Tag: M.W:100-200

58077-68-2, 4-(4-Methylpiperazin-1-yl)butanoic acid is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

58077-68-2, A solution of (1R,2R)-2-[[trans-2-[(1E,3E)-4-(4-cyano-2-fluorophenyl)-1,3-butadienyl]-1,3-dioxan-5-yl]thio]-1-(2,4-difluorophenyl)-1-[(1H-1,2,4-triazol-1-yl)methyl]propyl 2-(hydroxymethyl)benzoate (1.07 g, 1.58 mmol) obtained from Example 17-(4) in dichloromethane (20 ml) was cooled to 0C, and 4-(N,N-dimethylamino)pyridine (386.1 mg, 3.16 mmol), 4-(4-methyl-1-piperazinyl)butanoic acid (described in J. Med. Chem., 43, 1493 (2000); 529.5 mg, 2.84 mmol), and 1-ethyl-3-[3-(N,N-dimethylamino)propyl]carbodiimide (666.8 mg, 3.48 mmol) were added thereto. The reaction solution was stirred at room temperature for 2 hours, diluted with dichloromethane, and then the organic layer was washed successively with water and a saturated aqueous solution of sodium chloride. The solvent was evaporated under reduced pressure, and the residue was subjected to chromatography on a silica gel (50 g) column (eluent; ethyl acetate : methanol = 4 : 1) to give a mixture of the title target compound and 4-(N,N-dimethylamino)pyridine. The mixture was purified by recycle preparative HPLC [LC-908; Japan Analytical Industry Co., Ltd.; GPC column JAIGEL-1H (20 mm i.d. x 600 mm) and JAIGEL-2H (20 mm i.d. x 600 mm) connected in series for use; solvent, chloroform] to afford the title target compound (901.1 mg, 67% yield) as a colorless amorphous solid. NMR spectrum (400 MHz, CDCl3) delta ppm: 1.46 (3H, dd, J=7, 2 Hz), 1.85 (2H, quint., J=7 Hz), 2.27 (3H, s), 2.3-2.6 (8H, br), 2.37 (2H, t, J=7 Hz), 2.45 (2H, t, J=7 Hz), 3.05 (1H, tt, J=11, 5 Hz), 3.51 (1H, t, J=11 Hz), 3.53 (1H, t, J=11 Hz), 4.01 (1H, q, J=7 Hz), 4.10-4.20 (2H, m), 4.99 (1H, d, J=4 Hz), 5.30-5.56 (4H, m), 5.85 (1H, dd, J=15, 4 Hz), 6.57 (1H, dd, J=15, 10 Hz), 6.73 (1H, d, J=15 Hz), 6.88-7.00 (3H, m), 7.34 (1H, dd, J=10, 1 Hz), 7.37-7.46 (3H, m), 7.52-7.60 (3H, m), 7.79 (1H, d, J=8 Hz), 7.90 (1H, s), 7.95 (1H, s) IR spectrum nu max KBr cm-1: 2230, 1729, 1503, 1357, 1257, 1139, 1051, 973 Mass spectrum m/z (ESI): 845 (M++1) Specific rotation [alpha]D25 -1.8 (c=1.06, CHCl3). A solution of (1R,2R)-2-[[trans-2-[(1E, 3E)-4-(4-cyano-2-fluorophenyl)-1,3-butadienyl]-1,3-dioxan-5-yl]thio]-1-(2,4-difluorophenyl)-1-[(1H-1,2,4-triazol-1-yl)methyl]propyl] 2-[[4-(4-methyl-1-piperazinyl)butyryl]oxymethyl]benzoate (290.5 mg, 0.34 mmol) obtained above in ethyl acetate (5 ml) was cooled to 0C, and hydrogen chloride (4N ethyl acetate solution; 86 mul, 0.35 mmol) was added thereto, and then the mixture was stirred at 0C for 5 minutes. The solvent was distilled off under reduced pressure to afford the mono hydrochloric acid salt of the title compound (305.1 mg, quantitative yield) as a pale yellow amorphous solid. NMR spectrum (400 MHz, CDCl3) delta ppm: 1.46 (3H, dd, J=7, 2 Hz), 1.90 (2H, br), 2.47 (2H, t, J=7 Hz), 2.6-2.8 (13H, br d), 3.05 (1H, tt, J=11, 5 Hz), 3.51 (1H, t, J=11 Hz), 3.53 (1H, t, J=11 Hz), 4.01 (1H, q, J=7 Hz), 4.10-4.15 (1H, m), 4.18 (1H, ddd, J=11, 5, 2 Hz), 4.99 (1H, d, J=4 Hz), 5.44 (1H, d, J=14 Hz), 5.46-5.53 (2H, m), 5.55 (1H, d, J=15 Hz), 5.85 (1H, dd, J=15, 4 Hz), 6.57 (1H, dd, J=15, 11 Hz), 6.74 (1H, d, J=15 Hz), 6.89-6.93 (2H, m), 6.94 (1H, dd, J=15, 11 Hz), 7.34 (1H, dd, J=10, 1 Hz), 7.40-7.47 (3H, m), 7.54-7.62 (3H, m), 7.84 (1H, d, J=7 Hz), 7.89 (1H, s), 7.97 (1H, s) IR spectrum nu max KBr cm-1: 2230, 1729, 1503, 1274, 1256, 1139, 1051, 973 Mass spectrum m/z (ESI): 845 [M(free base)++1] Specific rotation [alpha]D25 -4.5 (c=0.89, CHCl3)

The synthetic route of 58077-68-2 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; Sankyo Company, Limited; EP1362856; (2003); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.4318-42-7,1-Isopropylpiperazine,as a common compound, the synthetic route is as follows.

Intermediate B58: 4-[4-(1 -methylethyl)-1 -piperazinyl]-2,5-bis(methyloxy)aniline; Step A/Intermediate B59: 1-[2,5-bis(methyloxy)-4-nitrophenyl]-4-(1- methylethyl)piperazine; 1-chloro-2,5-bis(methyloxy)-4-nitrobenzene (3.25g, 15 mmol, TCI America), isopropylpiperizine (3.84g, 30 mmol, Oakwood Products), cesium carbonate (9.8g, 30 mmol), Pd2dba3 (1.37g, 1.5 mmol), and XANTPHOS (1.3g, 2.25 mmol) were added to degassed dioxane (80 mL) and heated to 1000C under a water cooled reflux condenser for 12 hours. The dioxane was removed under reduced pressure and the solids were partitioned between methylene chloride (500 mL) and water (500 mL). The organic layer was dried over sodium sulfate, taken to a residue under reduced pressure, and purified by chromatography on SiO2 to give 1-[2,5- bis(methyloxy)-4-nitrophenyl]-4-(1-methylethyl)piperazine as a yellow solid (3.5g, 11.3 mmol, 76percent yield). 1 H NMR (400 MHz, CDCI3) delta ppm 1.09 (d, J=6.60 Hz, 6 H), 2.69 – 2.73 (m, 4 H), 2.75 (d, J=6.60 Hz, 1 H), 3.23 – 3.32 (m, 4 H), 3.88 (s, 3 H), 3.94 (s, 3 H), 6.48 (s, 1 H), 7.55 (s, 1 H)., 4318-42-7

The synthetic route of 4318-42-7 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; SMITHKLINE BEECHAM CORPORATION; WO2009/20990; (2009); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.474711-89-2,Piperazine-1-carboxamide hydrochloride,as a common compound, the synthetic route is as follows.,474711-89-2

Example 164: Preparation of 4-{4-[(3S)-2,3-dihydro[l,4]dioxino[2,3-b]pyridin-3- yl]benzyl}piperazine-l-carboxamide (164). To a solution of Intermediate C (30.0 g, 124 mmol) in DCM (500 mL) is added 164-1 (26.7 g, 161 mmol) followed by TEA (20.9 mL, 149 mmol). After stirring for 10 min at rt, sodium triacetoxyborohydride (36.0 g, 161 mmol) is added and the mixture stirred at rt for 24 hours. The reaction mixture is washed with sat.NaHCC (2 x 300 mL), and brine (400 mL). The organic layer is dried over Na2S04, filtered and concentrated. The solid is triturated twice in ethyl ether at 65C. After the second filtration, the resultant solid is recrystallized from ethanol to afford the title compound 164. (LC/MS method 11 : ES+ m/z 355.1 [M+H]+, Rt = 0.38 min).

474711-89-2 Piperazine-1-carboxamide hydrochloride 2769700, apiperazines compound, is more and more widely used in various fields.

Reference£º
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; BRUNETTE, Steven, Richard; ABEYWARDANE, Asitha; BURKE, Michael, J.; KAPADIA, Suresh, R.; KIRRANE, Thomas, Martin, Jr.; NETHERTON, Matthew, Russell; RAZAVI, Hossein; RODRIGUEZ, Sonia; SAHA, Anjan; SIBLEY, Robert; SMITH KEENAN, Lana, Louise; TAKAHASHI, Hidenori; TURNER, Michael, Robert; WU, Jiang-Ping; YOUNG, Erick, Richard, Roush; ZHANG, Qiang; ZHANG, Qing; ZINDELL, Renee, M.; WO2013/134226; (2013); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

67455-41-8, 4-(Piperazin-1-yl)aniline is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

67455-41-8, Example No. 188Preparation of N- (3- (7- ( (4- (piperazin-l-yl) phenyl) amino) -1H- pyrazolo [4, 3-d] pyrimidin- 5 -yl) phenyl) methanesulfonamideN- (3- (7-chloro-2- (4-methoxybenzyl) -2H-pyrazolo [4,3- d] pyrimidin- 5 -yl) phenyl) methanesulfonamide (0.16 mmol) and 4-(piperazin-l-yl) aniline (0.3 mmol 2 eq. , ) were suspended in MeOH (dry, 3mL) in a microwave vial (2-5mL) , HCl in dioxane(4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3mL) . The reaction mixture was irradiated in a microwave reactor for 5 min at 140C. The reaction mixture was concentrated and purified by semi- preparative HPLC-MS and freeze dried from water/t-BuOH 4/1. exact mass: 464.2094 g/molHPLC-MS: analytical method Lrt: 2.90 min – found mass: 465 (m/z+H)

67455-41-8 4-(Piperazin-1-yl)aniline 422925, apiperazines compound, is more and more widely used in various fields.

Reference£º
Patent; ORIGENIS GMBH; ALMSTETTER, Michael; THORMANN, Michael; TREML, Andreas; TRAUBE, Nadine; WO2012/143144; (2012); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.5308-25-8,1-Ethylpiperazine,as a common compound, the synthetic route is as follows.

To a stirred solution of 1 -(bromomethyl)-4-nitro-2-(trifluoromethyl)benzene (step 1 intermediate) (4.0 g, 14.1 mmol) in dichloromethane (40 mL) were added N-ethylpiperazine(1.88 mL, 14.7 mmol) followed by N,N-diisopropylethylamine (DIPEA) (3.27 mL, 19.1 mmol) at RT. The mixture stirred at RT for 16 h. The reaction mixture was diluted with dichloromethane and washed with saturated sodium bicarbonate solution followed by brine. The organic layer was dried over anhydrous sodium, filtered and concentrated under reduced pressure. The residue obtained was purified by column chromatography to yield 3.5 g of thedesired product. ?H NMR (400 MHz, DMSO-d6) oe 0.96 (t, J = 7.2 Hz, 3H), 2.28-2.5 1 (m,1OH), 3.72 (s, 2H), 8.09 (d, J= 8.4 Hz, 1H), 8.40 (s, 1H), 8.51 (dd, J, = 2.4 Hz, J2 = 8.8 Hz,1H)., 5308-25-8

As the paragraph descriping shows that 5308-25-8 is playing an increasingly important role.

Reference£º
Patent; GLENMARK PHARMACEUTICALS S.A.; PATEL, Vinod; REDDY, Venkateshwar; GHARAT, Laxmikant Atmaram; CHAUDHARI, Sachin Sundarlal; DAS, Sanjib; VELGALETI, Ranganadh; SHAH, Daisy Manish; BAJPAI, Malini; (262 pag.)WO2018/215668; (2018); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.75336-86-6,(R)-2-Methylpiperazine,as a common compound, the synthetic route is as follows.

[3-DICHLOROPYRIDINE] (2.94 [G, 20.] 0 [MMOL),] [(R)-2-METHYLPIPERAZINE] (2.75 g, 27.5 mmol) (Commercially available from [SIGMA-ALDRICH,] St. Louis, [MO] (www. sigma- [ALDRICH.] [COM)),] and triethylamine (3. [04] g, 30 mmol) were dissolved in 15 mL of dimethylsulfoxide and the resulting mixture was heated at about [100C FOR ABOUT] 24 [ H. THE] reaction mixture was then cooled to room temperature and extracted with a saturated aqueous sodium bicarbonate solution. The organic layer was dried, concentrated, and purified using a silica gel column eluted with a gradient elution (ethyl acetate to [2 : 1 ETHYL ] acetate : methanol) to provide Compound 1 [(N- (3-CHLOROPYRIDIN-2-YL)-PIPERAZINE) AS] a yellow liquid (90percent yield).

75336-86-6, 75336-86-6 (R)-2-Methylpiperazine 7330434, apiperazines compound, is more and more widely used in various fields.

Reference£º
Patent; EURO-CELTQUE, S.A.; WO2004/29031; (2004); A2;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

75336-86-6, (R)-2-Methylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

75336-86-6, To a 0 0C solution of (R)-2- methylpiperazine (5.0 g, 50 mmol, 1.0 equiv) in dry DCM (200 mL) was added triethylamine (21 mL, 150 mmol, 3 equiv) by syringe. A solution of BOC2O (10.4 g, 47.4 mmol, 0.95 equiv) was then added as a solution in dry DCM (100 mL) over the course of an hour. After stirring for an addition 15 min at 0 “C, the reaction mixture was stirred at room temperature for 30 min. The reaction mixture was then washed with aq. satd. NaHCO3 and brine. The resulting DCM solution was dried over sodium sulfate, filtered, and concentrated in vacuo, and used in the next step without further purification. The residue was dissolved in dry DCM (50 mL), and Et3N (21 mL, 150 mmol, 3 equiv) was added by syringe. To this room temperature solution was added CbzCI (8.4 mL, (>0 mmol, 1.2 equiv) dropwise by syringe. After stirring at room temperature for 30 minutes, the mixture was quenched by the addition of aq. satd. NaHCC<3. The solution was washed an additional time with aq. satd. NaHCO3, twice with aq. 1 N KHSO4, and twice with brine. The DCM layer was dried over sodium sulfate, filtered, and concentrated in vacuo. The resulting residue was dissolved in MeOH (100 mL), and HCl (4 N in dioxane, 150 mL, 600 mmol, 12 equiv) was added dropwise by syringe. After 2 h, the reaction mixture was concentrated in vacuo. To the resulting solid was added EtOAc and 1 N NaOH. The aqueous layer was extracted twice with EtOAc, and the organic layers were combined and washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to provide (/?)-benzyl 2-methylpiperazine-l-carboxylate (5.3 g, 45%). 75336-86-6 (R)-2-Methylpiperazine 7330434, apiperazines compound, is more and more widely used in various fields. Reference£º
Patent; CYTOKINETICS, INC.; WO2007/70683; (2007); A2;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.103-76-4,N-(2-Hydroxyethyl)piperazine,as a common compound, the synthetic route is as follows.

The 20 mmol 4, 6 – dichloro -2 – methyl pyrimidine, 35 mmol K3 PO4 Dissolved in 16 mmol 1 – butyl -3 – methyl imidazole glycine salt and stirring, adding 21 mmol N – hydroxyethyl piperazine, for 80 C reaction under 1.5 h after, cooling to room temperature, add-on enters 21 mmol2 – amino – N – (2 – chloro -6 – methyl phenyl) -5 – thiazole carboxamide, for 80 C continues reaction under 2 h, after the reaction, cooling to room temperature, the mixture extracted with ethyl ether 3 times (3 ¡Á 50 ml), the combined extraction liquid and concentrated, get the crude product (ionic liquid to the methylene chloride extraction, vacuum drying in order to remove the small amount of solvent, the residual viscous ionic liquid ethyl ether after being sufficiently washed directly used for the next reaction, without further purification). The crude product by adding 80% ethanol aqueous solution 100 ml, under stirring, by adding 2 g of activated carbon, reflux 30 min, is still hot filtration, filtrate refrigeration crystallization overnight, filtered, the filter cake of ice 80% ethanol aqueous solution washing, drying, to obtain white solid 9.01 g, yield 92.27%, purity of 99.94%., 103-76-4

As the paragraph descriping shows that 103-76-4 is playing an increasingly important role.

Reference£º
Patent; Shandong Luoxin Pharmaceutical Group Co., Ltd.; Shandong Luoxin Pharmaceutical Group Hengxin Pharmaceutical Co., Ltd.; Shandong Yuxin Pharmaceutical Co., Ltd.; Gao Hongjun; Zhang Hui; Ren Qingwei; (13 pag.)CN109503568; (2019); A;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

109-07-9, 2-Methylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Method 1 1-(t-Butoxycarbonyl)-3-methylpiperazine To a cold (-5¡ã C.) solution of 2-methylpiperazine (5.00 g, 0.05 mole) in 200 mL of CH2Cl2 under Ar was added a solution of di-t-butyl dicarbonate (10.9 g, 0.05 mole) in 100 mL of CH2Cl2 over 1 h. The resulting mixture was stirred at -5¡ã C. for 1 h and then at r.t. for 2 h. The solution was then washed (H2O), dried (Na2SO4) and evaporated to give an oil which was chromatographed (SiO2/ethyl acetate then ethyl acetate-MeOH-NH4OH 10:1:0.1) to give the product (4.30 g, 43percent) as an oil. This material was used without further purification: 1H nmr (200 MHz, CDCl3) delta4.15-3.75 (br s, 2H), 3.0-2.6 (m, 4H), 2.47-2.35 (m, 1H), 1.48 (s, 9H), 1.08 (d, J=6.7 Hz, 3H)., 109-07-9

As the paragraph descriping shows that 109-07-9 is playing an increasingly important role.

Reference£º
Patent; Fabre-Kramer Pharmaceuticals, Inc.; US2009/281114; (2009); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.21655-48-1,cis-2,6-Dimethylpiperazine,as a common compound, the synthetic route is as follows.

To a mixture of 5a (5.0g, 32.44 mmol, 1 equiv) and (2S,6R)-2,6-dimethylpiperazine (3.7g, 32.44 mmol, 1 equiv) in 60 mL DMSO was added K2CO3 (8.97g, 64.88mmol, 2 equiv). The mixture was heated at 110 C for 12h. The reaction mixture was diluted with 120 mL ice water. Ethyl acetate was added and the reaction mixture was partitioned between ethyl acetate and water. The organic phase was washed with water and brine, then dried over anhydrous Na2SO4, filtered and concentrated. The resulting residue was further purified via silica gel chromatography to give ethyl 4-((3R,5S)-3,5-dimethylpiperazin-1-yl)benzoate as a white solid (7.25g, 90%). NMR (300MHz, CDCl3) delta 7.85 (d, J=9.0Hz, 2H), 6.79 (d, J=9.0Hz, 2H), 4.26 (q, J=7.1Hz, 2H), 3.60 (d, J=12.0Hz, 2H), 2.96-2.88 (m, 2H), 2.32 (t, J=11.3Hz, 2H), 1.30 (t, J=7.1Hz, 3H), 1.08 (d, J=6.3Hz, 6H). The obtained methyl 4-((3R,5S)-3,5-dimethylpiperazin-1-yl)benzoate was dissolved in dichloromethane (DCM) and stirred for 15 min after adding 1 N NaOH (aq) (32.12 mL, 32.12 mmol, 1.1 equiv). Then a solution of di-tert-butyl dicarbonate ester in DCM was added dropwise. The reaction mixture was stirred at room temperature until the starting material was consumed completely. The reaction mixture was then extracted with DCM and the organic phase was washed with saturated NaHCO3 (aq) and brine, then dried over anhydrous Na2SO4, filtered and concentrated. The resulting residue was further purified via silica gel chromatography to give 6a as colorless oil. (10.00 g, 98%). 1H NMR (300 MHz, CDCl3) delta 7.77 (d, J = 8.8 Hz, 2H), 6.68 (d, J = 8.7 Hz, 2H), 4.20-4.08 (m, 4H), 3.44 (d, J = 12.5 Hz, 2H), 2.87 (dd, J = 12.4, 3.8 Hz, 2H), 1.35 (s, 9H), 1.20 (t, J = 7.1 Hz, 3H), 1.14 (d, J = 6.8 Hz, 6H). To a solution of 6a (10.00 g, 28.70 mmol, 1 equiv) dissolved in MeOH was added 1 N NaOH (aq) (57.40 mL, 57.40 mmol, 2 equiv). The mixture was heated at 60 C for 4 h and allowed to cool down to room temperature. The reaction mixture was acidified with 2 NHCl (aq) to adjust PH to 5-6. The resulting precipitate was collected by filtration, washed with water and dried to a constant weight to afford 4-((3R,5S)-4-(tert-butoxycarbonyl)-3,5-dimethylpiperazin-1-yl)benzoic acid (9.79 g, 98%). 1H NMR (300 MHz, DMSO) delta 7.76 (d, J = 8.7 Hz, 2H), 6.97 (d, J = 8.9 Hz, 2H), 4.18-4.05 (m, 2H), 3.75 (d, J = 12.8 Hz, 2H), 2.98 (dd, J = 12.9, 4.3 Hz, 2H), 1.42 (s, 9H), 1.19 (d, J = 6.7 Hz, 6H). The obtained acid (9.79 g, 29.28 mmol, 1 equiv) was dissolved in dry DCM and allowed to cool down to 0 C. DMF (22.57 mL, 292.8 mmol, 10 equiv) and thionyl chloride (4.25 mL, 58.56 mmol, 2 equiv) dissolved in dry DCM were added dropwise to the mixture above. Then the reaction mixture was allowed to warm up to room temperature slowly and left to stir for 2 h. The solvent was removed under reduced pressure at room temperature. Then the residue was redissolved in dry DCM, and was added to the DCM solution of NH4OH (11.28 mL, 292.8 mmol, 10 equiv), which was cooled down to 0 C already. The ice-bath was removed and the reaction mixture was stirred at room temperature for 4 h. The reaction mixture was then extracted with DCM and the organic phase was washed with saturated NaHCO3 (aq) and brine, then dried over anhydrous Na2SO4, filtered and concentrated. The resulting residue was further purified via silica gel chromatography to give 7a as a white solid (4.88 g, 50%). 1H NMR (300 MHz, CDCl3) delta 7.67 (d, J = 8.5 Hz,2H), 6.81 (d, J = 8.7 Hz, 2H), 5.87 (s, 2H), 4.29-4.10 (m, 2H), 3.50 (d, J = 12.3 Hz, 2H), 2.97 (dd, J = 12.3, 3.8 Hz, 2H), 1.43 (s, 9H), 1.25 (d, J = 6.8 Hz, 6H). 14 (8.0 g, 26.69 mmol, 1 equiv), methylamine hydrochloride (2.7 g, 40.04 mmol, 1.5 equiv), EDCl (7.68 g, 40.04 mmol, 1.5 equiv), HOBt (3.61 g, 26.69 mmol, 1.0 equiv) and DIPEA (11.02 mL, 66.72 mmol, 2.5 equiv) were dissolved in dry DCM and the reaction mixture was left to stir at room temperature overnight. The reaction mixture was then extracted with DCM and the organic phase was washed with saturated NaHCO3 (aq) and brine, then dried over anhydrous Na2SO4, filtered and concentrated. The resulting residue was further purified via silica gel chromatography to give 15 as white solid (8.0 g, 95.8%). 1H NMR (300 MHz, CDCl3) delta 8.40 (d, J = 9.2 Hz, 1H), 8.18 (d, J = 5.5 Hz, 1H), 7.81 (d, J = 8.3 Hz, 1H), 7.55 (d, J = 6.8 Hz, 1H), 7.51-7.42 (m, 2H), 7.24 (dd, J = 9.3, 2.3 Hz, 1H), 6.78 (d, J = 7.6 Hz, 2H), 6.05 (d, J = 4.0 Hz, 1H), 3.05 (d, J = 4.9 Hz, 3H). 7a (100 mg, 0.30 mmol, 1 equiv) and 15 (112.56 mg, 0.36 mmol, 1.2 equiv) were dissolved in 10 mL dry dioxane. Then Pd2(dba)3 (27.47 mg, 0.03 mmol, 0.1 equiv), Xantphos (34.72 mg, 0.06 mmol, 0.2 equiv) and Cs2CO3 (195.49 mg, 0.60 mmol, 2 equiv) were added to the mixture above. The reaction mixture was left to stir at 110 C for 5 h under nitrogen atmosphere. The reaction mixture was then extracted with DCM and the organic phase was washed with saturated NaHCO3 (aq) and brine, then dried over anhydrous…, 21655-48-1

As the paragraph descriping shows that 21655-48-1 is playing an increasingly important role.

Reference£º
Article; Wei, Manman; Peng, Xia; Xing, Li; Dai, Yang; Huang, Ruimin; Geng, Meiyu; Zhang, Ao; Ai, Jing; Song, Zilan; European Journal of Medicinal Chemistry; vol. 154; (2018); p. 9 – 28;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics