Heterocyclic Building Blocks-Pyrrolines

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.30364-60-4,Bis(2,5-dioxopyrrolidin-1-yl) succinate,as a common compound, the synthetic route is as follows.

To a solution of N-(2-(2-(2-(2 ammoethoxy)ethoxy)ethoxy)ethyl)- 4-(6,8-dichloro-2-methyl-l,2,3,4-tetrahydroisoquinolin-4 yl)benzenesulfonamide (compound 82) (200 mg, 0 37 mmol) in dry DMF (10 mL) under N2 was added bis(2,5- dioxopyrrolidm-1-yl) succinate (intermediate 177 1) (57 1 mg, 0 18 mmol) and triethylamine (111 mg, 1 10 mmol) The resulting solution was stirred for 4 h at 250C in an oil bath and monitored by LCMS The resulting mixture was concentrated under vacuum and the crude product was purified by Prep-HPLC with acetonitnle water (0 05% CF3COOH)(28%-35%) This resulted m 113 8 mg (45%) of the title compound as a TFA salt 1H-NMR (300MHz, CD3OD, ppm) 7 93-7 91 (d, J-8 IHz, 4H), 7 58- 7 57 (m, 2H), 7 50-748(m, 4H), 6 87 (s, 2H), 4 88-474 (m, 4H), 4 55-4 49 (d, ./=16 2Hz, 2H), 3 94-3 88 (m, 2H), 3 67-3 59 (m, 14H), 3 55-3 45 (m, 12H), 3 35-3 09 (m, 10H), 2 48 (s, 4H) LC-MS (ES, m/z) 588 [(M+2H)/2]+.

30364-60-4, 30364-60-4 Bis(2,5-dioxopyrrolidin-1-yl) succinate 161662, apyrrolidine compound, is more and more widely used in various fields.

Reference£º
Patent; ARDELYX, INC.; CHARMOT, Dominique; JACOBS, Jeffrey, W.; LEADBETTER, Michael, Robert; NAVRE, Marc; CARRERAS, Chris; BELL, Noah; WO2010/78449; (2010); A2;,
Pyrrolidine – Wikipedia
Pyrrolidine | C4H9N – PubChem

119020-01-8, (S)-1-Boc-2-(Aminomethyl)pyrrolidine is a pyrrolidine compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

STEP 1: (S)-2-[(2,2,2-Trifluoro-acetylamino)-methyl]-pyrrolidine-l-carboxylic acid tert-butyl ester (S)-l-Boc-2-(aminomethyl)pyrrolidine (10 g, 50 mmol) was dissolved in dry THF (200 mL) followed by the slow addition (within 5 min) of a solution of ethyl trifluoroacetate (9.75 g, 68 mmol) in THF (50 mL). Stirring at rt was continued for 2 h. The reaction mixture was evaporated to dryness and the residue dried at HV to give (S)-2-[(2,2,2- trifluoro-acetylamino)-methyl] -pyrrolidine- 1-carboxylic acid tert-butyl ester (14.8 g, quant, yield). LC-MS: tR = 0.93 min; [M+H]+ = 297.29.

119020-01-8, 119020-01-8 (S)-1-Boc-2-(Aminomethyl)pyrrolidine 1512533, apyrrolidine compound, is more and more widely used in various fields.

Reference£º
Patent; ACTELION PHARMACEUTICALS LTD; WO2008/139416; (2008); A1;,
Pyrrolidine – Wikipedia
Pyrrolidine | C4H9N – PubChem

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.104706-47-0,(R)-3-Hydroxypyrrolidine hydrochloride,as a common compound, the synthetic route is as follows.

Boc2O (1.02 mL, 4.5 mmol) was added to a solution of (R)-3-hydroxylpyrrolidine hydrochloride (R)-2a¡¤HCl (0.50 g, 4.1 mmol) in THF-satd NaHCO3 (1:1, 20 mL), and the reaction mixture was stirred at rt for 1.5 h. EtOAc was added, and the layers were separated. The aqueous layer was extracted three times with EtOAc. The combined organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to give tert-butyl (R)-3-hydoxypyrrolidine-1-carboxylate, which was used for the following reaction without further purification.The above-described tert-butyl (R)-3-hydoxypyrrolidine-1-carboxylate was dissolved in anhydrous DMF (20 mL), to which was added NaH (55% oil suspension, 0.71 g, 16.2 mmol) at 0 C. The ice-cold reaction mixture was stirred for 30 min, and Me2SO4 (0.77 mL, 8.1 mmol) was then added. The reaction mixture was stirred overnight at 50 C before being quenched with water. Hexane-EtOAc (1:1) was added, the layers were separated, and the aqueous layer was extracted three times with hexane-EtOAc (1:1). The combined organic layer was washed two times with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography (hexane-EtOAc, 2:1) to afford 0.69 g of tert-butyl (R)-3-methoxypyrrolidine-1-carboxylate [85% from (R)-2a¡¤HCl]. A colorless oil, -8.4 (c=0.52, CHCl3). 1H NMR (500 MHz, CDCl3) delta: 1.44 (9H, s), 1.84-2.02 (2H, m), 3.31 (3H, s), 3.34-3.49 (4H, m), 3.91 (1H, brs). 13C NMR (125 MHz, CDCl3) delta: 28.5, 30.0, 31.1, 43.5, 43.9, 50.3, 51.1, 56.5, 79.09, 79.14, 79.9, 154.5, 154.6. IR (CHCl3): 1686, 1416 cm-1. HRMS Calcd for C10H19NNaO3 [(M+Na)+] m/z: 224.1257, found: 224.1248.Under a nitrogen atmosphere, 4 M HCl in EtOAc (1.2 mL) was added to tert-butyl (R)-3-methoxypyrrolidine-1-carboxylate (50 mg, 0.25 mmol) at 0 C. The solution was stirred at rt for 30 min and concentrated in vacuo. The residue was dissolved in MeCN-water (10:1, 2.5 mL). Aqueous NH3 (30% w/w, 35 muL, 0.62 mmol) and 3 (162 mg, 0.62 mmol) were added to the solution at 0 C. The reaction mixture was stirred at rt for 30 min and concentrated in vacuo, and the residue was purified by flash column chromatography (CH2Cl2-MeOH, 15:1?10:1) to give 21 mg of (R)-1d (75%, 99% ee) and 7.1 mg of (R)-4-methoxy-1-pyrroline N-oxide (R)-4d (25%). The optical purity of (R)-1d was determined by Daicel CHIRALPAK AD-3 [hexane-iPrOH, 95:5, 2.0 mL/min; retention times 20.3 (R), 24.6 min (S)].(R)-1d. Pale yellow oil, +113 (c=0.85, CHCl3). 1H NMR (500 MHz, CDCl3) delta: 2.17 (1H, dddd, J=3.5, 5.0, 9.0, 14.5 Hz), 2.48-2.57 (1H, m), 3.35 (3H, s), 3.87 (1H, dddd, J=1.0, 6.5, 9.0, 15.5 Hz), 4.10-4.19 (1H, m), 4.56-4.61 (1H, m), 7.02 (1H, q, J=1.5 Hz). 13C NMR (125 MHz, CDCl3) delta: 27.0, 56.5, 61.4, 80.0, 133.3. IR (CHCl3): 1584, 1269, 1238 cm-1. HRMS Calcd for C5H9NNaO2 [(M+Na)+] m/z: 138.0526, found: 138.0534.(R)-4-Methoxy-1-pyrroline N-oxide [(R)-4d]. A pale yellow oil, -22.5 (c=0.66, CHCl3). 1H NMR (500 MHz, CDCl3) delta: 2.75 (1H, d, J=19.5 Hz), 2.94-3.03 (1H, m), 3.33 (3H, s), 3.94 (1H, d, J=15.0 Hz), 4.08-4.15 (1H, m), 4.19-4.24 (1H, m), 6.84-6.87 (1H, m). 13C NMR (125 MHz, CDCl3) delta: 36.1, 56.5, 67.3, 74.3, 133.1. IR (CHCl3): 1595, 1275, 1238 cm-1. HRMS Calcd for C5H9NNaO2 [(M+Na)+] m/z: 138.0526, found: 138.0533.

104706-47-0, 104706-47-0 (R)-3-Hydroxypyrrolidine hydrochloride 2759336, apyrrolidine compound, is more and more widely used in various fields.

Reference£º
Article; Nemoto, Hiroyuki; Tanimoto, Kouichi; Kanao, Yukiko; Omura, Sohei; Kita, Yasuyuki; Akai, Shuji; Tetrahedron; vol. 68; 36; (2012); p. 7295 – 7301;,
Pyrrolidine – Wikipedia
Pyrrolidine | C4H9N – PubChem

392338-15-7, (R)-tert-Butyl methyl(pyrrolidin-3-yl)carbamate is a pyrrolidine compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

UILK-I-17 (26) (50 mg, 0.13 mmol) was dissolve in DMSO (1 mL)and (R)-tert-Butyl [[pyrrolidin-3-yl]methyl]carbamate (53 mg,0.26 mmol) and DIPEA (100 mL) were added. The reaction washeated to 30 C and stirred for 21 h. To the crude reaction product1mL of 4 N aqueous hydrochloric acid and 5mL of ACN were addedand stirred for 24 h. The ACN was removed by rotatory evaporationand the remaining aqueous layer was frozen and lyophilized. PureUIJD-III-118 (5h) was isolated, 60 mg, 75%. 1H NMR (300 MHz, MeOD) d 9.45 (exchangeable) (bs, 2H), 9.22 (s, 1H), 7.86 (d,J 14.2 Hz, 1H), 7.67 (dd, J 15.0, 7.8 Hz, 3H), 7.49e7.41 (m, 3H),7.37 (d, J 7.2 Hz, 1H), 6.75 (d, J 7.4 Hz, 1H), 5.86 (s, 2H),3.85e3.66 (m, 4H), 3.58e3.46 (m, 1H), 2.59 (m, 3H), 2.31 (m, 2H).19F NMR (282 MHz, MeOD) d 126.52 to 126.83 (m). MS ESIcalculated for (M H) 472.2, found 472.2. Retention time(analytical HPLC) 19.5 min., 392338-15-7

As the paragraph descriping shows that 392338-15-7 is playing an increasingly important role.

Reference£º
Article; Delgado, Justine L.; Lentz, Sarah R.C.; Kulkarni, Chaitanya A.; Chheda, Pratik R.; Held, Hailey A.; Hiasa, Hiroshi; Kerns, Robert J.; European Journal of Medicinal Chemistry; vol. 172; (2019); p. 109 – 130;,
Pyrrolidine – Wikipedia
Pyrrolidine | C4H9N – PubChem

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.50609-01-3,4-(2-(Pyrrolidin-1-yl)ethoxy)aniline,as a common compound, the synthetic route is as follows.

To a round bottom flask was added 6-chloro-4- (S) – (tetrahydrofuran-2-yl) methylaminopyrimidine (0.1 g, 0.468 mmol)And 4- (2- (pyrrolidin-1-yl) ethoxy) aniline (0.088 mL, 0.468 mmol) was dissolved in 2-methoxyethanol (5 mL), a hydrochloric acid solution (4M dioxane solution, 0.1 mL) was added, and the mixture was stirred at 110 DEG C for 24 hours. When the reaction was completed, the solvent was removed by distillation under reduced pressure, and a saturated aqueous solution of sodium hydrogencarbonate was added to the reaction mixture, followed by extraction with dichloromethane. After drying over anhydrous magnesium sulfate, the solvent was removed by distillation under reduced pressure, and the resultant product was purified by column chromatography to obtain the title compound (0.095 g, 53%)., 50609-01-3

As the paragraph descriping shows that 50609-01-3 is playing an increasingly important role.

Reference£º
Patent; Korea Institute of Science and Technology; Lee So-ha; Ryu Gyeong-ho; Kim Tae-yeong; Ho Seu-ni-al-ri-, -e-seu-ram-mo-ha-me-deu; (27 pag.)KR101916773; (2018); B1;,
Pyrrolidine – Wikipedia
Pyrrolidine | C4H9N – PubChem

78648-27-8, 2-(Pyrrolidin-1-yl)benzoic acid is a pyrrolidine compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

General procedure: A mixture of aromatic acid (1 equiv., 0.2 mmol), Co(OAc)2 (0.1 equiv., 0.02mmol), (D, L)-tyrosine (0.15 equiv., 0.03 mmol) were dissolved in CH3CN (5mL), and stirred at 25 oC, then 1 atm of O2 was bubbled into the system for 10h. After the reaction finished, the solvent was evaporated under vacuum and purified by column chromatography to afford the desired product., 78648-27-8

78648-27-8 2-(Pyrrolidin-1-yl)benzoic acid 12707331, apyrrolidine compound, is more and more widely used in various fields.

Reference£º
Article; Shang, Xiao-Jie; Liu, Zhong-Quan; Tetrahedron Letters; vol. 56; 2; (2015); p. 482 – 484;,
Pyrrolidine – Wikipedia
Pyrrolidine | C4H9N – PubChem

119020-01-8, (S)-1-Boc-2-(Aminomethyl)pyrrolidine is a pyrrolidine compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

General procedure: 6-(methoxycarbonyl)pyridine-2-carboxylic acid, 8 was dissolved in dichloromethane, 1 equivalent of corresponding amine (for 11a-c) or R-sulfamide (for 9a-c), EDCI, DMAP was added consecutively. The reaction mixture was stirred at room temperature for 72 h. After that the solution was washed with 10% HCl solution and distilled water, the organic layer was dried over anhydrous sodium sulphate and concentrated under reduced pressure to provide an orange red oil, the crude product was purified by flash chromatography through deactivated silica, eluting with 19:1 dichloromethane-methanol mixture. After evaporation of the solvents, the title product was obtained as white solid.

119020-01-8, As the paragraph descriping shows that 119020-01-8 is playing an increasingly important role.

Reference£º
Article; Wang, Lei; Tang, Ruiren; Yang, Hua; Journal of the Korean Chemical Society; vol. 57; 5; (2013); p. 591 – 598;,
Pyrrolidine – Wikipedia
Pyrrolidine | C4H9N – PubChem