Category: indolines-derivatives

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

Electric Literature of 346-34-9, A common heterocyclic compound, 346-34-9, name is 4-Fluoroindoline-2,3-dione, molecular formula is C8H4FNO2, 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.

Intermediate 1 A6-bromo-2-(trifluoromethyl)quinoline-4-carboxylic acid 300 mg (1.33 mmol) of 5-bromo-1 H-indole-2,3-dione was suspended in 3 mL water in a microwave vial. 82 mg ( 1.46 mmol) potassium hydroxide, 152 muL (2.65 mmol) acetic acid and 152 mg (1.86 mmol) sodium acetate were added so that the pH was around 5. The solution was cooled to 10 C and 238 muL (2.65 mmol) 1 ,1,1 -trifluoroacetone was added rapidly, the microwave vial was sealed and heated in the microwave for 2 h at 120 C. The reaction was stopped by the addition of 10% aqueous hydrochloric acid solution and the resulting precipitate was isolated by filtration, washed with water and dried in a vacuum drying cabinet at 50 C overnight to obtain 409 mg (1.28 mmol, 96%) of the desired title compound .1 H NMR (300 MHz, DMSO d6): delta (ppm) = 8.14 (dd, 1 H), 8.21 (d, 1 H), 8.32 (s, 1 H), 9.09 (d, 1 H), 14.50 (br. s. , 1 H)._In analogy to intermediate l, 300 mg (1.81 mmol) 4-fluoro-1H-indole-2,3-dione washeated with 326 pL (3.63 mmoL) 1,1,1-trifluoroacetone, 112 mg (1.99 mmoL)potassium hydroxide, 208 pL (3.63 mmo[) acetic acid and 209 mg (2.54 mmoL) sodium acetate in 3 mL water for 2 h at 100CC in the microwave to obtain 315 mg (1.22 mmol, 67%) of the desired title compound after aqueous work-up.1H NMR (400MHz, DMSO d6): 6 (ppm) = 783 -7.92 (m, 1 H), 8.09 (dd, 1 H), 8.25 (s, 1 H), 8.90 (dd, 1 H), 14.50 (br. 5., 1 H).

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; BAYER PHARMA AKTIENGESELLSCHAFT; HEISLER, Iring; MUeLLER, Thomas; SIEBENEICHER, Holger; BUCHMANN, Bernd; CLEVE, Arwed; GUeNTHER, Judith; KOPPITZ, Marcus; HEROULT, Melanie; NEUHAUS, Roland; PETRUL, Heike; QUANZ-SCHOeFFEL, Maria; WO2015/91428; (2015); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Synthetic Route of 356068-93-4,Some common heterocyclic compound, 356068-93-4, name is (Z)-5-((5-Fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid, molecular formula is C16H13FN2O3, 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 stirred solution of compound 109 (220.0 mg, 0.73 mmol) in DMF (15 mL) at room temperature was added etaOBt (148.6 mg, 1.1 mmol), triethylamine(0.21 mL, 1.46 mmol), ECDI-etaC1 (210.2 mg, 1.1 mmol) and methyl 7- aminoheptanoate hydrochloride (157.1 mg, 0.8 mmol) successively. The mixture was stirred for 24 h at room temperature and was then diluted with water (20 mL), brine (20 mL) and saturated bicarbonate solution (20 mL). The peta of the mixture was adjusted to 11-12 with IO N NaOH. The mixture was filtered and the solid was washed with water, dried to obtain a crude product 110-15 as a yellow solid (0.3 g, 93.2%). LCMS: 442 [M+l]+; 1H NMR(DMSO-J6): delta 1.31 (m, 4eta), 1.50 (m, 4H), 2.31 (t, J= 7.35 Hz, 2H), 2.40 ( s, 3H), 2.42 (s,3H), 3.19 (m, 2H), 3.59 (s, 3H), 6.87 (m, 2H), 7.71 (m,3H), 10.91 (s, IH), 13.67 (s, IH).

The synthetic route of 356068-93-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; CURIS, INC.; WO2008/33747; (2008); A2;,
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;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Related Products of 87-48-9,Some common heterocyclic compound, 87-48-9, name is 5-Bromoindoline-2,3-dione, 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.

General procedure: Step 1: To a 250 mL flask equipped with a silicone oil bubbler was added commercially available isatin (7.7 g, 50 mmol) and anhydrous DMF (80 mL). the mixture was cooled down to 0 oC. To this solution was added NaH (1.32 g, 55 mmol), followed by the addition of CH3I in 15 min. Upon completion of the reaction (monitored by TLC), the mixture was diluted with saturated NH4Cl solution and extracted with ethyl acetate. The organic layer was washed with water, dried over Na2SO4, filtered, and concentrated to yield the crude N-methylindoline-2, 3-dione, which was used directly in the next step. Step 2: The N-methylindoline-2, 3-dione (7.58 g, 47 mmol) was refluxed in NH2¡¤NH2-H2O ( 35 %) for 1h. Then the mixture was cooled to rt. The crude product was extracted with ethyl acetate. The combined organic layer was then dried over Na2SO4, purified by flash chromatography on silica gel (petroleum ether/ethyl acetate = 10:1). 1-Methylindolin-2-one was obtained as a pink solid.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5-Bromoindoline-2,3-dione, its application will become more common.

Reference:
Article; Zhao, Jian-bo; Ren, Xinfeng; Zheng, Bu-quan; Ji, Jian; Qiu, Zi-bin; Li, Ya; Journal of Fluorine Chemistry; vol. 215; (2018); p. 44 – 51;,
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. 7477-63-6, name is 7-Chloroisatin, A new synthetic method of this compound is introduced below., Safety of 7-Chloroisatin

General procedure: In a 25 mL round bottom flask, isatins 1 (1 mmol), 3-phenylisoxazol-5(4H)-one 2 (1 mmol) or 3-ethylisoxazol-5(4H)-one 7 (1 mmol), pyrazol-5-amine 3 (1 mmol) or 6-aminopyrimidine-2,4-(1H,3H)-dione 5 (1 mmol), and Amberlyst-15 (100 mg) were stirred in CH3OH (5.0 mL) at 80 C. When the reaction was completed (detected by TLC), the spherical catalyst was separated by a sieve at once under hot condition. Then, the reaction mixture was cooled to room temperature, and solid precipitation occurred. After filtration, the crude product was recrystallized from EtOH and DMF to give pure compound.

The synthetic route of 7477-63-6 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Niu, Qingqing; Xi, Junhua; Li, Lei; Li, Li; Pan, Chengli; Lan, Meijun; Rong, Liangce; Tetrahedron Letters; vol. 60; 43; (2019);,
Indoline – Wikipedia,
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201940-08-1, name is tert-Butyl 5-bromoisoindoline-2-carboxylate, 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. Application In Synthesis of tert-Butyl 5-bromoisoindoline-2-carboxylate

5-Bromo-1,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester (2.97 g, 10 mmol) was azeotropically dried by evaporation from toluene. Tris(dibenzylideneacetone)dipalladium (0) (228 mg, 0.25 mmol), 2-(di-tert-butylphosphino)biphenyl (149 mg, 0.50 mmol) and sodium tert-butoxide (1.34 g, 13.9 mmol) were added and the flask was purged with nitrogen. Toluene (25 mL) then N-methylpiperazine (1.33 mL, 12 mmol) were added and the mixture was heated to 80 C. for 2 hours. After allowing to cool to r.t. the mixture was diluted with ether, filtered through Celite and concentrated to give a residue that was purified by flash chromatography on silica (2M methanolic ammonia/dichloromethane, 1% to 3% gradient). This afforded the title compound as a brown solid (1.45 g, 46%). 1H NMR (MeOH-d4) 7.15 (1H, m), 6.94-6.88 (2H, m), 4.60-4.54 (4H, m), 3.20-3.17 (4H, m), 2.63-2.60 (4H, m), 2.34 (3H, s), 1.52 (9H, s). MS: [M+H]+ 318.

The synthetic route of 201940-08-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ASTEX THERAPEUTICS LIMITED; US2010/152184; (2010); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

64483-69-8, name is 5-Acetylindolin-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. Safety of 5-Acetylindolin-2-one

5-Ethyl-2-oxindole To 5-Acetyl-2-oxindole (2 g) in 15 ML of trifluoroacetic acid in an ice bath was slowly added 1.8 g of triethylsilane; the reaction was then stirred at room temperature for 5 hours.. One ML of triethylsilane was added and the stirring continued overnight.. The reaction mixture was poured into ice water and the resulting precipitate collected by vacuum filtration, washed copiously with water and dried under vacuum to give 1.3 g (71% yield) of the title compound as a yellow solid.

The synthetic route of 64483-69-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Sugen, Inc.; US6350754; (2002); B2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Reference of 954-81-4, 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. 954-81-4, name is N-(5-Bromopentyl)phthalimide belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below.

To a solution of N-(5-bromopentyl)phthalimide (5 g, 16.9 mmol) in ACN (50 mL) was added N-benzylmethylamine (2.04 g, 16.9 mmol), followed by DIPEA (2.93 mL, 16.9 mmol). The reaction mixture was stirred at 50 C. for 3 hours and then the solvent was removed in vacuo. The residue was dissolved in DCM (100 mL), washed with brine (100 mL), dried over magnesium sulfate, filtered and concentrated. The residue was dissolved in MeOH (100 mL) and hydrogenated to remove the benzyl group using palladium on activated carbon (1 g, 10 wt. % (dry basis)) as a catalyst under a hydrogen gas balloon at room temperature overnight. The mixture was filtered through Celite and the solvent was removed in vacuo to yield 4.2 g of the title intermediate as a solid.

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, N-(5-Bromopentyl)phthalimide, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Theravance, Inc.; US2005/203083; (2005); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Electric Literature of 181140-34-1,Some common heterocyclic compound, 181140-34-1, name is (R)-(-)-N-(2,3-Epoxypropyl)phthalimide, molecular formula is C11H9NO3, 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.

A solution of 22.6 g (111.21 mmol) of S – (+) – N- (2,3-ethoxypropyl) phthalimide (SM1)5.34 g (27.80 mmol) of 4- (4-aminophenyl) morpholin-3-one (SM2) was added to 250 ml of a three-necked flask, followed by addition of 110 ml of absolute ethanol and the reaction was refluxed for 24 h.With tap water to 50 ~ 55 C , filter, remove the insoluble matter, collecting the filtrate, continue to cool to 10 ~ 15 C crystallization, filtration, a yellow solid. The yellow solid was dissolved in 80 ml of absolute ethanol and cooled to 5 to 10 The filter cake was dried at 50 to 60 C for 5 hours under reduced pressure. The product was obtained in a yield of 60.0% and a purity of 96.2%.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route (R)-(-)-N-(2,3-Epoxypropyl)phthalimide, its application will become more common.

Reference:
Patent; Chongqing Zhien Pharmaceutical Co., Ltd.; Deng Xianglin; Li Daming; Huang Chaoming; Huang Minghui; Feng Yongmei; Wang Fei; Liao Xingting; (29 pag.)CN106432218; (2017); A;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem