Heterocyclic Building Blocks-piperidine

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.

500 mg of (3R,4R)-1-benzyl-N,4-dimethylpiperidine-3-amine dihydrochloride was added to a 25-mL round-bottomed flask, and 5.00 mL of deionized water was added thereto. After 277 mg of 6-chloro-7-deazapurine and 1.08 of potassium carbonate (K2CO3) were added into the reaction mixture, the reaction mixture was refluxed for about 24 hours and then cooled at room temperature. The reaction mixture was extracted three times with 10.0 mL of dichloromethane (CH2Cl2) to collect an organic phase. The collected organic phase was concentrated under reduced pressure. The resulting residue was purified by flash column chromatography (MeOH:CH2Cl2=2:98). As a result, 282 mg of N-((3R,4R)-1-benzyl-4-methylpiperidine-3-yl)-N-methyl-7H-pyrrolo[2,3-d]pyrimidine-4-amine was obtained with a yield of about 48.9%. (0285) 282 mg of N-((3R,4R)-1-benzyl-4-methylpiperidine-3-yl)-N-methyl-7H-pyrrolo[2,3-d]pyrimidine-4-amine was added to a 25-mL round-bottomed flask, and then dissolved with 3.00 mL of methanol. After 280 mg of a 10w/w% palladium/ carbon (Pd/C) was added thereto, a hydrogen-containing balloon was installed on the reaction flask. The reaction mixture was vigorously stirred for about 24 hours and then filtered through a Celite 545 filter agent. The resulting filtrate was concentrated under reduced pressure. The resulting fraction was concentrated under reduced pressure and then further under vacuum. As a result, 200 mg of N-methyl-N-((3R,4R)-4-methylpiperidine-3-yl)-7H-pyrrolo[2,3-d]pyrimidine-4-amine was obtained with a yield of about 97.1%. (0286) 70.0 mg of N-methyl-N-((3R,4R)-4-methylpiperidine-3-yl)-7H-pyrrolo[2,3-d]pyrimidine-4-amine was added to a 5-mL round-bottomed flask, and then dissolved with 1.50 mL of dichloromethane (CH2Cl2). After 57.0 mg of 3-cyanobenzenesulfonyl chloride was added into the solution, the reaction mixture was treated with 0.0750 mL of N,N-diisopropylethylamine and then stirred overnight at room temperature. The reaction mixture was concentrated under reduced pressure, and then the resulting residue was purified by flash column chromatography (MeOH:CH2Cl2=2:98). The resulting fraction was concentrated under reduced pressure and then further under vacuum. As a result, 85.9 mg of 3-(((3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidine-4-yl)amino)piperidine-1-yl)sulfonyl)benzonitrile was obtained with a yield of about 73.4%. (0287) 1H NMR (400 MHz, CDCl3) delta10.40 (s, 1H), 8.27 (s, 1H), 8.09-8.08 (m, 1H), 8.03-8.01 (m, 1H), 7.95-7.92 (m, 1H), 7.64 (t, J = 3.6 Hz, 1H), 7.13 (d, J = 3.6 Hz, 1H), 6.66 (d, J = 3.6 Hz, 1H), 5.49 (d, J = 4.8 Hz, 1H), 3.79 (dd, J = 4.4, 12.4 Hz, 1H), 3.68 (s, 3H), 3.10 (dd, J = 4.4, 12.4 Hz, 1H), 2.83-2.77 (m, 1H), 2.20-2.11 (m, 1H), 1.92-1.86 (m, 3H), 0.98 (d, J = 6.8 Hz, 3H). (0288) LRMS (ESI) calcd for (C20H22N6O2S + H+) 411.2, found 411.1., 1062580-52-2

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

Reference：
Patent; Yangji Chemical Co., Ltd.; Han Wha Pharma Co., Ltd.; CHOUGH, Chieyeon; LEE, Sunmin; JOUNG, Misuk; JEONG, Hyun Uk; MOON, Hong-sik; (62 pag.)EP3327021; (2018); A1;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem

138377-80-7, 3-Aminopiperidin-2-one hydrochloride is a piperidines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

24.64 mg of 4 (0.087 mmol), 41.05 mg of sodium 2-ethyl-hexanoate (0.247 mmol), 20.16 mg of 15 (which may be prepared according to the procedures described in WO 2002/081480, and the content of which is incorporated herein by reference) (0.134 mmol) and 2 ml of THF are successively introduced into a 20 ml round-bottomed flask with stirring and under an argon atmosphere. Stirring is continued for 4 days at r.t. 20 ml of EtOAc are added to the reaction medium, which is then washed successively with 20 ml of NaOH solution (0.1 N), 20 ml of water and 20 ml of saturated NaCl solution. As product has visibly dissolved in the aqueous phase, this aqueous phase is extracted twice with a mixture of 50 ml of CH2Cl2 and 5 ml of MeOH. The 3 organic phases are combined, dried, filtered and then evaporated to dryness. The crude product is purified by PCC with a 93/7 CH2Cl2/MeOH mixture. 28.49 mg of product 16 are collected (Yld=83percent). TLC (90/10 CH2Cl2/MeOH): Rf=0.28 1H NMR (400 MHz, CDCl3): delta (ppm)=7.11 (d, 1H); 5.70 (d, 1H); 5.67 (m, 1H); 5.48 (dd, 1H); 4.72 (m, 1H); 4.20 (d, 1H); 4.02 (d, 1H); 3.80 (d, 1H); 3.50 (s, 1H); 3.49 (s, 3H); 3.36 (m, 2H); 2.54 (m, 2H); 1.96 (m, 2H); 1.47 (s, 6H); 1.02 (s, 9H) LCMS (ES+, 30 V): tR=2.92 mn|m/z=797+ (2M+H+); 399+ (M+H+); 341+ (M+H+[(H3C)2CO]); 841 (2 MH+HCOOH); 443 (MH+HCOOH), 138377-80-7

138377-80-7 3-Aminopiperidin-2-one hydrochloride 19795138, apiperidines compound, is more and more widely used in various fields.

Reference：
Patent; AVENTIS PHARMA S.A.; US2007/244087; (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.162166-99-6,1-Boc-3-Methanesulfonyloxymethyl-piperidine,as a common compound, the synthetic route is as follows.

Raw material 8 (1.0 eq) was added to the reaction flask, and a sufficient amount of ACE was added as a solvent. The mixture was stirred at room temperature, and LiBr (3.0 eq) was slowly added thereto, and the temperature was gradually raised to reflux, overnight. The reaction solution was cooled to room temperature, and the reaction mixture was quenched with water. The reaction mixture was evaporated to dryness, and then the mixture was evaporated and evaporated with EtOAc and water, and the oil layer was collected, and the oil layer was washed three times with saturated brine, and the oil layer was dried over Na 2 SO 4 Product 9, no purification required., 162166-99-6

The synthetic route of 162166-99-6 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Guangdong Zhongsheng Pharmaceutical Co., Ltd.; Chen Lijuan; Long Chaofeng; Chen Xiaoxin; Liu Zhuowei; Qian Zhiyong; Yang Jinliang; Xiang Mingli; (99 pag.)CN109970740; (2019); A;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem

62718-31-4,62718-31-4, 1-Benzylpiperidine-4-carbonitrile is a piperidines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Step a: To a solution of N^V-diisopropylamine (14.0 mL, 97.5 mmol) in THF (100 mL) was added (at -78 C and under N2) -butyllithium (1.6 M in hexane; 59.0 mL, 94.25 mmol) dropwise. The resulting mixture was stirred for 30 min at RT. 1-benzyl piperidine-4- carbonitrile (6.5 g, 32.5 mmol) in THF (50 mL) was added at -78 C. After stirring for 30 min at this temperature, -propyl iodide (20.5 mL, 211.3 mmol) was added. The resulting mixture was stirred at -78 C for 1 h. The mixture was quenched by addition of saturated aqueous ammonium chloride solution and it was extracted with EtOAc. The combined organic phases were washed with brine, dried over Na2S04, filtered and concentrated to obtain 1 -benzyl -4-propylpiperidine-4- carbonitrile (6.0 g, 24.8 mmol). This compound was used without further purification. MS m/z

The synthetic route of 62718-31-4 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; NOVARTIS AG; CHEN, Christine Hiu-tung; CHEN, Zhuoliang; FORTANET, Jorge Garcia; GRUNENFELDER, Denise; KARKI, Rajesh; KATO, Mitsunori; LAMARCHE, Matthew J.; PEREZ, Lawrence Blas; STAMS, Travis Matthew; WILLIAMS, Sarah; WO2015/107493; (2015); A1;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem

4629-78-1, 3-Methylpiperidin-4-one hydrochloride is a piperidines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Step 2: To a suspension of the product of step 1 in DCM at 0 C., DIPEA (4 eqv) was added slowly and stirred for 30 minutes at 25 C. The reaction mixture was cooled again to 0 C. and acetyl chloride (1.1 eqv) was added slowly. The resulting mixture was stirred at 25 C. for 16 hrs before being quenched by addition of saturated aqueous NaHCO3. The aqueous layer was back extracted three times with DCM. The combined organics were washed with H2O, dried (Na2SO4), filtered and evaporated. The residue was purified by SiO2 flash chromatography to give racemic 1-acetyl-3-methyl-piperidin-4-one (94% over two steps).

4629-78-1, 4629-78-1 3-Methylpiperidin-4-one hydrochloride 22728864, apiperidines compound, is more and more widely used in various fields.

Reference：
Patent; Bamberg, Joe Timothy; Hermann, Johannes Cornellius; Lemoine, Remy; Soth, Michael; US2010/144745; (2010); A1;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem

118133-15-6, 1-(Ethoxycarbonyl)piperidine-4-carboxylic acid is a piperidines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Example-3 Preparation of [1-(2-phenylethyl)-1H-imidazole-2-ylj(piperidin-4-yl)methanonedihydrobromideTo (51.12 grn) of the compound obtained in example-I, toluene (25 ml) and DMF (1.53 ml) was added, followed by the slow addition of thionyl chloride (45.39 grn). The reaction mixture was then heated to 50-55 C and maintained for 2 hours at the same temperature. After completion of the reaction, the excess of thionyl chloride and toluene from the reaction mixture was distilled undervacuum below 70C. The residue obtained was cooled to 5-10C under N2 atmosphere. To the cooled residue, a solution of compound obtained in exarnple-2 (25gm) in acetonitrile (125ml) was slowly added at 0-20C under N2 atmosphere followed by the slow addition of triethylamine (29.36gm) at 0-20C for 2 hours and maintained for 3 hrs at the same temperature. The progress of the reaction was monitored by HPLC. After the completion of the reaction, (125rnl) purified waterand (75 ml) ethyl acetate was added to the reaction mixture and stirred for 10 minutes. The organic layer was separated, washed with water and concentrated the organic layer at mass temperature below 55C under vacuum to get a residue. The residue was cooled to 25-30C and (249.57gm) aqueous HBr was added to the residue. The contents were stirred for 10 miii; then heated to 85- 90C and maintained for 12 hrs at the same temperature. The reaction mass was cooled to 55-60Cand (167.5 ml). Isopropyl alcohol was added to the cooled reaction mass, then heated to 65-70C and maintain for 1 hr at the same temperature. The reaction mass was filtered and dried the material in hot air oven at 60-65C for 8 hrs.Percentage Yield: 90%, 118133-15-6

As the paragraph descriping shows that 118133-15-6 is playing an increasingly important role.

Reference：
Patent; NEULAND LABORATORIES LIMITED; PONNAIAH, Ravi; HASHMI, Arshad Moosa; NEELA, Praveen Kumar; SEEMALA, Dhanunjaya Naidu; MOKKA, Raviteja; LAHOTI, Anandkumar Madanlal; DEEPTHI, V., P., S., S; SARADHI, G., Srinivas Pardha; WO2014/83571; (2014); A1;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem

885279-92-5,885279-92-5, 1-Boc-1,8-diaza-spiro[4.5]decane is a piperidines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

1002821 A flask was charged with N-(1H-pyrazol-3-yl)acetamide (1.00 g, 7.99 mmol, 1.00 equiv), DCM (15 mL) and DIPEA (2.06 g, 15.9 mmol, 1.99 equiv). 4-Nitrophenyl chloroformate (1.78 g, 8.83 mmol, 1.11 equiv) in DCM (5 mL) was added dropwise at 0 C. The mixture was stirred for 2 h at room temperature. Then t-butyl 1,8-diazaspiro[4.5]decane-1-carboxylate (1.92 g, 7.99 mmol, 1.00 equiv) was added. The resulting solution was stirred overnight at room temperature and quenched by water (20 mL), as described in Example 2, Step 6. The residue was chromatographed on a silica gel column to provide 2.23 g (71% yield) of t-butyl 8-(3-acetamido-1H-pyrazole-1- carbonyl)-1,8-diazaspiro[4.5]decane-1-carboxylate as an off-white solid. LCMS (ESI, m/z): 392 [M+H].

The synthetic route of 885279-92-5 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; ABIDE THERAPEUTICS, INC.; GRICE, Cheryl A.; WEBER, Olivia D.; BUZARD, Daniel J.; SHAGHAFI, Michael B.; WIENER, John J. M.; CISAR, Justin S.; DUNCAN, Katharine K.; (324 pag.)WO2018/217809; (2018); A1;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem

61869-08-7, (3S,4R)-3-((Benzo[d][1,3]dioxol-5-yloxy)methyl)-4-(4-fluorophenyl)piperidine is a piperidines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

1.0 g of oily paroxetine free base and 1.24 g of cholic acid were completely dissolved in 10 mL of N,N-dimethylacetamide while heating to 40 C. with shaking for 20 minutes. The solution was slowly added dropwise to 100 mL of ethyl ether to precipitate a solid, stirred at 0 C. for 3 hours, and filtered. The filtered residue was washed with 30 mL of ethyl ether, and dried under vacuum to yield 1.75 g of solid paroxetine cholate as a light gray powder., 61869-08-7

The synthetic route of 61869-08-7 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Lee, Sang Joon; Shin, Hee Jong; Ki, Min Hyo; Lee, Su Kyoung; Kim, Bok Young; Lee, Hong Woo; US2006/63747; (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.140645-24-5,(S)-3-(Aminomethyl)-1-N-Boc-piperidine,as a common compound, the synthetic route is as follows.

Intermediate 84: (S)-tert-butyl 3-(((4-(hydroxymethyl)-2- nitrophenyl)amino)methyl)piperidine-1-carboxylate DIPEA (7.65 mL, 43.8 mmol) was added to a stirred solution of 4-Fluoro-3-nitrobenzyl alcohol (2.50 g, 14.61 mmol) and (3S)-3-(aminomethyl)piperidine (4.70 g, 21.91 mmol in 2-Methyltetrahydrofuran (15 mL). The solution was heated to 80 oC ovenight , the reaction mixture cooled to room temperature and the resulting solid partitioned between EtOAc and sat. aq. NaHCO3. The aqueous layer was removed and the organic layer washed (1x sat. aq. NaHCO3, 1x brine). The organic portion was dried over MgSO4 and evaporated in vacuo to an orange oil. The residue was dissolved in DCM and purified by silica gel chromatography eluting with cyclohexane:EtOAc (10 – 66%). The product containing fractions were evaporated in vacuo to an orange oil foam. The oil was dissolved in TBME and evaporated in vacuo to an orange oil to give the title compound as an orange oil (5.52 g). The total yield of the reaction was 88%. LCMS (System C): tRET = 1.27 min, MH+ = 366.

140645-24-5, 140645-24-5 (S)-3-(Aminomethyl)-1-N-Boc-piperidine 1502022, apiperidines compound, is more and more widely used in various fields.

Reference：
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED; BIT, Rino Antonio; BROWN, John Alexander; HUMPHREYS, Philip G.; JONES, Katherine Louise; (240 pag.)WO2016/146738; (2016); A1;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem

25137-01-3, (R)-Ethyl piperidine-3-carboxylate is a piperidines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Step E. Ethyl (3JR)-l-[(2-cyclopentyl-2,3,4,5-tetrahydro-lH-pyrido[4,3-6]indol-8- yl)carbonyl]piperidine-3-carboxylateHATU (1.9 g, 5.0 mmol) and ethyl (3?)-piperidine-3-carboxylate (0.67 g, 4.2 mmol) were added to a solution of cyclopentyl-2,3,4,5-tetrahydro-lH-pyrido[4,3-?]indole-8- carboxylic acid (1.1 g, 3.8 mmol) and DIPEA (1.7 niL, 9.6 mmol) in DMF (25 mL). The reaction mixture was stirred for 2 hrs. and was then concentrated. The product was purified by normal-phase MPLC using 2% Et3N, 5% MeOH and 10% acetone in DCM to provide the title compound as colorless oil (1.6 g, 97 %). 1H NMR (400 MHz, CD3OD) ? 1.27 – 1.38 (m, 3 H)3 1.47 – 1.70 (m, 6 H), 1.70 – 1.87 (m, 5 H), 1.94 – 2.18 (m, 3 H), 2.85 – 3.07 (m, 6 H), 3.16 – 3.53 (m, 2 H), 3.75 – 3.88 (m, 2 H), 4.00 – 4.22 (m, 2 H), 7.12 (dd, J=8.30, 1.46 Hz, 1 H), 7.33 (dd, J=8.40, 0.59 Hz, 1 H), 7.48 (s, 1 H); MS (ESI) (M+H)+ 424.0.

25137-01-3, The synthetic route of 25137-01-3 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; ASTRAZENECA AB; WO2008/36021; (2008); A1;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem