-methylindoline 16a (1.30 g, 8.60 mmol, prepared according to the known method disclosed in “”) and 3b (1.47 g, 8.60 mmol) were dissolved in 40 mL of dichloromethane successively, and stirred for 2 hours. The reaction solution was then added with sodium triacetoxyborohydride (2.73 g, 12.90 mmol), and reacted for 12 hours after addition. The reaction solution was poured into 50 ml of water, and the water phase was extracted with dichloromethane (50 mL*2). The organic phases were combined, dried over anhydrous sodium sulfate, and filtered.

Reference:
Patent; Jiangsu Hengrui Medicine Co., Ltd.; Shanghai Hengrui Pharmaceutical Co., Ltd.; LI, Xin; HE, Wei; WANG, Bin; ZHANG, Zhigao; HE, Feng; TAO, Weikang; (104 pag.)EP3560918; (2019); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

The important role of 825-70-7

The synthetic route of 825-70-7 has been constantly updated, and we look forward to future research findings.

Reference of 825-70-7, These common heterocyclic compound, 825-70-7, name is 5-Fluoro-2-methylindoline, 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.

Example 15c and Example 16c Synthesis of (+)-2-{2-[5-fluoro-2-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-3-methyl-6-(morpholin-4-yl)pyrimidin-4(3H)-one and of (-)-2-{2-[5-fluoro-2-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-3-methyl-6-(morpholin-4-yl)pyrimidin-4(3H)-one 430 mg of 5-fluoro-2-methyl-2,3-dihydro-1H-indole (reference example 4c) and 872 mg of N-[3-(dimethylamino)propyl]-N?-ethylcarbodiimide hydrochloride are added to a solution of 1.1 g of sodium [1-methyl-4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate in 25 ml of N,N-dimethylformamide and 25 ml of pyridine. The reaction mixture is stirred at ambient temperature for 48 hours and then 100 ml of water are added and the mixture is extracted with ethyl acetate. The organic phase is washed successively with a 0.1N hydrochloric acid solution, water and a saturated sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue is purified by silica column chromatography, elution being carried out with a mixture of dichloromethane and methanol (95/05: v/v), so as to give 538 mg of 2-{2-[(5-fluoro-2-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-3-methyl-6-(morpholin-4-yl)pyrimidin-4(3H)-one.The enantiomers are separated by chiral chromatography on a Whelk 01 SS, 10 mum column (10 mum, 80¡Á350 mm), elution being carried out with a mixture of: heptane/dichloromethane/ethanol/methanol: 60/20/10/10; flow rate: 240 ml/min.212 mg of (+)-2-{2-[(5-fluoro-2-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-3-methyl-6-(morpholin-4-yl)pyrimidin-4(3H)-one are obtained, as first enantiomer, in the form of a white solid, the characteristics of which are the following:1H NMR spectrum (400 MHz): 1.28 (d, J=6.6 Hz, 3H); 2.70 (d, J=16.2 Hz, 1H); 3.33 (s, 3H); 3.36 to 3.44 (m, 5H); 3.58 (m, 4H); 4.02 (d, J=16.6 Hz, 1H); 4.27 (d, J=16.6 Hz, 1H); 4.73 (m, 1H); 5.36 (s, 1H); 7.00 (td, J=2.9 and 8.9 Hz, 1H); 7.16 (dd, J=2.9 and 8.9 Hz, 1H); 7.94 (dd, J=5.0 and 8.9 Hz, 1H)Mass spectrometry: method ARetention time Tr (min)=0.76;[M+H]+: m/z 387; [M-H]-: m/z 385;Optical rotation: alphaD=+72.0 (c=1.704 mg/0.5 ml CH3OH)Then the second enantiomer (Tr=17.61 min), 210 mg of (-)-2-{2-[(5-fluoro-2-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-3-methyl-6-(morpholin-4-yl)pyrimidin-4(3H)-one, is obtained in the form of a white solid, the characteristics of which are the following:1H NMR spectrum (400 MHz): 1.28 (d, J=6.4 Hz, 3H); 2.70 (d, J=16.2 Hz, 1H); 3.33 (s, 3H); 3.37 to 3.44 (m, 5H); 3.59 (m, 4H); 4.02 (d, J=16.6 Hz, 1H); 4.27 (d, J=16.6 Hz, 1H); 4.72 (m, 1H); 5.36 (s, 1H); 7.00 (td, J=3.0 and 8.8 Hz, 1H); 7.16 (dd, J=3.0 and 8.8 Hz, 1H); 7.93 (dd, J=5.1 and 8.8 Hz, 1H)Mass spectrometry: method ARetention time Tr (min)=0.76;[M+H]+: m/z 387; [M-H]-: m/z 385;Optical rotation: alphaD=-59.5 (c=2.182 mg/0.5 ml CH3OH)

The synthetic route of 825-70-7 has been constantly updated, and we look forward to future research findings.

The important role of 825-70-7

According to the analysis of related databases, 825-70-7, the application of this compound in the production field has become more and more popular.

Reference of 825-70-7, 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 825-70-7 as follows.

Step 2a:(R)-1-(5-Fluoro-2-methyl-2,3-dihydroindol-1-yl)-2-phenoxypropan-1-one: diastereoisomer A And(R)-1-(5-Fluoro-2-methyl-2,3-dihydroindol-1-yl)-2-phenoxypropan-1-one: diastereoisomer B 2.9 g of 5-Fluoro-2-methyl-2,3-dihydro-1H-indole and 5.3 g of N-[3-(dimethylamino)propyl]-N?-ethylcarbodiimide hydrochloride are added to a solution of 4.17 g of o-benzyl-D-lactic acid in 17 ml of DMF and 3.43 ml of pyridine.The reaction medium is stirred at ambient temperature for 18 hours.500 ml of ethyl acetate and 500 ml of water are added. After settling out, the organic phase is dried over magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue obtained is purified on a silica cartridge: eluent: heptane, then 95/05 heptane/ethyl acetate, then 90/10 heptane/ethyl acetate, so as to give 2.8 g of (R)-1-(5-fluoro-2-methyl-2,3-dihydroindol-1-yl)-2-phenoxypropan-1-one: diastereoisomer A in the form of a yellow oil, the characteristics of which are the following:Mass spectrometry: method ARetention time Tr (min)=1.08;[M+H]+: m/z 314And 2.63 g of (R)-1-(5-fluoro-2-methyl-2,3-dihydroindol-1-yl)-2-phenoxpropan-1-one: diastereoisomer B in the form of a white solid, the characteristics of which are the following:Mass spectrometry: method ARetention time Tr (min)=1.06;[M+H]+: m/z 314; base peak: m/z 242

According to the analysis of related databases, 825-70-7, the application of this compound in the production field has become more and more popular.