Month: March 2022

71985-80-3, 1-Methylpiperidine-4-carboxylic acid hydrochloride is a piperidines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

71985-80-3, 0-(1 H-BENZOTRIAZOL-1-YL)-N, N, N’, N’-tetramethyluronium hexafluorophosphate (395 mg, 1.04 MMOL) was added to a solution of 1-methylpiperidine-4-carboxylic acid hydrochloride (210 mg, 1.04 MMOL) in dichloromethane (10 ml) and the solution stirred for 30 minutes. The amine from example 4 (200 mg, 0.52 MMOL) was added and the reaction mixture was stirred at room temperature for 18 hours. The mixture was washed with aqueous sodium carbonate solution and the organic solution was dried over magnesium sulphate. The solution was evaporated under reduced pressure and the crude product was purified by column chromatography on silica gel using ethyl acetate: methanol : 0. 88 ammonia (90: 10: 1) as eluant, to afford the title compound as a white solid (195 mg). APCI MS M/Z 506 [MH] +

As the paragraph descriping shows that 71985-80-3 is playing an increasingly important role.

Reference：
Patent; PFIZER LIMITED; PFIZER INC.; WO2004/74291; (2004); A1;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.189333-49-1,3-Benzyl-3,9-diazaspiro[5.5]undecane,as a common compound, the synthetic route is as follows.

Example Bl a.; Preparation of final compound 1; A mixture of intermediate compound 3 (prepared according to Al.c) (0.02 mol), 3- (phenylmethyl)-3,9-diazaspiro-[5.5]-undecane (0.02 mol) and Ti(iPrO)4 (0.035 mol) in 1,2-dichloroethane (80 ml) was stirred at 50C for a overnight, then brought to room temperature under N2 flow. NaBH(OAc)3 (0.035 mol) was added portionwise. The mixture was stirred at room temperature for 8 hours and poured out on ice. K2C03 10% was added. The mixture was filtered over celite and washed with CH2C12. The filtrate was extracted with CH2Cl2. The organic layer was separated, dried (MgS04), filtered, and the solvent was evaporated. The residue (26 g) was purified by column chromatography over silica gel (eluent gradient: CH2Cl2/CH3OH/NH4OH 95/5/0.5 to 90/10/1; 20-45 mum). Three fractions were collected and the solvent was evaporated. Yield: 1.8 g of final’compound 1 (15 %).

189333-49-1, As the paragraph descriping shows that 189333-49-1 is playing an increasingly important role.

Reference：
Patent; JANSSEN PHARMACEUTICA N.V.; WO2005/97795; (2005); A1;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem

142851-03-4, Ethyl N-Boc-piperidine-4-carboxylate is a piperidines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Preparation Example 13 A mixture of 1-tert-butyl 4-ethylpiperidine-1,4-dicarboxylate (21 g), hydrazine monohydrate (40 mL), and ethanol (200 mL) was heated and refluxed for 22 hours. After leaving to be cooled, the solvent was evaporated under reduced pressure, to the residue were added saturated brine and ethyl acetate, and the organic phase was separated. The organic phase was dried over magnesium sulfate and the solvent was evaporated under reduced pressure. To the residue was added diisopropyl ether, followed by stirring for 1 hour, and the resulting solid was collected by filtration and dried under reduced pressure to obtain tert-butyl 4-(hydrazinocarbonyl)piperidine-1-carboxylate (17.8 g).

142851-03-4, The synthetic route of 142851-03-4 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Astellas Pharma Inc.; EP2308869; (2011); A1;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.1445-73-4,1-Methyl-4-piperidone,as a common compound, the synthetic route is as follows.

Pd/C (40 g, 5% w/w) was added into a 10 L autoclave reactor at room temperature under nitrogen. THF (2 L), 2 L of methylamine (27%-30% alcoholic solution, 2.1 eq.), and 800 g of compound 10A (7 mol, 1.0 eq.) were sequentially added into the reactor. The system was purged with hydrogen three times. The mixture was stirred at hydrogen pressure (50 psi) at 70-75 C overnight and was then filtered using a Biichner funnel and filter paper (pore size: 30-50 pm) over 10 minutes to remove the Pd/C. The filtrate was concentrated in a rotavapor under vacuum (30-40 mmHg) at 45-50 C for about 3 hours to obtain 933 g of yellow oil. The mixture was distilled without a column at atmospheric pressure and the 140-170 C portion was collected to obtain 763 g of compound 10 as a colorless oil (98.6% purity (AUC by HPLC, retention time = 4.8 minutes); 84.2% yield; 8000 ppm residual ethanol). A portion of the oil (563 g) was distilled using a 3 cm column at atmospheric pressure and the 140-170 C portion was collected to obtain 510 g of compound 10 (75.8% yield; 134 ppm residual ethanol). 1H- NMR (400 MHz, CDCb): d = 0.82 (bs, 1H), 1.10-1.12 (q, 2H), 1.66 (d, 2H), 1.73-1.81 (t, 2H), 2.05 (s, 3H), 2.08-2.19 (m, 1H), 2.22 (s, 3H), 2.60 (d, 2H). [00134] Step 10: Synthesis of HM04 fumarate salt, 1445-73-4

Big data shows that 1445-73-4 is playing an increasingly important role.

Reference：
Patent; HELSINN THERAPEUTICS (US) INC; HELSINN HEALTHCARE SA; HELSINN ADVANCED SYNTHESIS SA; RUBIO, Silvina Garcia; PERSEGHINI, Mauro; GUAINAZZI, Angelo; PIETRA, Claudio; GIULIANO, Claudio; (110 pag.)WO2019/118298; (2019); A1;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem

1039741-54-2, 1-Benzyl-3,3-difluoropiperidin-4-one is a piperidines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Di-tert-butyl dicarbonate (1.19 g, 5.44 mmol) was added to a solution of i-benzyl-3,3-difluoropiperidin-4-one (995mg, 4.42 mmol) in EtCH (60 mL) under nitrogen.Palladium hydroxide (Pd 20% on carbon, 148 mg, 1.05mmol) was added and the system was evacuated andflushed with hydrogen several times. The mixture was stirred at RT for 20 h under hydrogen. The residual hydrogen was removed and the mixture was filtered over Celite, and washed with EtCH. Purification gave titled compound (810 mg, 3.44 mmol, 78% yield) as a white solid.1H NMR (400 MHz, DMSC-d6, ): 3.66-3.52 (m, 2H), 3.39-3.33 (m, 2H), 1.69-i .64 (m, 2H), 1.38 (5, 9H)

1039741-54-2, 1039741-54-2 1-Benzyl-3,3-difluoropiperidin-4-one 49761227, apiperidines compound, is more and more widely used in various fields.

Reference：
Patent; REDX PHARMA PLC; GUISOT, Nicolas; (266 pag.)WO2017/103611; (2017); A1;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem

3612-20-2, 1-Benzylpiperidin-4-one is a piperidines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

A solution of 294.14 g 1-benzylpiperidin-4-one in 2.1 L methanol was added to a solution of 448 g ammonium carbonate in 2.1 L hot water. The yellow turbid reaction mixture was cooled with an ice bath. A solution of 77 g sodium cyanide in 200 ml water was added dropwise over 10 min (exothermic.). After the addition the ice bath was removed and the reaction mixture was stirred at ambient temperature for 3 days. The resulting precipitate was filtered, washed with water (3x) and dried in a vacuum oven at 50C to obtain the intermediate 1.38.Yield: quantitative, 3612-20-2

The synthetic route of 3612-20-2 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; DAHMANN, Georg; FIEGEN, Dennis; FLECK, Martin; HOFFMANN, Matthias; KLICIC, Jasna; EAST, Stephen, Peter; NAPIER, Spencer, Charles, R.; SCOTT, John; WO2012/101013; (2012); A1;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.888952-55-4,Methyl 1-Boc-3-methylpiperidine-3-carboxylate,as a common compound, the synthetic route is as follows.

Step 2. 1-tert-Butyl 3-methyl 3-methylpiperidine-1,3-dicarboxylate. To a solution of 1-tert-butyl 3-methyl 3-methylpiperidine-1,3-dicarboxylate (15.86 g, 0.062 mol) in THF (100 ml) and H2O (10 ml) was added LiOH.H2O (7.76 g, 0.186 mol) at room temperature. The mixture was refluxed at 70 C. for 6 h. After TLC (Petroleum ether/EtOAc, 4:1, stained by iodine) showed the starting material to be consumed, the mixture was concentrated to dryness. The residue was diluted with H2O (300 mL) and then extracted with MTBE (100 mL×2). The organic layers were discarded. The resulting aqueous layer was acidified to pH 1 with 1M HCl (aq.) and then extracted with MTBE twice. The combined organic layers were washed with brine, dried over Na2SO4 and concentrated to dryness to give 1-tert-butyl 3-methyl 3-methylpiperidine-1,3-dicarboxylate (13.97 g, 93%) as a white solid., 888952-55-4

888952-55-4 Methyl 1-Boc-3-methylpiperidine-3-carboxylate 46911995, apiperidines compound, is more and more widely used in various fields.

Reference：
Patent; Thorarensen, Atli; Brown, Matthew Frank; Casimiro-Garcia, Agustin; Che, Ye; Coe, Jotham Wadsworth; Flanagan, Mark Edward; Gilbert, Adam Matthew; Hayward, Matthew Merrill; Langille, Jonathan David; Montgomery, Justin Ian; Telliez, Jean-Baptiste; Unwalla, Rayomand Jal; US2015/158864; (2015); A1;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.90802-45-2,3-Aminopiperidine-2,6-dione hydrobromide,as a common compound, the synthetic route is as follows.

Add 55.0 g (0.263 mol) of 3-amino-2,6-piperidinone hydrobromide to a 1000 ml reaction flask.Triethylamine 75ml, 200ml acetonitrile, stirred and mixed at room temperature, heated to 80 C, adding a mixture of 72.1g (0.263mol) of methyl 2-bromomethyl-3-nitrobenzoate and 150ml of acetonitrile, heat preservation reaction for 10h, Cold to room temperature,Slowly add 200ml of water and stir for 0.5h.The product was obtained as an off-white solid, 49.6 g, yield 65.2%.

90802-45-2, The synthetic route of 90802-45-2 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Shijiazhuang Duen Pharmaceutical Technology Co., Ltd.; Fang Yu; Du Yumin; (8 pag.)CN109776493; (2019); A;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem

1000931-04-3, 1-Boc-3-Hydroxy-4-phenylpiperidine is a piperidines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

(j) A solution of 4.0 g tert-butyl (13.8 mmol) of tert-butyl (3RS,4RS)-3-hydroxy-4-phenyl-piperidine-1-carboxylate in 100 ml of methanol was hydrogenated at 150 bar at 100 C. for 18 hours using a rhodium(5%)-aluminium oxide catalyst. For the working up, the catalyst was filtered off, washed with methanol and the solution obtained was evaporated under reduced pressure. For purification, the residue was chromatographed on silica gel using a 4:1 mixture of hexane and ethyl acetate as the eluent. There were obtained 2.32 g (59% of theory) of tert-butyl (3RS,4RS)-4-cyclohexyl-3-(naphthalen-2-ylmethoxy)-piperidine-1-carboxylate as a colourless solid; MS: 283 (M)+., 1000931-04-3

As the paragraph descriping shows that 1000931-04-3 is playing an increasingly important role.

Reference：
Patent; Hoffmann-La Roche Inc.; US6051712; (2000); A;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.19365-08-3,3-Hydroxypiperidin-2-one,as a common compound, the synthetic route is as follows.

General procedure: Potassium carbonate or caesium carbonate (1.5-2.5 eq.) was baked in a reaction vessel under reduced pressure. It was cooled to RT and flooded with argon. Palladium acetate (0.1-0.36 eq.), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (Xantphos, 0.18-0.36 eq.) and dioxane (0.04-0.12M) were added, and the suspension was degassed in an argon stream at room temperature for 10 min. Subsequently, the appropriate amide (1.0-1.2 eq.) and the appropriate 7-chloro-4-oxo-1,4-dihydro-1,8-naphthyridine (1.0 eq.) were added. The mixture was stirred at 80-110 C. for 1 h (or until conversion was complete by analytical HPLC or thin-layer chromatography with appropriate eluent mixtures). The mixture was cooled to RT and all volatile components were removed under reduced pressure, or alternatively the reaction mixture was poured into water, the pH was adjusted to pH 1 with 1M aqueous hydrochloric acid, the mixture was extracted with ethyl acetate, the combined organic phases were washed with saturated aqueous sodium chloride solution, dried over magnesium sulphate and filtered, and the solvent was removed under reduced pressure. The crude product was then purified either by normal phase chromatography (eluent: cyclohexane/ethyl acetate mixtures or dichloromethane/methanol mixtures) or preparative RP-HPLC (water/acetonitrile gradient). According to GP2, 150 mg (283 mumol) of the compound from Example 80A were reacted with 39.1 mg (340 mumol) of rac-3-hydroxypiperidin-2-one in the presence of 58.7 mg (425 mumol) of potassium carbonate, 13 mg (57 mumol) of palladium(II) acetate and 33 mg (57 mumol) of Xantphos in 2.5 ml of dioxane. The crude product was purified by means of preparative HPLC (column: Chromatorex C18, 10 mum, 125*40 mm, solvent: acetonitrile/0.1% formic acid gradient; (0 to 3 min. 10% acetonitrile to 40 min. 90% acetonitrile and a further 3 min. 90% acetonitrile), and 102 mg (59% of theory, 100% purity) of the title compound were obtained. 1H NMR (400 MHz, DMSO-d6) delta [ppm]=11.34 (br. d, 1H), 8.89 (s, 1H), 8.70 (d, 1H), 8.17-8.09 (m, 1H), 7.94-7.75 (m, 1H), 7.68-7.56 (m, 2H), 7.41-7.27 (m, 3H), 6.51-6.39 (m, 1H), 5.52-5.46 (m, 1H), 4.27-4.17 (m, 1H), 3.71-3.58 (m, 1H), 3.54-3.40 (m, 1H), 2.12-2.01 (m, 1H), 1.86-1.71 (m, 1H), 1.71-1.57 (m, 1H). LC-MS (Method 3): Rt=2.11 min; 609 [M+H]+. 91.2 mg of the title compound (racemic diastereomer mixture) were separated into the enantiomeric diastereomers by chiral HPLC (preparative HPLC: column: Daicel Chiralpak AZ-H 5 mum 250×30 mm; eluent: 50% isohexane, 20% ethanol; temperature: 25 C.; flow rate: 50 ml/min; UV detection: 220 nm). This gave (in the sequence of elution from the column) 17.8 mg of diastereomer 1 (96.5% de) Rt=3.19 min, 14.5 mg (95% de) of diastereomer 2 Rt=4.21 min, 17.4 mg (97% de) of diastereomer 3 Rt=6.11 min, and 14.5 mg (97% de) of diastereomer 4 Rt=10.80 min. [Analytical HPLC: column: Daicel AZ-3 3 mum 50×4.6 mm; eluent: 50% isohexane, 50% ethanol; temperature: 30 C.; flow rate: 1 ml/min; UV detection: 220 nm] Example 248 1-(2,4-Difluorophenyl)-N-[1-(2,6-difluorophenyl)-2,2,2-trifluoroethyl]-7-[3-hydroxy-2-oxopiperidin-1-yl]-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxamide (diastereomer 1) 1H NMR (400 MHz, DMSO-d6) delta [ppm]=11.34 (br. d, 1H), 8.89 (s, 1H), 8.70 (d, 1H), 8.17-8.10 (m, 1H), 7.93-7.76 (m, 1H), 7.68-7.57 (m, 2H), 7.40-7.27 (m, 3H), 6.51-6.39 (m, 1H), 5.52-5.46 (m, 1H), 4.27-4.18 (m, 1H), 3.71-3.59 (m, 1H), 3.54-3.41 (m, 1H), 2.12-2.01 (m, 1H), 1.83-1.73 (m, 2H), 1.71-1.58 (m, 1H). LC-MS (Method 3): Rt=2.12 min; 609 [M+H]+. Example 249 1-(2,4-Difluorophenyl)-N-[1-(2,6-difluorophenyl)-2,2,2-trifluoroethyl]-7-[3-hydroxy-2-oxopiperidin-1-yl]-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxamide (diastereomer 2) 1H NMR (400 MHz, DMSO-d6) delta [ppm]=11.37-11.31 (m, 1H), 8.89 (s, 1H), 8.70 (d, 1H), 8.13 (dd, 1H), 7.94-7.75 (m, 1H), 7.68-7.56 (m, 2H), 7.41-7.26 (m, 3H), 6.51-6.38 (m, 1H), 5.52-5.46 (m, 1H), 4.27-4.16 (m, 1H), 3.72-3.58 (m, 1H), 3.53-3.39 (m, 1H), 2.12-2.01 (m, 1H), 1.83-1.73 (m, 2H), 1.72-1.57 (m, 1H). LC-MS (Method 3): Rt=2.13 min; 609 [M+H]+. Example 250 1-(2,4-Difluorophenyl)-N-[1-(2,6-difluorophenyl)-2,2,2-trifluoroethyl]-7-[3-hydroxy-2-oxopiperidin-1-yl]-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxamide (3rd diastereomer) 1H NMR (400 MHz, DMSO-d6) delta [ppm]=11.37-11.31 (m, 1H), 8.89 (s, 1H), 8.70 (d, 1H), 8.13 (dd, 1H), 7.94-7.75 (m, 1H), 7.68-7.56 (m, 2H), 7.40-7.26 (m, 3H), 6.51-6.39 (m, 1H), 5.52-5.46 (m, 1H), 4.26-4.17 (m, 1H), 3.72-3.59 (m, 1H), 3.52-3.40 (m, 1H), 2.12-2.01 (m, 1H), 1.84-1.73 (m, 2H), 1.72-1.58 (m, 1H). LC-MS (Method 3): Rt=2.12 min; 609 [M+H]+. Example 251 1-(2,4-Difluorophenyl)-N-[1-(2,6-difluorophenyl)-2,2,2-trifluoroethyl]-7-[3-hydroxy-2-oxopiperidin-1-yl]-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxamide (4th diastereomer) 1H NMR (400 MHz, DMSO-d6) delta [ppm]=11.34 (br. d, 1H), 8.89 (s, 1H), 8.70 (d, 1H), 8.17-8.09 (m, 1H), 7.93-7.76 (m, 1H), 7.68-7.57 (m, 2H), 7.40-7.2…

19365-08-3, As the paragraph descriping shows that 19365-08-3 is playing an increasingly important role.

Reference：
Patent; Bayer Pharma Aktiengesellschaft; TELLER, Henrik; STRAUB, Alexander; BRECHMANN, Markus; MUeLLER, Thomas; MEININGHAUS, Mark; NOWAK-REPPEL, Katrin; TINEL, Hanna; MUeNTER, Klaus; FLIEGNER, Daniela; MONDRITZKI, Thomas; BOULTADAKIS ARAPINIS, Melissa; MARQUARDT, Tobias; VAKALOPOULOS, Alexandros; REBSTOCK, Anne-Sophie; WITTWER, Matthias Beat; (342 pag.)US2018/297994; (2018); A1;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem