Heterocyclic Building Blocks-piperidine

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.690261-64-4,2-(Piperidin-4-yl)pyrimidine hydrochloride,as a common compound, the synthetic route is as follows.

690261-64-4, Ketone Intermediate 1 (100 mg, 0.253 mmol) was combined with 4- (5-pyrimidyl)-piperidine hydrochloride (prepared as described for Intermediate 5,90 mg, 0.38 mmol), triethylamine (105 P, L, 0.759 mmol), sodium triacetoxyborohydride (212 mg, 1.00 mmol) and 4 A molecular sieves (powder, 100 mg) in DCM (10 mL). The reaction mixture was stirred at rt for 2 days, then was filtered through a celite plug. The filtrate was concentrated and purified by preparative TLC (silica, 5% of 1: 9 NHMOH/METHANOL in DCM, then a second plate with 10% methanol/DCM) to afford two bands corresponding to the cis (top spot) and trans isomers (bottom spot). Both the cis and trans isomers were converted to HC1 salts by dissolving the free bases in-1 mL of DCM, adding excess 1 N HCL in ether, and concentrating. Top spot-ESI-MS calculated for C27H32F6N40: 542; Found: 543 (M+H). Bottom spot-ESI-MS calculated for C27H32F6N40: 542; Found: 543 (M+H). Single cis-enantiomers were obtained via chiral HPLC, using Diacel’s Chiralcel AD semipreparative column, eluting with 10% ethanol/hexane (using the free base). The observed retention times of the respective diastereoisomers were 25 and 38 minutes, respectively.

The synthetic route of 690261-64-4 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; MERCK & CO., INC.; WO2004/41777; (2004); A2;,
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With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.768-66-1,2,2,6,6-Tetramethylpiperidine,as a common compound, the synthetic route is as follows.

768-66-1, A cooled (-20C) solution of 2,2, 6, 6-TETRAMETHYLPIPERIDINE (28 ml, 165 mmol) in tetrahydrofuran (400 ml) was treated with n-butyllithium (63 ml of a 2.5M solution in hexanes, 157.5 mmol). This mixture was then cooled TO-78C. 1-Bromo-4-fluorobenzene (16.5 ml, 150 mmol) was then added neat and dropwise over 10 min and stirring AT-78C was continued for 3 h. Triisopropyl borate (40 ml, 172.5 mmol) was then added and stirring AT-78C continued for 30 min before removing the cooling bath. When the internal temperature of the reaction REACHED-40C, 5N hydrochloric acid was added (75 ml) and the mixture was stirred to ambient temperature. After stirring at ambient temp for 1 h the majority of the tetrahydrofuran was removed and the mixture partitioned between ether (500 ml) and IN hydrochloric acid (500 ml). The organics were then extracted with 2N sodium hydroxide (400 ml) and the organics were discarded. The aqueous was cooled in an ice-water bath and 5N hydrochloric acid (150 ml) was added dropwise over 15 min. The resulting white solid was collected and dried under vacuum to afford 5-bromo-2-fluorobenzeneboronic acid (25 g, 76%).

768-66-1 2,2,6,6-Tetramethylpiperidine 13035, apiperidines compound, is more and more widely used in various fields.

Reference：
Patent; MERCK SHARP & DOHME LIMITED; WO2004/41826; (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.768-66-1,2,2,6,6-Tetramethylpiperidine,as a common compound, the synthetic route is as follows.,768-66-1

General procedure: A dry and nitrogen-flushed-10 mL round bottom flask equipped with a magnetic stirrer and a septum was charged with amine 2 (0.5 mmol, 1 equiv) and was evacuated and refilled with nitrogen three times. Dry THF (0.5 mL) was added and the reaction flask was again evacuated and refilled with nitrogen three times. The reaction mixture was cooled to 0 C, and BuLi solution (0.55 or 1.05 mmol, 2.45 M in THF, 1.1 or 2.1 equiv) was added. After 5 min of stirring, 1a or 1b (0.5 mmol, 1 equiv) was added at 0 C and the reaction was checked by 19F NMR with PhOCF3 as internal standard. Reaction was quenched with saturated aqueous NaHCO3 and EtOAc was added. The organic phase was washed with water, dried over Na2SO4, and concentrated in vacuo. The crude residue was purified by flash chromatography to give the expected product.

The synthetic route of 768-66-1 has been constantly updated, and we look forward to future research findings.

Reference：
Article; Alazet, Sebastien; Ollivier, Kevin; Billard, Thierry; Beilstein Journal of Organic Chemistry; vol. 9; (2013); p. 2354 – 2357;,
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With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.1062580-52-2,(3R,4R)-1-Benzyl-N,4-dimethylpiperidin-3-amine dihydrochloride,as a common compound, the synthetic route is as follows.

Add SMA 11.0kg, SMB 12.8kg, DIPEA 19.5kg, DMSO to a 200L reactor50.0 kg, 15.0 kg of purified water, and the temperature was raised to 107C. After the reaction is complete, add 24.0kg absolute ethanol to room temperature and addWater 30.0kg, stirring and decrystallization 2h, suction filtration, drying at 60±5C, 17.2kg of white solid. Yield 93.0%, SMB residue0.3%, HPLC purity 98.9%., 1062580-52-2

1062580-52-2 (3R,4R)-1-Benzyl-N,4-dimethylpiperidin-3-amine dihydrochloride 45790119, apiperidines compound, is more and more widely used in various fields.

Reference：
Patent; Yangzijiang Pharmaceutical Group Co., Ltd.; Xiao Can; Xu Jingren; Cai Wei; Zhu Xiaohe; Zhang Haibo; Lv Huimin; Hu Tao; Wu Jianhua; Gu Cheng; Xu Chenjun; (12 pag.)CN107793418; (2018); A;,
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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.

To a suspension of 3-hydroxy-piperidin-2-one (500 mg, 4.34 mmol, 1.0 eq) and triethylamine (0.908 mL, 6.51 mmol, 1.5 eq) in dichloromethane (3 mL) at 0 C was added dropwise methanesulfonyl chloride (497 mg, 4.34 mmol, 1.0 eq) dissolved in dichloromethane (1 mL). The reaction was complete within 30 min as judged by LCMS. An orange precipitate was filtered, redissolved in dichloromethane and purified by column chromatography (MeOH/CH2Cl2) to give the title compound as a white waxy solid (204 mg, 1.056 mmol, 24.3% yield). 1 H NMR (400 MHz, chloroform-d) delta ppm 5.78 (br. s, 1 H) 4.94 – 5.05 (m, 1 H) 3.30 – 3.44 (m, 2 H) 3.27 (s, 3 H) 2.24 – 2.37 (m, 1 H) 2.08 – 2.21 (m, 1 H) 1 .98 – 2.08 (m, 1 H) 1 .79 – 1 .96 (m, 1 H). MS (m/z, MH+): 193.7., 19365-08-3

The synthetic route of 19365-08-3 has been constantly updated, and we look forward to future research findings.

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

EXAMPLE 2 A solution of 1-benzyl-4-piperidone in 40 ml. of absolute ethanol was added to a solution of 8.5 g. of methylamine in 40 ml. of ethanol. The resulting solution was added to a suspension of 0.5 g. of platinum oxide in 30 ml. of ethanol which had been pretreated with 50 psi of hydrogen for 1 hour. This suspension was reduced at 50 psi of hydrogen until one equivalent of hydrogen was consumed and then filtered. The filtrate was concentrated in vacuo to give 1-benzyl-4-methylaminopiperidine., 3612-20-2

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

Reference：
Patent; SmithKline Corporation; US3980788; (1976); A;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem

32559-18-5, Methyl piperidine-2-carboxylate hydrochloride is a piperidines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

(a) Piperidine-2-carboxamide. A mixture of methyl pipecolinate hydrochloride (15.0 g, 83 mmol, Aldrich) and 8% aqueous solution of ammonium hydroxide (150 mL) was stirred for 18 h at room temperature. The white precipitate was filtered and the filter cake was washed with water, and dried under vacuo to give the title compound. MS (ESI, pos. ion) m/z: 129 (M+1)., 32559-18-5

32559-18-5 Methyl piperidine-2-carboxylate hydrochloride 13246231, apiperidines compound, is more and more widely used in various fields.

Reference：
Patent; Norman, Mark H.; Pettus, Liping H.; Wang, Xianghong; Zhu, Jiawang; US2006/58308; (2006); 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.948894-26-6,4-Methylpiperidine-4-carbonitrile hydrochloride,as a common compound, the synthetic route is as follows.

948894-26-6, Example 28 (0905) 1 -(2-((2-ethoxy-4-(4-methyl-4 -/-1 ,2,4-triazol-3-yl)phenyl)amino)-6-methylpyrido[3,4-c/|pyrimidin-8- (0906) (0907) To a solution of 8-chloro-A/-(2-ethoxy-4-(4-methyl-4 -/-1 ,2,4-triazol-3-yl)phenyl)-6-methylpyrido[3,4- c/|pyrimidin-2-amine (Preparation 1 , 25 mg, 0.063 mmol) in NMP (2 ml_) was added 4- methylpiperidine-4-carbonitrile (20 mg, 0.126 mmol) and triethylamine (0.044 ml_, 0.316 mmol). The reaction was heated to 100 in a closed cap vial for 18 hours. Further 4-methylpiperidine-4- carbonitrile hydrochloride (40 mg, 0.252 mmol) was added and the reaction heated at 120 for a further 5 hours. The reaction mixture was diluted with EtOAc and water. The organic layer was dried (MgS04) and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with 0-50% EtOAc in cyclohexane followed by elution through an SCX-2 cartridge using MeOH followed by 1 M NH3 in MeOH. The residue was further purified by silica gel column chromatography eluting with 0-1 5% MeOH in EtOAc followed by elution through an SCX- 2 cartridge using MeOH followed by 1 M NH3 in MeOH to afford the title compound (5.1 mg, 17%). 1 H NMR (500 MHz, MeOH-d4): delta ppm 9.13 (s, 1 H), 8.80 (d, J = 8.5 Hz, 1 H), 8.56 (s, 1 H), 7.38 (d, J = 2.0 Hz, 1 H), 7.36 (dd, J = 8.5, 2.0 Hz, 1 H), 7.04 (s, 1 H), 4.70 (br d, J = 13.0 Hz, 2H), 4.29 (q, J = 7.0 Hz, 2H), 3.88 (s, 3H), 3.26 (t, J = 13.0 Hz, 2H), 2.50 (s, 3H), 2.1 0 (br d, J = 13.0 Hz, 2H), 1 .92 (td, J = 13.0, 3.5 Hz, 2H), 1 .56 (t, J = 7.0 Hz, 3H), 1 .51 (s, 3H). (0908) HRMS (ESI) MS m/z calcd for C26H31 N9O [M+2H]/2+ 242.632, found 242.6321 . (0909) MPS1 IC50 (muMu): 0.002

The synthetic route of 948894-26-6 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; CANCER RESEARCH TECHNOLOGY LIMITED; WOODWARD, Hannah; INNOCENTI, Paolo; NAUD, Sebastien; BLAGG, Julian; HOELDER, Swen; WO2015/128676; (2015); A1;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem

4801-58-5, Piperidin-1-ol is a piperidines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Example 3; 2-(1 -hvdroxypiperidin-2-yl)-5, -dimethylcvclohexane-1 ,3-dione:; A mixture of N-hydroxypiperidine (1 .01 g, 10 mmol), azodicarbonamide (1 .39 g, 12 mmol) and methanol (10 ml) was heated to reflux for 50 minutes. During this period the solid, initially orange in colour, changed into a whitish precipitate. After cooling to ambient temperature, said precipitate was separated by suction and washed twice with methanol (2 x 5 ml). All the methanol fractions were combined and under agitation 5, 5-dimethylcyclohexane-1 ,3-dione (10 mmol) was added. After 10 minutes, the methanol was removed under vacuum (water bath temperature 50QC) to give a crude compound of formula (3). This crude compound was dissolved in a methanol solution (15 ml) containing acetyl chloride (0.86 g, 1 1 mmol). The methanol was removed under vacuum and the residue of formula (3) in hydrochloride form was ground in acetone.Yield: 62%Formula: C13H22CINO3MW: 275.8 g/molAcid dissociation constants: pKai = 3.47, pKa2 = 6.92 m.p.: 174.5-175.5QC1H-NMR (DMSO-c/e): delta 0.98 (6H, s), 1.48 (1H, m), 1.66 (2H, d, J=12.5 Hz), 1.83 (2H, broad s), 1.94-2.07 (1H, m), 2.33 (4H, broad s), 3.23 (1H, broad s), 3.67 (1H, d, J=11.0 Hz), 4.36 (1 H, d, J=11.5 Hz), 10.93 (1 H, broad s), 11.32 (1 H, broad s). 13C-NMR (DMSO-c/e): delta 21.9, 23.6, 27.9, 28.7, 32.0, 46.2 (broad), 59.4, 64.4, 107.4.

4801-58-5, 4801-58-5 Piperidin-1-ol 20935, apiperidines compound, is more and more widely used in various fields.

Reference：
Patent; ABIOGEN PHARMA S.p.A.; NAPOLITANO, Elio; BASAGNI, Simone; TRASCIATTI, Silvia; WO2011/76930; (2011); A1;,
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85908-96-9, N-Boc-2-Piperidone is a piperidines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Tert-butyl 2-oxopiperidine-1-carboxylate (8.22 g, 41.3 mmol) was dissolved in dry tetrahydrofuran (80 mL) and the system was cooled to -78 C. LiHMDS (1.0 M in THF, 103 mL, 103 mmol) was added dropwise under nitrogen atmosphere. After stirring for a further 20 minutes, 3-bromoprop-1-ene (10.7 mL, 124 mmol) was added. The resulting reaction mixture was stirred at this temperature for 15 minutes. The reaction mixture was then cooled to room temperature and quenched by addition of water (15 mL). The reaction mixture was concentrated under reduced pressure. The resulting residue was diluted with water (30 mL) and extracted with ethyl acetate (50 mL x 3). The combined organic layers were washed with brine (50 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (EtOAc / PE (v / v) = 1/50) to give the title compound as a yellow oil (3.95 g, 35%).

85908-96-9, 85908-96-9 N-Boc-2-Piperidone 7577838, apiperidines compound, is more and more widely used in various fields.

Reference：
Patent; Guangdong Dongyangguang Pharmaceutical Co., Ltd.; Jiatuo Sciences Corporation; Xi Ning; Li Minxiong; Hu Haiyang; Wang Tingjin; (91 pag.)CN104672250; (2017); B;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem