1254319-51-1 Archives - Indolines-derivatives

Sep-21 News Machine Learning in Chemistry about 1254319-51-1

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. 1254319-51-1, name is 6-Bromo-2-methylisoindolin-1-one belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below. Related Products of 1254319-51-1

6-Bromo-2-raethylisoindolin-l-one (723 mg, 3.41 mmol), bis(pinacolato)diboron (1.04 g, 4.09 mmol), potassium acetate (1.00 g, 10.2 mmol) and PdCl2(dppf) catalyst (139 mg, 0.17 mmol) were weighed into a flask which was sealed under N2. DMSO (15 mL) was added, and the entire mixture stirred at 90C for 5 h. Upon cooling, the reaction mixture was diluted with water (250 mL) and extracted with CH2C12 (5×50 mL). The combined CH2C12 fractions were in turn washed with water (2×100 mL), brine (100 mL), dried (Na2S04), filtered and the solvent removed under reduced pressure to yield the crude product. Purification was carried out by flash column chromatography on silica gel (20% THF/CH2C12 as eluant) to give the title compound as a crystalline beige solid (262 mg, 28%). NMR [400 MHz, (CD3)2SO] delta 7.91 (br s, 1 H), 7.85 (dd, J = 7.6, 1.0 Hz, 1 H), 7.59 (dd, J = 7.5, 0.6 Hz, 1 H), 4.49 (s, 2 H), 3.07 (s, 3 H), 1.32 (s, 12 H). LRMS (APCI+) calcd for Ci5H2iBN03 274 (MH+), found 274.

The synthetic route of 1254319-51-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; PETER MACCALLUM CANCER INSTITUTE; SPICER, Julie Ann; HUTTUNEN, Kristiina Maria; LYONS, Dani Michelle; TRAPANI, Joseph Albert; SMYTH, Mark John; DENNY, William Alexander; WO2011/75784; (2011); A1;,
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The origin of a common compound about C9H8BrNO

Synthetic Route of 1254319-51-1,Some common heterocyclic compound, 1254319-51-1, name is 6-Bromo-2-methylisoindolin-1-one, molecular formula is C9H8BrNO, 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 stirred solution of 2,6-bis(benzyloxy)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)pyridine 25-1 (2.19 g, 5.25 mmol) and 6-bromo-2-methylisoindolin-1-one (31-1) (474 mg, 2.10 mmol) in dioxane/water (30 mL), in a sealed tube, was degassed for 10 minutes under an argon atmosphere. PdCl2(dppf)-DCM (153 mg, 210 mumol) was added and the reaction was heated to 80 C for 10 h. TLC was checked in 30% ethyl acetate/hexane, which showed the complete consumption of starting material and formation of the desired spot at rf 0.4 in 30% ethylacetate- hexane. The reaction mixture was diluted with ethyl acetate, washed with water. The layers were separated and the organic layer was concentrated under reduced pressure. The crude residue was purified using combiflash (50% ethyl acetate/hexane) and concentrated to afford 6-(2,6-Bis- benzyloxy-pyridin-3-yl)-2-methyl-2,3-dihydro-isoindol-1-one (31-1) (725 mg, 1.66 mmol, 79% yield). LC MS: ES+ 437.2.

The synthetic route of 1254319-51-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; C4 THERAPEUTICS, INC.; PHILLIPS, Andrew, J.; NASVESCHUK, Chris, G.; HENDERSON, James, A.; LIANG, Yanke; HE, Minsheng; LAZARSKI, Kiel; VEITS, Gesine, Kerstin; VORA, Harit, U.; (794 pag.)WO2017/197046; (2017); A1;,
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Introduction of a new synthetic route about C9H8BrNO

Synthetic Route of 1254319-51-1, A common heterocyclic compound, 1254319-51-1, name is 6-Bromo-2-methylisoindolin-1-one, molecular formula is C9H8BrNO, 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.

The synthetic route of 1254319-51-1 has been constantly updated, and we look forward to future research findings.

Analyzing the synthesis route of C9H8BrNO

Related Products of 1254319-51-1,Some common heterocyclic compound, 1254319-51-1, name is 6-Bromo-2-methylisoindolin-1-one, molecular formula is C9H8BrNO, 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 mixed solution of compound 2b (5 g, 22 mmol), bisboronic acid pinacol (8.5 g, 33 mmol) and KOAc (3.2g, 33 mmol) in 1,4 dioxane (50 ml) was added Pd(dppf)2Cl2 (1g), and flushed with nitrogen. The reaction flask wassealed and the reaction was stirred overnight at 85C. After cooling to room temperature, an aqueous Na2CO3 solution(2.5M, 10ml), Pd(dppf)2Cl2 (1g) and 2,5-dibromo-3-nitropyridine (9 g, 33 mmol) were added. After flushed with nitrogenfor 10 minutes, the reaction flask was sealed and the mixture was stirred overnight at 85C. The reaction was pouredinto water and extracted with ethyl acetate. The organic phase mixture was dried over Na2SO4, dried by suction andpurified by silica gel column chromatography (PE:EA=10:1 to 1:1) to provide compound 2c as a yellow solid.HNMR(DMSO),9.1(s,1H),8.8(s,1H),7.7-7.8(m,3H),4.5(s,2H),3.1(s,3H).MS(ESI)m/z:347.9(M +H)+.

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-2-methylisoindolin-1-one, its application will become more common.

Reference:
Patent; NINGBO WENDA PHARMA TECHNOLOGY LTD.; WANG, Nenghui; (65 pag.)EP3406612; (2018); A1;,
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Extended knowledge of 1254319-51-1

To a solution of 6-bromo-2-methylisoindolin-1-one (5 g,22.1 mmol) in dmf (30 mL) was added bis(pinacolato)diboron (6.18 g,24.3 mmol) and potassium acetate (6.51 g,66.4 mmol). The reaction mixture was degassed and backfilled with N2 gas,and 1,1 ?-bis(diphenylphosphino)fenocene palladium(II)dichloride dichloromethane (0.903 g,1.106 mmol) was added.The reaction mixture was stined at 80 C for 10 hours. After diluting with EtOAc and water, The organic layer was concentrated and purified on silica column (100% EtOAc) to get the product as a mixture of the title compound as a boronic ester and boronic acid,which was not further purified.MS: 274 (m+1)?H NMR (500 MHz,CDCl3): oe 8.33 (s,1H),7.98 (d,7.5 Hz,1H),7.46 (d,7.5 Hz,1H),4.41 (s,2H),3.22 (s,3H),1.38 (s,12H). The following intermediates in table c were preparedaccording to scheme c using the procedure outlined in the synthesis intermediate cl using 1,1?-bis(di-tert-butylphosphino)fenocene palladium dichloride or 1,1 ?-bis(diphenylphosphino)ferrocene palladium(II)dichloride dichloromethane complex as the palladium catalyst with toluene or dmf as the reaction solvent. The starting material bromide was either commercially available,known in the literature,or prepared using the protocol in scheme B.

Reference:
Patent; MERCK SHARP & DOHME CORP.; MSD R&D (CHINA) CO., LTD.; ACTON, John J.; BAO, Jianming; EGBERTSON, Melissa; GAO, Xiaolei; HARRISON, Scott Timothy; KNOWLES, Sandra Lee; LI, Chunsing; LO, Michael Man-Chu; MAZZOLA, Robert D., Jr.; MENG, Zhaoyang; RUDD, Michael T.; SELYUTIN, Oleg; TELLERS, David M.; TONG, Ling; WAI, Jenny Miu-Chun; (125 pag.)WO2017/107089; (2017); A1;,
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The important role of C9H8BrNO

Electric Literature of 1254319-51-1, 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. 1254319-51-1, name is 6-Bromo-2-methylisoindolin-1-one belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below.

To a solution of 6-bromo-2-methylisoindolin-l-one (5 g, 22.1 mmol) in DMF (30 mL) was added bis(pinacolato)diboron (6.18 g, 24.3 mmol) and potassium acetate (6.51 g, 66.4 mmol). The reaction mixture was degassed and backfilled with N2 gas, and l, l’-bis(diphenyl-phosphino)ferrocene palladium(II)dichloride dichloromethane (0.903 g, 1.106 mmol) was added. The reaction mixture was stirred at 80 C for 10 hours. After diluting with EtOAc and water, the organic layer was concentrated and purified on silica column (100% EtOAc) to get the product as a mixture of the title compound as a boronic ester and boronic acid, which was not further purified. MS: 274 (M+1). 1H MR (500 MHz, CDC13): delta 8.33 (s, 1 H), 7.98 (d, 7.5 Hz, 1 H), 7.46 (d, 7.5 Hz, 1 H), 4.41 (s, 2 H), 3.22 (s, 3 H), 1.38 (s, 12 H).

The synthetic route of 6-Bromo-2-methylisoindolin-1-one has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MERCK SHARP & DOHME CORP.; MSD R&D (CHINA) CO., LTD.; ACTON, John, J., III; BAO, Jianming; DENG, Qiaolin; EGBERTSON, Melissa; FERGUSON, Ronald, III; GAO, Xiaolei; HARRISON, Scott Timothy; KNOWLES, Sandra, L.; LI, Chunsing; LO, Michael Man-Chu; MAZZOLA, Robert, D., Jr.; MENG, Zhaoyang; NA, Meng; RUDD, Michael, T.; SELYUTIN, Oleg, B.; TELLERS, David, M.; TONG, Ling; ZHANG, Fengqi; (195 pag.)WO2019/5587; (2019); A1;,
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Discovery of 1254319-51-1

Reference of 1254319-51-1,Some common heterocyclic compound, 1254319-51-1, name is 6-Bromo-2-methylisoindolin-1-one, molecular formula is C9H8BrNO, 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-bromo-2-methylisoindolin-1-one (10.1 g) in THE (250 mL) was addedLDA (33.5 mL, 2 M in THE) at -20C. The mixture was stirred at 0C for 30 minutes andthen methyl 2-bromoacetate (10.3 g) was added at 0C. The mixture was allowed towarm to RT and stirred for 20 hours. The mixture was poured into water (300 mL) and then extracted with EA (200 mL x 3). The combined organic phases were washed with brine (50 mL) and dried over Na2504. After filtration and evaporation of the solvent, the obtained residue was purified by column chromatography on silica gel eluting with ENPE = 1:3 to provide the title compound. MS ESI: mlz = 298 [M+H].

Reference:
Patent; SANOFI; SCHWINK, Lothar; BUNING, Christian; GLOMBIK, Heiner; GOSSEL, Matthias; KADEREIT, Dieter; HALLAND, Nis; LOHMANN, Matthias; POeVERLEIN, Christoph; RITTER, Kurt; WO2015/150565; (2015); A1;,
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Continuously updated synthesis method about 1254319-51-1

The synthetic route of 1254319-51-1 has been constantly updated, and we look forward to future research findings.

Potassium acetate (294 mg, 3.00 mmol), bis(pinacolato)diboron (305 mg, 1.200 mmol), 6-bromo-2- methylisoindolin-l-one (271 mg, 1.200 mmol) and 2nd Generation XPHOS precatalyst (59.0 mg, 0.075 mmol) were added to a 8 mL reaction vial equipped with a stir bar. The vial was evacuated and charged 3x with nitrogen. 1,4-Dioxane (8 mL) was added, the vial was again evacuated and charged (3x) with nitrogen, and the borylation reaction was heated to 100C. Monitored by LCMS; once borylation was complete the reaction was cooled to room temperature and 2-chloro-3 -(-(( 1- fluorocyclopentyl)methyl)-lH-pyrazol-4-yl)-6-methylpyridine (INTERMEDIATE F7; 294 mg, 1.0 mmol) and l, -bis(di-tert-butylphosphino)ferrocene palladium dichloride (48.9 mg, 0.075 mmol) were added to the reaction. The vial was evacuated and charged 3x with nitrogen, then added 3M aqueous K2C03 (1.0 mL, 3.00 mmol). The reaction was then heated to 70C overnight. LCMS shows reaction is substantially complete. Cooled to room temperature, then partitioned between water and ethyl acetate. The organic was filtered over a bed of sodium sulfate. The aqueous was extracted twice more with ethyl acetate, and the organic from those extractions was used to wash the sodium sulfate as well. The combined filtrate was evaporated and taken up again in DCM, then purified by silica gel chromatography, eluting with 20-100% 3 : 1 EtOAc:EtOH in hexanes. The major peak was isolated and the volatiles were evaporated. The solid was scraped to a small particle size and treated with diethyl ether. The suspension was filtered and the solid was collected as the title compound. MS: 405 (M+l). 1H NMR (500 MHz, CDC13): delta 7.89 (s, 1H), 7.67 (d, J=7.5 Hz, 1H), 7.58 (d, J=7.7 Hz, 1H), 7.39 (d, J=7.7 Hz, 1H), 7.21 (s, 1H), 7.18 (d, J=7.8 Hz, 1H), 7.04(s, 1H), 4.39 (s, 2H), 4.23 (d, J=21.6 Hz, 2H), 3.20 (s, 3H), 2.62 (s, 3H), 1-77-1.58 (m, 8H).

The synthetic route of 1254319-51-1 has been constantly updated, and we look forward to future research findings.

Brief introduction of 1254319-51-1

(S)-tert-Butyl 4-( 1 -amino- 1 -oxo-3-(4-(4,4,5 ,5 -tetramethyl- 1 ,3 ,2-dioxaborolan-2- yl)phenyl)propan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (Example 16, step (i), 300 mg), 6-bromo-2-methylisoindolin-l-one (Example 30, step (i), 131 mg) and potassium acetate (171 mg) in a mixture of acetonitrile (15 mL) and water (5 mL) was stirred under nitrogen at 900C with 1,1 delta(di-fert-butylphosphino)ferrocene palladium dichloride (378 mg). After 4 h the reaction mixture was cooled to room temperature and diluted with water (50 mL). The products were extracted with ethyl acetate (3 x 50 mL) and the combined extracts dried over magnesium sulfate and concentrated to afford the sub-titled compound (200 mg).m/e (MultiMode+) 436 [M+2Eta-BOC]+

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; FORD, Rhonan; METE, Antonio; MATHER, Andrew; MILLICHIP, Ian; WO2010/128324; (2010); A1;,
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New learning discoveries about 1254319-51-1

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 6-Bromo-2-methylisoindolin-1-one, and friends who are interested can also refer to it.

Adding a certain compound to certain chemical reactions, such as: 1254319-51-1, name is 6-Bromo-2-methylisoindolin-1-one, 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 1254319-51-1, Recommanded Product: 6-Bromo-2-methylisoindolin-1-one

General procedure: 5-Bromo-2-methylisoindolin-1-one (520 mg, 2.30 mmol) and thiophene-2-boronic acid (442mg, 3.45 mmol) were dissolved in a mixure of toluene (12 mL) and EtOH (6 mL). A solutionof 2 M Na2CO3 (3 mL) and Pd(dppf)Cl2 (94 mg, 0.12 mmol) were added and the entiremixture heated at reflux under N2 for 2 h. Additional thiophene-2-boronic acid (294 mg, 2.30mmol) was added and reflux continued under N2 overnight. Upon cooling, the mixture wasdiluted with water (100 mL) and extracted with CH2Cl2 (6×50 mL). The combined organicfractions were dried (Na2SO4), filtered, and the solvent removed under reduced pressure togive a crude solid which was purified by flash column chromatography on silica gel (EtOAcas eluant). The title compound was isolated as a light-brown solid (510 mg, 97%).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 6-Bromo-2-methylisoindolin-1-one, and friends who are interested can also refer to it.

Reference:
Article; Spicer, Julie A.; Miller, Christian K.; O’Connor, Patrick D.; Jose, Jiney; Huttunen, Kristiina M.; Jaiswal, Jagdish K.; Denny, William A.; Akhlaghi, Hedieh; Browne, Kylie A.; Trapani, Joseph A.; Bioorganic and Medicinal Chemistry Letters; vol. 27; 4; (2017); p. 1050 – 1054;,
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