Heterocyclic Building Blocks-Tetrahydropyrans

4677-20-7,With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.4677-20-7,4-(2-Bromoethyl)tetrahydropyran,as a common compound, the synthetic route is as follows.

Into a 50-mL 3-necked round-bottom flask, was placed tert-butyl N-[2-[([3-[4-(3- hydroxycyclobutoxy)phenyl] -1 -(oxan-2-yl)- 1 H-pyrazol-4-yl]methyl)(methyl)amino] ethyl] – N-methylcarbamate (500 mg, 0.97 mmol, 1.00 equiv),N,N-dimethylformamide (10 mL). The temperature was cooled to 0C. To this was added sodium hydride (120 mg, 5.00 mmol, 5.15 equiv, 60% in mineral oil) in batches. The mixture was stirred for 1 h at R.T. Then to the mixture was added 4-(2-bromoethyl)oxane (470 mg, 2.43 mmol, 2.51 equiv). The resulting solution was stirred overnight at room temperature. The reaction was then quenched by the addition of 30 mL of water. The resulting solution was extracted with 3×3 0 mL of ethyl acetate. The resulting mixture was washed with 3×30 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (0%-60%). The collected fractions were combined and concentrated under vacuum. This resulted in 450 mg (74%) of tert-butyl N-methyl-N-[2- [methyl([ [1 -(oxan-2-yl)-3 -(4- [3 -[2-(oxan-4-yl)ethoxy] cyclobutoxy]phenyl)1H-pyrazol-4-yl]methyl])amino]ethyl]carbamate as yellow oil. LCMS (Method A, ESI): RT = 1.37mm, m/z =627.4 [M+H].

The synthetic route of 4677-20-7 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; EPIZYME, INC.; MITCHELL, Lorna, Helen; SWINGER, Kerren, Kalai; SHAPIRO, Gideon; BORIACK-SJODIN, Paula, Ann; (104 pag.)WO2016/44556; (2016); A2;,
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.7525-64-6,4-Methyltetrahydro-2H-pyran-4-ol,as a common compound, the synthetic route is as follows.

7525-64-6, To a suspension of sodium hydride, 60% in mineral oil (207 mg, 5.17 mmol) in THF (20 mL) was added 4-methyltetrahydro-2H-pyran-4-ol (500 mg, 4.30 mmol) at 0 C. After stirring 30 min, the solution was transferred to a solution of di(pyridin-2-yl)carbonate (931 mg, 4.30 mmol) in THF (20 mL) through a cannula. The formed slurry was stirred at 0 C. for 30 min. The slurry was warmed to rt and stirred for 2 h. At room temperature, to the reaction mixture was added sat. aq. NH4Cl (1 mL) upon which brief and significant effervescence was observed. The mixture was transferred to a 250 mL separatory funnel and was diluted with Et20 (50 mL). The solution was washed with water:brine (25 mL: 25 mL). The aq. phase was extracted with EtOAc (100 mL). The combined organics were dried over MgSO4; filtered; then concentrated in vacuo. The resulting residue was dissolved in acetone and then concentrated onto Celite in vacuo. The resulting powder was subjected to SiO2 purification on the Biotage system [90 g SiO2column, hexanes:EtOAc 90:10 to 60:40 over 8 CV] to get the product as a clear oil.1H NMR (400 MHz, CHLOROFORM-d) delta 8.48-8.39 (m, 1H), 7.87-7.76 (m, 1H), 7.30-7.24 (m, 2H), 7.16-7.09 (m, 1H), 3.83-3.69 (m, 4H), 2.29-2.16 (m, 2H), 1.80 (ddd, J=14.3, 8.9, 5.9 Hz, 2H), 1.66 (s, 3H)

7525-64-6 4-Methyltetrahydro-2H-pyran-4-ol 12347118, aTetrahydropyrans compound, is more and more widely used in various fields.

Reference£º
Patent; Bristol-Myers Squibb Company; Hiebert, Sheldon; Rajamani, Ramkumar; Sun, Li-Qiang; Mull, Eric; Gillis, Eric P.; Bowsher, Michael S.; Zhao, Qian; Meanwell, Nicholas A.; Renduchintala, Kishore V.; Sarkunam, Kandhasamy; Nagalakshmi, Pulicharla; Babu, P.V.K. Suresh; Scola, Paul Michael; (403 pag.)US9527885; (2016); B2;,
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.1228779-96-1,3-Nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)benzenesulfonamide,as a common compound, the synthetic route is as follows.

Into a 40-mL round-bottom flask, was placed 4-(4- [[2-(4-chlorophenyl)-4,4-dimethylcyclohex- i-en-i – ylj methyljpiperazin- 1 -yl)-2- [ i4-oxa-2,4, iO-triazatricyclo [7.5 .0.0?[3 ,7j jtetradeca- 1 (9),2,5,7- tetraen-iO-yljbenzoic acid (50 mg, 0.08 mmol, 1 equiv), DCM (3 mL), 3-nitro-4-[[(oxan-4- yl)methyljaminojbenzene-i-sulfonamide (25.2 mg, 0.08 mmol, 1.00 equiv), EDCI (30.6 mg, 0.16 mmol, 2 equiv), DMAP (39.0 mg, 0.32 mmol, 4 equiv). The resulting solution was stirred for overnight at 25 degrees C. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with dichloromethane/methanol (10:1). The crude product was purified by Flash-Prep-HPLC with the following conditions (IntelFlash-i): Column, Ci8 reversed phase column; mobile phase, Water (1OMMOL/L NH4HCO3+0.05%NH3.H20) and CH3CN (20.0% CH3CN up to 90.0% in 30 mm); Detector, UV 220 nm. This resulted in 19.1 mg (25.90%) of 4-(4- [[2-(4-chlorophenyl)-4,4-dimethylcyclohex- i-en-i -ylj methyljpiperazin- 1 -yl)N-(3-nitro-4-[[(oxan-4-yl)methylj aminojbenzenesulfonyl)-2- [ i4-oxa-2,4, 10- triazatricyclo [7.5 .0.0?[3,7j jtetradeca- 1 (9),2,5,7-tetraen- iO-yljbenzamide as a yellow solid. LCMS: (ES, m/z): M+i=923, R,T= 3.463 mm. The measurements of the retention were done with a reversed phase column (C 18). Shimadzu LCMS 2020; 50*3.0 Agilent Poroshell HPH-Ci8, 2.7um; Eluent A: water (0.05 % ammonia water); Eluent B: Acetonitrile; linear gradient from 5 % acetonitrile to 95 % acetonitrile in 7.0 minutes; Oven temperature 40 C; flow: 1.5 mL/min. ?H NMR (300 MHz, DMSO-d6,ppm) 11.91 (s, iH), 11.26 (s, iH), 8.56 (s, iH), 8.47 (d, J= 2.1 Hz, iH), 7.61 (d, J = 9.0 Hz, iH), 7.48 (d, J = 9.2 Hz, iH), 7.37 (d, J = 8.3 Hz, 2H), 7.20 (s, iH), 7.07 (d, J = 8.3 Hz, 2H), 6.99 – 6.83 (m, 2H), 6.76 (d, J = 29.2 Hz, 2H), 6.14 (s, iH), 4.21 (s, 2H), 3.85 (d, J = 9.3 Hz, 2H), 3.52 (s, 2H), 3.30 – 3.14 (m, 8H), 2.79 (s, iH), 2.23 (d, J = 20.0 Hz, 5H), 1.99 (s, 4H), 1.85 (s, iH), 1.61 (d, J= 11.3 Hz, 2H), 1.42 (s, 2H), 1.25 (s, 2H), 1.03-0.79 (m, 6H). The measurements of the NMR spectra were done with Bruker Avancelli HD300MHz with a probe head of BBOF.

1228779-96-1, 1228779-96-1 3-Nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)benzenesulfonamide 57474953, aTetrahydropyrans compound, is more and more widely used in various fields.

Reference£º
Patent; NEWAVE PHARMACEUTICAL INC.; CHEN, Yi; LOU, Yan; (108 pag.)WO2019/40550; (2019); 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.1240390-36-6,tert-Butyl ((3R,4R)-4-aminotetrahydro-2H-pyran-3-yl)carbamate,as a common compound, the synthetic route is as follows.

10517] A 50-mE 1-neck round bottom flask was charged with reactant 22-A (0.50 g, 2.31 mmol), 6-8 (0.80 g, 2.31 mmol) and NaHCO3 (0.39 g, 4.6 mmol) in ethanol (10 ml) and water (10 ml). The reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated down, re-dissolved in EtOAc (100 mE), washed with water (2x) and dried over Na2504. After concentration, the crude was dissolved in 4N HC1/Dioxane (11 ml) and stirred atroom temperature for 3 hours to dc-Hoc. The reaction mixture was concentrated down again. The residue and DRU (1.58 g, 10.4 mmol) were dissolved in EtOH (10 mE). Heated to 50 C. for 20 minutes. Afier concentration, the crude was purified by column chromatography on silica gel with hexane-EtOAc to obtain 22-C. ECMS-ESI (mlz): [M+H]. found: 399., 1240390-36-6

1240390-36-6 tert-Butyl ((3R,4R)-4-aminotetrahydro-2H-pyran-3-yl)carbamate 68077633, aTetrahydropyrans compound, is more and more widely used in various fields.

Reference£º
Patent; Gilead Sciences, Inc.; Bacon, Elizabeth M.; Cai, Zhenhong R.; Cottell, Jeromy J.; Ji, Mingzhe; Jin, Haolun; Lazerwith, Scott E.; Morganelli, Philip Anthony; Pyun, Hyung-jung; (101 pag.)US2016/176870; (2016); A1;,
Tetrahydropyran – Wikipedia
Tetrahydropyran – an overview | ScienceDirect Topics

127956-11-0, Methyl 4-oxotetrahydro-2H-pyran-3-carboxylate is a Tetrahydropyrans compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

127956-11-0, A mixture of crude 4-oxo-tetrahydro-pyran-3-carboxylic acid methyl ester (1780 g, 1 1 mol) and triethylamine (830 g, 8.2 mol) in MeOH (3560 mL) was cooled to 0C under N2. A solution of 2-chloro-acetamidine (567 g, 4.4 mol) in 890 mL of MeOH was added dropwise over 50 minutes. The reaction mixture was stirred at 0C for 30 minutes and then at about 20C for 16 hours. LCMS at 215nm and TLC (DCM:MeOH=10:1) analysis showed that most of 4-oxo-tetrahydro-pyran-3-carboxylic acid methyl ester was consumed. The mixture was then filtered and concentrated to give black oil, which was subsequently purified by flash column chromatography on silica gel and eluted with DCM to give yellow solid/oil mixture, which was further triturated with MTBE (-1200 mL) and H20: CH3CN: EA=1 :1 :2 (-600 mL) to give the title compound as a white solid (318 g). MS m/z 201 .2 (M+H). CHN analysis: calculated (results). C 47.89 (47.95), H 4.52 (4.401), N 13.96 (13.76).

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

Reference£º
Patent; NOVARTIS AG; CHEN, Christine Hiu-Tung; CHIN, Noel Chin; DIPIETRO, Lucian V.; FAN, Jianme; PALERMO, Mark G; SHULTZ, Michael David; TOURE, Bakary-Barry; WO2013/8217; (2013); A1;,
Tetrahydropyran – Wikipedia
Tetrahydropyran – an overview | ScienceDirect Topics

101691-65-0, (Tetrahydro-2H-pyran-4-yl)methyl 4-methylbenzenesulfonate is a Tetrahydropyrans compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

A mixture of sodium hydride (60 wt.% in mineral oil, 15.74 mg) in DMF (0.7 mL) was added to a solution of tert-butyl 2-chloro-5-(5-chloro-2-fluoropyridin-4-yl)phenylcarbamate (213 mg, 0.596 mmol) in DMF (0.70 mL) at 0 C. The resulting mixture was stirred at 0 C for 30 min. To this stirred mixture was then added (tetrahydro-2H-pyran-4-yl)methyl 4- methylbenzenesulfonate (161 mg, 0.596 mmol) in one portion. The mixture was warmed to 40 C and maintained at this temperature for 16 hrs. The reaction mixture was diluted with EtOAc, washed with IN aqueous sodium hydroxide solution, water and brine, dried over sodium sulfate, filtered off and concentrated under reduced pressure. The residue was purified by preparative TLC [silica gel, 1 mm; EtO Ac/heptane = 15/85] providing [2-chloro-5-(5-chloro-2-fluoro- pyridin-4-yl)-phenyl]-(tetrahydro-pyran-4-ylmethyl)-carbamic acid tert-butyl ester (176 mg) as a colorless oil. LCMS (m/z): 355.0/356.9 [M+H, loss of t-Bu]; Retention time = 1.21 min., 101691-65-0

The synthetic route of 101691-65-0 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; NOVARTIS AG; ANTONIOS-MCCREA, William R.; BARSANTI, Paul A.; HU, Cheng; JIN, Xianming; MARTIN, Eric J.; PAN, Yue; PFISTER, Keith B.; SENDZIK, Martin; SUTTON, James; WAN, Lifeng; WO2012/66065; (2012); 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.125995-03-1,Atorvastatin lactone,as a common compound, the synthetic route is as follows.

Example 3. Synthesis of Atorva-HA ((3R,5R)-7-[2-(4-Fluoro-phenyl)-5-isopropyl-3- phenyl-4-phenylcarbamoyl pyrrol-l-yl]-3,5-dihydroxy-N-hydroxyheptanamide) [00356] By a procedure similar to Lova-HA, atorvastatin (168 mg, 0.31 mmol, in the lactone form) was treated with MgBr2 (115 mg, 0.62 mmol), hydroxylamine hydrochloride (184 mg, 2.6 mmol), and sodium bicarbonate (209 mg, 2.5 mmol) in anhydrous THF/MeOH (7:3, 1 mL) at ambient temperature for 20 h to give Atorva-HA (91 mg, 51%). The purity was 95% as shown by HPLC analysis on an HC-Cig column (Agilent, 4.6 x 250 mm, 5 muiotaeta), tR = 14.8 min (gradients of 30-100%) aqueous CH3CN in 30 min). C33H36FN305; colorless oil; [alpha]26omicron = -1.3 (EtOAc, c = 1.0); TLC (CH2Cl2/MeOH (9: 1)) Rf= 0.33; IR vmax (neat) 3405, 3301, 3059, 2960, 2926, 1738, 1657, 1595, 1527, 1508, 1436, 1314, 1241, 1223, 1157, 1108, 1078, 1046, 843, 753, 692 cm”1; 1H NMR (DMSO-< 6, 400 MHz) delta 10.31 (1 H, br s), 9.77 (1 H, br s), 8.68 (1 H, br s), 7.50 (2 H, d, J= 7.6 Hz), 7.18-7.24 (6 H, m), 7.07 (4 H, br s), 6.98-7.00 (2 H, m), 4.69 (1 H, br s), 4.60 (1 H, d, J= 4.0 Hz), 3.92-3.95 (1 H, m), 3.72-3.83 (2 H, m), 3.53 (1 H, br s), 3.21-3.25 (1 H, m), 2.01 (2 H, d, J= 6.0 Hz), 1.63 (1 H, br s), 1.53 (1 H, br s), 1.28-1.38 (8 H, m) ppm; 13C NMR (DMS0 , 100 MHz) delta 167.4, 166.1, 162.8, 160.3, 139.4, 135.9, 134.9, 133.4, 129.1 (2 x), 128.7, 128.4 (2 chi), 127.6 (2 chi), 127.3, 125.3, 122.9, 120.6, 119.4 (2 chi), 117.5, 115.4, 115.2, 66.0, 65.6, 43.8, 40.9, 40.7, 25.6, 22.3 (2 chi) ppm; ESI-HRMS (negative mode) calcd. for C33H35FN305: 572.2561, found: m/z 572.2562 [M - H] . 125995-03-1, The synthetic route of 125995-03-1 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; ACADEMIA SINICA; NATIONAL TAIWAN UNIVERSITY; LIANG, Chi-Ming; CHEN, Ching-Chow; CHEN, Jhih-Bin; WEI, Tzu-Tang; LIN, Jung-Hsin; FANG, Jim-Min; CHERN, Ting-Rong; WO2014/15235; (2014); A2;,
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.2081-44-9,Tetrahydro-2H-pyran-4-ol,as a common compound, the synthetic route is as follows.

To an ice-cooled solution of oxan-4-ol (1.00 g, 9.79 mmol), Et3N (1.36 ml, 9.79 mmol) and catalytic amount DMAP in 20 ml of CH2Cl2 was added dropwise MsCl (0.76 ml, 9.79 mmol). The resulting mixture was stirred for 1 h and diluted with water. The mixture was extracted with CH2Cl2. The organic phase was washed with brine, dried over anhydrous Na2SO4 and concentrated under vacuum. The crude product was pure enough for use in the next step (1.65 g, 93.5 % yield).

2081-44-9, 2081-44-9 Tetrahydro-2H-pyran-4-ol 74956, aTetrahydropyrans compound, is more and more widely used in various fields.

Reference£º
Article; Zhang, Dengyou; Ai, Jing; Liang, Zhongjie; Li, Chunpu; Peng, Xia; Ji, Yinchun; Jiang, Hualiang; Geng, Meiyu; Luo, Cheng; Liu, Hong; Bioorganic and Medicinal Chemistry; vol. 20; 17; (2012); p. 5169 – 5180;,
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.1197-66-6,2,2,6,6-Tetramethyl-2H-3,5,6-trihydropyran-4-one,as a common compound, the synthetic route is as follows.

A 2 L RBF under light nitrogen flow was charged with 2,2,6,6-tetramethyldihydro-2H-pyran-4(3H)-one (1.00 equiv; 49.10 mL; 43.45 g), (a known compound which may be prepared as described in, for example, MAGNUS, P., et al., ?Synthesis of the ABCD-rings of the insecticidal indole alkaloid nodulisporic acid?, Tet. Lett., 1999, pp 6909-6912, Vol. 40) 2-methyl-THF (375.00 mL; 322.05 g) and DBU (76.67 mL; 77.67 g). The resulting mixture was stirred and cooled to about 2 C. with a water-ice bath. NfsulphF (1.20 equiv; 56.07 mL; 94.20 g) was introduced into a dropping funnel and the NfsulphF was then added to the reaction mixture over 20 minutes, with a light exotherm is observed. After complete addition, the water-ice bath was taken away and the temperature allowed to rise to room temperature. Precipitation was observed to start forming, resulting in a yellow suspension. The yellow suspension was stirred overnight at room temperature and yielded yield a brown suspension. [0249] To the brown suspension was slowly added water (1.12 L; 1.12 kg), with an observed exotherm. The resulting mixture was warmed 44 C., resulting in a multi-phase mixture with good separation (the organic layer was the top layer). The mixture was stirred for 20 minutes and the phases warm separated at about 44 C. The aqueous (orange colored) layer was returned to the RBF, and then extracted with 2-methyl-THF (185.00 mL; 158.88 g) by stirring 20 minutes at 44 C., then warm separating the resulting layers. The organic layers were then combined. Water (190.00 mL; 190.00 g) was added and the resulting mixture stir for 20 minutes, and the resulting layers warm separated at 44 C. The organic layer was then washed second time with water (190.00 mL; 190.00 g), with some white fluffy precipitation observed in the water layer. The organic layer was then evaporated on a rotavap at 45 C. The resulting biphasic residue included a thick brown bottom layer (129.17 g) and light colored material on top. To the residue was added HEPTANE 50% (a mixture of 50% n-heptane, 20% other heptane isomers and 30% methyl cyclohexane; 250.00 mL; 176.75 g), then acetonitrile (19.00 mL; 14.88 g). The resulting mixture was stirred firmly, the acetonitrile was observed to take up the oily layer, resulting in a biphasic system. The mixture was then stirred for 1 hour, the layers separated. The heptane layer was evaporated on a rotovap at 42 C. to yield the title compound as a residue (102.60 g) [0250] Actual Yield: 93.52% 102.60 g, 234.08 mmol [0251] Theoretical Yield: 100% 109.58 g, 250.00 mmol, 1197-66-6

As the paragraph descriping shows that 1197-66-6 is playing an increasingly important role.

Reference£º
Patent; Janssen Pharmaceutica NV; KOLODZIEJCZYK, Krzysztof; Stappers, Alfred Elisabeth; Teleha, Christopher A.; Weerts, Koen Johan Herman; US2014/45789; (2014); A1;,
Tetrahydropyran – Wikipedia
Tetrahydropyran – an overview | ScienceDirect Topics

1245724-46-2, (S)-Tetrahydro-2H-pyran-3-amine hydrochloride is a Tetrahydropyrans compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

To a mixture of ethyl 4-chloro-6-(6-(methoxymethyl)pyridin-3-yl)quinoline-3- carboxylate (2 g, 5.61 mmol) and (5)-tetrahydro-2H-pyran-3-amine hydrochloride (0.926 g, 6.73 mmol) in DMF (10 ml) was added DIPEA (3.5 ml, 20.04 mmol) and the solution stirred at 80C for three h then allowed to cool. The reaction mixture was stirred with water (100 ml) and the solid was filtered off, washed thoroughly with water and sucked dry. The crude product was purified by FCC, elution gradient 0 to 3% 2N methanolic ammonia in DCM and pure fractions were evaporated to dryness to afford (5)-ethyl 6-(6-(methoxymethyl)pyridin-3-yl)-4- ((tetrahydro-2H-pyran-3-yl)amino)quinoline-3-carboxylate (1.640 g, 69.4 %) as a white solid. NMR Spectrum: 1H NMR (500MHz, DMSO-d6) 5 1.36 (3H, t), 1.47 – 1.64 (1H, m), 1.67 – 1.94 (2H, m), 1.96 – 2.2 (1H, m), 3.40 (3H, s), 3.56 (1H, dd), 3.61 (2H, t), 3.87 (1H, dd), 4.22 (1H, dd), 4.36 (2H, q), 4.56 (2H, s), 7.54 (1H, dd), 7.95 (1H, d), 8.10 (1H, dd), 8.19 (1H, dd), 8.40 (1H, d), 8.91 (1H, s), 8.92 – 8.93 (1H, m), 8.94 (1H, dd). Mass Spectrum: m/z (ES+)[M+H]+ = 422., 1245724-46-2

1245724-46-2 (S)-Tetrahydro-2H-pyran-3-amine hydrochloride 60145922, aTetrahydropyrans compound, is more and more widely used in various fields.

Reference£º
Patent; ASTRAZENECA AB; BARLAAM, Bernard, Christophe; PIKE, Kurt, Gordon; HUNT, Thomas, Anthony; (110 pag.)WO2017/153578; (2017); A1;,
Tetrahydropyran – Wikipedia
Tetrahydropyran – an overview | ScienceDirect Topics