Heterocyclic Building Blocks-Tetrahydropyrans

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.127956-11-0,Methyl 4-oxotetrahydro-2H-pyran-3-carboxylate,as a common compound, the synthetic route is as follows.

To a solution of methyl 4-oxotetrahydro-2H-pyran-3-carboxylate (51.1 g, 323 mmol) and benzyl 2-amino-2-iminoethylcarbamate hydrochloride (78.8 g, 323 mmol) in anhydrous ethanol was added sodium ethoxide (122 mL, 323 mmol, 21 % in ethanol). The mixture was mechanically stirred, heated at reflux for 24 h, cooled down to ambient temperature, and filtered to give the title compound (55.6 g, 55% yield). 1 H NMR (400 MHz, DMSO- d6) delta 12.40 (br. s., 1 H), 7.69 (t, J=5.8 Hz, 1 H), 7.15 – 7.44 (m, 5 H), 4.99 – 5.08 (m, 2 H), 4.35 (s, 2 H), 4.04 – 4.1 1 (m, 2 H), 3.84 (t, J=5.3 Hz, 2 H), 2.48 – 2.57 (m, 2 H). MS m/z 316.2 (M+1 ), retention time = 1.10 min.

As the paragraph descriping shows that 127956-11-0 is playing an increasingly important role.

Reference£º
Patent; NOVARTIS AG; CHEUNG, Atwood, Kim; CHIN, Donoval, Noel; FAN, Jianmei; SHULTZ, Michael, David; TOMLINSON, Ronald, Charles; WO2013/10092; (2013); A1;,
Tetrahydropyran – Wikipedia
Tetrahydropyran – an overview | ScienceDirect Topics

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.3301-94-8,6-Butyltetrahydro-2H-pyran-2-one,as a common compound, the synthetic route is as follows.

General procedure: The lactonase, phosphotriesterase, and esterase hydrolyses of GkaP were monitored by absorbance changes in a UV-2550 spectrophotometer (Shimadzu, Kyoto, Japan) at a constant temperature of 75C with 1 mL reaction volumes (path length = 1cm). Analysis of reaction samples for each substrate was performed at a constant enzyme concentration. The delta-decanolactone substrate was dissolved in dimethyl sulfoxide (DMSO), whereas the p-nitrophenylcaprylate and OP substrates in acetonitrile as stock solutions. For enzymatic kinetics assay, aliquots of the stock were added to the reaction buffer for defined concentrations. The hydrolysis of lactone was monitored using a pH-sensitive colorimetric assay [33]. Briefly, the reactions were performed in 2.5 mM Bicine (pH 8.3) containing 0.2MNaCl, 0.2 mM cresol purple, and 0.02-20 mM lactone substrate. Upon mixture of the substrate with the enzyme, the decrease inabsorbance was monitored at 577 nm (epsilon577 = 47300 M-1cm-1, 1%DMSO). The enzyme was diafiltrated with 10 mM bicine (pH 8.3), with a PD-10 column (GE Healthcare, Shanghai, China) before use. Kinetic measurements with p-nitrophenyl caprylate (pNPC8), and ethyl-paraoxon were performed in 50 mM phosphate buffer (pH 8.0). The reaction rates were monitored bythe release of p-nitrophenol (epsilon405 = 16000M-1cm-1, 2% acetonitrile). The initial rates were corrected for the background rate of spontaneous hydrolysis in the absence of enzymes, which were subtracted from the enzymatic rates. The kinetic parameters (kcat, Km) were obtained byfitting the data to the Michaelis-Menten equation [V = S¡ÁE¡Ákcat/(S+Km)] or to the pseudo first-order form of it at S<Article; Zhang, Yu; An, Jiao; Yang, Guang-Yu; Bai, Aixi; Zheng, Baisong; Lou, Zhiyong; Wu, Geng; Ye, Wei; Chen, Hai-Feng; Feng, Yan; Manco, Giuseppe; PLoS ONE; vol. 10; 2; (2015);,
Tetrahydropyran – Wikipedia
Tetrahydropyran – an overview | ScienceDirect Topics

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.40191-32-0,Tetrahydro-2H-pyran-4-carbonyl chloride,as a common compound, the synthetic route is as follows.

The (S)-pyrrolidin-3-ol hydrochloride (3.69g, 29.9 mmol) and triethylamine (6.65 g, 9.16 mL, 65.7 mmol) were put in CH2CI2(15 mL). The suspension was cooled at ~3C. To this mixture, a solution of tetrahydro-pyran-4-carbonyl chloride (4.67g, 29.9 mmol) in CH2CI2(15 mL) was added slowly. Then the resulting reaction mixture was stirred for 1 .5h at 3-10C. The reaction mixture was then concentrated to give a powder. To this powder, addition of EtOAc (100 mL). The solid was filtered and washed with EtOAc. The recovered filtrate was then concentrated to give ((S)-3-hydroxy-pyrrolidin-1 -yl)-(tetrahydro-pyran-4-yl)-methanone as beige powder. (6.77 g, 98% yield).1H-NMR (400 MHz, Methanol-d4 298 K): delta ppm 1 .59-2.15 (m, 6H) 2.69-2.86 (m, 1 H) 3.43-3.75 (m, 6H) 3.94-4.00 (m, 2H) 4.37-4.48 (m, 1 H). LCMS: [M+H]+= 199.9, Rt(6)= 0.86 min

As the paragraph descriping shows that 40191-32-0 is playing an increasingly important role.

Reference£º
Patent; NOVARTIS AG; COOKE, Nigel Graham; FERNANDES GOMES DOS SANTOS, Paulo Antonio; FURET, Pascal; HEBACH, Christina; HOeGENAUER, Klemens; HOLLINGWORTH, Gregory; KALIS, Christoph; LEWIS, Ian; SMITH, Alexander Baxter; SOLDERMANN, Nicolas; STAUFFER, Frederic; STRANG, Ross; STOWASSER, Frank; TUFILLI, Nicola; VON MATT, Anette; WOLF, Romain; ZECRI, Frederic; WO2013/88404; (2013); A1;,
Tetrahydropyran – Wikipedia
Tetrahydropyran – an overview | ScienceDirect Topics

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.103260-44-2,Ethyl 2-(tetrahydro-2H-pyran-4-yl)acetate,as a common compound, the synthetic route is as follows.

To a mixture of ethyl 2-(tetrahydro-2H-pyran-4-yl)acetate(20 g, 116 mmol) in anhydrous THF (300 mE) was addedlithium aluminum hydride (8.8 g, 232 mmol) portionwise at0 C. The mixture was stirred at 11-13 C. for 18 h. TEC(petroleum ether: ethyl acetate=3: 1) showed no startingmaterial remaining. The mixture was quenched with water(9 mE), 10% aq. NaOH solution (9 mE) and water (18 mE)successively at 0 C., filtered and concentrated underreduced pressure to give crude 2-(tetrahydro-2H-pyran-4-yl)ethanol (11.7 g, 77%) as an oil, which was used for thenext step directly without further purification. ?H NMR(CDC13, 400 MHz): oe 3.86-3.90 (m, 2H), 3.58-3.61 (t, J=6.4Hz, 2H), 3.32-3.35 (t, J=11.6 Hz, 2H), 2.69-2.70 (m, 1H),1.61-1.63 (m, 3H), 1.54-1.60 (m, 2H), 1.43-1.45 (m, 2H).

As the paragraph descriping shows that 103260-44-2 is playing an increasingly important role.

Reference£º
Patent; Vitae Pharmaceuticals, Inc.; Claremon, David A.; Yuan, Jing; Zhao, Wei; Zheng, Yajun; (54 pag.)US9481674; (2016); B1;,
Tetrahydropyran – Wikipedia
Tetrahydropyran – an overview | ScienceDirect Topics

108-55-4, Dihydro-2H-pyran-2,6(3H)-dione is a Tetrahydropyrans compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Into a 3L three-necked RB flask were charged [500ML] of methylene chloride, 250gr of aluminum chloride and 45gr of fluorobenzene (benzene content 300ppm) under nitrogen atmosphere. ‘The reaction mixture was cooled to [10C] and a solution of [LOOGR] of glutaric anhydride, 45gr of fluorobenzene (benzene content 300ppm) and [500ML] of methylene chloride was added slowly over a period of 3hrs between [10-15C.] The reaction mixture was maintained for another one hour at the same temperature. The reaction mixture was slowly poured onto a mixture of crushed ice (700gr) and conc. HCI [(300ML)] below [10C.] The reaction mass temperature was allowed to reach [25C] and methylene chloride distilled off from the reaction mixture below [50C.] After cooling the reaction mixture to [20C,] solids were filtered off and washed with [500ML] of water. The wet cake thus obtained was suspended in [250-300ML] of methylene chloride and filtered. The solid compound was dissolved in [600ML] of 4% sodium hydroxide, treated with [LOGR] of activated charcoal and filtered. The filtrate was acidified with conc. HCI and the precipitated acid was filtered. After washing the wet cake with [500ML] of water, it was dissolved in [500ML] of acetone. The acetone solution was slowly cooled to [15-20C] and the solid filtered, washed with chilled acetone (50ml) and dried at [50-70C] to get 122gr of white crystalline solid, m. p. [143C.] Purity by [HPLC] is 99.65%. Desfluoro impurity is less than 0.05%. Example 2 Preparation of [4- (4-FLUOROBENZOY) LBUTYRIC ACID] of formula-I using fluorobenzene (benzene content [500PPM)] with methylene chloride as solvent: Into a 3L three-necked RB flask were charged [500MI] of methylene chloride, 250gr of aluminum chloride and 45gr of fluorobenzene (benzene content 500ppm) under nitrogen atmosphere. The reaction mixture was cooled to [10C] and a solution of [LOOGR] of glutaric anhydride, 45gr of fluorobenzene (benzene content [500PPM)] and [500ML] of methylene chloride was added slowly over a period of 3hrs between [10-15C.] The reaction mixture was maintained for another one hour at the same temperature. The reaction mixture was slowly poured onto a mixture of crushed ice (700gr) and conc. [HCL] [(300ML)] below [10C.] The reaction mass temperature was allowed to reach [25C] and methylene chloride distilled off from the reaction mixture below [50C.] After cooling the reaction-mixture to [20OC-1 SOLIDS :] were filtered off and washed with [500ML] of water. The wet cake thus obtained was suspended in [250-300ML OF] methylene chloride and filtered. The solid compound was dissolved in [600ML] of [4%] sodium hydroxide, treated with [10GR] of activated charcoal and filtered. The filtrate pH was adjusted’to 1.0-2. 0 with conc. [HCL] and the precipitated acid of formula-I was filtered. After washing the wet cake with [500ML] of water, it was dissolved in [500ML] of acetone. The acetone solution was slowly cooled to [15-20C,] maintained for 2h, and the solid filtered, washed with chilled acetone [(50ML)] and dried at [50-70C] to get 120gr of white crystalline solid of [FORMULA-1,] m. p. 143-143. [5C.] Purity by [HPLC] is 99. [7%.] Desfluoro impurity is less than 0.05%. Example 3 Preparation of [4- (4-FLUOROBENZOY)] lbutyric acid of formula-I using fluorobenzene (benzene content 700ppm) with methylene chloride as solvent: Tnto a 3L three-necked RB flask were charged 500ml of methylene chloride, 250gr of aluminum chloride and 45gr of fluorobenzene (benzene content [700PPM)] under nitrogen atmosphere. The reaction mixture was cooled to [10C] and a solution of [LOOGR] of glutaric anhydride, 45gr of fluorobenzene (benzene content 700ppm) and [500ML] of methylene chloride was added slowly over a period of 3hrs between [10-15C.] The reaction mixture was maintained for another one hour at the same temperature. The reaction mixture was slowly poured onto a mixture of crushed ice (700gr) [AND CONC. HCI (300ML)] below [10C.] The reaction mass temperature was allowed to reach [25C] and methylene chloride distilled off from the reaction mixture below [50C.] After cooling the reaction mixture to [20C,] solids were filtered off and washed with [500ML] of water. The wet cake thus obtained was suspended in [250-300ML] of methylene chloride and filtered. The solid compound was dissolved in [600ML] of 4% sodium hydroxide, treated with [LOGR] of activated charcoal and filtered. The filtrate pH was adjusted to 1.0-2. 0 with conc. [HCL] and the precipitated acid of formula-I was filtered. After washing the wet cake with [500ML] of water, it was dissolved in 500ml of acetone. The acetone solution was slowly cooled to [15-20C,] maintained for 2h, and the solid filtered, washed with chilled acetone [(50ML)] and dried at [50-70C] to get 123gr of white crystalline solid [OF FORMULA-1,] m. p. [143C.] Purity by [HPLC] is 99.6%. Desfluoro impurity is less than 0.05%.

108-55-4 Dihydro-2H-pyran-2,6(3H)-dione 7940, aTetrahydropyrans compound, is more and more widely used in various.

Reference£º
Patent; Natco Pharma Limited; Venkaian Chowdary Nannapaneni; WO2003/104180; (2003); A1;,
Tetrahydropyran – Wikipedia
Tetrahydropyran – an overview | ScienceDirect Topics

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.344329-76-6,Tetrahydro-2H-pyran-4-carboxamide,as a common compound, the synthetic route is as follows.

(2) cooling the 4-formamide tetrahydropyran mixed solution prepared in the step 1 to a temperature of 5 ¡ã C, adding a NaOH solution,After stirring uniformly, NaBrO solution was added dropwise thereto. After the completion of the dropwise addition, the reaction was continued at this temperature for 2 hours, and then the temperature was raised to 50 ¡ã C for 1 hour, then cooled to room temperature, extracted with dichloromethane, and the organic phase was combined. After dichloromethane was removed by pressure distillation, recrystallization was carried out to obtain 4-aminotetrahydropyran.Preferably, the molar volume ratio of tetrahydropyran-4-carboxylic acid to water in the step (1) is 5 mol/L.The concentration of ammonia water in the step (1) is 13 mol/L; the amount of tetrahydropyran-4-carboxylic acid and ammonia in the step (1)The molar volume ratio is 10:1 mol/L.The mass concentration of the NaOH solution in the step (2) is 40percent, the 4-formamide tetrahydropyran mixed solution and the NaOH solutionThe volume-to-volume ratio was 7:1; the mass concentration of the NaBrO solution in the step (2) was 15percent.The molar ratio of tetrahydropyran-4-carboxylic acid to NaBrO was 1:1.5.The obtained 4-aminotetrahydropyran had a purity of 99.2percent and a product yield of 91.8percent.

The synthetic route of 344329-76-6 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; Suzhou Aitike Pharmaceutical Chemical Co., Ltd.; Hu Haiwei; (6 pag.)CN108003122; (2018); A;,
Tetrahydropyran – Wikipedia
Tetrahydropyran – an overview | ScienceDirect Topics

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.101691-94-5,4-(Iodomethyl)tetrahydro-2H-pyran,as a common compound, the synthetic route is as follows.

To a solution of diisopropylamine (2.19 ml. 15.36 mmol) in TetaF (20 mL) at-78 C, was added ?-butyl lithium ( 6.46 ml, 2.5M in hexane, 16.15 mmol) dropwise. The resulting mixture was stirred at -78 C for 30 min and was then added to a mixture of 1 ,1 -dimethylethyl {2-[[(l/?,2/?)-2-hydroxy-l-methyl-2- phenylethyl](methyl)amino]-2-oxoethyl}methylcarbamate (2.65 g ,7.88 mmol) and lithium chloride (2.Og, 47.3 mmol) via cannula at -23 C. The resulting mixture was stirred for 24 h and allowed to warm to room temperature before it was recooled in an ice bath and quenched with HCl (IM, 15.8 ml ). The mixture was then extracted with EtOAc (3 x 20 ml) and the combined extracts washed with saturated NH Cl, brine, dried, filtered, and concentrated. This crude product was purified by column chromatography (16O g silica gel 60, 230-400 mesh, 25,30,40, then 50% EtOAc/hexanes) to provide 1,1 -dimethylethyl [(15)-2-[[(l/?,2/?)-2-hydroxy-l- methyl-2-phenylethyl](methyl)amino]-2-oxo-l-(tetrahydro-2H-pyran-4- ylmethyl)ethyl]methylcarbamate (510 mg, 95% pure and 1.2 g, 80% pure, 42% combined yield). MS (m/z) 435.2 (M+eta+).

101691-94-5 4-(Iodomethyl)tetrahydro-2H-pyran 2795507, aTetrahydropyrans compound, is more and more widely used in various.

Reference£º
Patent; VITAE PHARMACEUTICALS, INC.; WO2008/156817; (2008); A2;,
Tetrahydropyran – Wikipedia
Tetrahydropyran – an overview | ScienceDirect Topics

33821-94-2, 2-(3-Bromopropoxy)tetrahydro-2H-pyran is a Tetrahydropyrans compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Potassium hydride (30% w/w in mineral oil, 2.2 g, 16.5 mmol) was suspended in 1 ,2- dimethoxyethane (20.0 mL) and the suspension cooled to 0-5C (ice bath). A solution of 2- methyl-2-(methylsulfonimidoyl)propanenitrile (Int-5, 2.0 g, 13.7 mmol) in 1 ,2-dimethoxyethane (15 mL) was added dropwise over 10 min. The ice bath was removed and the mixture was stirred for 3 h at room temperature. After that, it was cooled again to 0-5C and tetrabutylammonium bromide (235 mg, 730 muiotaetaomicron) followed by 2-(3-bromopropoxy)tetrahydro-2H-pyran (Int-6, 3.95 g, 3.00 mL, 17.7 mmol) was added. The reaction mixture was stirred for 16 h at room temperature. Then, the mixture was poured onto a saturated aqueous solution of sodium hydrogencarbonate (60 mL) and diluted with ethyl acetate (180 mL). After phase separation, the aqueous phase was extraced with ethyl acetate (2 x 50 mL), the combined organic extracts were dried (sodium sulfate) and concentrated in vacuo to afford a yellow biphasic oil as crude product. This was purified by column chromatography (silica gel, 100 g, eluting with ethyl acetate / n- heptane, gradient 40:60 to 100:0) to yield, after drying in vacuo (50C, 5 mbar), the title compound as mixture of diastereoisomers as a colorless viscous oil (3.28 g, 83%). HPLC (method LCMS_gradient) tR = 1.6 min. 1H NMR (CDC13, 400 MHz): delta 1.47-1.60 (m, 4 H), 1.68- 1.77 (m, 1 H), 1.76 (br s, 6 H), 1.78-1.88 (m, 3 H), 3.06 & 3.07 (2s, 3 H, dias ), 3.20-3.41 (m, 2 H), 3.45-3.54 (m, 2 H), 3.79-3.91 (m, 2 H), 4.56-4.60 (m, 1 H). MS (ES+) m/z 205.1 [M+H- (CsHgO)] .

The synthetic route of 33821-94-2 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; BARTELS, Bjoern; CUENI, Philipp; DOLENTE, Cosimo; GUBA, Wolfgang; HAAP, Wolfgang; KUGLSTATTER, Andreas; OBST SANDER, Ulrike; PETERS, Jens-Uwe; ROGERS-EVANS, Mark; VIFIAN, Walter; WOLTERING, Thomas; (231 pag.)WO2016/55496; (2016); A1;,
Tetrahydropyran – Wikipedia
Tetrahydropyran – an overview | ScienceDirect Topics

220641-87-2, N-Methyltetrahydro-2H-pyran-4-amine is a Tetrahydropyrans compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Example 10; 1-[(E)-3-(3,4-Dichloro-phenyl)-acryloyl]-4-{4-[methyl-(tetrahydro-pyran-4-yl)-amino]-butyl}-[1,4]diazepan-5-one; 1-[(E)-3-(3,4-Dichloro-phenyl)-acryloyl]-4-{4-[methyl-(tetrahydro-pyran-4-yl)-amino]-butyl}-[1,4]diazepan-5-one; A solution of 0.100 g (0.20 mmol) of 1-[(E)-3-(3,4-dichloro-phenyl)-acryloyl]-4-(4-iodo-butyl)-[1,4]diazepan-5-one (example 9B) in 3.1 ml of DMA was treated with free methyl-(tetrahydro-pyran-4-yl)-amine in 1 ml of toluene [0.035 g (0.22 mmol) methyl-(tetrahydro-pyran-4-yl)-amine hydrochloride were dissolved in 0.8 ml of 0.5 N NaOH was extracted with toluene (2 ml). The organic phase was dried over Na2SO4] and stirred for 22 h at RT, 0.06 ml (0.40 mmol) of Et3N was added and stirring was continued for 18 h at 50 C. Again methyl-(tetrahydro-pyran-4-yl)-amine in 1 ml of CH2Cl2 [0.035 g (0.22 mmol) methyl-(tetrahydro-pyran-4-yl)-amine hydrochloridewere dissolved in 0.5 ml aqueous 10% NaCl solution/0.4 ml of 1 N NaOH was extracted with CH2Cl2 (1 ml). The organic phase was dried over Na2SO4] was added and heated for 9 h at 50 C. The reaction was extracted with aqueous saturated NaHCO3/Et2O (3¡Á). The organic phases were washed with aqueous 10% NaCl, dried (Na2SO4), concentrated and evaporated. Purification by catridges, Si-Amine, 70 ml, 20 g (n-heptane/EtOAc 1:4 to 1:9) gave 0.004 g (4%) of the title compound as a light yellow semisolid. MS: 482.3 (MH+, 2Cl).

The synthetic route of 220641-87-2 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; Aebi, Johannes; Green, Luke; Mattei, Patrizio; Ricklin, Fabienne; Roche, Olivier; Zahm, Peter; US2007/249589; (2007); A1;,
Tetrahydropyran – Wikipedia
Tetrahydropyran – an overview | ScienceDirect Topics

31608-22-7, 2-(4-Bromobutoxy)tetrahydro-2H-pyran is a Tetrahydropyrans compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

2-[4-(2,3-Difluorophenoxy)butoxy]-tetrahydropyran (20) To a solution of 2-(4-bromobutoxy)-tetrahydropyran (18) (1 equi.) and commercially available 2,3-difluorophenol (19) (1 equi.) in DMF (3 mL/mmole), cesium carbonate (1.25 equi.) was added at room temperature. The reaction mixture was stirred at that temperature for 24 h, quenched with water, extracted with ethyl acetate:hexane (1:1), washed with brine, dried over MgSO4, and concentrated in vacuo. Purification by chromatography on silica gel (5% EtOAc/hexanes) and recrystallization from acetonitrile gave 2-[4-(2,3-difluorophenoxy)-butoxy]-tetrahydropyran(20), as a white solid (84%).

31608-22-7 2-(4-Bromobutoxy)tetrahydro-2H-pyran 559019, aTetrahydropyrans compound, is more and more widely used in various.

Reference£º
Patent; Wand, Michael; Gough, Neil; Chen, Xin Hua; US2003/17278; (2003); A1;,
Tetrahydropyran – Wikipedia
Tetrahydropyran – an overview | ScienceDirect Topics