Tag: M.W=200-300

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. 104618-31-7, name is 2-(4-Hydroxycyclohexyl)isoindoline-1,3-dione, A new synthetic method of this compound is introduced below., category: indolines-derivatives

190gms(0.7755mole) 4-phthalimido cyclohexanol are dissolve in 1480ml chloroform.Add solution of H2SO4 (435.87gm, 4.4476mole cone. H2SO4 was added in 900 mlwater). Cool mass to 25C,add lot wise 180.5gm(0.6139mole) potassium dichromate inone hour. Stir mass for three hours, add 900 ml water and separate organic phase.Organic phase was washed with water and 2% NaHCO3 solution, after drying andconcentration of extracts product was isolated by adding methanol and water mixture.YIELD: 175g(92.4%)PURITY: 96.01%.

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; ALEMBIC LIMITED; WO2006/3677; (2006); A1;,
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Related Products of 2436-29-5, 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. 2436-29-5, name is 3-(1,3-Dioxoisoindolin-2-yl)propanal, This compound has unique chemical properties. The synthetic route is as follows.

Example 26Synthesis of 2-(3-((7-methoxy-3-(2-(methylamino)pyrimidin-4-yl)naphthalen-1-yl)amino)propyl)isoindoline-1,3-dione (181) To a slurry of 4-(4-amino-6-methoxynaphthalen-2-yl)-N-methylpyrimidin-2-amine (150 mg, 0.42 mmol) in 1,2-dichloromethane (10 ml) was added N,N-diisopropylethylamine (250 mul) followed by acetic acid (0.5 ml), 3-(1,3-dioxoisoindolin-2-yl)propanal (140 mg) and sodium triacetoxyborohydride (200 mg). The mixture was stirred at room temperature for 24 hours before being poured into ethyl acetate (100 ml) washed with water (250 ml) and dried over anhydrous magnesium sulfate. Evaporation to dryness gave a yellow oil which was purified by silica gel chromatography eluting with 40-60% ethyl acetate in hexanes to yield 2-(3-((7-methoxy-3-(2-(methylamino)pyrimidin-4-yl)naphthalen-1-yl)amino)propyl)isoindoline-1,3-dione 181 as a yellow foam (95 mg). 1H NMR (CDCl3) 400 MHz delta 8.34 (d, J=5.2 Hz, 1H), 7.87 (s, 1H), 7.86-7.83 (m, 3H), 7.8 (d, J=8.8 Hz, 1H), 7.75-7.71 (m, 2H), 7.34 (s, 1H), 7.31 (d, J=2.4 Hz, 1H), 7.18 (dd, J=2.4 and 8.8 Hz, 1H), 7.08 (d, J=4.8 Hz, 1H), 5.24 (m, 1H), 4.9 (m, 1H), 4.04 (s, 3H), 3.9 (t, J=6.0 Hz 2H), 3.5 (t, J=6.0 Hz, 2H), 3.11 (d, J=5.2 Hz, 3H), 2.24 (m, 2H), 2.2-2.14 (m, 2H), LCMS m/e 468 (M+H)

The chemical industry reduces the impact on the environment during synthesis 3-(1,3-Dioxoisoindolin-2-yl)propanal. I believe this compound will play a more active role in future production and life.

Reference:
Patent; ArQule, Inc.; US2011/166137; (2011); A1;,
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Application of 118289-55-7, These common heterocyclic compound, 118289-55-7, name is 6-Chloro-5-(2-chloroethyl)indolin-2-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.

88.7 g (0.837 mols, 3.21 molar equivalents) of sodium carbonate, 600 ml of acetonitrile and 66.7 g (0.261 mols, 1.0 molar equivalent) of 3- (1-piperazinyl) -1, 2- benzisothiazole hydrochloride [hydrochloride of the compound of formula (III) ] are added into a beaker –> equipped with a magnetic stirrer. The resulting white suspension is stirred for 10 minutes. At this point 60.0 g (0.261 mols, 1.0 molar equivalent) of 5- (2- chloroethyl) -6-chloro-l, 3-dihydro-indole-2- (2H) -one [compound of formula (II) wherein X is chlorine] and 0.3 g (0.002 mols, 0.008 molar equivalents) of NaI are added. The resulting brown suspension is charged into a 1 L reactor vessel, which is purged with nitrogen and heated to 120-125 C (internal pressure increases to 400-500 kPa) for 25 hours. The reaction is cooled to room temperature, stirred for 30 minutes, filtered and the solid washed with acetonitrile. A wet mixture of zipradisone and inorganic salts is obtained.The resulting wet mixture is stirred with 675 ml of water at reflux temperature for 1 h to remove inorganic salts . The suspension is cooled at room temperature, stirred for 30 minutes and filtered. The solid is washed with water, and 140 g of wet solid (corresponding to 87 g of dry material) are obtained.The wet solid is stirred again with water at reflux temperature for 1 h to remove residual inorganic salts. The suspension is cooled to room temperature, stirred for 30 minutes and filtered. The solid is washed with water, and 170 g of wet solid (corresponding to 81 g of dry- material) are obtained. HPLC analysis reveals a purity of 97.8%.To remove starting materials present in the wet solid obtained in the previous step, it is stirred twice with 400 ml of tetrahydrofuran at reflux temperature. The solution is cooled to room temperature, stirred for 30 –> minutes and filtered. The solid is washed twice with 40 ml of tetrahydrofuran at room temperature and 60 g of wet solid, corresponding to 54.8 g of dry material, are obtained.The solid obtained is ziprasidone base having a purity of 99.4% by HPLC and the global yield from the starting compound (II) or (III) is 51% molar. Potentiometric titration with HClO4: 100.03% Optionally, Ziprasidone base could be converted to ziprasidone hydrochloride.;Example 3. Large scale preparation of ziprasidone baseInto a 100 1 Hastelloy reactor are loaded:- 8 kg (31.3 mols 1.0 molar equivalent) of 3-(l- piperazinyl) -1, 2-benzisothiazole hydrochloride[hydrochloride of compound of formula (III) ] ,- 8.64 kg (37.5 mols, 1.2 molar equivalents) of 5- (2- chloroethyl) -6-chloro-l, 3-dihydro-indole-2- (2H) -one [compound of formula (II) wherein X is chlorine] ,- 10.6 kg (100 mols, 3.20 molar equivalents) of sodium carbonate,- 0.038 kg (0.25 mols, 0.008 molar equivalents) of NaIThe reactor is closed and blanketed with vacuum/nitrogen. Then, 56.3 kg of acetonitrile are loaded and the mixture is stirred for 10 minutes. The reactor is heated to reflux (80-82 C) . Then the reactor is closed and –> continued to be heated up to 120-125 C (internal pressure increases to 300 kPa) . The reaction mixture is kept under these conditions for 25 hours. Then the content is cooled down to room temperature and the solid is centrifuged and washed with 2 x 12 kg of acetonitrile. A wet solid containing ziprasidone base and inorganic salts is obtained.The resulting solid is loaded in a 100 1 Hastelloy reactor. The reactor is blanketed and 52 kg of water are loaded. The suspension is stirred at reflux conditions(80-850C; due to the presence of acetonitrile) for 1 h to remove inorganic salts. The suspension is cooled down to room temperature, stirred for 30 minutes and the solid is centrifuged and washed with 2 x 9 kg of water. 17.97 kg of wet solid are obtained.The wet solid from the previous step is loaded in a 100 1 Hastelloy reactor. The reactor is blanketed and 57 kg of tetrahydrofuran are loaded. The suspension is stirred at reflux conditions for 1 h. The suspension is cooled down to room temperature, stirred for 30 minutes and the solid is filtered through a Nutsche Filter and washed with 2 x 16 kg of tetrahydrofuran. 10.53 kg of wet solid (corresponding to 8.57 kg of dry material) are obtained.The solid obtained is ziprasidone base having a purity by HPLC of 99.2%. The global yield from the starting compound (III) is 66.3% (molar yield) . Optionally, Ziprasidone base could be converted to ziprasidone hydrochloride.Example 4 : Preparation of ziprasidone base –> 13.26 g (0.400 mols, 3.20 molar equivalents) of sodium carbonate, 10.00 g (0.039 mols, 1.0 molar equivalent) of3- (1-piperazinyl) -1, 2-benzisothiazole hydrochloride [hydrochloride of the compound of formula (III)], 10.80 g(0.0469 mols, 1.2 molar equivalent) of 5- (2-chloroethyl) -6-chloro-l, 3-dihydro-indole-2- (2H) -one [compound of formula (II) wherein X is chlorine] and 7.030 g (0.0469 mols, 1.2 molar equivalents) of NaI are added into a 250 ml round bottom, three necked reaction vessel, equi…

The synthetic route of 118289-55-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MEDICHEM, S.A.; WO2006/34964; (2006); 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. 104618-32-8, name is 2-(4-Oxocyclohexyl)isoindoline-1,3-dione, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: 2-(4-Oxocyclohexyl)isoindoline-1,3-dione

Example 11 3-Amino-6-(N-methylsulphonamidomethyl)-1,2,3,4-tetrahydrocarbazole oxalate Reaction of 4-phthalimidocyclohexanone (0.42 g) with 4-(N-methylsulphonamidomethyl) phenyl hydrazine hydrochloride (0.44 g), and subsequent deprotection by the method described in example 3, gave the title compound free base. This was treated with oxalic acid to give the oxalate salt (0.15 g), mp 218-222C dec.

According to the analysis of related databases, 104618-32-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; SMITHKLINE BEECHAM PLC; EP603432; (1994); A1;,
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Reference of 99365-40-9, 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. 99365-40-9, name is 6-Bromoindolin-2-one belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below.

A solution of 28 (3.74 g, 17.64 mmol) in dry THF (150mL) was degassed with N2 for 15 min. The solution was then cooled to-78 C and a solution of NaHMDS (1 M in THF, 88.2 mL) was added dropwise over a10 min period. The reaction was stirred at -78 C for 1 h before adding solid N-benzyl-2-chloro-N-(2-chloroethyl)ethan-1-amine HCl salt (5.20 g, 19.40 mmol) in oneportion. The reaction was stirred at -78 C for 1 h before removing the coldbath and allowing the reaction to warm to rt. Upon reaching rt, the reactionwas heated to 70 C (reflux) for 15 hours. The mixture was cooled to 0 C and asaturated aq. NH4Cl solution (150 mL) was added followed by EtOAc(300 mL) for the workup. The organic layer was separated and the aqueous layerwas extracted twice with EtOAc (50 mL x 2).The organic layers were combined, washed with brine, dried using Na2SO4and evaporated to afford the crude product. This crude product wastriturated using hot petroleum ether to give 29 (6.10 g, 93%) as a pink colored solid.

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

Reference:
Article; Lotesta, Stephen D.; Marcus, Andrew P.; Zheng, Yajun; Leftheris, Katerina; Noto, Paul B.; Meng, Shi; Kandpal, Geeta; Chen, Guozhou; Zhou, Jing; McKeever, Brian; Bukhtiyarov, Yuri; Zhao, Yi; Lala, Deepak S.; Singh, Suresh B.; McGeehan, Gerard M.; Bioorganic and Medicinal Chemistry; vol. 24; 6; (2016); p. 1384 – 1391;,
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Application of 99365-40-9, 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. 99365-40-9, name is 6-Bromoindolin-2-one, This compound has unique chemical properties. The synthetic route is as follows.

n-Butyllithium (2.25 M in hexane, 130 mL, 259.4 mmol) was added drop wise at -40C to a solution of 6-bromoindolin-2-one (25.0 g, 117.9 mmol) and diisopropylamine (36.54 mL, 259.4 mmol) in THF (500 mL).The mixture was stirred for 45 mm at that temperature, 1,2-dibromoethane (31.0 mL, 353.7 mmol) wasadded drop wise and stirring was continued for 16 h while the temperature was slowly raised to RT. Thereaction mixture was quenched with 4 N HCI (400 mL) and the aqueous part was separated andextracted with EtOAc (3x 100 mL). The combined organic layers were washed with brine and dried overNa2504. The solvents were evaporated and the residue was triturated with EtOAchexane (1:4, 200 mL),filtered and washed with EtOAc/hexane (1:4, 100 mL). Brown solid. Yield: 26.0 g (92%). HPLC (method 1): R = 2.92 mi mlz [M+H] = 240.0 (MW calc. 238.08)

The chemical industry reduces the impact on the environment during synthesis 6-Bromoindolin-2-one. I believe this compound will play a more active role in future production and life.

Reference:
Patent; GRUeNENTHAL GMBH; KONETZKI, Ingo; JAKOB, Florian; WAGENER, Markus; WELBERS, Andre; HESSLINGER, Christian; (138 pag.)WO2017/108203; (2017); A1;,
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These common heterocyclic compound, 1029691-06-2, name is 2-(3-Oxocyclopentyl)isoindoline-1,3-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. COA of Formula: C13H11NO3

Mix (±)-2-(3-oxo-cyclopentyl)-isoindole- 1 ,3-di- one (12.7 g, 55.3 mmol) and 4-cyanophenylhydrazine-HC1 (8.53 g, 50.3 mmol) in HOAc (200 mE) and 4N HC1 dioxane (50 mE). Using mechanical stirring, heat the reaction to 90 C. for 18 h, then add additional 4N HC1 dioxane (20 mE). Heat the reaction to 100 C. for 18 h. Dilute the reaction mixture with water (600 mE) and collect a black solid by vacuum filtration. Sonicate the solid with MeOH (200 mE), then collect and dry in a vacuum oven to give 10.94 g (66%) of a gray-brown solid. MS (mlz): 328 (M+H), 326 (M-H)

The synthetic route of 2-(3-Oxocyclopentyl)isoindoline-1,3-dione has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Eli Lilly and Company; Benson, Charles Thomas; (29 pag.)US2017/172992; (2017); A1;,
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Application of 20780-72-7, These common heterocyclic compound, 20780-72-7, name is 4-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.

Take 4-bromo indolone 1.0g (4.4mmol) into a 25mL round bottom flask,4 mL of N, N-dimethylformamide was added,Stirring to make it fully dissolved, and then adding 1.83 g (13.2 mmol) of anhydrous potassium carbonate,Further, 1.0 g (6.6 mmol) of methyl iodide was added.The reaction at room temperature for 8h, TLC detection of raw materials disappeared, adding 30mL of water,Then, the mixture was extracted with ethyl acetate (100 mL × 3), the combined organic phases were dried over anhydrous sodium sulfate,The solvent was decanted and the residue purified by petroleum ether: ethyl acetate = 10: 1200-300 mesh silica gel column.There was obtained 0.90 g of 1-methyl-4-bromoindodione in 85percent yield.

Statistics shows that 4-Bromoisatin is playing an increasingly important role. we look forward to future research findings about 20780-72-7.

Reference:
Patent; Tianjin Kunjian Bio-pharmaceutical Co., Ltd.; Yu Peng; Han Kailin; Mao Huihua; Qiu Dongxu; (12 pag.)CN104402794; (2017); B;,
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These common heterocyclic compound, 18711-13-2, name is 4,7-Dichloroindoline-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. category: indolines-derivatives

4,7-Dichloroisotin (30.05 g, 139.1 mmol, 1.0 equiv, Alfa Aesar lot 10173559) and MeOH (450 mL, 15 vol) were charged to a 2-L, three-neck, round-bottom flask equipped with nitrogen line, overhead mechanical stirrer, and a temperature probe. Diethylamine (3.25 g, 0.32 equiv, Sigma- Aldrich lot SHBD5313V) was added over 3 min (the slurry becomes dark red). A very slight increase in temperature (from 17.5 C to 18.8 C) was observed. 1- [4-(Dimethylamino)phenyl]ethanone 2 (44.3 g, 1.95 equiv, ArkPharm lot 0000197- 130717000) was then added via a plastic funnel and the funnel was rinsed with MeOH (75 mL, 2.5 vol). A decrease in the reaction temperature to 15.1 C was observed. Upon stirring for a few minutes, a dark red solution with a few undissolved particles was obtained. The solution was stirred at ambient temperature and periodically sampled for in-process control (IPC) by HPLC. After 23 h of reaction, additional diethylamine was added via syringe (1.42 g, 0.14 equiv) and the stirring continued at ambient temperature. After 40.5 h, a light slurry formed. Solid 2 was added in portions (54.1 g, 2.38 equiv, ArkPharm lot 0000197- 130717000 and 3.2 g, 0.14 equiv, TCI lot GK01-BRAH) for a total of 4.47 equiv of acetophenone 2. After 88 h of reaction, IPC by HPLC showed less than 1% AUC of isatin 1 present in the reaction mixture. A heavy precipitate had formed. After 4.5 days, the reaction mixture was concentrated under reduced pressure (water bath <40 C), then under high vacuum to afford approximately 84 g of a solid mixture, lot BIO-W-22-11. The solid was dissolved in a mixture of dichloromethane (385 mL) and MeOH (140 mL) and adsorbed over 100 g of silica gel. The solvent was removed under reduced pressure and the dry product/silica mixture was loaded onto a column containing silica gel (1 kg, pre-packed with heptanes) for a flash chromatographic purification. Elution was started with 10% ethyl acetate in heptanes and a gradient up to 100% ethyl acetate was applied, and then switched to 10% methanol in ethyl acetate. Fractions of 500 mL and up to 2 L were collected. The product containing fractions, where product had started to precipitate, were combined and concentrated down to approximately 1 L. The resulting precipitate was filtered out, reslurried in EtOAc/MeOH (75:25 ratio, 200 mL), filtered, and washed with MeOH to afford a first crop of compound. The first filtrate was concentrated to a low volume, added MeOH to precipitate a second crop of compound. Filtrates from isolation of both crops were combined, concentrated to a low volume, taken up in 25 mL of MeOH, and the resulting solid was filtered to afford a third crop of compound. All three crops were dried under high vacuum at ambient temperature for a day and at 40 C for four days. The total combined weight was 40.03 g, corresponding to 76% yield of compound (uncorrected by purity or solvent content). Solid is off-white (with a very pale yellow to peach shade. The synthetic route of 4,7-Dichloroindoline-2,3-dione has been constantly updated, and we look forward to future research findings. Reference:
Patent; TOKALAS, INC.; VERNIER, Jean-michael; (82 pag.)WO2016/57698; (2016); A1;,
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Application of 2058-72-2, These common heterocyclic compound, 2058-72-2, name is 5-Bromo-1-methylindoline-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.

A mixture of 2- (1-benzyl-2-oxoindol-3-yl) acetic acid67.4 mg (0.24 mmol),5-Bromo-1-methyl isatin 47.7mg (0.2mmol),N, N’-2- (7-benzo benzotriazole) -N, N, N ‘, N’-tetramethyluronium hexafluorophosphate (106.4 mg, 0.28 mmol)Triethylamine 50.6 mg (0.5 mmol)And 2 mL of tetrahydrofuran were placed in a 25 mL two-necked flask,Reaction at 0 C for 6 h,The reaction solution was concentrated,Eluting with a mixed solvent of petroleum ether: ethyl acetate ratio of 3: 1 as elution column,Collecting the eluted fraction of all the products detected,Rotate the solvent to give the product 90.3mg,The yield was 90% and the Dr value was 4: 1.

Statistics shows that 5-Bromo-1-methylindoline-2,3-dione is playing an increasingly important role. we look forward to future research findings about 2058-72-2.

Reference:
Patent; China Pharmaceutical University; Du Ding; Cao Jing; Dong Shuding; (14 pag.)CN106749295; (2017); A;,
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