Tag: M.W=200-300

Synthetic Route of 919103-45-0,Some common heterocyclic compound, 919103-45-0, name is 6-Iodoindolin-2-one, molecular formula is C8H6INO, 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 nitrogen purged vessel is loaded with starting material 6-lodoindolinone (1 05kg,405mo1, 1,0 eq), catalyst 4-dimethylaminopyridine (DMAP) (2,52 kg) under argoncounter flow. Then triethylamine (145 kg, 3,5 eq) and solvent 2-methyltetrahydrofuran(605 kg) are charged to the vessel and the resulting solution is cooled to -15 00 to-S00 (preferentially -10C). Benzoylchloride (176,6 kg, 3,1 eq) is added to this mixture atan internal temperature of 100C to 50C within at least 30mm.The addition funnel is then flushed with 2-methyltetrahydrofuran (22 kg) and the reaction mixture is stirred for an additional hour at an internal temperature of 10 to 30C. If the content of starting material 6-iodoindolinone is greater than 2,5 area%(H PLC), another portion of benzoylchloride (5,7 kg) is added to complete the reaction. If the content of starting material 6-iodoindolinone is smaller than 2,5 area% (H PLC), lithium hydroxide (59,4 kg, 6,0 eq) is added in 5 differently sized portions (1st: 18,0 kg, 2?: 6,0 kg, 3: 6,0 kg, 41h: 15,0 kg, 5th: 14,4 kg) in a temperature controlled manner:After the two first portions, the mixture is stirred for 1 hour. After portion 3 and 4, the mixture is stirred for 30mm. After the last portion, the mixture is stirred for two hours. The reaction mixture (suspension) is then stirred for at least 12 hours at an internal temperature of 20 to 30 C. If the content of the non isolated intermediate of formula (V) is smaller than 0,5 area% (H PLC), water (525 L) is added and the mixture is heatedto an internal temperature of 60 to 7000 under stirring. Then the stirrer is switched off, the mixture is settled down and the phases are separated at an internal temperature of 60 to 70C. To the upper organic layer, water (525 L) is added and a second phase separation is carried out at an internal temperature of 60 to 70C. (Optionally, the mixture might be left stand at room temperature for up to 24 hours.) Then a partial solvent switch to tetrahydrofuran is carried out: Solvent is distilled off three times at a jacket temperature of 70C down to a residual volume of 390L followed by addition of tetrahydrofuran (1st: 233 kg, 2nd. 233 kg, 3rd. 117 kg). For crystallization, firstly, methanol (83 kg) is added.Optionally, the mixture might be left stand at room temperature for up to 24 hours. Secondly, water (112 L) is added at an internal temperature of 60 to 70C, followed by addition of conc. hydrochloric acid (156,2 kg). The addition funnel is flushed with water (20 L). The resulting suspension is cooled to 20 to 30C within at least 70mm (optionally, the mixture might be left stand at room temperature for up to 72 hours) and then to an internal temperature of minus 5 to 5 C within at least 30mm. The suspension is then centrifuged and the solid is washed with water (368 L) followed by methanol (112 kg) and dried at a jacket temperature of 50C until <= 1% of residual solvent is reached. The enol product of formula (IV) is obtained as solid in 84,6% yield. The synthetic route of 919103-45-0 has been constantly updated, and we look forward to future research findings. Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; MAIER, Gerd-Michael; BAUM, Anke; BETZEMEIER, Bodo; HENRY, Manuel; HERTER, Rolf; REISER, Ulrich; SINI, Patrizia; WEBER, Dirk; WERTHMANN, Ulrike; ZAHN, Stephan Karl; WO2014/9318; (2014); A1;,
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Some common heterocyclic compound, 20780-72-7, name is 4-Bromoisatin, 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. category: indolines-derivatives

Diethylaminotrifluorosulfur (1.5 mL, 11.06 mmol) was added to a solution of 4-bromo-1H-indole-2,3-dione (1.0 g, 4.4 mmol) in dichloromethane (44 mL) at 0¡ãC. The mixture was stirred at room temperature for 54 hours and then quenched with methanol-water. The organic layer and the aqueous layer were separated, and the aqueous layer was then extracted with dichloromethane. The organic layers were combined, dried over sodium sulfate and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give 4-bromo-3,3-difluoro-1,3-dihydro-indol-2-one as a yellow solid (559 mg, 51percent). MS (ESI) m/z = 246 (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 20780-72-7, its application will become more common.

Reference:
Patent; Chugai Seiyaku Kabushiki Kaisha; EP2433940; (2012); A1;,
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Electric Literature of 18711-13-2, 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. 18711-13-2, name is 4,7-Dichloroindoline-2,3-dione, This compound has unique chemical properties. The synthetic route is as follows.

General procedure: To a solution of isatin derivative (0.68mmol, 1.0eq) in DMF (4mL) was added K2CO3 (0.68mmol, 1.0eq) at room temperature, the mixture was stirred for about 30min, and then the propargyl bromide (0.75mmol, 1.1eq) was added dropwise. The mixture was stirred for 6-10hat room temperature depending on the isatin derivative used. Upon completion, EtOAc and H2O were added. The aqueous layer was extracted with EtOAc; the combined organic layers were washed with H2O for several times to remove the DMF, and then washed with brine, dried over MgSO4 and evaporated to give the products. Saffron solid, yield: 76%, m. p.: 151.8-153.3C, Rf=0.52 (petroleum ether/ethyl acetate=2/1). 1H NMR (400MHz, CDCl3) delta 7.51 (d, J=8.7Hz, 1H), 7.10 (d, J=8.7Hz, 1H), 4.94 (d, J=2.4Hz, 2H), 2.34 (t, J=2.4Hz, 1H).13C NMR (100MHz, CDCl3) delta 178.68, 157.00, 146.19, 140.48, 133.05, 126.79, 117.16, 116.11, 77.22, 73.27, 31.94

The chemical industry reduces the impact on the environment during synthesis 4,7-Dichloroindoline-2,3-dione. I believe this compound will play a more active role in future production and life.

Reference:
Article; Yu, Bin; Qi, Ping-Ping; Shi, Xiao-Jing; Huang, Ruilei; Guo, Hao; Zheng, Yi-Chao; Yu, De-Quan; Liu, Hong-Min; European Journal of Medicinal Chemistry; vol. 117; (2016); p. 241 – 255;,
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Adding a certain compound to certain chemical reactions, such as: 132898-96-5, name is 2,3-Dioxoindoline-5-sulfonyl chloride, 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 132898-96-5, Safety of 2,3-Dioxoindoline-5-sulfonyl chloride

Step 2: Preparation of N, N-dimethyl-2,3-dioxoindoline-5-sulfonamide (148) To a mixture of 2,3-dioxoindoline-5-sulfonyl chloride (0.800 g, 3.26 mmol) in dry THF (10 ml), cooled at 0C under nitrogen, DI PEA (1 .138 ml, 6.51 mmol) and dimethylamine 2M in TH F (2.1 17 ml, 4.23 mmol) were added and the mixture was allowed to stir at room temperature for 2.5 hours. The mixture was partitioned between ethyl acetate and water, and the aqueous layer was extracted three times with ethyl acetate. The combined organic layers were dried over sodium sulfate and evaporated to dryness to give N ,N-dimethyl-2,3-dioxoindoline-5-sulfonamide (0.639 g, 2.51 mmol, 77% yield). MS/ESI+ 254.9 [MH] +.

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, 2,3-Dioxoindoline-5-sulfonyl chloride, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; CHIESI FARMACEUTICI S.P.A.; ARMANI, Elisabetta; AMARI, Gabriele; CAPALDI, Carmelida; CARZANIGA, Laura; LA PORTA, Elena; GUALA, Matilde; WO2013/57013; (2013); A2;,
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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, name: 2-(4-Hydroxycyclohexyl)isoindoline-1,3-dione

Under nitrogen, the 2-(4-hydroxycyclohexyl)-1H-isoindole-1,3(2H)-dione (1.23g, 5.01 mmol) obtained in Example 385, (b), the 4-methoxy-1H-indazol-5-ol (0.906 g, 5.52 mmol) obtained in Example 469 and 90%-cyanomethylenetri-n-butylphosphorane (161 g, 6.02 mmol) were dissolved in toluene (20 ml), and the resulting solution was heated under reflux for 5 hours. The reaction solution was cooled to room temperature and water and a 1N-aqueous sodium hydroxide solution were added thereto. The resulting solution was separated by the addition of toluene and the desired compound was extracted from the aqueous layer with toluene. The combined toluene layer was washed with a saturated aqueous sodium chloride solution, dried by the addition of anhydrous magnesium sulfate, and then filtered. The solvent was distilled off under reduced pressure and the concentration residue thus obtained was purified by a silica gel column chromatography (eluent: n-hexane/ethyl acetate = 2/1, 1/1) to obtain 2-[4-[(4-methoxy-1H-indazol-5-yl)oxy]cyclohexyl]-1H-isoindole-1,3(2H)-dione (1.29 g, yield 66%). IR (neat)cm-1; 3373, 2949, 2360, 1697, 1508, 1375, 1350, 1238, 1219, 1076, 1035, 1018.

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; Sumitomo Pharmaceuticals Company, Limited; EP1403255; (2004); A1;,
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Synthetic Route of 87-48-9, These common heterocyclic compound, 87-48-9, name is 5-Bromoindoline-2,3-dione, 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 2-bromoaniline or 3-bromoaniline (110 mmol, 18.9 g), chloral hydrate (118.8 mmol,19.6 g), anhydrous sodium sulfate (880 mmol, 125 g), and hydroxylamine hydrochloride (347.6mmol, 24.2 g) in water (700 mL) was heated under reflux for 25 min to form a yellow precipitate. 50mL of ethanol was added after that and left to boil for another 4 min before filtration. The resultedisonitrosoacetanilide was then heated with sulfuric acid (150 mL) at 70 C for about 10 min thenpoured into ice water to form an orange precipitate. When using 3-bromoaniline, an extra step ofseparation is required by solving the resulted mixture in 0.25 M NaOH (1 L), filtering it, then addingacetic acid (100 mL) to afford 4-bromoistain as a precipitate. 6-Bromoistin can be then obtained whenlowering the pH of the solution to 1 by hydrochloric acid 37%.All substituted bromo-isatins were methylated by stirring (22 mmol, 4.97 g) with sodiumhydride (2 mmol, 0.968 g) and dimethylsulfate (23.1 mmol, 2.19 mL) in dried DMF (50 mL) undernitrogen atmosphere. The resulting mixture was poured after 2 h in ice water (100 mL) to form anorange precipitate.The methylated bromo-isatins (2 mmol, 0.480 g) were treated after that with oxindole (2 mmol,0.226 g) in a 100:1 mixture of glacial acetic acid and hydrochloric acid 37% (12 mL) in reflux for about 3 h. Then, they were poured in ice water (50 mL) to afford 5-, 6- and 7-bromomeisoindigo. While 4′-, 5′-, 6′- and 7′-bromomeisoindigo were obtained by reacting unmethylated bromo-isatins(2 mmol, 0.452 g) with 1-methyloxindole (2 mmol, 0.294 g) in the same conditions. The resultedprecipitates were washed with water, ethanol (2 x 10 mL), and diethylether (2 10 mL) then dried. 3.2.1. 5-Bromo-1-MeisoindigoYield: 70%. 1H-NMR (400 MHz, DMSO, d6) delta ppm 3.19 (s, 3H), 6.83 (dd, 3J = 7.8 Hz, 4J = 0.5 Hz, 1H)6.96 (m, 1H), 6.97 (d, 3J = 8.4 Hz, 1H), 7.35 (td, 3J = 7.6 Hz, 4J = 1.1 Hz), 7.58 (dd, 3J = 8.4 Hz, 4J = 2.1 Hz),9.06 (dd, 3J = 8.1 Hz, 4J = 0.5 Hz), 9.31 (d, 4J = 2.0 Hz, 1H), 10.94 (s, 1H). 13C-NMR (100 MHz, DMSO,d6) delta ppm 26.6, 110.2, 110.7, 114.0, 121.8, 121.9, 123.0, 130.2, 131.1, 131.5, 133.8, 134.8, 135.6, 144.4, 145.0,167.2, 169.3. Anal. calcd. for C17H11BrN2O2: C 57.49, H 3.12, N 7.89; found: C 57.44, H 3.18, N 793.HRMS (ESI) calculated m/z: 376.9896; found C17H11BrN2O2; m/z: 376.9896 [M + H]+.

The synthetic route of 87-48-9 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Tegethoff, Jana; Bischoff, Roland; Saleh, Sawsan; Blagojevic, Biljana; Merz, Karl-Heinz; Cheng, Xinlai; Molecules; vol. 22; 9; (2017);,
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6326-79-0, name is 6-Bromoisatin, 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. COA of Formula: C8H4BrNO2

Synthesis of 1-Methyl-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1,3-dihydro-indol-2-one (R7) Step 1: Synthesis of Intermediate I-4.1 [0293] To R12 (25.0 g, 111 mmol) in acetonitrile (750 mL) is added MeI (15 mL, 241 mmol) and K2CO3 (60.0 g, 434 mmol) and the reaction mixture is stirred at 60 C. for 2 h. The reaction mixture is filtered and concentrated. Water and ethyl acetate are added to the residue. The organic layer is extracted twice with water, dried over MgSO4 and concentrated. Yield 56%, m/z 240/242 [M+H]+, rt 0.48 min, LC-MS Method X001-004.

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

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; ANDERSKEWITZ, Ralf; GRUNDL, Marc; MORSCHHAEUSER, Gerd; OOST, Thorsten; PAUTSCH, Alexander; US2014/275114; (2014); A1;,
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Application of 20780-72-7, The chemical industry reduces the impact on the environment during synthesis 20780-72-7, name is 4-Bromoisatin, I believe this compound will play a more active role in future production and life.

Commercially available 4-bromoisatin (2.50 g, 11.1 mmol) was dissolved in a 1.5 mol/L sodium hydroxide aqueous solution (20 mL), and 33percent hydrogen peroxide water (1 mL) was dropped at 55¡ãC. After being stirred at 55¡ãC for 30 minutes, the reaction mixture was cooled to room temperature, neutralized with 2.0 mol/L hydrochloric acid, and purified with HP-20 resin to give 2-amino-6-bromobenzoic acid (1.60 g, 67percent).

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, 4-Bromoisatin, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Kyowa Hakko Kirin Co., Ltd.; OTSUBO, Nobumasa; OKAZAKI, Shuko; TSUKUMO, Yukihito; IIDA, Kyoichiro; NAKOJI, Masayoshi; EP2708540; (2014); A1;,
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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. 435273-55-5, name is 4-Bromo-2-methylisoindolin-1-one, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: 435273-55-5

To a mixed solution of compound 3b (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 cooled 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=10:2 to 1:1) to provide compound 3c as a yellow solid.MS(ESI)m/z:347.9(M+H)+.

Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 435273-55-5.

Reference:
Patent; NINGBO WENDA PHARMA TECHNOLOGY LTD.; WANG, Nenghui; (65 pag.)EP3406612; (2018); A1;,
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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. 1035235-27-8, name is tert-Butyl 4-bromoisoindoline-2-carboxylate, This compound has unique chemical properties. The synthetic route is as follows., COA of Formula: C13H16BrNO2

A mixture of tert-butyl 4-bromoisoindoline-2-carboxylate (1.70 g, 5.70 mmol),4,4,4?,4?,5 ,5 ,5 ?,S ?-octamethyl-2,2?-bi(1 ,3 ,2-dioxaborolane) (1.74 g, 6.84 mmol), potassiumacetate (1.68 g, 17.1 mmol), and PdC12(dppf) DCM adduct (0.466 g, 0.570 mmol) in 1,4-dioxane (25 mL) was bubbled with nitrogen and stirred at 80 C overnight. The mixture was cooled to room temperature, diluted with EtOAc, washed with water, dried and concentrated. The residue was subjected to colunm chromatography on silica gel, eluting with EtOAc-hexanes (gradient from 0-30%), to provide tert-butyl 4-(4,4,5 ,5 -tetramethyl5 1 ,3,2-dioxaborolan-2-yl)isoindoline-2-carboxylate as a white solid (1.50 g, 76% yield).

Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 1035235-27-8.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; AHMAD, Saleem; BATT, Douglas G.; LIU, Qingjie; MACOR, John E.; TINO, Joseph A.; WATTERSON, Scott Hunter; NAIR, Satheesh Kesavan; MAISHAL, Tarun Kumar; (247 pag.)WO2016/65236; (2016); A1;,
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