Category: 87691-88-1

3-Piperazinobenzisothiazole hydrochloride, cas is 87691-88-1, it is a common heterocyclic compound, the isothiazole compound, its synthesis route is as follows.,87691-88-1

4. Preparation of ZPR in water containing 10% n-BuOH. In a three necked flask was charged BITP HCl (4. 9g), Na2C03 (6.91g), CEI (4.68g), water (25ml) and n-BuOH (2. 5ml), and the mixture was heated. After about 20 hours reflux, ziprasidone was 75.5% area from the reaction mixture, and after 35h reflux the conversion to ZPR was 88%. The solid was filtrated from the reaction mixture, washed with water and dried. The HPLC purity of the product was 93.6% area.

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Reference£º
Patent; TEVA PHARMACEUTICAL INDUSTRIES LTD.; TEVA PHARMACEUTICALS USA, INC.; WO2005/40160; (2005); A2;,
Isothiazole – Wikipedia
Isothiazole – ScienceDirect.com

3-Piperazinobenzisothiazole hydrochloride, cas is 87691-88-1, it is a common heterocyclic compound, the isothiazole compound, its synthesis route is as follows.,87691-88-1

EXAMPLE 6 The mixture of 2.1 g of 4-(1,2-benzisothiazol-3-yl)piperazine hydrochloride, 2.0 g of 3-(3-chloropropionyl)-2-methyl-4,6,7,8-tetrahydro-5H-thieno[3,2-b]azepin-5-one, 2,2 g of potassium carbonate and 1.2 g of potassium iodide in 15 ml of N,N-dimethylformamide and 15 ml of toluene was stirred at 60 C. for 5 hours. After the mixture was cooled in a water bath, water was added thereto and the mixture was extracted with ethyl acetate. The organic layer was washed with saline solution, dried over magnesium sulfate and concentrated. The residue was purified by column chromatography on a silica gel, dissolved in isopropyl alcohol and crystallized from isopropyl alcohol-isopropyl ether. The resulting crystals were recrystallized from ethanol to give 1.30 g of 3-(3-(4-(1,2-benzisothiazol-3-yl)piperazin-1-yl)propionyl)-2-methyl-4,6,7,8-tetrahydro-5H-thieno[3,2-b]azepin-5-one as white crystals, m.p. 146-147 C.

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Reference£º
Patent; Yoshitomi Pharmaceutical Industries, Ltd.; US5532240; (1996); A;,
Isothiazole – Wikipedia
Isothiazole – ScienceDirect.com

3-Piperazinobenzisothiazole hydrochloride, cas is 87691-88-1, it is a common heterocyclic compound, the isothiazole compound, its synthesis route is as follows.,87691-88-1

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…

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Reference£º
Patent; MEDICHEM, S.A.; WO2006/34964; (2006); A1;,
Isothiazole – Wikipedia
Isothiazole – ScienceDirect.com

87691-88-1, 3-Piperazinobenzisothiazole hydrochloride is a isothiazole compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

87691-88-1, The above intermediate IV (0.01 mol) and the hydrochloride salt of the piperazine compound (V) (0.01 mol) were dissolved in DMF (100 mL), and K2CO3 (0.02 mol) was added.According to the general operation three,Preparation of 3-(3-(4-(benzo[d]isothiazol-3-yl)piperazin-1-yl)propyl)-1H-indole-5-hydroxy(VI-10) hydrochloride 3.21g, yield 75%

The synthetic route of 87691-88-1 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; Shanghai Pharmaceutical Industry Institute; China Pharmaceutical Industry Zongyuan; Li Jianqi; Gu Zhengsong; Zhou Ainan; Xiao Ying; (26 pag.)CN109467554; (2019); A;,
Isothiazole – Wikipedia
Isothiazole – ScienceDirect.com

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.87691-88-1,3-Piperazinobenzisothiazole hydrochloride,as a common compound, the synthetic route is as follows.

87691-88-1, Example 5Preparation of 5-[2-[4-(l,2-benzisothiazol-3-yl)-l-piperazinyn]ethyl]-6- chloro-l,3-di hydro-2H- indol-2-one:Charge 1.0 litre water, 100 gm of 5-(2-chloroethvl)-6-chlorooxindole product, 122.4 gm 3-(l-piperazinyl)-l,2-benzisothiazole HCI and 138.2 gm of sodium carbonate into a 3 litre three neck flask at 25 to 30 C. Stir for 15 minutes and heat to reflux temperature 95 to 100 C. Maintain at reflux temperature for 15 hrs. Cool the reaction mixture to 45 – 50C. Add 1.0 It of water into the reaction mixture and stir for 30 minutes. Filter at 45 to 50 C and wash with water. Suck dry for 30 minutes to yield crude product. Charge 2 It of water and above crude product and heat the mixture gradually to 45 to 50C and stir for 30 minutes. Filler the product at 45 to 50C and wash with water. Suck dry the product for 30 minutes. Charge 2.0 It of water and 300 gm of crude product into a 1.0 litre three neck flask at 25 to 30C and heat the mixture gradually to 45 to 50C. Stir for 30 mins. Filter the product at 45 to 50C and wash with water till about neutral pH (6.5 to 7.0). Suck dry the product for 30 minutes to get wet crude base 5-[2-[4-(l,2-benzisothiazo.-3-yl)-l-piperazinyl]ethylj-6- chloro-i,3-di hydro- 2H- indol-2-one. Add 300.-gms of wet crude base and 1.0 It of isopropanol at 25 to 30C. Warm the reaction mixture to 50 to 55C and stir for 1.0 hr. Cool the reaction mixture gradually to 10 to 15C and stir for 30 mins. Filter the product and wash with chilled isopropanol. Suck dry for 30 minutes. Charge 300gm of wet crude base and 6 It of tetrahydrofuran (THF). Heat the reaction mixture gradually to reflux temperature 65-70C. Reflux till clear solution. Cool to 50 to 55C and add charcoal and stir for 30 min at 50 to 55dC. Filter the charcoal and wash with hot THF. Distill out THF at 50 to 55 C under vacuum till residual volume is 1 It and cool the reaction mixture gradually to 5 to 10C and stir for 1 hr. Filter the product and wash with chilled THF. Suck dry the product for 30 minutes. Dry the product at 60 to 65C.

As the paragraph descriping shows that 87691-88-1 is playing an increasingly important role.

Reference£º
Patent; ARCH PHARMALABS LIMITED; GHOGARE, Bhausaheb Nana; DESHPANDE, Uday K.; PAI, Ganesh Gurpur; MANDAL, Arun Kanti; CHARANJIT, Sehgal; NEHA, Dixit Akshaya; WO2012/20424; (2012); A1;,
Isothiazole – Wikipedia
Isothiazole – ScienceDirect.com

3-Piperazinobenzisothiazole hydrochloride, cas is 87691-88-1, it is a common heterocyclic compound, the isothiazole compound, its synthesis route is as follows.,87691-88-1

To a flask equipped with mechanical stirrer, thermometer, condenser and nitrogen inlet was added 6-cUoro-5-(2-cHoroethyl)-l,3-dihydro-2H-indol-2- one (9.0 g, 39.1 mrnol), 3-(l-pirhoerazinyl)-l,2-benzoisothiazole hydrochloride (10.0 g, 39.1 mmol), sodium carbonate (9.96 g, 117.5 mmol) and poly(ethylene glycol) methyl ether (Mn= 350, 40 mL) and the suspension was heated to 120- 1250C under nitrogen for about 48 hrs. The suspension was cooled and poured into water. The suspension was cooled to 20-250C, the product was collected by filtration on a Buchner funnel and the filter cake was rinsed with water at 20-250C. The damp product was transferred to a flask equipped with mechanical stirrer, 100 mL of water were added and the suspension stirred at ambient temperature for 1 h. The suspension was filtered, washed with water and transferred to a drying oven and dried in vacuo. This afforded 14.2 g (88% yield) of crude ziprasidone.

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Reference£º
Patent; APOTEX PHARMACHEM INC.; WO2006/47893; (2006); A1;,
Isothiazole – Wikipedia
Isothiazole – ScienceDirect.com

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.87691-88-1,3-Piperazinobenzisothiazole hydrochloride,as a common compound, the synthetic route is as follows.

87691-88-1, EXAMPLE 36 3-[4-[1-(1,2-Benzisothiazol-3-yl)-4-piperazinyl]butyl]-5,5-dimethyl-4-thiazolidinone hydrochloride A mixture of 3-(4-bromobutyl)-5,5-dimethyl-4-thiazolidinone (3.50 g), 1-(1,2-benzisothiazol-3-yl)piperazine hydrochloride (3.70 g), K2 CO3 (6.34 g), NaI (330 mg) and acetonitrile (175 mL) was heated at 95 C. (bath temperature) under nitrogen. After 21 hours, TLC analysis (silica gel, 5% MeOH/CH2 Cl2) showed the absence of starting bromide and the presence of a major product, Rf =0.33. The reaction mixture was cooled to room temperature, ethyl acetate (150 mL) was added, and the mixture filtered. The filtrate was concentrated in vacuo to an oil which was triturated with ethyl acetate. The mixture was filtered again and the filtrate, after concentration, was chromatographed (Waters Prep 500, one silica gel column, 3% MeOH/CH2 CL2) to give 3.48 g of a viscous oil. The oil was dissolved in diethyl ether (500 mL), the solution filtered to remove a fluffy solid, and the filtrate acidified to pH=1 (hydrion paper) with an HCl/diethyl ether solution. The resultant salt (3.23 g) was recrystallized from ethanol/ethyl acetate yielding 2.29 g of white needles, mp 222-227 C. ANALYSIS: Calculated for C20 H28 N4 OS2 *HCl: 54.46%C; 6.63%H; 12.70%N; 8.04%Cl. Found: 53.93%C; 6.73%H; 12.58%N; 8.57%Cl.

As the paragraph descriping shows that 87691-88-1 is playing an increasingly important role.

Reference£º
Patent; Hoechst-Roussel Pharmaceuticals Inc.; US4933453; (1990); A;,
Isothiazole – Wikipedia
Isothiazole – ScienceDirect.com

3-Piperazinobenzisothiazole hydrochloride, cas is 87691-88-1, it is a common heterocyclic compound, the isothiazole compound, its synthesis route is as follows.,87691-88-1

EXAMPLE 6 The mixture of 2.1 g of 4-(1,2-benzisothiazol-3-yl)piperazine hydrochloride, 2.0 g of 3-(3-chloropropionyl)-2-methyl-4,6,7,8-tetrahydro-5H-thieno[3,2-b]azepin-5-one, 2,2 g of potassium carbonate and 1.2 g of potassium iodide in 15 ml of N,N-dimethylformamide and 15 ml of toluene was stirred at 60 C. for 5 hours. After the mixture was cooled in a water bath, water was added thereto and the mixture was extracted with ethyl acetate. The organic layer was washed with saline solution, dried over magnesium sulfate and concentrated. The residue was purified by column chromatography on a silica gel, dissolved in isopropyl alcohol and crystallized from isopropyl alcohol-isopropyl ether. The resulting crystals were recrystallized from ethanol to give 1.30 g of 3-(3-(4-(1,2-benzisothiazol-3-yl)piperazin-1-yl)propionyl)-2-methyl-4,6,7,8-tetrahydro-5H-thieno[3,2-b]azepin-5-one as white crystals, m.p. 146-147 C.

With the rapid development of chemical substances, we look forward to future research findings about 87691-88-1

Reference£º
Patent; Yoshitomi Pharmaceutical Industries, Ltd.; US5532240; (1996); A;,
Isothiazole – Wikipedia
Isothiazole – ScienceDirect.com

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.87691-88-1,3-Piperazinobenzisothiazole hydrochloride,as a common compound, the synthetic route is as follows.

87691-88-1, 3-Piperazin-1-yl-benzoisothiazole hydrochloride (5. 29 G, 20.7 MMOL) and 4, 5-dimethoxy-2-nitrophenylacetic acid (5 g, 20.7 MMOL) were combined in 200 mL methylene chloride with triethylamine (5.77 mL, 41.4 MMOL). This solution stirred for 15 min before BIS- (2-OXO-3-OXAZOLIDINYL) phosphinic chloride (5.26 g, 20.7 MMOL) was added. After stirring overnight at rt, the reaction was quenched with water and extracted into methylene chloride. The organic layer was washed with 0.5 N HCI, water, sodium bicarbonate then water before it was dried over NA2SO4 and concentrated. The residue was taken up in methylene chloride and washed with water. The organic layer was dried over sodium sulfate, and concentrated then purified by MPLC using a Biotage prepacked silica gel cartridge eluting with 3% methanol in methylene chloride to afford 6.5 g of a tan solid. Yield 71% ; 100% purity at 214 nm; LCMS (APCI) : 443 [M+H] + ; MP 170C.

As the paragraph descriping shows that 87691-88-1 is playing an increasingly important role.

Reference£º
Patent; WARNER-LAMBERT COMPANY LLC; WO2004/41793; (2004); A1;,
Isothiazole – Wikipedia
Isothiazole – ScienceDirect.com

3-Piperazinobenzisothiazole hydrochloride, cas is 87691-88-1, it is a common heterocyclic compound, the isothiazole compound, its synthesis route is as follows.,87691-88-1

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…

With the rapid development of chemical substances, we look forward to future research findings about 87691-88-1

Reference£º
Patent; MEDICHEM, S.A.; WO2006/34964; (2006); A1;,
Isothiazole – Wikipedia
Isothiazole – ScienceDirect.com