Month: September 2020

As a common heterocyclic compound, it belongs to quinuclidine compound,Quinuclidine-4-carboxylic acid hydrochloride,40117-63-3,Molecular formula: C8H14ClNO313,mainly used in chemical industry, its synthesis route is as follows.,39093-93-1

To a solution of 2-(4-(bromomethyl)phenyl)-4,4,5 ,5 -tetramethyl- 1,3,2-dioxaborolane (0.50 g, 1.68 mmol) in DMF (8 mL) were added K2C03 (0.58 g, 4.21mmol) and thiomorpholine 1,1-dioxide (0.27 g, 2.02 mmol). The reaction mixture was stirred at rt for 2 h. The reaction mixture was diluted with water and ethyl acetate. The organic layer was separated and washed with brine, dried over MgSO4. The filtrate was concentrated in vacuo to give the title compound as a white solid (0.53 g, 89%). ?H NMR(DMSO-d6) oe 7.65 (d, J= 8.1 Hz, 2 H), 7.35 (d, J= 7.9 Hz, 2 H), 3.68 (s, 2 H), 3.16 -3.01 (m, 4 H), 2.85 (dd, J 6.2, 4.0 Hz, 4 H), 1.29 (s, 12 H); MS(ESIj mlz 352.1 (M + H).

With the synthetic route has been constantly updated, we look forward to future research findings about Thiomorpholine 1,1-dioxide,belong Thiomorpholine compound

Reference£º
Patent; BRISTOL-MYERS SQUIBB COMPANY; KIM, Kyoung S.; ZHANG, Liping; PURANDARE, Ashok Vinayak; SEITZ, Steven P.; WO2015/77193; (2015); A1;,
Thiomorpholine – Wikipedia
Thiomorpholine | C4H9NS – PubChem

As a common heterocyclic compound, it belongs to Thiomorpholine compound, name is Thiomorpholine 1,1-dioxide, and cas is 39093-93-1, its synthesis route is as follows.,39093-93-1

Example 5; l-(5-tert-Butyl-3-(thiomorpholine-l,l-dioxide-4-carbonyl)thiophen-2-yl)-3-(4-(2- (methylcarbamoyl)pyridin-4-yloxy)phenyl)urea [0228] To a solution of 6-tert-butyl-l/f-thieno[2,3-cTj[l,3]oxazine-2,4-dione (3.7 g, 15 mmol) in dioxane (30 mL) was added 4-(4-aminophenoxy)-N-methylpicolinamide (3.4 g, 14 mmol), and the reaction mixture was heated at 90 0C for 4 h. The volatiles were evaporated under reduced pressure to give the crude product which was used in the next step without further purification. EPO [0229] To a solution of 5-tert-butyl-2-(3-(4-(rhoyridin-4-yloxy)rhohenyl)ureido)thiorhohene-3- carboxylic acid (ca 14 mmol) in THF (70 mL) were added thiomorpholine 1,1 -dioxide (2.27 g, 16.8 mmol, 1.2 eq), HOBt (2.08 g, 15,4 mmol, 1.1 eq), EDCI (3.22 g, 16.8 mmol, 1.2 eq), and the mixture was stirred at room temperature for 16 h. The volatiles were evaporated under reduced pressure to give the crude product which was extracted with saturated sodium bicarbonate (3 x 40 mL) and ethyl acetate (150 mL). The organic layer was dried and diluted with ethanol (40 mL). Upon concentration of the solution using rotary evaporator, precipitation of solid occurred. The solid was digested with ethanol (70 mL), filtered, washed with ethanol to give the product which was dried under vacuum at 70 0C for 24 h. (yield = 7.2 g, 82percent). 1H NMR (400 MHz, DMSOd6) delta 9.89 (s, IH), 9.63 (s, IH), 8.73 (m, IH), 8.47 (d, J = 6.8 Hz, IH), 7.54 (d, J = 8.8 Hz, 2H), 7.35 (d, J = 2.8 Hz, IH), 7.13 (d, J = 8.8 Hz, 2H), 7.11 (m, IHO, 6.65 (s, IH), 3.93 (m, 4H), 3.27 (m, 4H), 2.75 (d, J = 5.2 Hz3 3H), 1.30 (s, 9H).

With the complex challenges of chemical substances, we look forward to future research findings about 39093-93-1,belong Thiomorpholine compound

Reference£º
Patent; LOCUS PHARMACEUTICALS, INC.; MOORE, JR., William, R.; SPRINGMAN, Eric; MICHELOTTI, Enrique; WO2006/62984; (2006); A2;,
Thiomorpholine – Wikipedia
Thiomorpholine | C4H9NS – PubChem

As a common heterocyclic compound, it belongs to quinuclidine compound,Quinuclidine-4-carboxylic acid hydrochloride,40117-63-3,Molecular formula: C8H14ClNO230,mainly used in chemical industry, its synthesis route is as follows.,39093-93-1

Step g: crystalline (U-dioxo-1 6-thiomorpholin-4-yl)-{6-r3-(4-fluoro-phenyl)-5-methyl-isoxazol-4-ylmethoxyl-pyridin-3-yl|-methanone in anhydrous polymorphic form A (Form A ({drug4a})) To a solution of 6-[3-(4-fluoro-phenyl)-5-methyl-isoxazol-4-ylmethoxy]-nicotinic acid (99 mg, 0.33 mmol (69 mg, 0.2 mmol)) in DMF (300 mu) were added 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (71 mg, 0.22 mmol), N,N-diisopropyl ethyl amine (171 mul, 1.0 mmol) and thiomorpholine-S,S-dioxide (17.3 mul, 0.22 mmol). The resulting reaction mixture was stirred for 1 h at room temperature. Concentration and purification by chromatography (Si02, heptane:ethyl acetate = 100:0 to 1: 1) afforded the title compound (73 mg, 55%) as a white solid. MS: m/e = 446.1 [M+H]+.

With the complex challenges of chemical substances, we look forward to future research findings about Thiomorpholine 1,1-dioxide,belong Thiomorpholine compound

Reference£º
Patent; IP Gesellschaft fuer Management mbH; Trinius, Frank; EP2792360; (2014); A1;,
Thiomorpholine – Wikipedia
Thiomorpholine | C4H9NS – PubChem

Name is Thiomorpholine 1,1-dioxide, as a common heterocyclic compound, it belongs to Thiomorpholine compound, and cas is 39093-93-1, its synthesis route is as follows.,39093-93-1

A mixture of thiomorpholine 1,1-dioxide (270 mg, 2.0 mmol) in DMF (10 ml) was prepared at room temperature and sodium hydride (60 wtpercent in oil, 96 mg, 2.40 mmol) added in one portion and the mixture stirred at room temperature for 1h. 1-Bromo-4-(bromomethyl)benzene was then added in one portion and the mixture stirred overnight for 17.5 h under argon. The mixture was then quenched with saturated aqueous ammonium chloride solution (10 ml) and diluted with ethyl acetate (30 ml). The mixture was partitioned and the aqueous layer removed. The organic layers were then washed with 5percent aqueous lithium chloride solution (2x 10 ml), brine (10 ml), dried over magnesium sulphate and the solvent removed under reduced pressure. The crude product was then purified by column (0-5percent methanol/dichloromethane) to afford 4-(4- bromobenzyl)thiomorpholine 1,1-dioxide as a colourless solid (283 mg, 0.93 mmol,47percent). 1H NMR (500 MHz; CDCl3) delta 2.98 (brs, 4H), 3.06 (brs, 4H), 3.60 (5, 2H), 7.20 (d, 2H, J 8.1 Hz), 7.47 (d, 2H, J= 8.3 Hz) ppm.Purity by LCMS (UV Chromatogram, 190-450nm) 95percent, rt = 5.0 min m/z 306 (M+H)+

With the complex challenges of chemical substances, we look forward to future research findings about Thiomorpholine 1,1-dioxide

Reference£º
Patent; UNIVERSITY OF DUNDEE; GILBERT, Ian Hugh; NORCROSS, Neil; BARAGANA RUIBAL, Beatriz; PORZELLE, Achim; WO2013/153357; (2013); A1;,
Thiomorpholine – Wikipedia
Thiomorpholine | C4H9NS – PubChem

As a common heterocyclic compound, it belongs to Thiomorpholine compound, name is Thiomorpholine 1,1-dioxide, and cas is 39093-93-1, its synthesis route is as follows.,39093-93-1

Preparation 14 4-(4-bromobenzyl)thiomorpholine 1,1-dioxide A mixture of thiomorpholine 1,1-dioxide (270 mg, 2.0 mmol) in DMF (10 ml) was prepared at room temperature and sodium hydride (60 wt percent in oil, 96 mg, 2.40 mmol) added in one portion and the mixture stirred at room temperature for 1 h. 1-Bromo-4-(bromomethyl)benzene was then added in one portion and the mixture stirred overnight for 17.5 h under argon. The mixture was then quenched with saturated aqueous ammonium chloride solution (10 ml) and diluted with ethyl acetate (30 ml). The mixture was partitioned and the aqueous layer removed. The organic layers were then washed with 5percent aqueous lithium chloride solution (2*10 ml), brine (10 ml), dried over magnesium sulphate and the solvent removed under reduced pressure. The crude product was then purified by column (0-5percent methanol/dichloromethane) to afford 4-(4-bromobenzyl)thiomorpholine 1,1-dioxide as a colourless solid (283 mg, 0.93 mmol, 47percent). 1H NMR (500 MHz; CDCl3) delta 2.98 (brs, 4H), 3.06 (brs, 4H), 3.60 (s, 2H), 7.20 (d, 2H, J=8.1 Hz), 7.47 (d, 2H, J=8.3 Hz) ppm. Purity by LCMS (UV Chromatogram, 190-450 nm) 95percent, rt=5.0 min, m/z 306 (M+H)+

With the complex challenges of chemical substances, we look forward to future research findings about 39093-93-1,belong Thiomorpholine compound

Reference£º
Patent; Gilbert, Ian Hugh; Norcross, Neil; Baragana Ruibal, Beatriz; Porzelle, Achim; US2015/45354; (2015); A1;,
Thiomorpholine – Wikipedia
Thiomorpholine | C4H9NS – PubChem

Name is Thiomorpholine 1,1-dioxide, as a common heterocyclic compound, it belongs to Thiomorpholine compound, and cas is 39093-93-1, its synthesis route is as follows.,39093-93-1

B. Synthesis of 5?-O-DMT-3?-O-[methyl-(N,N-diisopropyl)]-phosphoramidite-2?-O-thiomorpholino-1, 1-dioxidethionocarbamateuridine. 3?-5?-tetraisopropyldisiloxane Uridine (ChemeGenes), 10 mmol, 4.8 grams was dissolved in 100mls of anhydrous acetonitril in a 500 ml roundbottom flask fitted with a serum stopper. To the reaction 1.9 grams of1, 1?-thiocarbonyldiimidazole (Aldrich) was added with 0.2 grams of 4-(dimethyl)aminopyridine. The reaction washeated using a heat gun and stirred until the reagents had dissolved and the solution was clear. The reaction wasallowed to stir overnight (12 hours). After 12 hours, the reaction mixture was a slurry of crystals. The crystals wereisolated by filtration through a medium sintered glass funnel. The product was washed with cold acetonitrile anddried under vacuum. TLC analysis confirmed that the product was a single species giving 5.97 grams of product(100percent) ESI-Q-TOF mass spectroscopy analysis confirmed the product as the 5?,3?-O-(tetraisopropyldisiloxane-1,3-diyl)-2?-thionoimidazole with a mass of M+1, 598.12 m/e. The product was redissolved in 100 ml of anhydrousacetonitrile by heating using a heat gun. To the reaction was added 11 mmol of thiomorpholine-1, 1-dioxide (TCIAmerica) and 1.1 mmol of 4-(dimethyl)aminopyridine. The reaction was stoppered and stirred for 12 hours. After 12hours, the reaction mixture was a slurry of crystals. The crystals were isolated by filtration through a medium sinteredglass funnel. The product was washed with cold acetonitrile and dried under vacuum. TLC analysis confirmed thatthe product was a single species giving 6.61 grams of product (99percent). ESI-Q-TOF mass spectroscopy analysisconfirmed the product as the 5?,3?-O-(tetraisopropyldisiloxane-1, 3-diyl)-2?-O-thiomorpholino-1, 1-dioxidethionocarbamatewith a mass of M+1, 664.21 m/e. Hydrogen fluoride-pyridine complex (HF:Py 7:3, 7 mL) was carefully toice-cold solution of pyridine (8 mL) in acetonitrile (46.5 mL). The pyridine-HF reagent so formed (32 mL) was thentransferred to the flask with 5?, 3?-O-(tetraisopropyldisiloxane-1,3-diyl)- 2?-O-thiomorpholino-1, 1-dioxidethionocarbamateprotected uridine (10 mmole), and the mixture was stirred at room temperature for 2 hours. The reactionwas quenched with 5percent solution of calcium chloride in water (300 mL). Crude product was extracted with EtOAc(3-5 times), and dried with anhydrous Na2SO4. After filtration organic layer was concentrated to a viscous oil giving3.4 grams (80percent yield) of product shown as a single spot by TLC with a confirmed identity of the 2?-O-thiomorpholino-1, 1-dioxidethionocarbamate protected uridine by ESI-Q-TOF mass spectroscopy with a mass of M+ 1, 422.10 m/e.2?-O-thiomorpholino-1, 1-dioxidethionocarbamate protected uridine (8.0 mmole) was redissolved in anhydrous THF(80 mL), 2,4,6-collidine (60 mmole) and dimethoxytrityl chloride (10.0 mmole) were added, and the mixture wasstirred at room temperature until TLC (CHCl3/MeOH 9:1) showed full disappearance of nucleoside substrate (16-24hours). 2,4,6-Collidine (8.0 mmole) and 1-methylimidazole (4.0 mmole) were added in one portion and N,N-diisopropylmethylphosphonamidicchloride (20 mmol) was added slowly to the reaction mixture over 10-15 minutes. Thereaction mixture was then stirred for another 2 hours. The solvent was removed in vacuo, and the crude productwas purified by column chromatography using hexanes with a gradient of EtOAc (0-50percent).

With the complex challenges of chemical substances, we look forward to future research findings about Thiomorpholine 1,1-dioxide

Reference£º
Patent; Agilent Technologies, Inc.; Dellinger, Douglas J.; Sierzchala, Agnieska; Turner, John; Myerson, Joel; Kupihar, Zoltan; Ferreira, Fernando; Caruthers, Marvin H.; EP2476689; (2015); B1;,
Thiomorpholine – Wikipedia
Thiomorpholine | C4H9NS – PubChem

As a common heterocyclic compound, it belongs to quinuclidine compound,Quinuclidine-4-carboxylic acid hydrochloride,40117-63-3,Molecular formula: C8H14ClNO374,mainly used in chemical industry, its synthesis route is as follows.,39093-93-1

To a well stirred suspension of thiomorpholine 1,1 -dioxide (0.36 g, 2.7 mmol) and potassium carbonate (0.37 g, 2.7 mmol) in acetone (5 mL) was added l-bromo-4- chloromethyl-benzene (0.50 g, 2.4 mmol). The mixture was stirred for 48 hours at room temperature. The mixture was filtered and the volatiles were evaporated. The residue was suspended in ether (100 mL), filtered and evaporated to a solid. The material was purified via chromatography utilizing an ISCO automated purification apparatus (24 g silica gel column 10percent – >;100percent ethyl acetate in hexane). 4-(4-Bromo-benzyl)-thiomorpholine 1,1- dioxide was isolated as a white solid (0.72 g, 97percent). 1H NMR (400 MHz, CDCl3, delta, ppm): 7.47 (d, J=7.6 Hz, 2H), 7.19 (d, J=7.7 Hz, 2H), 3.60 (s, 2H), 3.08-2.94 (m, 8H). MS = 304, 306 (MH)+.

With the synthetic route has been constantly updated, we look forward to future research findings about Thiomorpholine 1,1-dioxide,belong Thiomorpholine compound

Reference£º
Patent; CEPHALON, INC.; CURRY, Matthew A.; DORSEY, Bruce D.; DUGAN, Benjamin J.; GINGRICH, Diane E.; MESAROS, Eugen F.; MILKIEWICZ, Karen L.; WO2010/141796; (2010); A2;,
Thiomorpholine – Wikipedia
Thiomorpholine | C4H9NS – PubChem

Name is Thiomorpholine 1,1-dioxide, as a common heterocyclic compound, it belongs to Thiomorpholine compound, and cas is 39093-93-1, its synthesis route is as follows.,39093-93-1

General procedure: To a vial containing a solution of urea acid, 8a, (369.7 mg, 1 mmol), EDCI (230.8 mg, 1.2 mmol) and HOBt (147.6 mg, 1.1 mmol) in 1:1 DCM:N,N-dimethylformamide (DMF; 10 mL) was added 1,1-dioxothiomorpholine (133.1 mg, 1 mmol). The vial was capped, and the solution was stirred at room temperature for 27 h. The reaction mixture was diluted with EtOAc and washed with water (x3) and brine (x1). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under vacuum. Purification by silica flash column using 97:3 DCM:MeOH gave 401.0 mg (82percent) of 13a as a white solid. 1H NMR (400 MHz, acetone-d6): delta 10.03 (s, 1H), 9.23 (s, 1H), 8.11 (d, J = 8.4 Hz, 1H), 8.00 (d, J = 7.2 Hz, 1H), 7.86 (d, J = 8.0 Hz, 1H), 7.67 (d, J = 8.2 Hz, 1H), 7.49-7.41 (m, 2H), 7.40-7.34 (m, 1H), 6.70 (s, 1H), 4.14-4.05 (m, 4H), 3.20 (t, J = 4.8 Hz, 4H), 1.30 (s, 9H). MS m/z (APCI+) Found (M+H): 486.2

With the complex challenges of chemical substances, we look forward to future research findings about Thiomorpholine 1,1-dioxide

Reference£º
Article; Moffett, Kristofer; Konteatis, Zenon; Nguyen, Duyan; Shetty, Rupa; Ludington, Jennifer; Fujimoto, Ted; Lee, Kyoung-Jin; Chai, Xiaomei; Namboodiri, Haridasan; Karpusas, Michael; Dorsey, Bruce; Guarnieri, Frank; Bukhtiyarova, Marina; Springman, Eric; Michelotti, Enrique; Bioorganic and Medicinal Chemistry Letters; vol. 21; 23; (2011); p. 7155 – 7165;,
Thiomorpholine – Wikipedia
Thiomorpholine | C4H9NS – PubChem

As a common heterocyclic compound, it belongs to Thiomorpholine compound, name is Thiomorpholine-1-oxide hydrochloride, and cas is 76176-87-9, its synthesis route is as follows.,76176-87-9

To a solution of thiomorpholine 1-oxide hydrochloride (340 mg) and triethylamine (0.31 mL) in N,N-dimethylformamide (25 mL) were added [2-(7-ethyl-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetic acid (500 mg), 1-hydroxybenzotriazole (300 mg) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (420 mg) under ice-cooling, and the mixture was stirred under ice-cooling and then at room temperature for 15 hr. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with aqueous sodium hydrogen carbonate solution and saturated brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography (ethyl acetate:methanol = 100:0 to 80:20, volume ratio), and the obtained pale-yellow crystals were recrystallized from tetrahydrofuran-ethyl acetate to give the title compound (354 mg, yield 58%) as colorless crystals. melting point 194-196C. MS 561 (MH+).

With the complex challenges of chemical substances, we look forward to future research findings about Thiomorpholine-1-oxide hydrochloride

Reference£º
Patent; Takeda Pharmaceutical Company Limited; EP2371826; (2011); A1;,
Thiomorpholine – Wikipedia
Thiomorpholine | C4H9NS – PubChem

Name is Thiomorpholine-1-oxide hydrochloride, as a common heterocyclic compound, it belongs to Thiomorpholine compound, and cas is 76176-87-9, its synthesis route is as follows.,76176-87-9

To a suspension of Intermediate 41 (68.4 mg, 0.146 mmol, 1.0 eq) in anhydrous CH2CI2 (3 mL) was added 1-oxide thiomorpholine hydrochloride (45.6 mg, 0.293 mmol, 2.0 eq) and sodium acetate (24.0 mg, 0.293 mmol, 2.0 eq) and the resulting suspension was stirred at 42 C for 6 h. After cooling to rt, NaBH(OAc)3(62.1 mg, 0.293 mmol, 2.0 eq) was added and the reaction mixture was stirred at rt for 16 h. Additional portions of sodium acetate (12.0 mg, 0.147 mmol, 1.0 eq), 1-oxide thiomorpholine hydrochloride (22.8 mg, 0.147 mmol, 1.0 eq) and NaBH(OAc)3 (31.1 mg, 0.147 mmol, 1.0 eq) were added and the reaction was stirred at 40C for 18 h. Upon cooling to rt, the reaction was quenched with 1 Maqueous NaOH (5 mL) then poured into H20 (15 mL) and extracted with CH2CI2(3 x 15 mL). The combined organic extracts were concentrated in vacuo andpurified by silica gel chromatography using EtOAc/MeOH (1 :0-13:1). The productwas re-dissolved in CH2CI2/MeOH (4:1, 10 mL) and swirled with MP-TMT resin(157 mg, 0.173 mmol) at rt overnight. The solution was filtered and the resinwashed with CH2CI2/MeOH (4:1, 100 mL). The filtrate was concentrated in vacuoand purified a second time by silica gel column chromatography with CH2CI2/MeOH (1:0-12:1) to yield Example S as a white solid (37.6 mg, 45%).1H NMR (300MHz, DMSO-d5) oH. 12.47 (5, 1H), 8.54-8.67 (m, 2H), 8.28 (dd, J=7.4, 0.8 Hz, 1H), 7.98 (5, 1H), 7.64 (d, J=8.1 Hz, 1H), 7.40-7.52 (m, 1H), 4.08-4.19 (m, 4H), 3.81-3.92 (m, 6H), 2.86-3.02 (m, 4H), 2.68-2.80 (m, 4H).19F NMR (282MHz, DMSO-d5) 0F. -58.8 (5, 3F).MS (ESj 571.0 (100%, [M+H]j.

With the complex challenges of chemical substances, we look forward to future research findings about Thiomorpholine-1-oxide hydrochloride

Reference£º
Patent; KARUS THERAPEUTICS LTD; SHUTTLEWORTH, Stephen Joseph; SILVA, Franck Alexandre; CECIL, Alexander Richard Liam; ALEXANDER, Rikki Peter; GATLAND, Alice Elizabeth; FINNEMORE, Daniel John; (123 pag.)WO2017/29521; (2017); A1;,
Thiomorpholine – Wikipedia
Thiomorpholine | C4H9NS – PubChem