Month: April 2021

Reference of 59-48-3,Some common heterocyclic compound, 59-48-3, name is Indolin-2-one, molecular formula is C8H7NO, 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: 5-nitroindolin-2-one: To a stirred solution of oxindole (20 g, 150.21 mmol) in 100 mL of concentrated H2S04 at -15C was added fuming HN03 (9.47 g, 150.206 mmol) dropwise and maintained the reaction temperature at -15C. After completion of addition, the mixture was stirred for 30 min and then poured into ice water. A yellow precipitate was formed which was isolated by filtration (13 g, 48%). -NMR (300 MHz, DMSO-ito): delta 11 (s, 1H), 8.2 (d, 1H), 8.1 (s, 1H), 7.0 (d, 1H), 3.6 (s, 2H).

The synthetic route of 59-48-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ORION CORPORATION; UJJINAMATADA, Ravi Kotrabasaiah; HOSAHALLI, Subramanya; SAMAJDAR, Susanta; ABBINENI, Chandrasekhar; WO2015/92118; (2015); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Synthetic Route of 675109-26-9, These common heterocyclic compound, 675109-26-9, name is 6-Bromoisoindolin-1-one, 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.

Preparation 63: 6-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-2,3-dihydro-1 H-isoindol-1 – one (1578) (1579) A stirred mixture of 6-bromo-2,3-dihydro-1 H-isoindol-1 -one (780 mg, 3.68 mmol), (1580) bis(pinacolato)diboron (1.089 g, 4.28 mmol) and potassium acetate (1.26 g, 12.87 mmol) anhydrous 1 ,4-dioxane (12 mL) was degassed with nitrogen for 5 minutes. 1 ,1′- bis(diphenylphosphino)ferrocene-palladium(ll)dichloride dichloromethane complex (150 mg, 0.18 mmol) was then added and the reaction heated under nitrogen at 100C for 16 hours. After cooling to room temperature the mixture was diluted with water and extracted with EtOAc (x3). The combined organic layers were washed with brine, dried over MgS04, filtered and concentrated under vacuum to yield the title compound (1.1 g, 115 %) which was used crude without purification. MS: [M+H]+ = 260.

Statistics shows that 6-Bromoisoindolin-1-one is playing an increasingly important role. we look forward to future research findings about 675109-26-9.

Reference:
Patent; OTSUKA PHARMACEUTICAL CO., LTD.; BERDINI, Valerio; BUCK, Ildiko Maria; DAY, James Edward Harvey; GRIFFITHS-JONES, Charlotte Mary; HEIGHTMAN, Thomas Daniel; HOWARD, Steven; MURRAY, Christopher William; NORTON, David; O’REILLY, Marc; WOOLFORD, Alison Jo-Anne; COOKE, Michael Liam; COUSIN, David; ONIONS, Stuart Thomas; SHANNON, Jonathan Martin; WATTS, John Paul; (867 pag.)WO2017/68412; (2017); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Electric Literature of 2058-72-2,Some common heterocyclic compound, 2058-72-2, name is 5-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.

General procedure: A solution of 6 g (0.05 mol) of 4-aminophenol in a mixture of 50 mL of water and 15 mL of 32% hydrochloric acid was cooled on an ice bath to 0C. At continuous stirring maintaining the temperature below 5C a solution was added of 4 g (0.055 mol) of sodium nitrite in 15 mL of water. The obtained solution of a diazonium salt was stirred for 40 min. It was then added to a cooled to -5C solution of tin(II) chloride obtained by dissolving 30 g of tin in a mixture of 50 mL of water and 100 mL of 32% hydrochloric acid. After stirring for 2 h to the reaction mixture was added a solution of 0.05 mol of an appropriate isatin in a sufficient amount of 2-propanol, also a solution was added of 6 g (0.07 mol) of sodium acetate in 35 mL of water. The mixture obtained was stirred for 2 h, heated to 50C, and left standing for crystallization. The separated precipitate was filtered off and several times washed with water on the filter. The filtrate was additionally diluted with water, the separated precipitate was filtered off, washed with water on the filter, the precipitates were combined and dried.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5-Bromo-1-methylindoline-2,3-dione, its application will become more common.

Reference:
Article; Murashevich; Nichik; Zamyatina; Toropin; Burmistrov; Russian Journal of Organic Chemistry; vol. 52; 5; (2016); p. 650 – 654; Zh. Org. Khim.; vol. 52; 5; (2016); p. 665 – 669;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Electric Literature of 239463-85-5,Some common heterocyclic compound, 239463-85-5, name is (R)-3-(5-(2-Aminopropyl)-7-cyanoindolin-1-yl)propyl benzoate (2R,3R)-2,3-dihydroxysuccinate, molecular formula is C26H31N3O8, 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. 80L water was added 200L reactor, adding sodium carbonate 6.2Kg stirring to clarify;2. Add ethyl acetate 50L, stirring,10 Kg of 5 – [(2R) -2-aminopropyl] -2,3-dihydro-1- [3- (benzoyloxy) propyl] -1H-indole-7-carbonitrile tartarate was added, Stir for 2 hours;3. Let stand liquid, the aqueous phase was extracted once with 20 L of ethyl acetate, the combined organic phase;The organic phase was washed twice with 15 L of saturated brine and the organic phase was dried over anhydrous sodium sulfate for 4 hours.5. Suction filtration, desiccant was washed with ethyl acetate; the solvent was dried under reduced pressure to give an oil 7Kg,Is 5 – [(2R) -2-aminopropyl] -2,3-dihydro-1- [3- (benzoyloxy) propyl] -1H-indole-7-carbonitrile, 99%.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route (R)-3-(5-(2-Aminopropyl)-7-cyanoindolin-1-yl)propyl benzoate (2R,3R)-2,3-dihydroxysuccinate, its application will become more common.

Reference:
Patent; Beijing Tiantaihenghua Pharmaceutical Co., Ltd.; Li Xueqin; Liu Wenhui; (21 pag.)CN106995399; (2017); A;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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. 924304-73-4, name is 4-Chloroisoindoline hydrochloride, This compound has unique chemical properties. The synthetic route is as follows., Computed Properties of C8H9Cl2N

Compound 26; Step 2: Synthesis of (2S,4R)-1-(tert-butoxycarbonyl)-4-(4-chloroisoindoline-2- carbonyloxy)pyrrolidine-2-carboxylic acid; To a solution of (25″,4lambda)-1-tert-butyI 2-methyl 4-hydroxypyitauolidme-1,2- dicarboxylate (500 mg, 2 04 mmol) in dry THF (6 mL) was added CDI (430 mg, 2 65 mmol) m one portion and the mixture was stirred at rt for 6 h The amine, 4-chloroisomdoline hydrochloride (0 89 g, 4 7 mmol) was then added in portions, followed by slow addition of DIEA (1 07 mL, 6.12 mmol). The reaction was stirred at rt for overnight. The reaction was diluted with 120 mL EtOAc, washed with IN HCl (2 x 50 mL), water and brine (50 mL each), and dried over Na2SO4 and concentrated down to a thick brownish oil The crude was purified by silica chromatography (eluent = hexanes/EtOAc 2 1), giving the ester product, (25,4J?)-1-tert-butyl 2-methyl 4-(4-chloroisoindolme-2-carbonyloxy)pyrrolidine-1,2- dicaiboxylate, as a light pinkish foamy solid (0 79 g, 91 % yield); (25′,4R)-1-(tert-butoxycarbonyl)-4-(4-chloroisoindoIine-2-carbonyloxy)pyrrolidine-2- carboxylic acid; To a solution of (2S,4R)- 1 -tert-butyl 2-methyl 4-hydroxypyrrolidine-1,2- dicarboxylate (0.50 g, 2.04 mmol) in dry THF (6 niL) was added CDI (430 mg, 2.65 mmol) in one portion and the mixture was stirred at rt for 6 h. 4-chloroisoindoline hydrochloride (0.89 g, 4.69 mmol) was then added in portions, followed by slow addition of DIEA (1.07 mL, 6.12 mmol). The reaction was stirred at rt for overnight. The reaction was diluted with 120 mL EtOAc, washed with IN HCl (2 x 50 mL), water and brine (50 mL each), and dried over Na2SC>4 and concentrated down to a thick brownish oil. The crude was purified by silica chromatography (eluent = hexanes/EtOAc 2: 1), giving (2S,4R)-1-tert-butyl 2-methyl 4-(4- chloroisoindoIine-2-carbonyloxy)pyrrolidine-l ,2-dicarboxylate as a light pinkish foamy solid (0.79 g, 91 % yield).

According to the analysis of related databases, 924304-73-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; INTERMUNE, INC.; ARRAY BIOPHARMA; WO2008/141227; (2008); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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 239463-85-5 as follows. Recommanded Product: (R)-3-(5-(2-Aminopropyl)-7-cyanoindolin-1-yl)propyl benzoate (2R,3R)-2,3-dihydroxysuccinate

Example 10: Preparation of 5-((R)-2-aminopropyl)-l-(3-hydroxypropyl) indoline- 7-carbonitrile of Formula ICTo a mixture of Tartrate salt of 3-(5-((R)-2-aminopropyl)-7-cyanoindolin-l-yl) propyl benzoate of Formula (I) (5 gm) in methanol (50 ml) and water (50 ml) was added potassium hydroxide and stirred the reaction mass for overnight at room temperature. The mixture was concentrated under reduced pressure and water (100 ml) was added. The mixture was extracted three times with 5% of Methanol: Methylene Dichloride (3 x 100 ml) and the combined organic layers were distilled to give 1.7 gm of 5-((R)-2- aminopropyl)- 1 -(3 -hydroxypropyl)indoline-7-carbonitrile of Formula IC.

According to the analysis of related databases, 239463-85-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; PANACEA BIOTEC LTD; JAIN, Rajesh; RAO, Jagadeeshwar R; RAO, Siripragada Mahender; WO2012/131710; (2012); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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. 446292-08-6, name is (S)-2-((2-Oxo-3-(4-(3-oxomorpholino)phenyl)oxazolidin-5-yl)methyl)isoindoline-1,3-dione, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: 446292-08-6

100 g (S)-2-((2-oxo-3-(4-(3-oxo-morpholino)phenyl)oxazolidin-5- yl)methyl)isoindoline-l,3-dione of Formula (I), 1000 ml methanol and 119 g methyl amine were added to RBF at 25C to 35C. The reaction was heated to 60C to 65C for 1-2 hours. To the reaction mass succinic acid (15g) was added till to pH 5.5 to 6.0 and maintained for 30 minutes. The reaction mass was cooled to 45 to 50C and maintained for 30 minutes. The reaction mass was cooled to 25 to 35C and maintained for 30 minutes. The product was filtered and washed with methanol (50 ml x 2) afforded succinate salt of (S)-4-(4-(5-(aminomethyl)-2-oxo-^xazolidin-3- yl)phenyl)morpholin-3-one of Formula (JS).

According to the analysis of related databases, 446292-08-6, the application of this compound in the production field has become more and more popular.

Reference:
Patent; CADILA HEALTHCARE LIMITED; DWIVEDI, Shriprakash, Dhar; PRASAD, Ashok; PAL, Daya, Ram; SHARMA, Mukul, Hari, Prasad; JAIN, Kuldeep, Natwarlal; PATEL, Naitik, Bharatbhai; WO2013/98833; (2013); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Related Products of 6326-79-0, These common heterocyclic compound, 6326-79-0, name is 6-Bromoisatin, 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.

To a solution of 6-bromorsatin (CASNo. 6326-79-0, 4 52 g, 20 0 mmol) in acetonrtrile (150 mL) was added potassium carbonate (11 1 g, 80 mmol) followed by iodomethane (2 75 mL, 44 0 mmol) The reactron was then placed at 60 C and stirred for 40 minutes The reaction was then cooled to room temperature, tittered and concentrated to 10% of the original volume The reaction was then diluted with dichloromethane, water and brine The layers were separated and the aqueous layer was extracted two additional times with dichloromethane. The organic extracts were combined, dried over anhydrous sodium sulfate filtered and concentrated to provide 6-bromo-1-methyl-1 H-iotandole-2,3- dione as an orange solid without the need for further punfication The beta-bromo-1-methyl- 1 H-iotandole-2,3-diotaone (1 0 g, 4 2 mmol) was then treated with hydrazine hydrate (7 0 mL, 225 mmol) The reaction was heated to 130 C and stirred for 80 minutes, at which time the reaction was placed at room temperature and cooled by the addition of ice Once the reaction was cooled to room temperature it was diluted with dichloromethane and water and the layers were separated The aqueous layer was extracted an additional two times with dichloromethane, and the organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated The resulting residue was purified by silica gel flash chromatography (ethanol-dichloromethane 0 to 2%) to afford 6-bromo- 1-methyl-1 ,3-diotahydro-mdol-2-one, MS (ES+) m/z 225 9 (IvH-H)*

The synthetic route of 6326-79-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; NOVARTIS AG; ADAMS, Christopher Michael; CHAMOIN, Sylvie; HU, Qi-Ying; ZHANG, Chun; WO2010/130794; (2010); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 14389-06-1, The chemical industry reduces the impact on the environment during synthesis 14389-06-1, name is 5-Chloro-7-methylindoline-2,3-dione, I believe this compound will play a more active role in future production and life.

To a suspension of 3-bromo-l-(3-chloro-2-pyridinyl)-lH-pyrazole-5-carboxylic acid (see PCT Patent Publication WO 03/015519 for preparation) (97.6% purity, 13.02 g, 42 mmol) and 5-chloro-7-methylindoline-2,3-dione (K. Tsuji et al., Bioorg. Med. Chem. Letters, 2002, 72(17), pp 2427-2430) (7.82 g, 40 mmol) in dry acetonitrile (50 mL) was added 3-picoline (11.9 g, 127 mmol). The mixture was cooled to 0 C, and then methanesulfonyl chloride (6.87 g, 60 mmol) was added dropwise at 0-10 0C. After stirring 5 minutes at this temperature, the mixture was warmed to room temperature for 20 hours. The precipitated solids were filtered, washed with acetonitrile (3 x 5 mL), and dried under nitrogen to afford the title product, a compound of the present invention, as a yellow powder, 14.90 g (77.6% yield), m.p. 173-177 0C (decomp.).1H NMR (CDCl3) delta 2.16 (s, 3H), 7.14 (s, IH), 7.38 (dd, J = 8.1, 4.8 Hz, IH), 7.53 (d, /= 2.1 Hz, IH), 7.60 (d, /= 2.1 Hz, IH), 7.89 (dd, /= 8.1, 1.5 Hz, IH), 8.39 (dd, / = 4.8, 1.5 Hz, IH). The NMR spectrum also showed that some 3-picoline salts were present in the crude product.

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, 5-Chloro-7-methylindoline-2,3-dione, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; E. I. DU PONT DE NEMOURS AND COMPANY; WO2007/24833; (2007); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 19155-24-9, A common heterocyclic compound, 19155-24-9, name is 3,3-Dimethylindolin-2-one, molecular formula is C10H11NO, 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.

3,3-dimethyl-indol-2-one (0.65 g, 4.03 mmol) and sodium acetate (0.33 g, 4.07 mmol) were stirred in acetic acid (5 cm3) then bromine (0.66 g, 4.13 mmol) in acetic acid (5 cm3) was added drop-wise to the reaction mixture. The reaction was stirred for 50 min., then poured into water. The mixture was basified with sodium carbonate, extracted with ethyl acetate (.x.3), dried (MgSO4), filtered, and evaporated to give the subtitled compound (0.89 g, 92percent) 1H NMR (DMSO-d6) delta 1.21 (s, 6 H), 6.76 (d, 1 H, J=8.22 Hz), 7.29 (dd, 1 H, J=2.12 Hz, 8.23 Hz), 7.49 (d, 1 H, J=2.03 Hz), 10.4 (s, 1H).

The synthetic route of 19155-24-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; American Home Products Corporation; Ligand Pharmaceuticals, Inc.; US6355648; (2002); B1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem