Heterocyclic Building Blocks-Thiomorpholine

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. 39093-93-1, name is Thiomorpholine 1,1-dioxide. 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. 39093-93-1

To a solution of thiomorpholine 1,1-dioxide (37.4 mg, 0.277 mmol) in ethanol (1 mL) was added (S)i sopropyl 2-(6-(bromomethyl)-4-(4,4-dimethylpiperidin- l-yl)-5 -(2-(4-fluoro-2- methylbenzyl)- 1,2,3 ,4-tetrahydroi soquinolin-6-yl)-2-methylpyridin-3 -yl)-2-(tert-butoxy)acetate (20 mg, 0.028 mmol) and the resulting mixture was stirred at room temp for 16 h. Mixture was then treated with iON NaOH (0.028 mL, 0.277 mmol) at 80 ¡ãC for 4 h. Mixture was then cooled and purified by prep HPLC to afford (S)-2-(tert-butoxy)-2- (4-(4,4-dimethylpiperidin- 1 -yl)-6-((1, 1 -dioxidothiomorpholino)methyl)-5-(2-(4-fluoro-2- methylbenzyl)- 1,2,3 ,4-tetrahydroi soquinolin-6-yl)-2-methylpyridin-3 -yl)acetic acid (15.8mg, 0.021 mmol, 78 percent yield). ?HNMR (500MHz, DMSO-d6) oe 7.40-7.27 (m, 1H),7.25 -7.15 (m, 1H), 7.14-6.96 (m, 3H), 6.90 (br. s., 1H), 5.79 (br. s., 1H), 3.61 (br. s.,4H), 3.47 – 3.34 (m, 3H), 3.34 – 3.18 (m, 2H), 2.94 (br. s., 2H), 2.84 (d, J=9.9 Hz, 3H),2.77 – 2.68 (m, 6H), 2.47 (s, 3H), 2.36 (br. s., 3H), 2.12 (br. s., 1H), 1.89 – 1.79 (m, 1H),1.49 (br. s., 1H), 1.35 – 1.14 (m, 2H), 1.12 (s, 9H), 1.06-0.91 (m, 1H), 0.85 (br. s., 3H),0.61 (br. s., 3H). LCMS (M+H) = 735.1.

While traditionally a conservative industry, chemical producers will need to modernize their PR strategies to stay relevant. 39093-93-1, we look forward to future research findings about .

Reference£º
Patent; VIIV HEALTHCARE UK (NO.5) LIMITED; EASTMAN, Kyle J.; KADOW, John F.; NAIDU, B. Narasimhulu; PARCELLA, Kyle E.; PATEL, Manoj; SIVAPRAKASAM, Prasanna; TU, Yong; (275 pag.)WO2017/25915; (2017); A1;,
Thiomorpholine – Wikipedia
Thiomorpholine | C4H9NS – PubChem

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. 39093-93-1, name is Thiomorpholine 1,1-dioxide. This compound has unique chemical properties. The synthetic 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)+.

While traditionally a conservative industry, chemical producers will need to modernize their PR strategies to stay relevant. 39093-93-1, we look forward to future research findings about .

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

20196-21-8, A common heterocyclic compound, 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., 20196-21-8

(15) A mixture of 5-chloro-N-((1-(4-iodophenyl)-1H-imidazol-4-yl)methyl)thiophene-2-carboxamide 1-6 prepared in Example 1 (230 mg, 0.518 mmol), 3-thiomorpholinone (121 mg, 1.03 mmol), 1,2-trans-diaminocyclohexane (26 muL, 0.21 mmol) and K3PO4 (220 mg, 1.04 mmol) in dioxane (2 mL) was degassed with Ar before being charged with CuI (40 mg, 0.21 mmol). The mixture in a sealed tube was heated at 110 C. overnight. It was then purified by HPLC to give the title compound (58 mg). MS 433.1 and 435.0 (M+H, Cl pattern)., 20196-21-8

The chemical industry reduces the impact on the environment during synthesis, 20196-21-8, I believe this compound will play a more active role in future production and life.

Reference£º
Patent; Millennium Pharmaceuticals, Inc.; US2007/259924; (2007); A1;,
Thiomorpholine – Wikipedia
Thiomorpholine | C4H9NS – PubChem

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.39093-93-1, Thiomorpholine 1,1-dioxide it is a common compound, a new synthetic route is introduced below., 39093-93-1

i) (1,1-Dioxo-1,6-thiomorpholin-4-yl)-{6-[3-(5-fluoro-pyridin-2-yl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-pyridin-3-yl}-methanone; To a solution of 6-((3-(5-fluoropyridin-2-yl)-5-(hydroxymethyl)isoxazol-4-yl)methoxy)nicotinic acid (384 mg, 1.11 mmol) in DMF (10 mL) was added thiomorpholine 1,1-dioxide (165 mg, 1.22 mmol), N,N,N’,N’-tetramethyl-O-(benzotriazole-1-yl)-uronium tetrafluoroborate (393 mg, 1.22 mmol) and N,N-diisopropyl ethylamine (0.95 mL, 5.56 mmol). The reaction mixture was stirred for 30 min at room temperature. After evaporation of the solvent the residue purified by chromatography (silica, ethylacetate_heptane=1:1 to 1:0) to afford the title compound (422 mg, 82percent) as a white solid. MS: m/e=463.2 [M+H]+.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 39093-93-1, and friends who are interested can also refer to it.

Reference£º
Patent; Buettelmann, Bernd; Gabriel, Stephen Deems; Hanlon, Steven Paul; Jakob-Roetne, Roland; Lucas, Matthew C.; Spurr, Paul; Thomas, Andrew; Waldmeier, Pius; US2010/256127; (2010); A1;,
Thiomorpholine – Wikipedia
Thiomorpholine | C4H9NS – PubChem

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. 39093-93-1, name is Thiomorpholine 1,1-dioxide. 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. 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).

While traditionally a conservative industry, chemical producers will need to modernize their PR strategies to stay relevant. 39093-93-1, we look forward to future research findings about .

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

Thiomorpholine 1,1-dioxide, A common heterocyclic compound, 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., 39093-93-1

A mixture of 4-bromobenzyl bromide (1.0 g, 4.0 mmol), triethylamine (0.84 mL,6.0 mmol) and thiomorpholine 1,1-dioxide (1.09 g, 8.0 mmol) in THF (10 mL) was stirred at ambient temperature for 16 h. The solvent was evaporated and the resultant residue diluted with saturated aqueous sodium bicarbonate solution and extracted with ethyl acetate (2 x 50 mL). The combined organic layer was dried over sodium sulfate, filtered and evaporated to afford the title compound (0.90 g, 74percent). 1H NMR (CDCl3, 300MHz): 7.50-7.44 (m, 2H), 7.22-7.16 (m, 2H), 3.60 (s, 2H), 3.09-3.02 (m, 4H), 3.00-2.94 (m, 4H).

The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. 39093-93-1. We look forward to the emergence of more reaction modes in the future.

Reference£º
Patent; GENENTECH, INC.; WO2009/151598; (2009); A1;,
Thiomorpholine – Wikipedia
Thiomorpholine | C4H9NS – PubChem

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.128453-98-5, 4-(tert-Butoxycarbonyl)thiomorpholine-3-carboxylic acid it is a common compound, a new synthetic route is introduced below., 128453-98-5

To a solution of N-Boc thiomorpholine carboxylic acid (1.36 g, 5.51 mmol) in dichloromethane (13.6 ml) were added under N2, at r.t., TBTU (1.95 g, 6.06 mmol) and DIPEA (1.92 ml, 11.02 mmol) and the solution was stirred for 30 mins. To a suspension of L-serine methyl ester hydrochloride (1.71 g, 11.02 mmol) in dichloromethane (13.6 ml) was added DIPEA (1.92 ml, 11.02 mmol) and the resulting solution was stirred for 30 mins. Then the solution containing the serine free base was added to the reaction mixture and it was left stirring for 16 hrs. Water was added to the reaction mixture and the aqueous layer was extracted with dichloromethane (x3) and the combined organic phases were dried (Na2SO4) and evaporated to dryness. The crude title compound (3.87 g) was used in the next step without further purification. UPLC/MS: m/z= 371 (M+Na); 349 (M+1 ); 293 (M-fBu); 249 (M-BOC+1 ) (at) t=0.59 min

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 128453-98-5, and friends who are interested can also refer to it.

Reference£º
Patent; SMITHKLINE BEECHAM CORPORATION; WO2007/28654; (2007); A1;,
Thiomorpholine – Wikipedia
Thiomorpholine | C4H9NS – PubChem

Adding a certain compound to certain chemical reactions, such as: Thiomorpholine 1,1-dioxide, cas is 39093-93-1,the Thiomorpholine compound, can increase the reaction rate and produce products with better performance than those obtained under traditional synthetic methods. Here is a downstream synthesis route of the compound 39093-93-1,the Thiomorpholine, compound., 39093-93-1

To a solution of (E)-3-((lR,3aR,5aR,5bR,7aR,l laS,l lbR,13aR,13bR)-9-(4-(tert- butoxycarbonyl)phenyl)-5a,5b,8,8, 11 a-pentamethyl- 1 -(prop- l-en-2-yl)- 2,3,3a,4,5,5a,5b,6,7,7a,8,l l,l la,l lb,12,13,13a,13b-octadecahydro-lH- cyclopenta[a]chrysen-3a-yl)acrylic acid (100 mg, 0.16 mmol) and thiomorpholine 1,1- dioxide (25 mg, 0.19 mmol) in CH2CI2 (5 mL) was added DIPEA (0.14 mL, 0.78 mmol) followed by HATU (89 mg, 0.23 mmol). The solution was stirred at RT for 1 h. The reaction mixture was concentrated under reduced pressure. The crude mixture was purified on silica gel to give the title compound (115 mg, 97percent) as a solid. MS: m/e 758.6 (M+H)+, 2.80 min (method 1). XH NMR (400MHz, CHLOROFORM-d) delta 7.89 (d, J=8.3 Hz, 2H), 7.29 (d, J=14.3 Hz, IH), 7.17 (d, J=8.3 Hz, 2H), 6.31 (d, J=15.6 Hz, IH), 5.28 (d, J=4.5 Hz, IH), 4.74 (s, IH), 4.64 (s, IH), 4.20 – 4.04 (m, 4H), 3.17 – 3.01 (m, 4H), 2.57 (dt, J=l l. l, 5.9 Hz, IH), 2.10 (dd, J=l 7.2, 6.4 Hz, IH), 1.96 – 0.85 (m, 21H), 1.72 (s, 3H), 1.60 (s, 9H), 1.03 (s, 3H), 1.02 (s, 3H), 0.97 (s, 3H), 0.92 (s, 6H).

If you are interested in these compounds, 39093-93-1, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference£º
Patent; BRISTOL-MYERS SQUIBB COMPANY; SIT, Sing-Yuen; CHEN, Jie; CHEN, Yan; SWIDORSKI, Jacob; REGUEIRO-REN, Alicia; MEANWELL, Nicholas A.; (109 pag.)WO2016/77572; (2016); A1;,
Thiomorpholine – Wikipedia
Thiomorpholine | C4H9NS – PubChem

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. 76176-87-9, name is Thiomorpholine-1-oxide hydrochloride. A new synthetic method of this compound is introduced below. 76176-87-9

To the stirred solution of 3-(4-amino-5-iodo-pyrrolo[2,3-d]pyrimidin-7-yl)-cyclobutanone (Intermediate BG; 680 mg, 2.05 mmol), 1.2-dichloroethane (55 ml) and diisopropylethylamine (1.79 ml, 10.25 mmol) was subsequently added 1-oxo-thiomorpholine hydrochloride (638 mg, 4.10 mmol) and sodium triacetoxyborohydride (652 mg, 3.08 mmol) at 0 C. The reaction mixture was stirred for 1 h at room temperature and then poured into the stirred mixture of water (150 ml) and EtOAc (150 ml). The precipitate was filtered and washed with water and EtOAc. The solid collected was dried in vacuo to afford the title compound as beige crystals. HPLC-MS: M+H = 432.1 (R, = 0.43); TLC; Rf = 0 36 (DCM/MeOH/NH3aq, 200:20:1).

While traditionally a conservative industry, chemical producers will need to modernize their PR strategies to stay relevant. 76176-87-9, we look forward to future research findings about .

Reference£º
Patent; NOVARTIS AG; IRM LLC; CHEN, Bei; FAIRHURST, Robin, Alec; FLOERSHEIMER, Andreas; FURET, Pascal; GUAGNANO, Vito; JIANG, Songchun; LU, Wenshuo; MARSILJE, Thomas, H.; MCCARTHY, Clive; MICHELLYS, Pierre-Yves; STAUFFER, Frederic; STUTZ, Stefan; VAUPEL, Andrea; WO2011/29915; (2011); A1;,
Thiomorpholine – Wikipedia
Thiomorpholine | C4H9NS – PubChem

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. 39093-93-1, name is Thiomorpholine 1,1-dioxide. A new synthetic method of this compound is introduced below. 39093-93-1

Step 1: 2-bromo-5-iodopyridine (1.24 g, 4.35 mmol), thiomorpholine-1,1-dioxide (882 mg, 6.53 mmol) and NaOtBu (1 .04 g, 10.87 mmol) were charged to a screw cap tube, dry toluene (25 mL) was added and the mixture was degassed by nitrogen bubbling for 5 mm. Then XantPhos (250 mg, 0.44 mmol) and Pd2(dba)3 (200 mg, 0.22 mmol) were incorporated and the tube was closed under nitrogen atmosphere. The reaction mixture was stirred at rt for 4 days. EtOAc and water were added. The phases were separated. The organic layer was dried over Mg504, filtered and the solution was concentrated to dryness. The crude material was absorbed on silica gel and purified by column chromatography eluting with CH2CI2 and a gradient of CH2CI2/MeOH from [100:0] to [95:5]. The product fractions were combined and concentrated to dryness to afford 4-(6-bromopyridin-3-yl)-1-thiomorpholine-1 ,1-dione Ex.36a (730 mg, 57percent) as yellow solid.

While traditionally a conservative industry, chemical producers will need to modernize their PR strategies to stay relevant. 39093-93-1, we look forward to future research findings about .

Reference£º
Patent; GENFIT; DELHOMEL, Jean-Francois; PERSPICACE, Enrico; MAJD, Zouher; PARROCHE, Peggy; WALCZAK, Robert; BONNET, Pascal; FOGHA, Jade; (144 pag.)WO2018/138359; (2018); A1;,
Thiomorpholine – Wikipedia
Thiomorpholine | C4H9NS – PubChem