Heterocyclic Building Blocks-piperidine

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.

A solution of 2,2,6,6-tetramethylpiperidine (0.567 ml, 3.36 mmol) in dry tetrahydrofurane was cooled in a Schlenk tube to -20 C. N-Butyllithium in hexane (1.6 M, 2.0 ml) was added. The resulting orange solution was stirred for 10 min at -20 C. and was then cooled to -78 C. A solution of N-Butyloxycarbonylindole (0.652 g, 3 mmol) in a small amount of dry tetrahydrofurane was added. Stirring was continued for 90 min at -78 C. before a fresly prepared 1.5 M Zinc chloride solution i tetrahydrofurane (3.3 ml) was added. The reaction mixture was allowed to reach room temperature slowly. This yellow mixture was added to a flask containing bis(tri-t-butylphosphine) palladium (50 mg) and 4-bromo-nitobenzene ((0,509 g, 2.25 mmol). After stirring for 1 h at room temperature the temperature was raised to 60 C. over night. The reaction mixture was diluted with dichloromethane (20 ml) and was washed with saturated aqueous ammonium chloride (2×30 ml). The organic layer was dried (magnesium sulfate) and concentrated under reduced pressure. The residue was filtered hot in heptane and then crystalized to give the title compound in 63% yield (0.480 g). 1H NMR (400 MHz, CHLOROFORM-D), delta ppm 1.33 (m, 9 H), 6.61 (s, 1 H), 7.27 (m, 1 H), 7.36 (t, J=7.83 Hz, 1 H), 7.56 (m, 3 H), 7.67 (d, J=8.08 Hz, 2 H), 8.21 (d, J=8.59 Hz, 1 H).

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

Reference：
Patent; Novo Nordisk A/S; US2007/10559; (2007); A1;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem

53617-36-0, 1-Methyl-4-(piperidin-4-yl)piperazine is a piperidines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

53617-36-0, 3h) (R)-1-(4-methyl-2-oxo-2,3-dihydro-benzoxazol-6-ylmethyl -2-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-2-oxo-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate A solution of 510 mg (1.0 mmol) (R)-1-carboxy-2-(4-methyl-2-oxo-2,3-dihydrobenz-oxazol-6-yl)-ethyl 4-(2-oxo-1,2,4,5,-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate, 365 mg (1.12 mmol) TBTU, 230 muL (1.31 mmol) ethyldiisopropylamine in 80 mL THF was stirred for 30 min at RT, then combined with 210 mg (1.12 mmol) 1-methyl-4-piperidin-4-yl-piperazine and stirred for 22 h at RT. To complete the reaction the mixture was again combined with 100 mg (0.3 mmol) TBTU and 50 mg (0.27 mmol) 1-methyl-4-piperidin-4-yl-piperazine and 40 mL THF and stirred for a further 4 h at RT. The reaction solution was diluted with 250 mL EtOAc and extracted twice with 60 mL saturated NaHCO3 solution. The organic phase was dried over Na2SO4, filtered and evaporated down i.vac. The residue was purified by chromatography (Alox, DCM/MeOH 50:1 to 25:1), the fractions containing the product were combined, evaporated down i.vac., combined with diethyl ether, filtered off and dried. Yield: 440 mg (65percent of theory) ESI-MS: (M+H)+=674 Rf=0.46 (Polygram-Alox, DCM/MeOH 25:1)

The synthetic route of 53617-36-0 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Boehringer Ingelheim International GmbH; US2005/256099; (2005); A1;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem

1062580-52-2, (3R,4R)-1-Benzyl-N,4-dimethylpiperidin-3-amine dihydrochloride is a piperidines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

S1. Add 180 g of (3R,4R)-1-benzyl-N,4-dimethylpiperidine-3-amine dihydrochloride,200g 2,4-dichloro-7H pyrrole[2,3-D]pyrimidine,153g potassium carbonate and 650mL water, Stir and heat to 90C and monitor the reaction by TLC; After the reaction is complete, Cooling the reaction solution,The aqueous layer was extracted twice with 1000 mL of ethyl acetate. Combined organic phases,Dried over anhydrous magnesium sulfate, Concentrated under reduced pressure, 205 g of compound I was obtained as a pale yellow solid (yield 89.5%, HPLC purity 95.3%);

1062580-52-2, As the paragraph descriping shows that 1062580-52-2 is playing an increasingly important role.

Reference：
Patent; Sichuan University; Dong Lin; Xu Huibei; He Yuan; Liu Hao; (20 pag.)CN110724146; (2020); 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.1187173-43-8,2,7-Diazaspiro[4.5]decan-1-one hydrochloride,as a common compound, the synthetic route is as follows.

2,7-Diazaspiro[4.5]decan-1 -one hydrogen chloride (100 mg, 0.524 mmol) was dissolved in dichloromethane (10 mL) and triethylamine (0.219 mL, 1 .573 mmol). Then, 3-fluoro-5-(trifluoromethyl)benzenesulfonyl chloride (165 mg, 0.629 mmol) was added and stirred for 17 h. The mixture was concentrated in vacuo and the resulting residue was purified by MDAP to give 7-{[3-fluoro-5-(trifluoromethyl)phenyl]sulfonyl}- 2,7-diazaspiro[4.5]decan-1 -one (87.9 mg, 0.226 mmol, 43% yield) as a white solid. 1 H NMR (400 MHz, DMSO-d6) delta ppm 1.39 – 1 .49 (m, 2 H) 1.52 – 1 .64 (m, 1 H) 1.66 – 1 .75 (m, 1 H) 1.87 – 1.97 (m, 1 H) 1.99 – 2.09 (m, 1 H) 2.29 – 2.41 (m, 2 H) 3.14 – 3.24 (m, 2 H) 3.41 (d, J=1 1 .73 Hz, 1 H) 3.68 (d, J=1 1 .89 Hz, 1 H) 7.76 (s, 1 H) 7.84 (s, 1 H) 8.01 (d, J=7.84 Hz, 1 H) 8.16 (d, J=8.55 Hz, 1 H). MS ES+ve m/z 381 (M+H)., 1187173-43-8

1187173-43-8 2,7-Diazaspiro[4.5]decan-1-one hydrochloride 45074126, apiperidines compound, is more and more widely used in various fields.

Reference：
Patent; CONVERGENCE PHARMACEUTICALS LIMITED; GLEAVE, Robert James; HACHISU, Shuji; PAGE, Lee William; BESWICK, Paul John; WO2011/141728; (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.19099-93-5,1-Cbz-Piperidin-4-one,as a common compound, the synthetic route is as follows.

Step 2: benzyl-7′-chloro-2′-oxo-1′,2′-dihydrospiro[piperidin-4,4′-pyrido[2,3d][1,3]oxazin]-1-carboxylate; Under a nitrogen atmosphere 26.0 mL (173 mmol) N,N,N,N-tetramethylene-ethylenediamine in 180 mL THF were cooled to -20 C. and combined with 70.0 mL (175 mmol) 2.5 M butyllithium solution. After 30 minutes’ stirring the reaction mixture was cooled to -78 C., and at this temperature 17.8 g (78.0 mmol) tert-butyl (6-chloro-pyridin-2-yl)-carbamate in 120 mL THF were slowly added dropwise. The reaction mixture was stirred for 2.5 h at -78 C. and then combined with 27.2 g (117 mmol) Cbz-protected piperidone in 60 mL of THF. After one hour at -78 C. the mixture was heated to RT and then stirred for 18 h at 40 C. The reaction mixture was decomposed by the dropwise addition of 150 mL saturated sodium hydrogen carbonate solution. Then it was extracted with DCM. The combined organic phases were washed with water, dried and evaporated down. The residue was triturated with PE/EtOAc (1/1), the precipitate formed was suction filtered, washed with PE/EtOAc (1/1) and dried.Yield: 16.4 g (54% of theoretical)ESI-MS: m/z=388 (M+H)+ Rt(HPLC): 1.57 min (method B), 19099-93-5

The synthetic route of 19099-93-5 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Boehringer Ingelheim International GmbH; US2011/172218; (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.108612-54-0,tert-Butyl methyl(piperidin-4-yl)carbamate,as a common compound, the synthetic route is as follows.

EXAMPLE 255; N-1- [4- (BENZOTHIAZOL-2-YLOXY)-BENZYL]-PIPERIDIN-4-YL}-N-METHYL- methanesulfonamide; A. {1-[4-(Benzothiazol-2-yloxy)-benzyl]-piperidin-4-yl}-methyl-carbamic acid ter-butyl ester; A mixture of 4-(benzothiazol-2-yloxy)-benzaldehyde (4.4 g, 17.2 MMOL), METHYL-PIPERIDIN-4-YL-CARBAMIC acid tert-butyl ester (4.06 g, 18. 9 MMOL) in CICH2CH2CI (172 mL) was stirred at room temperature for 40 min. To the resulting reaction mixture was added NaBH (OAC) 3 portion wise over 1.5 h (4 x 1.82 g, 34.4 MMOL). The resulting mixture was stirred at room temperature for 24 h, filtered through diatomaceous earth and rinsed with CH2Cl2 (300 mL). The filtrate was washed with sat. aq. NAHCO3 (1 x 50 mL), dried (NA2SO4) and concentrated under reduced pressure to yield the crude product as a pale yellow oil. The crude product was purified on SI02 (330 g; 0-100percent ethyl acetate/hexanes) to give a light yellow foam (3.75 g, 48percent yield). MS (ESI) : mass calculated for C25H31N303S, 453.2 ; m/z found, 454.5 [M+H]+. 1H NMR (400 MHz, CDC13) : 7.73 (d, J = 8.1, 1 H), 7.66 (d, J = 8.1, 1 H), 7.41-7. 35 (m, 3H), 7.33-7. 23 (m, 3H), 4.13-3. 94 (m, 1H), 3.53 (s, 2H), 2.93 (d, J= 11.6, 2H), 2.74 (s, 3H), 2.08 (t, J = 11.6, 2H), 1.81-1. 69 (m, 2H), 1.65-1. 57 (m, 2H), 1.46 (s, 9H), 108612-54-0

As the paragraph descriping shows that 108612-54-0 is playing an increasingly important role.

Reference：
Patent; JANSSEN PHARMACEUTICA N.V.; WO2005/12296; (2005); 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.61869-08-7,(3S,4R)-3-((Benzo[d][1,3]dioxol-5-yloxy)methyl)-4-(4-fluorophenyl)piperidine,as a common compound, the synthetic route is as follows.,61869-08-7

203-L isopropanol (water 0. 05% w/v) and 13.5 Kg Paroxetine base are charged simultaneously in a reactor and stirred for 15 min to get clear solution. The solution is filtered through sparkler filter to remove suspended particles. The reactor and sparkler filters are washed with 2 x 13.5-L isopropanol. The filtrate and washing solutions are collected into a glass-lined reactor. To this solution of Paroxetine base a solution of 20% w/v hydrogen chloride in isopropanol is added from addition funnel during 120 minutes at 30-35C to bring the pH of the reaction mass between 3-4 (checked on pH paper), at this pH Paroxetine hydrochloride crystallizes. The slurry is stirred for 15 minutes and then slowly heated to 80-82C, 135 L isopropanol is distilled off at atmospheric pressure and then cooled. The product crystallized out at 45C, which is then further cooled to 30-35C and stirred for 1 hr at this temperature. The product is centrifuged and washed with 2 x 13.5-L isopropanol. The wet cake is then transferred to a vacuum tray dryer. The product is dried at 30-35C for 2 hrs, at 50-55C for 6 hrs and finally at 70-75C for 12 hrs under reduced pressure of 30 mm, reducing isopropanol content to less than 3%. The yield of anhydrous Paroxetine hydrochloride is 13.5 Kg Water content of distillate 0.6% Melting point 116-117C Purity (by HPLC) 99.72% Water (by KFR) 1.48% isopropanol (by GC) 2.4%; Example 2 20 g of Paroxetine base is dissolved in 360-ml isopropanol (water <0.05%). The solution is filtered through filter pad in Buchner funnel. The pad is washed twice with 20-ml isopropanol. To the clear filtrate is added 20% w/v hydrogen chloride solution in isopropanol at 30-35C to bring the pH of the reaction mass between 3-4 (checked on pH paper). Paroxetine hydrochloride is CRYSTALLISED out. The slurry is stirred for 15 minutes and then slowly heated to 80-82C to obtain a clear solution, which is then subjected to distillation for the removal of 200 ml isopropanol at atmospheric pressure. The solution is then cooled and the product crystallised out at 30-35C. Slurry thus obtained is stirred for 1 hr at the same temperature. The product is filtered and washed with 4 x 20-ml isopropanol. The wet cake is dried in vacuum oven at 65C for 4 hrs and between the range 70-75C for 16 hrs under reduced pressure of 30 mm to afford 19.9 g Paroxetine hydrochloride. Melting point 116-117C Water content of distillate 0.55% Purity by HPLC 99.96%, Isopropanol (by GC) 2.96% Water (by KFR) 1.5%; Example 3 20 g of Paroxetine base is dissolved in 360-ml isopropanol (water <0.05%). The solution is filtered through filter pad in Buchner funnel. The pad is washed twice with 20 ml isopropanol. To the clear filtrate is added 20% hydrogen chloride solution in isopropanol at 30-35C to bring the pH of the reaction mass between 3-4 (checked on pH paper). Paroxetine hydrochloride is crystallized out at this pH. The slurry is stirred for 15 min. and then slowly heated to 80-82C to obtain a clear solution, which is then subjected to distillation for removal of 200 ml isopropanol at atmospheric pressure. The solution is then cooled to 30 to 35 C and the product crystallized out. The slurry thus obtained is stirred for 1 hour. The product is filtered and washed with 4 x 20-ml isopropanol. The wet cake is dried in vacuum oven between the range 70-75C for 16 hrs under reduced pressure of 30 mm to afford 19.5 g of Paroxetine hydrochloride. Melting point 116-117C Water content of distillate 0.6% Purity by HPLC 99.96%, Isopropanol (by GC) 2.18% Water (by KFR) 1.46% The synthetic route of 61869-08-7 has been constantly updated, and we look forward to future research findings. Reference：
Patent; CADILA HEALTHCARE LIMITED; WO2005/19209; (2005); A2;,
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, The mixture of 4-methylpiperidine-4-carbonitrile (200 mg, 696 mupiiotaomicron, 1 equiv) and 3- chloro-4-((5-chloro-3-methylpyrazin-2-yl)thio)pyridin-2-amine (112 mg, 696 mupiiotaomicron, 1 equiv) in DIPEA (2.00 mL) was stirred at 120 C under an inert atmosphere for 2 hours. The reaction mixture was then poured into H20 (5 mL), and the aqueous phase was extracted with EtOAc (3 x 5 mL). The combined organic extracts were washed with brine (1 mL), dried with anhydrous Na2SC”4, filtered, and concentrated under reduced pressure. The crude residue was then purified by column chromatography to give l-(5-((2-amino-3-chloropyridin-4-yl)thio)-6-methylpyrazin- 2-yl)-4-methylpiperidine-4-carbonitrile (100 mg, 266 mupiiotaomicron, 38% yield) as a white solid. 1H NMR (400 MHz, chloroform-i ) delta 8.05 (s, 1H), 7.67 (d, J= 5.29 Hz, 1H), 5.87 (d, J= 5.51 Hz, 1 H), 4.84 (br s, 2H), 4.43 (br d, J = 13.01 Hz, 2H), 3.26 (br t, J = 12.24 Hz, 2H), 2.47 (s, 3H), 2.07 (br s, 1H), 1.41 – 1.47 (m, 4H).

As the paragraph descriping shows that 948894-26-6 is playing an increasingly important role.

Reference：
Patent; REVOLUTION MEDICINES, INC.; JOGALEKAR, Ash; WON, Walter; KOLTUN, Elena S.; GILL, Adrian; MELLEM, Kevin; AAY, Naing; BUCKL, Andreas; SEMKO, Christopher; KISS, Gert; (496 pag.)WO2018/13597; (2018); A1;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem

5773-58-0, 3-Methylpiperidin-4-one is a piperidines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated,5773-58-0

3-Methylpiperidin-4-one (1.34 g, 11.9 mmol) was dissolved in dichloromethane (30 ml), Et3N (6.12 ml) was added followed by 4-chlorobenzyl bromide (2.46 g, 12 mmol) and the reaction mixture was stirred at room temperature over night, partitioned between dichloromethane and water. The organic layer was dried over Na2SO4, filtered and the filtrate was concentrated in vacuo. The residue was dissolved in pyridine (30 ml), NH2OH HCl (1.53 g) was added and the mixture was stirred at room temperature over night, partitioned between ethyl acetate and water. The organic layer was washed with water, dried over Na2SO4, filtered and the filtrate was concentrated in vacuo to give l-(4- chlorobenzyl)-3-methylpiperidin-4-one-oxime (2.1 g). 1H-NMR (CDCl3, 400 MHz): 58.39 (br.s, IH); 7.28 (s, 4H); 3.47 (m, 2H); 3.00 (m, IH); 2.77 (m, 2H); 2.58 (m, IH); 2.26 (m, 2H); 2.05 (dd, J= 9.2, 11.0 Hz, IH); 1.08 (d, J= 6.6 Hz, 3H). APCI-MS : m/z 253 (MH+).

5773-58-0 3-Methylpiperidin-4-one 12284277, apiperidines compound, is more and more widely used in various fields.

Reference：
Patent; ASTRAZENECA AB; WO2007/53082; (2007); 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.912368-73-1,(S)-tert-Butyl 3-(methylamino)piperidine-1-carboxylate,as a common compound, the synthetic route is as follows.

To a solution of 3,5-dichloropyrazine-2-carbonitrile (1035 mg, 5.98 mmol) in DMF (10 mL) were added (S)-tert-butyl 3-(methylamino)piperidine-1-carboxylate (1280 mg, 5.98 mmol) and DIPEA (1.25 mL, 7.2 mmol) in a dropwise manner. The mixture was stirred at room temperature for 3 hrs. The reaction mixture was diluted with 200 mL EtOAc, washed with brine x3, dried, concentrated in vacuo and subjected to silica flash column with 0 to 60% EtOAc in hexane to give (S)-tert-butyl 3-((6-chloro-5-cyanopyrazin-2-yl)(methyl)amino)piperidine-1- carboxylate (1.50 g, 71%)., 912368-73-1

The synthetic route of 912368-73-1 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; PHARMACYCLICS LLC.; ATALLAH, Gordana, Babic; CHEN, Wei; JIA, Zhaozhong, J.; POZZAN, Alfonso; RAVEGLIA, Lucal, Francesco; ZANALETTI, Riccardo; (815 pag.)WO2016/196776; (2016); A2;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem