Category: 5747-48-8

5747-48-8, 11-(Piperazin-1-yl)dibenzo[b,f][1,4]thiazepine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

5747-48-8, ll-Piperazin-l-yldibenzo[b,f][l,4]thiazepine was screened for potential salt formation with 30 acids listed below in Table 1. Stock solutions (0.05 M) of each of the acids were prepared in methanol. A stock solution (0.05 M) of amorphous 11-piperazin-l- yldibenzo[b,f][l,4]thiazepine (free base) was also prepared. A 150 muL aliquot of free base solution was mixed with a 150 muL aliquot of each of the acid solutions in individual wells of a glass 96-well plate. Each combination was prepared in duplicate. The methanol was allowed to evaporate either at room temperature (rt) or at 50 0C. Each well was then viewed microscopically at a magnification of 4Ox initially, under crossed-polars, to determine the nature (crystalline or non-crystalline) of any solid material that was formed.A 300 muL aliquot of another solvent (either acetone, acetonitrile or ethyl acetate) was added to each well. The plate was then sonicated to re-dissolve the solid material, followed by storage at room temperature or 50 C, allowing evaporation of solvent. Each well was then viewed microscopically at a magnification of 4Ox initially, under crossed-polars, to determine the nature (crystalline or non-crystalline) of any solid material that was formed. Results are shown in Table 1. The symbol “A” indicates formation of solid amorphous particles/film. The symbol “B” indicates formation of amorphous cake. The symbol “C” indicates formation of ciystalline particles. The symbol “P” indicates precipitation after mixing and formation of crystalline particles.Table 1

As the paragraph descriping shows that 5747-48-8 is playing an increasingly important role.

Reference£º
Patent; ASTRAZENECA AB; WO2007/62336; (2007); A2;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

5747-48-8,With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.5747-48-8,11-(Piperazin-1-yl)dibenzo[b,f][1,4]thiazepine,as a common compound, the synthetic route is as follows.

A 1 liter round bottom flask equipped with stirring rod, thermo pocket, water condenser was charged with solution of 11- piperazinyldibenzo[b,f] [l,4]thiazepine in toluene 350 cc [63.0 g (0.22 moles)] and the mixture was stirred for 15 min 25- 30C, and, to which, was added sodium carbonate [41.0 gm (0.39 moles)], tetra butyl ammonium bromide [16.0 gm (0.05 moles)] and 2-(2-chloroethoxy)ethanol [32.0 gm (0.257 moles)] at room temperature. The reaction mixture was heated to reflux at 110- 112C. The reaction mixture was maintained at reflux for 10-12 hrs. The reaction mixture was analyzed by HPLC (to check absence of compound of formula IV) and was cooled to 25C to 30C. To which, was added 150 cc DM water. Then the reaction mixture was stirred for 30 min at 25-30C. The layers were separated and the aqueous layer extracted with 50 cc toluene. The extracts and the organic layer were combined, and the pH was adjusted to 2-3 using IN HCl solution in DM (demineralized) water, the reaction mixture was then stirred for 30 min at 25-30C. The layers were separated and the aqueous layer washed with 100 cc toluene twice. To the aqueous layer was added 250 cc toluene, and the pH was adjusted to 8-10 using sodium carbonate, the reaction mixture was stirred for 30 min at 25-30C. The layers were separated and the aqueous layer extracted with 125 cc toluene. The extracts and the organic layer were combined, and washed with DM (demineralized) water 300 cc twice. The organic layer was distilled – off under vacuum below 70C to afford 2-(2-(4-dibenzo[b,f]-[l,4] thiazepine- l l-yl-l-piperazinyl)ethoxy)ethanol Purity of 2-(2-(4-dibenzo[b,f]-[l,4] thiazepine- l l-yl-l-piperazinyl)ethoxy)ethanol was 99.0 (area % by HPLC).

The synthetic route of 5747-48-8 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; TEVA PHARMACEUTICAL INDUSTRIES LTD.; TEVA PHARMACEUTICALS USA, INC.; WO2008/121415; (2008); A2;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.5747-48-8,11-(Piperazin-1-yl)dibenzo[b,f][1,4]thiazepine,as a common compound, the synthetic route is as follows.

Example II. Synthesis of quetiapine by reductive alkilation of 11-piperazindibenz[b,f][1,4]thioazepine with (2-hydroxyethoxy)acetaldehyde in the presence of magnesium borohydride. The mixture of 11-piperazindibenz[b,f][1,4]thioazepine (1 g, 0,0034 mol), sodium acetate (0,8 g, 0,01 mol), glacial acetic acid (4 cm3), (2-hydroxyethoksy)acetaldehyde (0,35g, 0,0034 mol) and water (50 cm3) is cooled to 0C. Next sodium borohydride was slowly (40 min) added (7 g, 0,13 mol) in temperature 0C. After this time the mixture was stirred for 1 h in temperature 10C and 10% aq NaOH was added (to pH about 8-9). The mixture was extracted with diethyl ether (3×30 cm3), organic faze was dried by sodium sulfate. The product (1.09g) was obtain with purity about 90% (HPLC), 5747-48-8

The synthetic route of 5747-48-8 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; Celon Pharma Sp. z o.o.; EP1602650; (2005); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.5747-48-8,11-(Piperazin-1-yl)dibenzo[b,f][1,4]thiazepine,as a common compound, the synthetic route is as follows.

5747-48-8, General procedure: To a solution of isocyanate (1.877mmol) in toluene (2.5mL) was added a solution of a monosubstituted piperazine (1.877mmol) in toluene (1.0mL). The reaction mixture was heated at 40-45C for 30 to 60min. The reaction mixture was then cooled down to room temperature (22-25C) and the resulting solids were filtered and washed with more toluene (2.0mL). The wet solids were then placed in 2.0mL of toluene, stirred at room temperature for about 30min, filtered and washed with toluene (1.0mL) to obtain the crude disubstituted piperazine derivative. Finally, all crude derivatives were purified by silica-gel column chromatography using a mixture of dichloromethane/methanol (9:1) to afford pure piperazines products.

The synthetic route of 5747-48-8 has been constantly updated, and we look forward to future research findings.

Reference£º
Article; Patil, Mahadev; Noonikara Poyil, Anurag; Joshi, Shrinivas D.; Patil, Shivaputra A.; Patil, Siddappa A.; Bugarin, Alejandro; Bioorganic Chemistry; vol. 92; (2019);,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

5747-48-8, 11-(Piperazin-1-yl)dibenzo[b,f][1,4]thiazepine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

In 5 mL of acetonitrile was dissolved 500 mg (1.693 mmol) of 11-piperazin-l- yldibenzo[b,fj[l,4]thiazepine. In 5 mL of acetonitrile at room temperature was dissolved 166 mg (1.693 mmol) H2SO4. The solutions were combined resulting in immediate precipitation of a gummy solid. The solid did not redissolve upon reheating, but did triturate into a free-flowing solid. The solids collapsed overnight into a gummy mass which was redissolved in methanol (50 mL) and stripped down to a granular solid which was triturated under acetone (20 mL), filtered, and dried under vacuum at 40 0C resulting in 660 mg (99%). mp 100-105 0C (sharp). 1H NMR (DMSO-dbeta) was consistent with the title salt.Polarized light microscopy revealed the material to be composed of agglomerates of very small crystalline particles. DSC revealed two large and three small endothermic events (Figure 7). Of the two large events, the lower temperature event may correspond to water/solvent loss and the higher temperature event may correspond to melt/decomposition. The three small events may correspond to form changes. DVS revealed that the material is hygroscopic with isotherms characteristic of a weak multi-hydrate (Figure 8). The experiment was terminated near the end of sorption phase of the second cycle. Data from the first cycle indicated that moisture was lost during the desorption phase that had not been lost during the initial drying phase. Approximately 2.5 mole equivalents of water were gained in the first cycle while nearly 4 mole equivalents were gained during the second cycle., 5747-48-8

Big data shows that 5747-48-8 is playing an increasingly important role.

Reference£º
Patent; ASTRAZENECA AB; WO2007/62336; (2007); A2;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

5747-48-8, 11-(Piperazin-1-yl)dibenzo[b,f][1,4]thiazepine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

EXAMPLE 5; Preparation of Quetiapine from ll-piperazinyldibenzo[b,f][l,4]thiazepine; [0040] 33.1 g of extra fine potassium carbonate is added to the r¡ã-butanol solution of 1 l-piperazinyldibenzo[b,fj[l54]thiazepine with continuous stirring. Then, 16.48 g of sodium iodide and 35.97 g of 2-(2-chloroethoxy)ethanol are respectively added with stirring. With continued mixing, the reaction mixture is heated to a temperature of 102 C and maintained at that temperature for 12 – 16 hours. The conversion of 11- piperazinyldibenzo[b,fj[l,4]thiazepine to quetiapine can be monitored by HPLC analysis. Once the conversion of is complete, the reaction mixture is cooled to a temperature of less than about 80 0C and about 500 g of water is added to adjust the reaction mixture to a temperature of about 40 – 50 C and the mixing is continued for at least about 30 minutes. The biphasic mixture is transferred to a separatory funnel and the aqueous and organic phases are allowed to separate. The lower aqueous phase is isolated and discarded. The upper organic phase containing crude quetiapine is transferred to a flask. Another 25O g of water is added to the quetiapine solution and the reaction mixture is stirred at a temperature of about 40 – 50 C for at least 30 additional minutes. The biphasic mixture is again transferred to a separatory funnel and the aqueous and organic phases are allowed to separate. The lower aqueous phase is removed and discarded. The upper organic phase containing crude quetiapine is recovered and transferred to a flask and distillation setup suitable for vacuum distillation to azeotropically remove water. Vacuum is applied to the distillation setup as the solution is heated, possibly to a temperature as high as 55 – 65 C at the end of the distillation, to remove water. The distillation is continued until no more water is observed collecting in the collection trap. The still bottoms may be checked by KF moisture analysis; the amount of KF water should be less than 0.5% by weight. Once the distillation is complete, the crude quetiapine solution is cooled to a temperature of less than 30 0C., 5747-48-8

The synthetic route of 5747-48-8 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; CAMBREX CHARLES CITY, INC.; WO2006/135544; (2006); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

5747-48-8,5747-48-8, 11-(Piperazin-1-yl)dibenzo[b,f][1,4]thiazepine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Example 11 2-(2-(4-dibenzo[b,f][1,4]thiazepine-11-yl-1-piperazinyl)ethoxy)ethanol OR 11-[4-[2-(2-hydroxyethoxy)ethyl]-1-piperazinyl]dibenzo[b,f][1,4]thiazepine A 1 liter round bottom flask equipped with stirring rod, thermo pocket, water condenser was charged with solution of 11-piperazinyldibenzo[b,f][1,4]thiazepine in toluene 350 cc [63.0 g (0.22 moles)] and the mixture was stirred for 15 min at 25-30 C. Sodium carbonate [41.0 gm (0.39 moles)], tetra butyl ammonium bromide [16.0 gm (0.05 mole)] and 2-(2-chloroethoxy)ethanol [32.0 gm (0.257 moles)] were added at room temperature. The reaction mixture was heated to reflux at 110-112 C. The reaction mixture was maintained at reflux for 10-12 hrs. The reaction mixture was analyzed by HPLC (to check the absence of compound of Formula IV) and was cooled to 25 C. to 30 C., and was added 150 cc DM water. The reaction mixture was then stirred for 30 min at 25-30 C. The layers were separated and the aqueous layer extracted with 50 cc toluene. The extract and the organic layer were combined, to which was added 250 cc water and was acidified with formic acid to obtain a pH of 2-3. The reaction mixture was stirred for 30 min at 25-30 C. The layers were separated and the aqueous layer washed with 100 cc toluene twice. To the aqueous layer was added 250 cc toluene, and the pH adjusted to 8-10 using sodium carbonate. The resulting reaction mixture was stirred for 30 min at 25-30 C. The layers were separated and the aqueous layer extracted with 125 cc toluene. The organic layers were combined and washed with DM water 300 cc twice. The organic layer was distilled off under vacuum below 70 C. to afford 2-(2-(4-dibenzo[b,f]-[1,4]thiazepine-11-yl-1-piperazinyl)ethoxy)ethanol. Purity of 2-(2-(4-dibenzo[b,f]-[1,4]thiazepine-11-yl-1-piperazinyl)ethoxy)ethanol was 99.0% (area % by HPLC).

The synthetic route of 5747-48-8 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; Kansal, Vinod Kumar; Ahmad, Suhail; Lal, Kanhaiya; Patil, Bhatu Tumba; US2008/241949; (2008); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

5747-48-8,With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.5747-48-8,11-(Piperazin-1-yl)dibenzo[b,f][1,4]thiazepine,as a common compound, the synthetic route is as follows.

(a) 11-[4-[2-(2-hydroxyethoxy)ethyl]-1-piperazinyl]dibenzo[b,f][1,4]thiazepine. 11-Piperazinyldibenzo[b,f][1,4]thiazepine (0.1 mole), sodium carbonate (0.18 mole), sodium iodide (0.016 mole) and 2-chloroethoxyethanol (0.108 mole) were combined together in toluene (250 ml) and N-methylpyrrolidone (55 ml). The reaction was heated at reflux over 24 hours. The reaction was cooled and washed with water (1 * 175 ml., 2 * 60 ml.). The organic phase was dried by azeotropic distillation. A solution of fumaric acid (0.06 mole) in ethanol (110 ml) was added to the toluene solution at 60-70C. On cooling the hemifumarate salt crystallized out and was isolated by filtration in 75% yield, m.pt 172-173C.

As the paragraph descriping shows that 5747-48-8 is playing an increasingly important role.

Reference£º
Patent; IMPERIAL CHEMICAL INDUSTRIES PLC; EP282236; (1988); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

5747-48-8, 11-(Piperazin-1-yl)dibenzo[b,f][1,4]thiazepine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

5747-48-8, Preparation BA toluene solution of 1 l-piperazin-l-yldibenzo[b,fj[l,4]thiazepine (1500 mL, 0.686 mol) prepared by reaction of piperazine with 1 l-chloro-dibenzo[b,fj[l,4]-thiazepine in toluene (see, e.g., U. S. Pat. No. 4,879,288) was treated with 1500 mL deionized water and 90 mL of HCl (32% w/w). The resulting mixture was heated to 70 0C and agitated for 45 min. Agitation was ceased and the mixture allowed to settle and phase separate for 30 min. The lower aqueous phase, containing the HCl salt of 1 l-piperazin-l-yldibenzo[b,fj[l54]thiazepine was isolated. The aqueous phase was then treated with 1000 mL of toluene and 99 g of aqueous NaOH (47% w/w). The resulting mixture was heated to 70 C and agitated for 45 EPO min. Agitation was ceased and the mixture allowed to settle and phase separate for 30 min. The lower aqueous phase was discarded and the upper organic phase retained to which 300 mL of deionized water was added. The resulting mixture was agitated for 15 min and then allowed to settle for 30 min. The aqueous phase was discarded and the organic phase retained. The organic phase was extracted once more with 300 mL of deionized water. About 750 mL of toluene from the organic phase was distilled out. The resulting concentrate was cooled to 60 C, then 200 mL of methyl-t-butyl ether (MTBE) was added. The resulting mixture was cooled to ambient temperature then seeded with Form A seed crystals. The seeded mixture was then cooled to 10 C and held at this temperature for 3 hours under slow agitation. The resulting solid was isolated under suction via a no. 3 sinter. The solid product was then washed with 120 mL of MTBE at ambient temperature and dried at 40 C under vacuum resulting in 175 g (86.4%) of crystalline product. Assay 99.9% w/w by HPLC area %.

The synthetic route of 5747-48-8 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; ASTRAZENECA AB; WO2006/73360; (2006); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.5747-48-8,11-(Piperazin-1-yl)dibenzo[b,f][1,4]thiazepine,as a common compound, the synthetic route is as follows.

5747-48-8, In 5 mL of acetonitrile was dissolved 500 mg (1.693 mmol) of 11-piperazin-l- yldibenzo[b,f][l,4]thiazepine. In 5 mL of acetonitrile at room temperature was dissolved H3PO4 (85% assay; 163 mg, 1.693 mmol). The solutions were combined resulting in immediate precipitation of a slightly gummy solid. The solid did not redissolve upon reheating, but did triturate into a free-flowing solid. There was no change upon standing overnight. The solids were collected, washed with acetonitrile (5 mL) and dried under vacuum at 40 0C resulting in 588 mg (88.7 %) of ciystalline solid, nip 227-233 0C (dec). 1H NMR (DMSO-d6) was consistent with the title salt.Polarized light microscopy revealed the material to be composed of rod-shaped crystalline particles. DSC revealed a series of endothermic events at higher temperatures likely corresponding to melting and degradation (see Figure 9). The TGA also indicated slight water loss of 0.5% at 105 0C (see Figure 9). DVS revealed that the material was slightly hygroscopic (see Figure 10). The moisture gain was reversible with some hysteresis on the first cycle (characteristic of a channel hydrate). The cycles overlapped well with no evidence of form change.

The synthetic route of 5747-48-8 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; ASTRAZENECA AB; WO2007/62336; (2007); A2;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics