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., Safety of 2-(4-Hydroxycyclohexyl)isoindoline-1,3-dione

The title compound from Step A above (28 g, 114 mmol) was dissolved in dichloromethane (990 mL) and pyridinium chlorochromate (33.6 g, 157 mmol) was added in portions. The reaction mixture was stirred at room temperature for 8 h. Then another batch of pyridinium chlorochromate (10.4 g, 48.6 mmol) was added in portions and stirring at room temperature was continued for 18 h. The reaction mixture was filtered through a pad of Celite and the Celite pad was washed with dichlormethane (400 mL). The combined filtrate was concentrated under reduced pressure and the residue was purified by chromatography on silica using ethyl acetate/n-heptane (60/40) as a mobile phase to afford the title compound as a white solid (24.62 g, 88%)1H-NMR (400 MHz, CDCl3): delta=2.17-2.24 (m, 2H), 2.60-2.71 (m, 4H), 2.80-2.90 (m, 2H), 4.78 (tt, 1H), 7.84-7.88 (m, 2H), 7.97-8.02 (m, 2H)

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; AC Immune, S.A.; US2011/280808; (2011); A1;,
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Some common heterocyclic compound, 118289-55-7, name is 6-Chloro-5-(2-chloroethyl)indolin-2-one, molecular formula is C10H9Cl2NO, 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: C10H9Cl2NO

119 ml (90.1 g, 0.698 mols, 3.21 molar equivalents) of N,N-diisopropylethylamine, 500 ml of acetonitrile and 55.8 g (0.218 mols, 1.0 molar equivalents) of 3-(l- piperazinyl) -1, 2-benzisothiazole hydrochloride (addition salt of compound of formula (III) and hydrochloric acid) are added into a beaker equipped with a magnetic stirrer. The resulting suspension is stirred for 10 minutes. At this point 50 g (0.217 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 0.26 g (1.174 mmols, 0.008 molar equivalents) of NaI are added. The resulting brown suspension is charged into a 1 L reactor vessel, which is heated to 121-122 C (internal pressure increases to 200 kPa) for 25 hours. The reaction is cooled to room temperature and filtered. The solid is washed with acetonitrile, and 56 g of a wet solid are obtained. –> The resulting wet solid is stirred with 4 volumes of water at reflux temperature for 1 h to remove inorganic salts. The suspension is cooled to room temperature and filtered. The solid is washed with water. Ziprasidone base is obtained in 56% molar yield and the purity is 97.8% by HPLC.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 118289-55-7, its application will become more common.

Reference:
Patent; MEDICHEM, S.A.; WO2006/34964; (2006); A1;,
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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. 675109-26-9, name is 6-Bromoisoindolin-1-one, A new synthetic method of this compound is introduced below., COA of Formula: C8H6BrNO

(4) The compound obtained in step (3) (80 g, 0.38 mol) was dissolved in 1 L of dichloromethane.A 1 N solution of borane tetrahydrofuran (1 L) was added dropwise and stirred at room temperature for 4 hours.Then heated to reflux for 3 hours. The system cooled down,100 ml of 2N hydrochloric acid was added dropwise and the mixture was stirred at room temperature for 3 hours and then refluxed for 4 hours. Cooling filtration,The cake was washed with dichloromethane to give an off-white powder that was the target.

The synthetic route of 675109-26-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Shanghai Xinyuan Pharmaceutical Technology Co., Ltd.; Wu Tianjun; (9 pag.)CN107474006; (2017); A;,
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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. 6326-79-0, name is 6-Bromoisatin belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below. Product Details of 6326-79-0

For example, Compound 3 (N-benzyl-6-bromoindoline-2,3-dione) was prepared according to Scheme 1a: 6-Bromoisatin (SM1) (984 mg, 4.35 mmol, 1.0 equiv) was dissolved in N,N-dimethylformamide (8.70 mL), and the orange solution was cooled to 0 C. Sodium hydride (183 mg, 4.57 mmol, 60% dispersion in mineral oil, 1.05 equiv) was added in two portions, and the resulting purple suspension was maintained at 0 C. for 15 min. Benzyl bromide (604 muL, 5.05 mmol, 1.16 mmol) was added dropwise, and the resultant orange solution was maintained at 0 C. for 30 min. Water (30 mL) was added, and the biphasic mixture was extracted with EtOAc (4¡Á50 mL). The combined organics were dried over Na2SO4 and concentrated. Purification of the residue by silica gel flash column chromatography (gradient 1:3 EtOAc-hexanes to 100% EtOAc) gave Compound 3 (1.31 g, 95%) as an orange solid: mp 190192 C.; Rf 0.69 (3:7 EtOAc-hexanes); 1H NMR (500 MHz, CDCl3): delta 7.47 (d, J=7.9 Hz, 1H), 7.417.36 (m, 2H), 7.367.31 (m, 3H), 7.287.24 (m, 1H), 6.96 (d, J=1.4, 1H), 4.91 (s, 2H); 13C NMR (125 MHz, CDCl3): delta 182.1 (C), 158.3 (C), 151.6 (C), 134.2 (C), 133.7 (C), 129.4 (CH), 128.6 (CH), 127.6 (CH), 127.3 (CH), 126.5 (CH), 116.5 (C), 114.7 (CH), 44.4 (CH2); IR (film): 1733, 1603 cm1; HRMS-ESI (m/z) [M+Na]+ calcd. for C15H10NO2BrNa, 337.9792; found, 337.9786.

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

Reference:
Patent; Horne, David A.; Jove, Richard; Lincoln, Christopher; Nam, Sangkil; Overman, Larry; Xie, Jun; US2013/225637; (2013); A1;,
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Some common heterocyclic compound, 205383-87-5, name is tert-Butyl 2-oxospiro[indoline-3,3′-pyrrolidine]-1′-carboxylate, molecular formula is C16H20N2O3, 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. Safety of tert-Butyl 2-oxospiro[indoline-3,3′-pyrrolidine]-1′-carboxylate

A mixture containing commercially available tert-butyl 2-oxospiro [indoline-3, 3′-pyrrolidine] -1′-carboxylate (391 mg, 1.36 mmol) and NBS (290 mg, 1.63 mmol) in THF (5 mL) was heated to reflux and stirred for 20 h. The reaction mixture was then cooled, quenched with water, and extracted with EtOAc. The organic layer was concentrated and purified by chromatography on SiO2(2-20MeOH/DCM) to provide tert-butyl 5-bromo-2-oxospiro [indoline-3, 3′-pyrrolidine] -1′-carboxylate. MS (EI) calc’d for C16H20BrN2O3[M+H]+, 367 found, 367.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 205383-87-5, its application will become more common.

Reference:
Patent; MERCK SHARP & DOHME CORP.; ACHAB, Abdelghani Abe; CHRISTOPHER, Matthew P.; FRADERA LLINAS, Francesc Xavier; KATZ, Jason D.; METHOT, Joey L.; ZHOU, Hua; XU, Shimin; FU, Jianmin; FU, Ning; LI, Yabin; WANG, Xichao; (228 pag.)WO2017/166104; (2017); A1;,
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Synthetic Route of 5181-35-1, 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. 5181-35-1, name is 2-(2-Bromoethoxy)isoindoline-1,3-dione, This compound has unique chemical properties. The synthetic route is as follows.

To a mixture of 2-(2-bromoethoxy)isoindoline-l,3-dione (20 g, 74 mmol) and ethyl lH-tetrazol-5-ylacetate (11.55 g, 74 mmol) in DMF (100 ml) was added cesium carbonate (29 gm, 0.088 mol) in portion wise at 25-30 C under stirring. The stirring was continued for 16 hrs. The reaction mixture was filtered and the collected filtrate was slowly poured onto chilled water (700 ml) under stirring. The formed precipitates of compound were filtered on Buchner funnel and washed with water (70 ml). The solid compound was dried at 40C for 2 hour under reduced pressure to yield crude compound 18.0 g. The crude compound was column purified using hexane and acetone. The non-polar spot isolated at 10-15% concentration of acetone in hexane and yielded 8.0 g of ethyl (2-{2-[(l,3-dioxo-l,3-dihydro-2H-isoindol-2-yl)oxy]ethyl}-2H- tetrazol-5-yl)acetate. The polar spot isolated at 20-25% concentration of acetone in hexane, and the pure fractions were collected and concentrated on rota evaporator which yielded 5.0 g of ethyl (1- {2-[(l,3-dioxo-l,3-dihydro-2H-isoindol-2-yl)oxy]ethyl}-lH-tetrazol-5-yl)acetate as white solid in 53% yield. Analysis: Mass: 346.3 (M+H); for Molecular weight: 345 and Molecular formula: C15H15N5O5. 1HNMR (CDCI3): delta 7.84-7.26 (m, 4H), 5.05 (t, 2H, J=5.2 Hz), 4.77 (t, 2H, J=5.6 Hz), 4.23-4.18 (q, 2H), 3.97 (s, 2H), 1.27 (t, 3H, J= 7.2 Hz).

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

Reference:
Patent; WOCKHARDT LIMITED; TADIPARTHI, Ravikumar; PATIL, Vijaykumar Jagdishwar; DEKHANE, Deepak; SHAIKH, Mohammad Usman; BIRAJDAR, Satish; DOND, Bharat; PATEL, Mahesh Vithalbhai; (100 pag.)WO2017/81615; (2017); A1;,
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Synthetic Route of 118289-55-7, A common heterocyclic compound, 118289-55-7, name is 6-Chloro-5-(2-chloroethyl)indolin-2-one, molecular formula is C10H9Cl2NO, 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.

Example 2; The mixture of methylene chloride (130 ml) and 1-(1,2-Benzisothiazol-3- yl)piperazine (9.5 gm) is stirred for 10 minutes, triethylamine (17 ml) is added drop wise for 15 minutes at 25 – 300C and then tetrabutyl ammonium bromide (4 gm) is added. Then trimethylsilyl chloride (9.5 ml) is added to the contents drop EPO wise for 20 minutes and stirred for 1 hour. The reaction mass is heated to 400C and methylene chloride is distilled off under vacuum. Then the reaction mass is cooled to 300C, dimethylformamide (75 ml) is added and stirred for 15 minutes. The reaction mass is filtered on hi-flo and washed with 50 ml of dimethyl formamide.The mixture of 5-(2-Chloroethyl)-6-chloro-oxindole (10 gm), water (25 ml), dimethyl formamide (35 ml) and sodium carbonate (10 gm) is heated to 1100C and to this mixture, above filtrate is slowly added drop wise at same temperature for 30 minutes. Then the reaction mass is stirred until completion of the reaction and then cooled to 300C. The reaction mass is added to chilled water (500 ml) and stirred for 20 minutes. The solid is filtered, slurried in isopropyl alcohol (200 ml). Then the solid is filtered, washed with isopropyl alcohol (100 ml), the solid is again slurried in isopropyl alcohol at reflux and refluxed for 1 hour. Then resulting solid is filtered at reflux point and washed with isopropyl alcohol (60 ml) to give 10 gm of ziprasidone (HPLC purity: 99.05%)..

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

Reference:
Patent; HETERO DRUGS LIMITED; WO2006/80025; (2006); A1;,
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1029691-06-2, name is 2-(3-Oxocyclopentyl)isoindoline-1,3-dione, 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. Recommanded Product: 2-(3-Oxocyclopentyl)isoindoline-1,3-dione

Example 58B 2-(3-hydroxy-3-phenylcyclopentyl)isoindoline-1,3-dione A solution of Example 58A (1.00 g, 4.36 mmol) and THF (20 mL) was cooled to <-70 C. and phenylmagnesium chloride (2.40 mL, 4.80 mmol) was added at <-70 C. After 2 hours, saturated aqueous NH4Cl (20 mL) was added and the mixture was extracted with MTBE (50 mL). The organic layer was dried (Na2SO4) and concentrated. The residue was puridifed by flash column chromatography (0-20% EtOAc/hexanes, gradient elution), to provide the title compound (370 mg, 1.20 mmol, 27.6% yield). The synthetic route of 1029691-06-2 has been constantly updated, and we look forward to future research findings. Reference:
Patent; ABBOTT LABORATORIES; US2012/245163; (2012); A1;,
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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 132898-96-5 as follows. COA of Formula: C8H4ClNO4S

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.

According to the analysis of related databases, 132898-96-5, the application of this compound in the production field has become more and more popular.

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;,
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Application of 20870-78-4, 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. 20870-78-4 name is 5-Bromoindolin-2-one, 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.

5-Bromo-2-oxindole 16 (150 mg, 0.71 mmol), benzeneboronic acid (113 mg, 0.92 mmol), tetrakis(triphenylphosphine)palladium(0) (61 mg, 0.05 mmol) and Natrium carbonate (250 mg, 2.41 mmol) were suspended in toluene (1.5 mL) and ethanol (1.5 mL) and refluxed for 12 h at 100 C. Water was added and extracted 3 times with ethyl acetate. The combined organic layers were wash with 1N hydrochloric acid, brine, dried over MgSO4, filtered and concentrated in vacuum to give 75 mg (51%) as a light brown solid and was used for the next step without further structure determination.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 5-Bromoindolin-2-one, and friends who are interested can also refer to it.

Reference:
Article; Goering, Stefan; Taymans, Jean-Marc; Baekelandt, Veerle; Schmidt, Boris; Bioorganic and Medicinal Chemistry Letters; vol. 24; 19; (2014); p. 4630 – 4637;,
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