Tag: M.W=200-300

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 87-48-9 as follows. Safety of 5-Bromoindoline-2,3-dione

Step 90a: 5-Bromoindolin-2-one (Compound 0601-194)[0597]To a mixture of 5-bromoindole-2,3-dione (2.25 g, 10 mmol), ethyleneglycol (45 mL) and hydrazine hydrate (1.06 g, 21.10 mmol) was added KOH (1.68 g, 30 mmol). The reaction mixture was stirred at 80 C. for 4 hours. The mixture was cooled to room temperature and poured into ice cold water and the mixture was adjusted to pH 1-2 with 12N hydrochloric acid and stirred at room temperature for 12 hours. The mixture was filtered and solid was washed with water (5 mL) and dried to get the crude product which was purified by column chromatography on silica gel (methanol in dichloromethane, 0.5% v/v) to give 0601-194 (785 mg, 37%) as a yellow solid. LCMS: 214 [M+1]+. 1H-NMR (400 MHz. DMSO-d6) delta 3.51 (s, 2H), 6.76 (d, J=8.0 Hz, 1H), 7.34 (dd, J=8.0, 2.0 Hz, 1H), 7.38 (m, 1H), 10.49 (s, 1H).

According to the analysis of related databases, 87-48-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Curis, Inc.; Bao, Rudi; Lai, Chengjung; Qian, Changgeng; US2013/102595; (2013); A1;,
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Application of 667463-64-1,Some common heterocyclic compound, 667463-64-1, name is 6-Bromo-1-methylindoline-2,3-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.

1-3. I (JS.O g, 63 nunol) and hydrazine hydrate (30 mL, 618 nunol) are heated to 12S C for 72 h.To the cool reaction mixtw-e DCM is added and extracted with water and 1 M HCI. The organiclayer is dried over MgS04 and concentrated. The crystaJlized 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%, mz 226/228 [M+H]+, rt J.l6 min, LC-MSMethod VOOJ 003.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 6-Bromo-1-methylindoline-2,3-dione, its application will become more common.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; GRAUERT, Matthias; ANDERSKEWITZ, Ralf; GRUNDL, Marc; OOST, Thorsten; PAUTSCH, Alexander; PETERS, Stefan; WO2014/140081; (2014); A1;,
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Synthetic Route of 20780-72-7, A common heterocyclic compound, 20780-72-7, name is 4-Bromoisatin, molecular formula is C8H4BrNO2, 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.

(3) 10 mL DMF dissolution step (2) The obtained compound 4.4 mmol, 1.8 g of potassium carbonate, 1.1 g of 4-chlorobenzyl bromide, and stirred under argon atmosphere for 2 hours at room temperature; TLC analysis determined that after the reaction was completed, The reaction was quenched by the addition of excess ice water and stirred for 30 minutes; Filter the suspension and dry the filter cake. Obtained as a red solid (Compound 4b 1.34 g, yield 90percent, without further purification);

The synthetic route of 20780-72-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Tianjin University of Science and Technology; Diao Aipo; Li Yuyin; Yu Peng; Liu Yang; Li Zhipeng; (15 pag.)CN109574907; (2019); A;,
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Synthetic Route of 169037-23-4, A common heterocyclic compound, 169037-23-4, name is 5-(Trifluoromethoxy)indoline-2,3-dione, molecular formula is C9H4F3NO3, 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 indoline-2,3-dione 1 (1mmol), l-tryptophan (2a) or l-histidine 2b (1mmol) and (E)-(2-nitrovinyl)benzene 3 (1.1mmol) was heated while stirred in [bmim]Br as the reaction medium (3mL) for 1hat 100C. After completion of the reaction (TLC), EtOAc (5mL) was added and the reaction mixture was stirred for 10min. This treatment was repeated and the combined ethyl acetate layers were removed in vacuo. The crude product was purified by recrystallization of the residue from EtOH (compounds 4) or by column chromatography (compounds 5). After extraction of the product, the ionic liquid was dried under vacuum at 80C for 2h to eliminate any water and could be reused for subsequent runs of the reaction.

The synthetic route of 169037-23-4 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Arumugam, Natarajan; Almansour, Abdulrahman I.; Kumar, Raju Suresh; Periasamy, Vaiyapuri Subbarayan; Athinarayanan, Jegan; Alshatwi, Ali A.; Govindasami, Periyasami; Altaf, Mohammad; Menendez, J. Carlos; Tetrahedron; vol. 74; 38; (2018); p. 5358 – 5366;,
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Application of 169037-23-4, 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. 169037-23-4 name is 5-(Trifluoromethoxy)indoline-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.

General procedure: A mixture of beta-nitrostyrenes, isatin and tyrosine (1:1:1) was stirredunder heating at 100 C for 1 h in [bmim]Br (200 mg). After the reaction was completed, 10 mL of ethyl acetate was added to the reaction mixture and stirred for 15 min. The organic layer was separated, washed with water, and dried. The cycloadduct was further purified using hexane: ethyl acetate (3:2 v/v) as eluent employing column chromatography technique. After extraction of the cycloadduct, [bmim]Br wasdried under vacuum at 80 C for 2 h to exclude any water trapped from moisture and reused for subsequent runs.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 5-(Trifluoromethoxy)indoline-2,3-dione, and friends who are interested can also refer to it.

Reference:
Article; Kumar, Raju Suresh; Almansour, Abdulrahman I.; Arumugam, Natarajan; Mohammad, Faruq; Kotresha; Menendez, J. Carlos; Bioorganic and Medicinal Chemistry; vol. 27; 12; (2019); p. 2487 – 2498;,
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Adding a certain compound to certain chemical reactions, such as: 104618-31-7, name is 2-(4-Hydroxycyclohexyl)isoindoline-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 104618-31-7, Quality Control of 2-(4-Hydroxycyclohexyl)isoindoline-1,3-dione

Step 2 A solution of 2-(4-hydroxycyclohexyl)-1H-isoindole-1,3(2H)-dione (3.10 g, 12.6 mmol) in CH2Cl2 (25.0 mL) was added to a slurry of PCC (4.10 g, 19.0 mmol) in CH2Cl2 (15.0 mL) and stirred at room temperature for 3.5 hours. The reaction was diluted with Et2O (60.0 mL), decanted and the residue swirled with Et2O (2*40.0 mL). The combined ether layers were filtered through florisil and concentrated in vacuo to dryness, and the residue was recrystallized from ethyl acetate/hexane to give 2.01 g (65%) of 2-(4-oxocyclohexyl)-1H-isoindole-1,3(2H)-dione as colorless needles: mp 140.3-142.1 C.; 1H NMR (400 MHz, CDCl3) delta7.84, 7.74, 4.64, 2.72, 2.54, 2.09; 13C NMR (100 MHz, CDCl3) delta208.9, 168.1, 134.1, 131.9, 123.3, 48.4, 39.9, 28.6; IR (mull) 3062, 3031, 2958, 2949, 2919, 2885, 1775, 1762, 1721, 1708, 1611, 1465, 1436, 1419, 1393, 1379, 719 cm-1; HRMS (FAB) calcd for C14H14NO3: 244.0974, found 244.0976; Anal. Calcd for C-14H14NO3: C, 69.12; H, 5.39; N, 5.76. Found: C, 68.87; H, 5.47; N, 5.73.

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, 2-(4-Hydroxycyclohexyl)isoindoline-1,3-dione, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Fu, Jian-Min; US2003/100596; (2003); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Synthetic Route of 959235-95-1,Some common heterocyclic compound, 959235-95-1, name is 6-(Trifluoromethoxy)indoline, molecular formula is C9H8F3NO, 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 stirring solution of 2-(4-chloro-2-(4-methoxy-3,3-dimethyl-4- oxobutoxy)phenyl)acetic acid 14b (576 mg, 1 .83 mmol), 6- (trifluoromethoxy)indoline [CAS 959235-95-1 ] (409 mg, 2.01 mmol) anddiisopropylethylamine (907 muIota_, 5.49 mmol) in DMF (7.5 ml_) under N2-atm was added HATU (1 .07 g, 2.75 mmol), and the reaction mixture was stirred at room temperature for 5 h. Water (30 ml_) was added, and the product was extracted (2x) with Et2O. The combined organic layers were washed with brine, dried overMgSO4, filtered, and evaporated under reduced pressure. The residue was purified by flash chromatography on silica gel (40 g) using a gradient of heptane/EtOAc 100/0 to 0/100. The desired fractions were combined and evaporated under reduced pressure, and co-evaporated with toluene. The residue was dried under vacuum at 45C to provide methyl 4-(5-chloro-2-(2-oxo-2-(6- (trifluoromethoxy)indolin-1 -yl)ethyl)phenoxy)-2,2-dimethylbutanoate 14c (790 mg) as a powder.

The synthetic route of 959235-95-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; JANSSEN PHARMACEUTICALS, INC.; KATHOLIEKE UNIVERSITEIT LEUVEN; KESTELEYN, Bart Rudolf Romanie; BONFANTI, Jean-Francois; COESEMANS, Erwin; RABOISSON, Pierre Jean-Marie Bernard; MARCHAND, Arnaud Didier M; BARDIOT, Dorothee Alice Marie-Eve; (92 pag.)WO2018/178240; (2018); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Reference of 87-48-9, 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 87-48-9 as follows.

In a 5L four-necked flask, add 5-bromoisatin 250.0g,1000ml absolute ethanol, stirring, and then slowly add hydrationHydrazine (80%) 81.4g, heated to reflux (80 C)Reaction 2h,Sampling HPLC test, no raw material remaining, the reaction liquid coolingTo about 15 , crystallization 15min, filtered, the filter cake was washed with a small amount of cold ethanol or mother liquor,Then at 50 oven drying 12h, get hydrazone crude. In a 5L four-necked flask, put the crude hydrazide obtained above,Ethylene glycol 1000ml, stirring, adding sodium hydroxide 32.5g,Heated to reflux,Reflux temperature gradually increased from 95 to 115 , the reaction 7h,Sample HPLC test, no raw material remaining, stop heating, cooling to below 30 , the reaction solution was transferred to a 10L bottle, add water 1500ml, with concentrated hydrochloric acid to adjust PH = 2.5 or so, adding methylene chloride 1500ml, The floc was precipitated, filtered, and the layers were separated. The aqueous layer was further extracted with 500 ml of dichloromethane, and the organic layers were combined.The solvent was distilled off under reduced pressure to give 402.4 g of bromoindolinone (Formula II).

According to the analysis of related databases, 87-48-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Ningbo Jiu Sheng Chuangxin Pharmaceutical Technology Co., Ltd.; Li Changlong; Yu Lihuang; He Guojin; Tao Weijian; (7 pag.)CN104693019; (2017); B;,
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Indoline | C8H9N – PubChem

Adding a certain compound to certain chemical reactions, such as: 4403-36-5, name is 2-(1,3-Dioxoisoindolin-2-yl)ethanesulfonylchloride, 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 4403-36-5, Computed Properties of C10H8ClNO4S

Example 42 N-({(2R,3S)-3-[(4-azepan-1-ylpyrimidin-2-yl)amino]-1-cyclohexylpyrrolidin-2-yl }methyl)-2-(1,3 -dioxo-1,3-dihydro-2H-isoindol-2-yl)ethanesulfonamide (compound 42) N-[(2R,3S)-2-(aminomethyl)-1-cyclohexylpyrrolidin-3-yl]-4-azepan-1-ylpyrimidine-2-amine (33.2 mg) was dissolved in anhydrous tetrahydrofuran (0.8 mL) and dimethylformamide (0.4 mL) under an argon atmosphere at room temperature, trietylamine (24.8 muL) and 2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethanesulfonyl chloride (48.8 mg) were added into the solution and the solution was stirred at room temperature for overnight. The reaction solution was added aqueous saturated sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate and then concentrated. The residue was purified by Flash tube (trade mark) to obtain sulfonamide compound (49.0 mg). TLC: Rf 0.67 (chloroform: methanol = 5:1).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-(1,3-Dioxoisoindolin-2-yl)ethanesulfonylchloride, and friends who are interested can also refer to it.

Reference:
Patent; ONO PHARMACEUTICAL CO., LTD.; EP1852432; (2007); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Synthetic Route of 132898-96-5, 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. 132898-96-5 name is 2,3-Dioxoindoline-5-sulfonyl chloride, 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: To a stirred solution of the N-Boc-protected pyrrolidine (1.0 mmol) in dry DCM (3 mL) at 0 C under argon atmosphere, TFA (1.14 g, 10.0 mmol) was added dropwise. The obtained solution was stirred at 0 C for 30 min followed by stirring at r.t. for 2 h. Subsequently, the solution was poured to cold 10% aq. NaOH (15 mL) and extracted with DCM (3 ¡Á 15 mL). The combined organic phases were dried over MgSO4 and concentrated under reduced pressure resulting in the corresponding unprotected pyrrolidine, which was used in the next step without further purification. The free pyrrolidine (ca. 1 mmol) from the previous step was then taken up in CHCl3 (2.2 mL) and DIPEA (2.0 mmol) was added. The solution was added dropwise to a stirred solution of 5-chlorosulfonyl isatin (1.5 mmol) in CHCl3/THF (1:1, 15 mL) at room temperature. The resulting mixture was stirred further for 1 h and the solvent was removed under reduced pressure. After purification by flash column chromatography the target isatin sulfonamide was obtained.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2,3-Dioxoindoline-5-sulfonyl chloride, and friends who are interested can also refer to it.

Reference:
Article; Limpachayaporn, Panupun; Riemann, Burkhard; Kopka, Klaus; Schober, Otmar; Schaefers, Michael; Haufe, Guenter; European Journal of Medicinal Chemistry; vol. 64; (2013); p. 562 – 578;,
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