Heterocyclic Building Blocks-Tetrahydrofuran

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.88675-24-5,Tetrahydrofuran-3-amine,as a common compound, the synthetic route is as follows.

To a solution of (4S)-5-(pyridin-2-ylcarbamoyl)-2,3,4,5-tetrahydro-1,4-methanopyrido[2,3-b][1,4]diazepine-7-carboxylic acid (250 mg, 0.768 mmol) in N,N-Dimethylformamide (DMF) (5 mL) under nitrogen at room temp, HATU (584 mg, 1.537 mmol), DIPEA (0.268 mL, 1.537 mmol) and tetrahydrofuran-3-amine (100 mg, 1.153 mmol) were added and the reaction mixture was stirred at RT for 16 h. The reaction mixture was diluted with ice water and extracted with 2¡Á15 ml of ethyl acetate. The combined organic layer was washed with brine and dried over sodium sulfate and concentrated under reduced pressure to afford crude compound. The crude product was purified by flash column chromatography (100-200 silica gel eluted with 2percent of CH2Cl2/MeOH) to afford (4S)?N5-(pyridin-2-yl)-N7-(tetrahydrofuran-3-yl)-3,4-dihydro-1,4-methanopyrido[2,3-b][1,4]diazepine-5,7(2H)-dicarboxamide (140 mg, 0.353 mmol, 45.9percent yield) as off white solid. (TLC system: 10percent Methanol in DCM. Rf value: 0.35), LCMS (m/z): 395.23 [M+H]+. 1H NMR (400 MHz, DMSO-d6): delta ppm 13.01 (s, 1H), 8.30 (dd, J=4.93, 0.99 Hz, 1H), 7.98-8.17 (m, 2H), 7.93-7.77 (m, 1H), 7.74-7.60 (m, 2H), 7.13 (ddd, J=7.23, 4.93, 0.99 Hz, 1H), 5.48 (dd, J=5.70, 3.07 Hz, 1H), 4.75-4.44 (m, 1H), 4.05-3.55 (m, 4H), 3.23-2.81 (m, 4H), 2.37-2.15 (m, 2H), 2.16-2.05 (m, 1H), 2.16-1.78 (m, 1H).

The synthetic route of 88675-24-5 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; BLUM, Charles A.; Caldwell, Richard Dana; Casaubon, Rebecca; Disch, Jeremy S.; Fox, Ryan Michael; Koppetsch, Karsten; Miller, William Henry; NG, Pui Yee; Oalmann, Christopher; Perni, Robert B.; Szczepankiewicz, Bruce G.; White, Brian; US2015/152108; (2015); A1;,
Tetrahydrofuran – Wikipedia
Tetrahydrofuran | (CH2)3CH2O – PubChem

149809-43-8, ((3R,5R)-5-((1H-1,2,4-Triazol-1-yl)methyl)-5-(2,4-difluorophenyl)tetrahydrofuran-3-yl)methyl 4-methylbenzenesulfonate is a Tetrahydrofurans compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

2-[(l S2S)-l-Ethyl-2-benzyloxypropyl]-2,4-dihydro-4-[4-[4-(4-hydroxyphenyl)-l- piperozinyl] phenyl]-3H-l,2,4-triazol-3-one (1 kg) was added to the Flask along with Dimethylsulfoxide (8 lit) at room temperature and stirred for 15 min. Solution of Sodium hydroxide (0.15 kg) in Water (0.3 lit) was added at same temperature and maintained for 1 hr. ((3S,5R)-5-((lH-l,2,4-triazol-l-yl)methyl)-5-(2,4- difluorophenyl)-tetrahydrofuran-3-yl)methyl-4-methylbenzene sulfonate (1.2 kg) was added and maintained for 4-5 hrs. Water (10 lit) was added to the reaction mixture and stirred for 15 min. Ethyl acetate (7.5 lit) was added and stirred for 15 min. Aqueous layer and Ethyl acetate layer were separated and aqueous layer was extracted with Ethyl acetate (3 lit). Aqueous layer and Ethyl acetate layer were separated and total aqueous layer was washed with Water (5 lit) and stirred for 15 min. Aqueous layer and Ethyl acetate layer were separated and Ethyl acetate layer was washed with brine solution. Aqueous layer and Ethyl acetate layer were separated and Ethyl acetate layer was dried over Sodium sulfate and distilled under vacuum at below 50C. The resultant crude was treated with Isopropyl alcohol (10 lit) and heated to 75-80C, maintained for material dissolved and treated with activated Carbon (0.05 kg) and maintained for 1 hr. The material was filtered through the Hyflow bed and washed with Isopropyl alcohol (1 lit). The resultant mass was cooled to room temperature, maintained for 2 hrs, filtered the solid and washed with Isopropyl alcohol (1 lit). Yield: 1.3Kg; HPLC: 98.6%.

The synthetic route of 149809-43-8 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; METROCHEM API PVT LTD.; NANDEPU, Venkateswara Rao; BIJJULA, Venkata krishna Reddy; BATHINA, Satyanarayana; (44 pag.)WO2019/77627; (2019); A1;,
Tetrahydrofuran – Wikipedia
Tetrahydrofuran | (CH2)3CH2O – PubChem

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.22929-52-8,Dihydrofuran-3(2H)-one,as a common compound, the synthetic route is as follows.

A. Methyl magnesium iodide (3.0M in Et2 O, 20 mL) was added to a solution of tetrahydrofuran-3-one (1.6 g, 18.6 mmol) in 15 mL of Et2 O at 0¡ã C. After stirring 4 h at 0¡ã C. the mixture was quenched with sat. aq. NH4 Cl solution and extracted with Et2 O. The combined extracts were dried over MgSO4 and concentrated under reduced pressure to give the crude material. Purification by chromatography (CH2 Cl2 to 1percent MeOH/CH2 Cl2 to 2percent MeOH/CH2 Cl2) gave 3-hydroxy-3-methyltetrahydrofuran (0.290 g). 1 H NMR consistent with structure.

As the paragraph descriping shows that 22929-52-8 is playing an increasingly important role.

Reference£º
Patent; Vertex Pharmaceuticals Incorporated; US5691372; (1997); A;,
Tetrahydrofuran – Wikipedia
Tetrahydrofuran | (CH2)3CH2O – PubChem

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.184950-35-4,(Tetrahydrofuran-3-yl)methanamine hydrochloride,as a common compound, the synthetic route is as follows.

5- (1-naphthylmethoxymethyl) isoxazole-3-carboxylic acid (0.46 g, 1.6 mmol), Tetrahydrofuran-3-ylmethylamine hydrochloride (0.26 g, 1.9 mmol), Triethylamine (0.19 g, 1.9 mmol) And 1-hydroxybenzotriazole (0.02 g, 0.19 mmol) Was added to chloroform (amylene addition product) (3 mL). To the mixture, 1-Ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.37 g, 1.9 mmol) was added at room temperature, After stirring overnight, And concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, Extracted twice with ethyl acetate. The organic layer was washed with saturated brine, After drying with anhydrous sodium sulfate, And concentrated under reduced pressure. The residue was subjected to silica gel column chromatography, Represented by the following equation N- (tetrahydrofuran-3-ylmethyl) -5- (1-naphthylmethoxymethyl) isoxazole-3-carboxamide (Hereinafter referred to as the amide compound (27)) 0.31 g was obtained.

As the paragraph descriping shows that 184950-35-4 is playing an increasingly important role.

Reference£º
Patent; SUMITOMO CHEMICAL COMPANY LIMITED; SUMITA, YUSUKE; (264 pag.)JP2015/51963; (2015); A;,
Tetrahydrofuran – Wikipedia
Tetrahydrofuran | (CH2)3CH2O – PubChem

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.184950-35-4,(Tetrahydrofuran-3-yl)methanamine hydrochloride,as a common compound, the synthetic route is as follows.

Production Example 267 (0588) 5-(4-Chloro-3-fluorobenzyloxymethyl)isoxazole-3-carbo xylic acid (0.54 g, 2.0 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.41 g, 3.0 mmol), triethylamine (0.30 g, 3.0 mmol) and 1-hydroxybenzotriazole (0.03 g, 0.2 mmol) were added to chloroform (amylene addition product) (5 mL). 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (0.46 g, 2.4 mmol) was added to the mixture at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the residue, and the mixture was extracted three times with ethyl acetate. The organic layer was washed with a saturated aqueous sodium bicarbonate solution and saturated saline water and dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The residue was applied to a silica gel column chromatography to obtain 0.18 g of N-(tetrahydrofuran-3-ylmethyl)-5-(4-chloro-3-fluorobenzylox ymethyl)isoxazole-3-carboxamide (hereinafter, referred to as Compound of Present Invention (276)) represented by the following formula. 1H-NMR (CDCl3, TMS, delta (ppm)) : 1.62-1.74 (1H, m), 2.05-2.14 (1H, m), 2.52-2.64 (1H, m), 3.47 (2H, t), 3.59 (1H, dd), 3.73-3.80 (1H, m), 3.83-3.95 (2H, m), 4.57 (2H, s), 4.67 (2H, s), 6.74 (1H, s), 6.94 (1H, br s), 7.04-7.08 (1H, m), 7.16 (1H, dd), 7.38 (1H, t)

184950-35-4 (Tetrahydrofuran-3-yl)methanamine hydrochloride 17750392, aTetrahydrofurans compound, is more and more widely used in various.

Reference£º
Patent; Sumitomo Chemical Company, Limited; MITSUDERA, Hiromasa; AWASAGUCHI, Kenichiro; AWANO, Tomotsugu; UJIHARA, Kazuya; EP2952096; (2015); A1;,
Tetrahydrofuran – Wikipedia
Tetrahydrofuran | (CH2)3CH2O – PubChem

184950-35-4, (Tetrahydrofuran-3-yl)methanamine hydrochloride is a Tetrahydrofurans compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Production Example 13 (0324) 5-Benzyloxymethylisoxazole-3-carboxylic acid (0.59 g, 2.5 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.39 g, 2.8 mmol), triethylamine (0.28 g, 2.8 mmol) and 1-hydroxybenzotriazole (0.04 g, 0.28 mmol) were added to chloroform (amylene addition product) (15 mL). 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (0.54 g, 2.8 mmol) was added to the mixture at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated saline water, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The residue was applied to a silica gel column chromatography to obtain 0.35 g of N-(tetrahydrofuran-3-ylmethyl)-5-benzyloxymethylisoxazole-3 -carboxamide (hereinafter, referred to as Compound of Present Invention (13)) represented by the following formula. 1H-NMR (CDCl3, TMS, delta(ppm)): 1.66-1.69(1H, m), 2.05-2.13(1H, m), 2.53-2.63(1H, m), 3.47-3.49(2H, m), 3.58-3.60(1H, m), 3.76-3.78(1H, m), 3.84-3.95(2H, m), 4.61(2H, s), 4. 65 (2H, s), 6.73(1H, d), 6.95(1H, br s), 7.31-7.40(5H, m)

The synthetic route of 184950-35-4 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; Sumitomo Chemical Company, Limited; MITSUDERA, Hiromasa; AWASAGUCHI, Kenichiro; AWANO, Tomotsugu; UJIHARA, Kazuya; EP2952096; (2015); A1;,
Tetrahydrofuran – Wikipedia
Tetrahydrofuran | (CH2)3CH2O – PubChem

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.19311-37-6,3-Bromotetrahydrofuran,as a common compound, the synthetic route is as follows.

[00494] To a solution of 119-1 (50 mg, 0.16 mmol, 1.00 eq) and 119-2 (32.2 mg, 0.21 mmol, 1.30 eq) in DMF (3 mL) was added K2C03 (45.3 mg, 0.33 mmol, 2.00 eq). The reaction was heated to 100C for 16 hr. LCMS showed that -80% of desired MS signal was detected. The reaction was diluted with EtOAc (20 mL) and washed with brine (2* 10 mL). The organic layer was dried over Na2S04 and concentrated. The crude product was purified by Prep.HPLC (acidic conditions) to give the title compound (17.36 mg, 46.25 umol, 28.24% yield). 1HNMR and LCMS confirmed that the desired product was obtained. LCMS (ESI): RT = 0.910 min, mass calc. for Ci8Hi6F3N50 375.13, m/z found 376.0[M+H]+; 1HNMR (400 MHz, CDC13) 9.05 (s, 1H), 8.21 (dd, J= 8.0, 1.6 Hz, 1H), 7.60 – 7.50 (m, 3H), 7.40 – 7.35 (m, 1H), 7.29 (d, J= 8.4 Hz, 2H), 7.05 (t, J= 8.0 Hz, 1H), 5.65- 5.50 (m, 1H), 4.40 – 4.25 (m, 3H), 4.15- 4.00 (m, 1H), 2.80 – 2.65 (m, 1H), 2.65- 2.50 (m, 1H).

19311-37-6 3-Bromotetrahydrofuran 12929516, aTetrahydrofurans compound, is more and more widely used in various.

Reference£º
Patent; VIVACE THERAPEUTICS, INC.; KONRADI, Andrei W.; LIN, Tracy Tzu-Ling Tang; (396 pag.)WO2018/204532; (2018); A1;,
Tetrahydrofuran – Wikipedia
Tetrahydrofuran | (CH2)3CH2O – PubChem

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.111769-27-8,(R)-Tetrahydrofuran-3-amine 4-methylbenzenesulfonate,as a common compound, the synthetic route is as follows.

c) Preparation of the intermediate compound (R)-l-(5,6-dichloro-lH-benzo[d]imidazol-2-yl)-N- (tetrahydrofuran-3-yl)piperidine-4-carboxamide l-(5,6-Dichloro-lH-benzo[d]imidazol-2-yl)piperidine-4-carboxylic acid (628 mg, 2.0 mmol), (R)-(+)-tetrahydrofuran-3-amine 4-methylbenzenesulfonate (622 mg, 2.4 mmol), 2-(7-aza-lH- benzotriazole-l-yl)-l,l,3,3-tetramethyluronium hexafluorophosphate (HATU, 912 mg, 2.4 mmol), JV,JV-diisopropylethylamine (Hunig’s base, DIEA, 775 mg, 6.0 mmol) and N5N- dimethylformamide (25 niL) was stirred at room temperature for 100 minutes. The reaction mixure was concentrated in vacuo, the residue purified on column (silica gel, flashchromatography, dichloromethane/methanol, gradient elution 4-20 % methanol) and finally precipitated from chloroform to give 378 mg (49 % yield) of (R)-l-(5,6-dichloro-lH- benzo[d]imidazol-2-yl)-N-(tetrahydrofuran-3-yl)piperidine-4-carboxamide as a white solid. LC- MS (m/z) 382.9 (M+ 1).

111769-27-8 (R)-Tetrahydrofuran-3-amine 4-methylbenzenesulfonate 14243169, aTetrahydrofurans compound, is more and more widely used in various.

Reference£º
Patent; NOVASAID AB; WANNBERG, Johan; ALTERMAN, Mathias; MALM, Johan; STENBERG, Patric; WESTMAN, Jacob; WALLBERG, Hans; WO2011/23812; (2011); A1;,
Tetrahydrofuran – Wikipedia
Tetrahydrofuran | (CH2)3CH2O – PubChem

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.111769-27-8,(R)-Tetrahydrofuran-3-amine 4-methylbenzenesulfonate,as a common compound, the synthetic route is as follows.

A mixture of (R)-l-(5,6-dichloro-lH-benzo[d]imidazol-2-yl)-N-(tetrahydrofuran-3-yl)- piperidine-4-carboxamide (100 mg, 0.261 mmol) dimethylsulfoxide (2 mL), caesium carbonate (0.392 mmol), 2-iodopyridine (0.783 mmol), 8-hydroxyquinoline (0.104 mmol), polyethylene glycol (0.511 mmol) and copper(I) oxide (0.0522 mmol) was subjected to microwave conditions for two hour at 120C. The reaction mixture was filtered and subjected to preparative hplc(performed on a Gilson-Finnigan ThermoQuest AQA system equipped with a Zorbax SB-C8 (5 muetaiota, 21.2 x 150 mm) column, using methanol/water (0.05 % formic acid) gradients at a flow rate of 15 mL/min with UV (214 or 254 nm) and MS (ESI) detection) to give 30 mg (25 % yield) of (R)- 1 -(5,6-dichloro- 1 -(pyridin-2-yl)- lH-benzo[d]imidazol-2-yl)-N-(tetrahydrofuran-3 – yl)piperidine-4-carboxamide as a pale yellow solid. LC-MS (m/z) 460.3 (M+l).

111769-27-8 (R)-Tetrahydrofuran-3-amine 4-methylbenzenesulfonate 14243169, aTetrahydrofurans compound, is more and more widely used in various.

Reference£º
Patent; NOVASAID AB; WANNBERG, Johan; ALTERMAN, Mathias; MALM, Johan; WO2012/117062; (2012); A1;,
Tetrahydrofuran – Wikipedia
Tetrahydrofuran | (CH2)3CH2O – PubChem

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.13031-04-4,4,4-Dimethyldihydrofuran-2,3-dione,as a common compound, the synthetic route is as follows.

Examples 1-4 [00041] The process of the present invention as set forth in FIG. 1 is typically initiated by dissolving the alpha ketocarbonyl compound and the modifier in vessel (1). The resulting solution contains from about 0.1 wt % to about 100 wt % of the alpha ketocarbonyl compound and from about 1¡Á10-5 wt % to about 0.5 wt % of modifier. [00042] The mass flow is started at the reaction temperature, for example, at 17 C. or 20 C. (Examples 1 and 2, respectively). The above solution containing an alpha ketocarbonyl compound and a modifier is pumped into the fixed bed reactor (2) and contacted with hydrogen to start the hydrogenation reaction. Before catalytic runs, the reactor is flushed with nitrogen. [00043] Subsequently, the content of vessel (1) is continuously pumped into the fixed bed reactor. The solution flow rate is preferably from about 0.1 to about 50 ml/minute, the preferred flow of the alpha ketocarbonyl compound is 2¡Á10-5-2¡Á10-2 mol/gcat/minute. More preferably, the solution flow rate is preferably from about 2.5 to about 10 ml/minute, and the flow of the alpha ketocarbonyl compound is from about 2¡Á10-4-3¡Á10-3 mol/gcat/minute. [00044] The modifier flow rate is preferably from about 2¡Á10-9 to about 2¡Á10-4 mol/gcat/minute, such as, for example, from about 2¡Á10-8 to about 7¡Á10-6 mol/gcat/minute. [00045] Hydrogen is continuously fed into the fixed bed reactor via flow line (3) containing a compressor (4) and a pressure control system (5). The inert gas, e.g. nitrogen, is fed into the reactor (2) via line (7). [00046] The hydrogen flow rate into the reactor is metered and monitored by a rotameter. Suitable hydrogen flow rates are from about 0.0001 mol/minute (2.4 ml/minute) to about 1 mol/minute (24000 ml/minute), for example, from about 5¡Á10-6 to about 10 mol/gcat/minute. [00047] The hydrogenation reaction can be carried out at a relatively low temperature ranging between about -20 C. and about 100 C., the preferred temperature range is from about -10 C. to about 50 C., such as for example from about 0 C. to about 20 C. [00048] The pressure in the reactor is suitably adjusted to between about 2 bar and about 150 bar, preferably from about 40 bar to about 100 bar. [00049] The effluent from the hydrogenation reaction zone is fed over a two-step expansion module (6) to a separator where the alpha hydroxy carbonyl compound is recovered. [00050] The process set forth in FIG. 2 is initiated by dissolving the alpha ketocarbonyl compound and the modifier in vessel (1) or by adding a solution containing the modifier to a liquid alpha ketocarbonyl compound. The resulting solution has the following concentration: [00051] about 0.1 wt % to about 100 wt % of alpha ketocarbonyl compound; and [00052] about 1¡Á10-6 wt % to about 0.5 wt % of modifier. [00053] The reactor vessel (2) is charged with a supercritical solvent via flow line (3) containing a compressor (4) and a pressure control system (5). [00054] The organic flow is started at a reaction temperature of, for example, about 50 C. (Example 3) or 36 C. (Example 4). The solution set forth above is pumped into the fixed bed reactor (2) and contacted with hydrogen to start the hydrogenation reaction. [00055] Subsequently, the content of vessel (1) is continuously pumped into the fixed bed reactor with the same solution flow rate as in the process according to FIG. 1. [00056] The flow rate of the supercritical co-solvent is preferably from about 50 ml/minute to about 5000 ml/minute. [00057] When using a liquid alpha ketocarbonyl compound, the supercritical co-solvent is used with a flow rate of about 50 ml/minute to about 5000 ml/minute. [00058] The modifier flow rate is preferably from about 2¡Á10-11 to about 2¡Á10-4 mol/gcat/min. [00059] Hydrogen is continuously fed into the fixed bed reactor via flow line (7) containing a pressure control system (5). The hydrogen flow rate into the reactor was metered and monitored by a rotameter. [00060] Suitable hydrogen flow rates are from about 0.0001 mol/minute (2.4 ml/minute) to about 1 mol/minute (24000 ml/minute) such as for example from 5¡Á10-6 to about 10 mol/gcat/minute. [00061] The hydrogenation reaction can be carried out at a relatively low temperature ranging between about 20 C. to about 100 C., preferably from about 30 C. to about 60 C., such as for example from about 35 C. to about 50 C. The pressure is suitably adjusted to between about 2 bar to about 150 bar, preferably about 40 bar to about 100 bar.

13031-04-4 4,4-Dimethyldihydrofuran-2,3-dione 39, aTetrahydrofurans compound, is more and more widely used in various.

Reference£º
Patent; Roche Vitamins Inc.; US6646135; (2003); B1;,
Tetrahydrofuran – Wikipedia
Tetrahydrofuran | (CH2)3CH2O – PubChem