Name: 40172-95-0|1-(2-Furoyl)piperazine|98%
Brand: Ambeed
SKU: A497413
Price: 14.0 USD
Availability: InStock
Rating: 95 (35 reviews)

1
[ 5878-61-5 ]
[ 40172-95-0 ]
7-<3-<4-(2-Furoyl)-1-piperazinyl>-ethyl>-theophyllin [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	at 100℃; for 3h;

Reference： [1]Thiele; Jahn; Geissmann; Zirngibl [Arzneimittel-Forschung/Drug Research, 1984, vol. 34, # 1, p. 1 - 4]

2
[ 13645-74-4 ]
[ 40172-95-0 ]
[ 102622-78-6 ]

Yield	Reaction Conditions	Operation in experiment
61%	With potassium carbonate In N,N-dimethyl-formamide for 6h; Heating;

Reference： [1]Gomez-Gil; Gomez-Parra; Sanchez; Torres [Archiv der Pharmazie, 1986, vol. 319, # 1, p. 60 - 64]

3
[ 36256-45-8 ]
[ 40172-95-0 ]
methyl 5-<2-<4-(2-furanylcarbonyl)-1-piperazinyl>acetyl>-2-hydroxybenzoate [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1981,vol. 24,p. 327 - 336

4
[ 83548-58-7 ]
[ 40172-95-0 ]
[ 107640-22-2 ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol for 5h; Heating;

Reference： [1]Boehm, R.; Pech, R.; Haubold, Gudrun; Hannig, E. [Pharmazie, 1986, vol. 41, # 1, p. 23 - 25]

5
[ 111218-89-4 ]
[ 40172-95-0 ]
[ 111218-73-6 ]

Reference： [1]Pharmaceutical Chemistry Journal,1987,vol. 21,p. 478 - 483
Khimiko-Farmatsevticheskii Zhurnal,1987,vol. 21,p. 802 - 807

6
[ 40172-95-0 ]
[ 42518-42-3 ]
[ 107640-27-7 ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol Heating;

Reference： [1]Boehm, R.; Pech, R.; Haubold, Gudrun; Hannig, E. [Pharmazie, 1986, vol. 41, # 1, p. 23 - 25]

7
[ 110-85-0 ]
[ 614-99-3 ]
[ 31350-27-3 ]
[ 40172-95-0 ]

Yield	Reaction Conditions	Operation in experiment
1: 6% 2: 89%	at 110℃; for 3h;

Reference： [1]Chou, Wen-Chih; Tan, Chang-Wei; Chen, Shyh-Fong; Ku, Hao [Journal of Organic Chemistry, 1998, vol. 63, # 26, p. 10015 - 10017]

8
[ 110-85-0 ]
[ 88-14-2 ]
[ 31350-27-3 ]
[ 40172-95-0 ]

Yield	Reaction Conditions	Operation in experiment
83%	With 1,1,1,3,3,3-hexamethyl-disilazane at 110℃; for 8h; Yields of byproduct given;

Reference： [1]Chou, Wen-Chih; Chou, Ming-Chen; Lu, Yann-Yu; Chen, Shyh-Fong [Tetrahedron Letters, 1999, vol. 40, # 17, p. 3419 - 3422]

9
[ 59870-43-8 ]
[ 40172-95-0 ]
4-amino-2-[4-(2-furoyl)piperazin-1-yl]quinazoline hydrochloride [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2005,vol. 13,p. 3681 - 3689

10
[ 94644-47-0 ]
[ 40172-95-0 ]
[ 94644-50-5 ]

Yield	Reaction Conditions	Operation in experiment
	In i-Amyl alcohol at 150℃; for 18h;

Reference： [1]Zunszain, Patricia A.; Federico, Cesare; Sechi, Mario; Al-Damluji, Saad; Ganellin, C. Robin [Bioorganic and Medicinal Chemistry, 2005, vol. 13, # 11, p. 3681 - 3689]

11
[ 75-15-0 ]
[ 39186-58-8 ]
[ 40172-95-0 ]
4-(furan-2-carbonyl)-piperazine-1-carbodithioic acid 3-cyano-3,3-diphenyl-propyl ester [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 4214 - 4219

12
[ 532-55-8 ]
[ 40172-95-0 ]
[ 937605-10-2 ]

Yield	Reaction Conditions	Operation in experiment
78.57%	In toluene at 0 - 20℃; for 24h;	369 A 250 ml, 2-necked round bottom flask was charged with furan-2-yl-piperazin-l- yl-methanone (0.056 mole) and 200 ml toluene and cooled to 0-50C. Then benzoyl isothiocyanate was added drop wise at 5°C. The reaction mixture was stirred for 24 hr. at room temperature. The white precipitate was filtered out and washed with cold toluene. The precipitate was again re-crystallized with ethyl acetate. Mobile phase: Toluene:Acetonitrile 7:3, Rf: 0.73. LC MS (M+l): 344. C17H17N3O3S. Yield: 78.57 %. IHNMR (DMSO-d6, δ, ppm): 3.26-4.25 (m, 8H of piperazine and IH of NH), 6.49-6.51 (m, IH of furan), 7.04-7.08 (m, IH of furan), 7.29-7.61 (m, 3H of phenyl and IH of furan), 7.86-7.88 (m, 2H of phenyl). Elemental Analysis: Observed; C, 59.46; H, 4.99; N, 12.24. Calculated; C, 59.76; H, 5.17; N, 12.70.

Reference： [1]Current Patent Assignee: B V PATEL PHARMACEUTICAL EDUCATION RESEARCH DEV; LOUISIANA STATE UNIVERSITY AND AGRICULTURAL AND MECHANICAL COLLEGE; PATEL PHARMACEUTICAL EDUCATION RES DEV PERD CT - WO2007/118149, 2007, A2 Location in patent: Page/Page column 99

13
[ 22536-63-6 ]
[ 40172-95-0 ]
2-[4-(2-furylcarbonyl)-1-piperazinyl]-4-methoxy-pyrimidine [ No CAS ]

Reference： [1]Patent: US6372746,2002,B1 .Location in patent: Example 1

14
[ 868610-50-8 ]
[ 40172-95-0 ]
N-2-adamantyl-2-[4-(2-furoyl)piperazin-1-yl]propanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56%	With sodium carbonate In DMF (N,N-dimethyl-formamide) at 70℃;	4 EXAMPLE 4 N-2-Adamantyl-2-[4-(2-furoyl)piperazin-1-yl]propanamide A solution of 2-chloro-N-adamantan-2-yl-propionamide (48 mg, 0.2 mmoles), from Example 2A, in dimethylformamide (DMF) (0.5 mL) and 2N aqueous sodium carbonate (0.1 mL) was treated with furan-2-yl-piperazin-1-yl-methanone. The solution was stirred overnight at 70° C. and DMF was removed under reduced pressure. The residue was partitioned between water and ethyl acetate. The organic layer was washed twice with water, dried over MgSO4 and filtered. The filtrate was concentrated under reduced pressure and purified by HPLC to provide the title compound as a white solid (43 mg, 56%). 1H NMR (300 MHz, CDCl3) δ. 7.67 (d, J=8.5 Hz, 1H), 7.48 (s, 1H), 7.01 (d, J=3.4 Hz, 1H), 6.48 (q, J=1.5,3.4 Hz, 1H), 4.05 (d, J=8.7 Hz, 1H), 3.84 (s, 4H), 3.12(q, J=7.2 Hz, 1H), 2.63 (m, 4H), 1.9-1.86 (m, 8H), 1.76-1.68 (m, 6H), 1.26 (d, 7.2, 3H),;MS (APCI+) m/z 386 (M+H)+.
56%	With sodium carbonate In DMF (N,N-dimethyl-formamide); water at 70℃;	4 example 4; N-2-adamantyl-2-[4-(2-furoyl)piperazin-1-yl]propanamide A solution of 2-chloro-N-adamantan-2-yl-propionamide (48 mg, 0.2 mmoles), from Example 2A, in dimethylformamide (DMF) (0.5 mL) and 2N aqueous sodium carbonate (0.1 mL) was treated with furan-2-yl-piperazin-1-yl-methanone. The solution was stirred overnight at 70° C. and DMF was removed under reduced pressure. The residue was partitioned between water and ethyl acetate. The organic layer was washed twice with water, dried over MgSO4 and filtered. The filtrate was concentrated under reduced pressure and purified by HPLC to provide the title compound as a white solid (43 mg, 56%). 1H NMR (300 MHz, CDCl3) δ 7.67 (d, J=8.5 Hz, 1H), 7.48 (s, 1H), 7.01 (d, J=3.4 Hz, 1H), 6.48 (q, J=1.5, 3.4 Hz, 1H), 4.05 (d, J=8.7 Hz, 1H), 3.84 (s, 4H), 3.12(q, J=7.2 Hz, 1H), 2.63 (m, 4H), 1.9-1.86 (m, 8H), 1.76-1.68 (m, 6H), 1.26 (d, 7.2, 3H); MS (APCI+) m/z 386 (M+H)+.

Reference： [1]Current Patent Assignee: ABBOTT LABORATORIES INC - US2005/261302, 2005, A1 Location in patent: Page/Page column 11
[2]Current Patent Assignee: ABBOTT LABORATORIES INC - US2005/245532, 2005, A1 Location in patent: Page/Page column 19

15
[ 83178-89-6 ]
[ 40172-95-0 ]
7-[4-(furan-2-carbonyl)piperazin-1-yl]-5-oxo-4,5-dihydro-thieno[3,2-b]pyridine-6-carboxylic acid ethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
99%	With 1,4-diaza-bicyclo[2.2.2]octane In ISOPROPYLAMIDE at 120℃; for 2 - 4h;	Synthesis of 7-[4-rfuran-2-carbonylVpiperazin-l-yl]-5-oxo-4,5-dihydro-thieno[3.2- bipyridine-6-carboxylic acid ethyl ester (10)[0147] 1,4-Diazabicyclo[2.2.2]octane (3.08 g, 27.45 mmol) was added to a solution of 7-chloro-5-oxo-4,5-dihydro-thieno[3,2-έ]pyridine-6-carboxylic acid ethyl ester (4) (3.54 mg, 13.77 mmol) and l-(2-furayl)-piρerazine (3.22 g, 17.87 mmol) in dry DMA. The solution was heated at 12O0C for 2 h. The solution was cooled and poured into ice water. The solids formed were filtered, washed by water, and dried to yield 7-[4-(furan-2- carbonyl)-piperazin-l -yl]-5-oxo-4,5-dihydro-thieno[3,2-έ]pyridine-6-carboxylic acid ethyl ester as brown solid. Yield 5.86 g (99 %). 1H-NMR (DMSO-d6) δ 1.26 (t, J = 7.2 Hz, 3H), 3.34 (m, 4H), 3.80 (br, 4H), 4.23 (q, J= 7.2 Hz, 2H), 6.65 (m, IH), 6.97 (d, J= 5.6 Hz, IH), 7.06 (dd, J= 0.8, 3.2 Hz, IH), 7.87 (dd, J= 0.8, 2.0 Hz, IH), 7.96 (d, J= 5.2 Hz, IH), 12.09 (br, IH); EIMS m/z 402 (M+l).

Reference： [1]Current Patent Assignee: OTSUKA HOLDINGS CO LTD - WO2006/102191, 2006, A1 Location in patent: Page/Page column 51; 78

16
[ 5878-61-5 ]
[ 40172-95-0 ]
7-[3-[4-(2-furoyl)-1-piperazinyl]-2-hydroxypropyl]-theophylline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride In dichloromethane	5 7-[3-[4-(2-furoyl)-1-piperazinyl]-2-hydroxypropyl]-theophylline (Sgd 269-76) STR10 EXAMPLE 5 7-[3-[4-(2-furoyl)-1-piperazinyl]-2-hydroxypropyl]-theophylline (Sgd 269-76) STR10 A mixture of 2 g (8.26 mMol) 7-(2-chloro-ethyl)-theophylline and 3.78 g (21 mMol) N-furoyl piperazine is melted at 100° C. upon an oil bath and held for 3 hours at that temperature. After cooling, the solidified mass is dissolved in methylene chloride. The solution is extracted with water and subsequently shaken twice with 10% hydrochloric acid. The combined aqueous phases are made alkaline with sodium hydroxide solution and again extracted with methylene chloride and the resulting extract is dried over MgSO4 and concentrated. The residue is washed twice with water at 60° C. and again dissolved in methylene chloride. The solution is dried over MgSO4, relieved of solvent by evaporation, and recrystallized in ethyl acetate, yielding the pure product having a melting point of 142°-144° C. C18 H22 N6 O4: 386.41: calc. C 55.95; H 5.74; N 21.75; fd. C 55.86; H 5.84; N 21.71

Reference： [1]Current Patent Assignee: SIEGFRIED CH 4800 ZOFINGEN - US4603204, 1986, A

17
[ 100986-89-8 ]
[ 40172-95-0 ]
C₂₂H₂₀FN₃O₆ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 1229 - 1236

18
[ 112811-72-0 ]
[ 40172-95-0 ]
[ 1018937-37-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2008,vol. 16,p. 2558 - 2569

19
tert-butyl 4-(furan-2-carbonyl)piperazine-1-carboxylate [ No CAS ]
[ 40172-95-0 ]

Yield	Reaction Conditions	Operation in experiment
	Acidic conditions;
	With hydrogenchloride; water In dichloromethane at 20℃;
	With hydrogenchloride In methanol; diethyl ether

	With trifluoroacetic acid In dichloromethane at 25℃;
	With trifluoroacetic acid In dichloromethane at 20℃; for 1h;	4.2.2. Synthesis of furan-2-yl(piperazin-1-yl)methanone (20) N-Boc protected piperazine 19 (10 mM) was dissolved in amixed solution of dichloromethane (20 mL) and TFA (0.5 mL), which was stirred at room temperature for 1 h. After completion ofthe reaction, the mixture was concentrated in vacuo. The residuewas purified by silica gel column chromatography to give 20 aswhite solid. M.p. 139-140 °C, which is full agreement with theliterature [25].
	With trifluoroacetic acid In dichloromethane at 20℃; for 12h;
	With hydrogenchloride; sodium hydroxide In dichloromethane
	With trifluoroacetic acid at 0 - 20℃; for 0.0833333h; Microwave irradiation;	General procedure: In the second step, TFA (8.56mmol) was added at 0° C and irradiated in a microwave oven 250W for 5min. Upon complete N-Boc-deprotection, the reaction mixture was cooled into ice and diluted with DCM (2mL) and 2M K2CO3 solution (2mL). The mixture was extracted with DCM (3×5mL), the combined organic layers were dried over Na2SO4, filtered, and concentrated under vacuo. The residue was treated with Et2O giving the desired known intermediates 9a-m. The chemical properties, as well as the structural assignments, for the resulting compounds 9a-m were in good agreement with the literature 39-44. The registered CAS numbers have been already assigned as reported in Supplementary Material (Table S2).
	With trifluoroacetic acid In dichloromethane at 0 - 20℃; for 3h; Inert atmosphere;

Reference： [1]Location in patent: scheme or table Wu, Yulin; Kuntz, Judith D.; Carpenter, Andrew J.; Fang, Jing; Sauls, Howard R.; Gomez, Daniel J.; Ammala, Carina; Xu, Yun; Hart, Shane; Tadepalli, Sarva [Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 8, p. 2577 - 2581]
[2]Location in patent: scheme or table Zulli, Allison L.; Aimone, Lisa D.; Mathiasen, Joanne R.; Gruner, John A.; Raddatz, Rita; Bacon, Edward R.; Hudkins, Robert L. [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 8, p. 2807 - 2810]
[3]Location in patent: scheme or table Kim, Heung Jae; Kwak, Woo Young; Min, Jong Pil; Sung, Si Young; Kim, Ha Dong; Kim, Mi Kyung; Kim, Hae Sun; Park, Kyung Jin; Son, Moon Ho; Kim, Soon Hoe; Lee, Bong Jin [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 17, p. 5545 - 5549]
[4]Wang, Ling-Xiao; Zhou, Xin-Bo; Xiao, Meng-Liang; Jiang, Ning; Liu, Feng; Zhou, Wen-Xia; Wang, Xiao-Kui; Zheng, Zhi-Bing; Li, Song [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 16, p. 3739 - 3743]
[5]Zhou, Yuan; Tao, Pingde; Wang, Meigui; Xu, Peng; Lu, Wei; Lei, Pan; You, Qiuyun [European Journal of Medicinal Chemistry, 2019, vol. 177, p. 105 - 115]
[6]Qin, Qiaohua; Wu, Tianxiao; Yin, Wenbo; Sun, Yixiang; Zhang, Xiangyu; Wang, Ruifeng; Guo, Jing; Zhao, Dongmei; Cheng, Maosheng [Archiv der Pharmazie, 2020, vol. 353, # 10]
[7]Chen, Miaojia; Huang, Honglin; Wu, Kaiyue; Liu, Yunfan; Jiang, Lizhi; Li, Yang; Tang, Guotao; Peng, Junmei; Cao, Xuan [Drug Development Research, 2022, vol. 83, # 1, p. 55 - 63]
[8]Mancuso, Francesca; Di Fiore, Anna; De Luca, Laura; Angeli, Andrea; De Simone, Giuseppina; Supuran, Claudiu T.; Gitto, Rosaria [Bioorganic and Medicinal Chemistry, 2021, vol. 44]
[9]Long, Huan; Hu, Xiaolong; Wang, Baolin; Wang, Quan; Wang, Rong; Liu, Shumeng; Xiong, Fei; Jiang, Zhenzhou; Zhang, Xiao-Qi; Ye, Wen-Cai; Wang, Hao [Journal of Medicinal Chemistry, 2021, vol. 64, # 16, p. 12089 - 12108]

20
[ 22312-81-8 ]
[ 40172-95-0 ]
[ 885920-20-7 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 2-chloromethyl-3-(2-methoxyphenyl)-3H-quinazolin-4-one With potassium carbonate In ethanol; acetonitrile at 150℃; for 0.0833333h; Microwave irradiation; Stage #2: N-(furan-2-carbonyl)piperazine In ethanol; acetonitrile at 150℃; for 0.166667h; Microwave irradiation;	General procedure for synthesis of compounds 1, 7-36 General procedure: To a solution of anthranilic acid 2 (0.40 mmol) and Hünig's base (0.60 mmol) in anhydrous acetonitrile (1.0 mL) was added a solution of chloroacetyl chloride (0.44 mmol) in acetonitrile (0.5 mL) at 4 °C. After stirring at r.t. for 2 h, POCl3 (112 µL, 1.2 mmol, 3.0 equiv) was added followed by a solution of aniline (0.60 mmol) in acetonitrile (0.50 mL). The reaction mixture was heated in a microwave reactor at 150 °C for 15 min, cooled to r.t. and treated with K2CO3 (300 mg) and EtOH (1.0 mL). The mixture was heated at 150 °C for 5 min in the microwave reactor. To this mixture, a solution of piperazine, morpholine, or piperidine (0.44 mmol) in EtOH (0.5 mL) was added. The mixture was heated in the microwave reactor for 10 min at 150 °C and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by preparative HPLC.

Reference： [1]Huang, Wenwei; Huang, Ruili; Attene-Ramos, Matias S.; Sakamuru, Srilatha; Englund, Erika E.; Inglese, James; Austin, Christopher P.; Xia, Menghang [Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 18, p. 5239 - 5243]

21
[ 1074-12-0 ]
[ 40172-95-0 ]
[ 1389334-25-1 ]

Yield	Reaction Conditions	Operation in experiment
62%	With selenium(IV) oxide In 1,4-dioxane; dichloromethane at 100℃; for 0.333333h; Microwave irradiation;	General procedure for preparation of aryl α-ketoamide 3. General procedure: To a mixture of phenylglyoxal monohydrate 1a (152 mg, 1.0 mmol), 1-phenylpiperazine 2a (251 mg, 1.5 mmol) in DCM (3 mL) and 1,4-dioxane (1 mL), selenium dioxide (111 mg, 1.0 mmol) was added to the solution. The resulting mixture was heated at 100 °C for 20 min under microwave irradiation. The solution was diluted with DCM (5 mL), washed with NaHCO3(sat) (10 mL) and brine (10 mL). The organic layer was dried over MgSO4, evaporated in vacuo to obtain the crude product 3a. The crude residue 3a was transferred to a pre-packed column (2.5 g) and was purified using the ISCOTM purification system (12 g silica gel flash column; eluent, ethyl acetate: hexane = 0 to 40%). The fractions containing the product were collected and the solvent was evaporated under reduced pressure and dried under high-vacuum system to afford 3a (176 mg, 60%).

Reference： [1]Location in patent: experimental part Shaw, Arthur Y.; Denning, Christine R.; Hulme, Christopher [Tetrahedron Letters, 2012, vol. 53, # 32, p. 4151 - 4153]

22
[ 328-26-7 ]
[ 40172-95-0 ]
[ 899713-86-1 ]

Reference： [1]Journal of the American Chemical Society,2012,vol. 134,p. 10345 - 10348

23
[ 50-00-0 ]
[ 96107-95-8 ]
[ 40172-95-0 ]
5,11,17,23,29,35-hexa[(piperazine-1-yl)(furan-2-yl)methanone]methylene-37,38,39,40,41,42-hexahydroxy-calix[6]arene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
59%	With acetic acid In tetrahydrofuran at 20℃; for 24h;

Reference： [1]Sayin, Serkan; Yilmaz, Mustafa [RSC Advances, 2014, vol. 4, # 5, p. 2219 - 2225]

24
[ 108-22-5 ]
[ 40172-95-0 ]
[ 768292-07-5 ]

Yield	Reaction Conditions	Operation in experiment
100%	In neat (no solvent) at 20℃; for 1h; Green chemistry;	PREPARATION OF THE ACETAMIDES General procedure: In a round-bottomed flask, a mixture of a suitable amine (1 eq.) and the appropriate enol ester (isopropenyl acetate or vinyl acetate) (3 eq.) was stirred at room temperature for the indicated time. The evolution of the reaction was monitored by TLC. After complete consumption of the amine, the crude reaction mixture was concentrated in vacuo and the amide was directly obtained pure. If it was not the case, a simple acidic work-up was required to purify the obtained acetamide.

Reference： [1]Alalla, Affef; Merabet-Khelassi, Mounia; Aribi-Zouioueche, Louisa; Riant, Olivier [Synthetic Communications, 2014, vol. 44, # 16, p. 2364 - 2376]

25
[ 350-46-9 ]
[ 40172-95-0 ]
[ 262375-97-3 ]

Yield	Reaction Conditions	Operation in experiment
78%	In N,N-dimethyl-formamide at 20℃;	1.1 General procedure for the synthesis of 1-(4-Nitro phenyl)-4-aryl/alkyl piperazine (1-18) General procedure: Synthesisof compounds (1-18) has been carriedout according to the procedure previously standardized in our laboratory with severalmodifications.1 Briefly, an equimolar mixture (0.01 mol) of 1-fluoro-4-nitrobenzeneand respective alkyl /heteroaryl/ aryl substituted piperazinein 30 ml of dried dimethylformamide (DMF)/ dried dimethylsulfoxide (DMSO) was stirredat room temperature for 4-8 h. Reaction completion was monitored by TLC andreaction mixture diluted with water (40 ml). Product has been extracted withchloroform and dried over anhydrous sodium sulphate. The chloroform was thenevaporated under reduced pressure to give pure 1-(4-nitro phenyl)-4-substituedpiperazine derivatives (1-18).
53%	In acetonitrile for 2h; Reflux;	4.2.1. General procedure to obtain nitrocompounds 7a-c General procedure: 1 mmol of 1-substituted piperazine was dissolved in 5 mL of CH3CN, then 2.5 mmol of 1-fluoro-4-nitrobenzene were added. The mixture was refluxed for 2 h, then the solvent was removed and the crude residue was purified by silica gel column chromatography, using dichloromethane/methanol (9:1) as eluent.
	In dimethyl sulfoxide; N,N-dimethyl-formamide at 20℃;

Reference： [1]Kumari, Shikha; Mishra, Chandra Bhushan; Tiwari, Manisha [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 5, p. 1092 - 1099]
[2]Moraca, Francesca; De Vita, Daniela; Pandolfi, Fabiana; Di Santo, Roberto; Costi, Roberta; Cirilli, Roberto; D'Auria, Felicia Diodata; Panella, Simona; Palamara, Anna Teresa; Simonetti, Giovanna; Botta, Maurizio; Scipione, Luigi [European Journal of Medicinal Chemistry, 2014, vol. 83, p. 665 - 673]
[3]Mishra, Chandra Bhushan; Kumari, Shikha; Tiwari, Manisha [Archives of Pharmacal Research, 2016, vol. 39, # 5, p. 603 - 617]

26
[ 1620488-80-3 ]
[ 40172-95-0 ]
[ 1620488-71-2 ]

Yield	Reaction Conditions	Operation in experiment
78%	With triethylamine In acetonitrile at 20℃; for 12h;	4.2.4. General procedure for the synthesis of (1H-imidazol-1yl)-ethyl carbamates 5a-f, 6a-c General procedure: 2-(1H-imidazol-1-yl)-1-phenylethanol (1mmol) was suspended in 5 mL of anhydrous CH3CN, then triphosgene (0.5 mmol) was added. After 12 h at r.t. the reaction mixture was treated with Et2O obtaining a white precipitate, subsequently the solvent was removed and the precipitate was suspended in anhydrous CH3CN and added with TEA (2.0 mmol) and 0.8 mmol of the selected amine. After 12 h at r.t., the solvent was removed under reduced pressure and the residue was treated with CH2Cl2 and extracted with saturated aqueous Na2CO3. The organic layer was dried over Na2SO4 and evaporated under vacuum to give a crude residue which was purified by silica gel column chromatography using CH2Cl2/MeOH (8:2) as eluent.

Reference： [1]Moraca, Francesca; De Vita, Daniela; Pandolfi, Fabiana; Di Santo, Roberto; Costi, Roberta; Cirilli, Roberto; D'Auria, Felicia Diodata; Panella, Simona; Palamara, Anna Teresa; Simonetti, Giovanna; Botta, Maurizio; Scipione, Luigi [European Journal of Medicinal Chemistry, 2014, vol. 83, p. 665 - 673]

27
[ 1620488-81-4 ]
[ 40172-95-0 ]
[ 1620488-62-1 ]

Yield	Reaction Conditions	Operation in experiment
60%	With triethylamine In acetonitrile at 20℃; for 12h;	4.2.4. General procedure for the synthesis of (1H-imidazol-1yl)-ethyl carbamates 5a-f, 6a-c General procedure: 2-(1H-imidazol-1-yl)-1-phenylethanol (1mmol) was suspended in 5 mL of anhydrous CH3CN, then triphosgene (0.5 mmol) was added. After 12 h at r.t. the reaction mixture was treated with Et2O obtaining a white precipitate, subsequently the solvent was removed and the precipitate was suspended in anhydrous CH3CN and added with TEA (2.0 mmol) and 0.8 mmol of the selected amine. After 12 h at r.t., the solvent was removed under reduced pressure and the residue was treated with CH2Cl2 and extracted with saturated aqueous Na2CO3. The organic layer was dried over Na2SO4 and evaporated under vacuum to give a crude residue which was purified by silica gel column chromatography using CH2Cl2/MeOH (8:2) as eluent.
	With triethylamine at 20℃;

Reference： [1]Moraca, Francesca; De Vita, Daniela; Pandolfi, Fabiana; Di Santo, Roberto; Costi, Roberta; Cirilli, Roberto; D'Auria, Felicia Diodata; Panella, Simona; Palamara, Anna Teresa; Simonetti, Giovanna; Botta, Maurizio; Scipione, Luigi [European Journal of Medicinal Chemistry, 2014, vol. 83, p. 665 - 673]
[2]De Vita, Daniela; Moraca, Francesca; Zamperini, Claudio; Pandolfi, Fabiana; Di Santo, Roberto; Matheeussen, An; Maes, Louis; Tortorella, Silvano; Scipione, Luigi [European Journal of Medicinal Chemistry, 2016, vol. 113, p. 28 - 33]

28
C₁₈H₁₅ClN₂O₂S [ No CAS ]
[ 40172-95-0 ]
2-[4-(2-furoyl)piperazin-1-yl]-N-[4-(2-(4-methoxyphenyl)thiazol-4-yl)phenyl]acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With potassium carbonate In acetone for 2h; Reflux;	2.2. General Procedure for the Synthesis of 2-(4-Arylpiperazine-1-yl)-N-[4-(2-(4-substituted phenyl)thiazol-4-yl)phenyl]acetamide Derivatives (6a-6p) General procedure: A mixture of compound 2-chloro-N-[4-(2-(4-substituted phenyl)-4-thiazolyl)phenyl]acetamide 5 (1.5 mmol), appropriate piperazine derivative (1.8 mmol) and K2CO3 (1.5 mmol) in acetone, was refluxed for 2 h. After cooling, the solvent was evaporated until dryness. The residue was treated with 25 mL of water. Solidified product was filtered, washed with water, and recrystallized from ethanol to give the compounds 6a-6p.

Reference： [1]Yurttaş, Leyla; Özkay, Yusuf; Karaca Gençer, Hülya; Acar, Ulviye [Journal of Chemistry, 2015, vol. 2015]

29
C₁₇H₁₂Cl₂N₂OS [ No CAS ]
[ 40172-95-0 ]
2-[4-(2-furoyl)piperazin-1-yl]-N-[4-(2-(4-chlorophenyl)thiazol-4-yl)phenyl]acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With potassium carbonate In acetone for 2h; Reflux;	2.2. General Procedure for the Synthesis of 2-(4-Arylpiperazine-1-yl)-N-[4-(2-(4-substituted phenyl)thiazol-4-yl)phenyl]acetamide Derivatives (6a-6p) General procedure: A mixture of compound 2-chloro-N-[4-(2-(4-substituted phenyl)-4-thiazolyl)phenyl]acetamide 5 (1.5 mmol), appropriate piperazine derivative (1.8 mmol) and K2CO3 (1.5 mmol) in acetone, was refluxed for 2 h. After cooling, the solvent was evaporated until dryness. The residue was treated with 25 mL of water. Solidified product was filtered, washed with water, and recrystallized from ethanol to give the compounds 6a-6p.

Reference： [1]Yurttaş, Leyla; Özkay, Yusuf; Karaca Gençer, Hülya; Acar, Ulviye [Journal of Chemistry, 2015, vol. 2015]

30
C₁₇H₁₂ClFN₂OS [ No CAS ]
[ 40172-95-0 ]
2-[4-(2-furoyl)piperazin-1-yl]-N-[4-(2-(4-fluorophenyl)thiazol-4-yl)phenyl]acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	With potassium carbonate In acetone for 2h; Reflux;	2.2. General Procedure for the Synthesis of 2-(4-Arylpiperazine-1-yl)-N-[4-(2-(4-substituted phenyl)thiazol-4-yl)phenyl]acetamide Derivatives (6a-6p) General procedure: A mixture of compound 2-chloro-N-[4-(2-(4-substituted phenyl)-4-thiazolyl)phenyl]acetamide 5 (1.5 mmol), appropriate piperazine derivative (1.8 mmol) and K2CO3 (1.5 mmol) in acetone, was refluxed for 2 h. After cooling, the solvent was evaporated until dryness. The residue was treated with 25 mL of water. Solidified product was filtered, washed with water, and recrystallized from ethanol to give the compounds 6a-6p.

Reference： [1]Yurttaş, Leyla; Özkay, Yusuf; Karaca Gençer, Hülya; Acar, Ulviye [Journal of Chemistry, 2015, vol. 2015]

31
[ 78754-94-6 ]
[ 40172-95-0 ]
3-{2-[4-(2-furoyl)piperazin-1-yl]-2-oxoethyl}quinazoline-2,4(1H,3H)-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	With dicyclohexyl-carbodiimide In dichloromethane at 0 - 20℃; Inert atmosphere;	General procedure for compounds 7-34. General procedure: A mixture of compound 4-6 (1 mmol) in 5 ml of dry DCM and piperazine derivative (1 mmol) was cooled in an ice bath. Then, 1.1 mmol of DCC in 5 ml of dry dichloromethane was added tothe mixture under nitrogen (N2) atmosphere. Reaction mixture was stirred for 0.5 hour in an ice bath, then 10-16 hours at room temperature. Reaction solvent was evaporated to the dryness. Residue was dissolved in hot acetonitrile then cooled in refrigerator to get the DCU precipitated. White crystalline DCU was removed by filtration. Liquid part was evaporated and crystallized from appropriate solvents to give compound 7-34
84%	With dicyclohexyl-carbodiimide In dichloromethane at 0 - 20℃; Inert atmosphere;	General procedure for compounds 7-34. General procedure: A mixture of compound 4-6 (1 mmol) in 5 ml of dry DCM and piperazine derivative (1 mmol) was cooled in an ice bath. Then, 1.1 mmol of DCC in 5 ml of dry dichloromethane was added to the mixture under nitrogen (N2) atmosphere. Reaction mixture was stirred for 0.5 hour in an ice bath, then 10-16 hours at room temperature. Reaction solvent was evaporated to the dryness. Residue was dissolved in hot acetonitrile then cooled in refrigerator to get the DCU precipitated. White crystalline DCU was removed by filtration. Liquid part was evaporated and crystallized from appropriate solvents to give compound 7-34

Reference： [1]Akgun, Hulya; Yilmaz, Demet Us; Atalay, Rengul Cetin; Gozen, Damla [Letters in drug design and discovery, 2016, vol. 13, # 1, p. 64 - 76]
[2]Akgun, Hulya; Yilmaz, Demet Us; Atalay, Rengul Cetin; Gozen, Damla [Letters in drug design and discovery, 2016, vol. 13, # 1, p. 64 - 76]

32
[ 615-20-3 ]
[ 40172-95-0 ]
(4-(benzo[d]thiazol-2-yl)piperazin-1-yl)(furan-2-yl)methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	In water at 20℃; for 2h; Green chemistry;	General experimental procedure for the amination of 2-chlorobenzothiazole General procedure: The reaction was carried out in a 25 mL round bottom flask equipped with magnetic stir bar charged with 2-chlorobenzothiazole (1 mmol), aminating agent (2.0 equiv), and water (2 mL). The resulting reaction mixture was stirred at room temperature for 30 min to 5 h (varies with nature of the amine). The reaction progress was monitored by TLC. After the reaction, it was worked up with ethyl acetate. Crude product was purified by column chromatography (for piperazine derivatives column is not required). The identity and purity of the product was confirmed by 1H NMR, 13C NMR, and ESI-MS.

Reference： [1]Uday Kumar; Reddy, K. Harsha Vardhan; Anil Kumar; Satish; Reddy, V. Prakash; Nageswar [Tetrahedron Letters, 2016, vol. 57, # 6, p. 637 - 640]

33
[ 615-18-9 ]
[ 40172-95-0 ]
(4-(benzo[d]oxazol-2-yl)piperazin-1-yl)(furan-2-yl)methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%	In water at 20℃; for 2h; Green chemistry;	General experimental procedure for the amination of 2-chlorobenzothiazole General procedure: The reaction was carried out in a 25 mL round bottom flask equipped with magnetic stir bar charged with 2-chlorobenzothiazole (1 mmol), aminating agent (2.0 equiv), and water (2 mL). The resulting reaction mixture was stirred at room temperature for 30 min to 5 h (varies with nature of the amine). The reaction progress was monitored by TLC. After the reaction, it was worked up with ethyl acetate. Crude product was purified by column chromatography (for piperazine derivatives column is not required). The identity and purity of the product was confirmed by 1H NMR, 13C NMR, and ESI-MS.

Reference： [1]Uday Kumar; Reddy, K. Harsha Vardhan; Anil Kumar; Satish; Reddy, V. Prakash; Nageswar [Tetrahedron Letters, 2016, vol. 57, # 6, p. 637 - 640]

34
N-(3-chloropropyl)isonicotinamide [ No CAS ]
[ 40172-95-0 ]
N-(3-(4-(furoyl)piperazin-1-yl)propyl)isonicotinamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%	Stage #1: N-(3-chloropropyl)isonicotinamide With sodium iodide In acetonitrile at 70℃; for 0.5h; Stage #2: N-(furan-2-carbonyl)piperazine With potassium carbonate In acetonitrile at 70℃; for 24h;	40 4.1.3. General procedure for the preparation of isonicotinamide derivatives (3a-t, 4a-t) General procedure: A mixture of N-(2-chloroethyl)isonicotinamide (2a, 0.500g, 2.71mmol) or N-(3-chloropropyl)isonicotinamide (2b, 0.500g, 2.52mmol) and NaI (1.1 equiv.) in acetonitrile (30mL) was stirred under reflux for 30 min. Then the appropriate 4-substituted arylpiperazine (1.0 equiv.) and anhydrous K2CO3 (1.1 equiv.) were added. The reaction mixture was stirred under reflux for 24h. After cooling to room temperature, the mixture was filtered, concentrated to dryness and the residue was dissolved in DCM (20mL) and washed with NaHCO3, water and brine. The combined organic layers were dried on anhydrous Na2SO4 and the solvent removed under vacuum. The crude mixture was purified by silica gel column chromatography using DCM/methanol (9.5:0.5 (v/v)) or ethyl acetate/methanol (9:1 (v/v)) as eluent, according to the used arylpiperazine. The crude products were crystallized from diethyl ether, affording final compounds 3a-q and 4a-q (yield 7-89%). The final compounds 3r-t and 4r-t were obtained in a pure form after conversion in the corresponding hydrochloride salts and crystallization from ethanol/diethyl ether. 1H NMR, 13C NMR and MS data for all final compounds were consistent with the proposed structures.

Reference： [1]Fiorino, Ferdinando; Ciano, Antonio; Magli, Elisa; Severino, Beatrice; Corvino, Angela; Perissutti, Elisa; Frecentese, Francesco; Di Vaio, Paola; Izzo, Angelo A.; Capasso, Raffaele; Massarelli, Paola; Nencini, Cristina; Rossi, Ilaria; Kedzierska, Ewa; Orzelska-Gorka, Jolanta; Bielenica, Anna; Santagada, Vincenzo; Caliendo, Giuseppe [European Journal of Medicinal Chemistry, 2016, vol. 110, p. 133 - 150]

35
1-(2-bromoethyl)-1,4-dihydro-7-methoxy-4,4-dimethylchromeno[4,3-c]pyrazole [ No CAS ]
[ 40172-95-0 ]
1-{2-[4-(2-furoyl)piperazinyl]ethyl}-1,4-dihydro-7-methoxy-4,4-dimethylchromeno[4,3-c]pyrazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
25%	Stage #1: N-(furan-2-carbonyl)piperazine With potassium carbonate In tetrahydrofuran at 20℃; for 0.166667h; Stage #2: 1-(2-bromoethyl)-1,4-dihydro-7-methoxy-4,4-dimethylchromeno[4,3-c]pyrazole In tetrahydrofuran Reflux;
25%	Stage #1: N-(furan-2-carbonyl)piperazine With potassium carbonate In tetrahydrofuran at 20℃; for 0.166667h; Stage #2: 1-(2-bromoethyl)-1,4-dihydro-7-methoxy-4,4-dimethylchromeno[4,3-c]pyrazole In tetrahydrofuran Reflux;	1 EXAMPLE 1- Preparation of 1-(2-(4-(2-furoyl)piperazinyl)ethyl)-1,4-dihydro-7-methoxy-4,4-dimethylchromeno[4,3-c]pyrazole 1-(2-Furoyl)piperazine (12 mg, 0.06 mmol) and K2CO3 (27 mg, 0.19 mmol) dissolved in THF was stirred at room temperature for 10 min. A solution of 1-(2-bromoethyl)-7-methoxy-4,4-dimethyl-1,4-dihydrochromeno[4,3-c]pyrazole (22 mg, 0.06 mmol) in THF was added to the mixture and heated at reflux overnight. The solvent was evaporated under vacuum. The crude oil dissolved in EtOAc was washed with water, dried over MgSO4, and after filtration the solvent was evaporated. 1-(2-(4-(2-Furoyl)piperazinyl)ethyl)-1,4-dihydro-7-methoxy-4,4-dimethylchromene [4,3-c] pyrazole was isolated by medium pressure chromatography (7 mg, 25%); 1H-NMR (CDCI 3) δ: 7.57 (d, J = 8.5 Hz), 7.33-7.28 (m, 1H), 7.11 (s, 1H), 6.96-6.92 (m, 1H), 6.60 (dd, J = 8.5) 1H), 6.39-6.36 (m, 1H), 4.22 (t, J = 6.6 Hz, 2H), 3.78 (s, 3H), 3.39-3.21 (m, 4H), 2.83 (t, J = 6.6 Hz, 2H), 2.72-2.64 (m, 4H), 1.52 (s, 6H) ppm; 13C-NMR (101 MHz, CDCI 3) δ: 162.0, 155.6, 153.1, 145.3, 142.6, 141.8, 124.1, 123.2, 121.3, 117.0, 112.2, 109.2, 108.4, 103.2, 76.1, 57.5, 55.1, 54.1, 50.7, 49.5 , 28.9 ppm; MS (ES+, m/z) 437 [M+H]+; HRMS C24H28N4O4: content. 436.2110, exp. 436.2107.

Reference： [1]Morales, Paula; Whyte, Lauren S.; Chicharro, Roberto; Gómez-Cañas, María; Pazos, M. Ruth; Goya, Pilar; Irving, Andrew J.; Fernández-Ruiz, Javier; Ross, Ruth A.; Jagerovic, Nadine [Journal of Medicinal Chemistry, 2016, vol. 59, # 5, p. 1840 - 1853]
[2]Current Patent Assignee: UNIVERSITY OF TORONTO; GOVERNMENT OF SPAIN - EP3305794, 2018, A1 Location in patent: Paragraph 0064

36
[ 32315-10-9 ]
(S)-1-(4-chlorophenyl)-2-(1H-1,3-diazol-1-yl)ethanol [ No CAS ]
[ 40172-95-0 ]
(S)-1-(4-chlorophenyl)-2-(1H-imidazol-1-yl)ethyl 4-(furan-2-carbonyl)piperazine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%	Stage #1: bis(trichloromethyl) carbonate; (S)-1-(4-chlorophenyl)-2-(1H-1,3-diazol-1-yl)ethanol In acetonitrile at 20℃; Stage #2: N-(furan-2-carbonyl)piperazine With triethylamine In acetonitrile at 20℃; for 12h;	4.1.5 (S)-1-(4-Fluorophenyl)-2-(1H-imidazol-1-yl)ethyl-4-(furan-2-carbonyl)piperazine-1-carboxylate [(S)-5a] General procedure: (S)-1-(4-fluorophenyl)-2-(1H-imidazol-1-yl)ethanol (206mg, 1mmol) was suspended in 5mL of dry CH3CN, then triphosgene (148mg, 0.5mmol) was added. The mixture was stirred overnight at RT. After the obtained mixture was treated with Et2O until the complete precipitation of a white precipitate. Subsequently the solvent was decanted off, the precipitate was suspended in dry CH3CN and added with TEA (278μL, 2.0mmol), then with 1-(2-furoyl)piperazine (144mg, 0.8mmol). After 12hat RT, the solvent was removed under reduced pressure, the obtained residue was treated with CH2Cl2 (10mL) and extracted with saturated aqueous Na2CO3. The organic layer dried over Na2SO4 and evaporated under vacuum give a crude residue which was purified by silica gel column chromatography (CH2Cl2/MeOH 80:20) resulting in (S)-5a as a waxy solid (257mg, 78%, e.e.>99%)

Reference： [1]De Vita, Daniela; Pandolfi, Fabiana; Cirilli, Roberto; Scipione, Luigi; Di Santo, Roberto; Friggeri, Laura; Mori, Mattia; Fiorucci, Diego; Maccari, Giorgio; Christopher, Robert Selwyne Arul; Zamperini, Claudio; Pau, Valentina; De Logu, Alessandro; Tortorella, Silvano; Botta, Maurizio [European Journal of Medicinal Chemistry, 2016, vol. 121, p. 169 - 180]

37
[ 32315-10-9 ]
(S)-1-(4-fluorophenyl)-2-(1H-imidazol-1-yl)ethanol [ No CAS ]
[ 40172-95-0 ]
(S)-1-(4-fluorophenyl)-2-(1H-imidazol-1-yl)ethyl 4-(furan-2-carbonyl)piperazine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	Stage #1: bis(trichloromethyl) carbonate; (S)-1-(4-fluorophenyl)-2-(1H-imidazol-1-yl)ethanol In acetonitrile at 20℃; Stage #2: N-(furan-2-carbonyl)piperazine With triethylamine In acetonitrile at 20℃; for 12h;	4.1.5 (S)-1-(4-Fluorophenyl)-2-(1H-imidazol-1-yl)ethyl-4-(furan-2-carbonyl)piperazine-1-carboxylate [(S)-5a] (S)-1-(4-fluorophenyl)-2-(1H-imidazol-1-yl)ethanol (206mg, 1mmol) was suspended in 5mL of dry CH3CN, then triphosgene (148mg, 0.5mmol) was added. The mixture was stirred overnight at RT. After the obtained mixture was treated with Et2O until the complete precipitation of a white precipitate. Subsequently the solvent was decanted off, the precipitate was suspended in dry CH3CN and added with TEA (278μL, 2.0mmol), then with 1-(2-furoyl)piperazine (144mg, 0.8mmol). After 12hat RT, the solvent was removed under reduced pressure, the obtained residue was treated with CH2Cl2 (10mL) and extracted with saturated aqueous Na2CO3. The organic layer dried over Na2SO4 and evaporated under vacuum give a crude residue which was purified by silica gel column chromatography (CH2Cl2/MeOH 80:20) resulting in (S)-5a as a waxy solid (257mg, 78%, e.e.>99%); IR (neat, cm-1): 1699, 1621 (C=O); 1H NMR (400MHz, CD3OD) δ (ppm): 3.50-3.79 (m, 8H), 4.42-4.49 (m,2H), 5.99 (t, J=6.0Hz, 1H), 6.61 (s, 1H), 6.97 (s, 1H), 7.08-7.14 (m,5H), 7.38-7.41 (m, 2H), 7.71 (s, 1H); 13C NMR (100MHz, CD3OD) δ (ppm): 52.5, 55.3, 73.5, 76.8, 112.5, 116.5 (J=22.0Hz), 118.0, 121.5, 129.0, 129.6 (J=8.0Hz), 134.7 (J=3.0Hz), 139.2, 146.1, 148.2, 155.3, 161.2, 164.2 (J=244.0Hz); MS (ESI): m/z calcd for C21H21FN4O4 413.16 [M+H]+, found: 412.99; Anal. calcd for C21H21FN4O4: C 61.16, H 5.13, N 13.59, found: C 61.39, H 5.14, N 13.42.

Reference： [1]De Vita, Daniela; Pandolfi, Fabiana; Cirilli, Roberto; Scipione, Luigi; Di Santo, Roberto; Friggeri, Laura; Mori, Mattia; Fiorucci, Diego; Maccari, Giorgio; Christopher, Robert Selwyne Arul; Zamperini, Claudio; Pau, Valentina; De Logu, Alessandro; Tortorella, Silvano; Botta, Maurizio [European Journal of Medicinal Chemistry, 2016, vol. 121, p. 169 - 180]

38
7-chloro-8-fluoro-6H,12H-indolo[2,1-b]quinazoline-6,12-dione [ No CAS ]
[ 40172-95-0 ]
8-fluoro-7-{4-[(furan-2-yl)carbonyl]piperazin-1-yl}-6H,12H-indolo[2,1-b]quinazoline-6,12-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	In 1-methyl-pyrrolidin-2-one at 70℃; for 2h;	43 Example 43 Weighing 7-chloro-8-fluoro-primary-color amine alkone 10μmol and 1 - (2-furoyl) piperazine 10μmol, adding N-methyl pyrrolidone (NMP) 5 ml, reaction 70 °C 2h, cooling after the reaction, the reaction solution is added in a proper amount of methanol, standstill, filtering, the filter cake is washed with methanol agent. Directly to obtain the target product.
80%	In 1-methyl-pyrrolidin-2-one at 70℃; for 2h;	4.3.3. Synthesis of 6a-6j General procedure: A secondary amine (1 mmol) was added to a solution of 1c(1 mmol) in NMP (5 mL). The mixture was stirred at 70 °C for 2 hand then cooled to room temperature. Methanol was subsequentlyadded to the reaction mixture to precipitate the product. The redprecipitate was filtered and dried to afford the target compound.Some of the residue was purified by column chromatography onsilica gel using petroleum ether/ethyl acetate (1:1) as eluent toprovide the desired product.

Reference： [1]Current Patent Assignee: NORTHWEST UNIVERSITY (CHINA) - CN105330666, 2016, A Location in patent: Paragraph 0371; 0372; 0373; 0374; 0375; 0376
[2]Chen, Huan; Hou, Baolong; Liu, Jianli; Liu, Li; Ma, Xiumei; Wang, Cuiling; Wang, Jilin; Wang, Rui; Wang, Yinyin; Zheng, Xudong [Tetrahedron, 2019, vol. 75, # 48]

39
7,8-dichloro-6H,12H-indolo[2,1-b]quinazoline-6,12-dione [ No CAS ]
[ 40172-95-0 ]
8-chloro-7-{4-[(furan-2-yl)carbonyl]piperazin-1-yl}-6H,12H-indolo[2,1-b]quinazoline-6,12-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	In 1-methyl-pyrrolidin-2-one at 70℃; for 2h;	42 Example 42 Weighing 7,8- two chlorine tryptamine alkone 10μmol and 1 - (2-furoyl) piperazine 10μmol, adding N-methyl pyrrolidone (NMP) 5 ml, reaction 70 °C 2h, cooling after the reaction, the reaction solution is added in a proper amount of methanol, standstill, filtering, the filter cake is washed with methanol agent. Directly to obtain the target product

Reference： [1]Current Patent Assignee: NORTHWEST UNIVERSITY (CHINA) - CN105330666, 2016, A Location in patent: Paragraph 0365; 0366; 0367; 0368; 0369; 0370

40
[ 75-15-0 ]
[ 40172-95-0 ]
sodium 4-(furan-2-carbonyl)piperazine-1-carbodithioate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With sodium hydroxide In methanol at 0℃; for 3h;
66%	Stage #1: N-(furan-2-carbonyl)piperazine With sodium hydroxide at 0℃; for 0.5h; Stage #2: carbon disulfide at 0 - 20℃;	4.2. Chemical synthesis General procedure: Compounds SA02-16, PA01-15, AH01-10 and AA01-10. Secondary/primary amines, aprylic hydrazide, and amino acids (1.0 eq) weretreated with NaOH, KOH, or Et3N (1.5 eq), 20 mL of MeOH/EtOH/Et2Oas a solvent was used, and the solutions were stirred at 0 C for 30 min.Then, carbon disulfide (2.0 eq) was added dropwise, and the mixturewas stirred at room temperature until starting material was consumedthrough TLC monitoring. The solvents were removed under vacuo at r.t.,and the residues obtained were dissolved in MeOH and filtered offthrough Celite and the filtrate was concentrated in vacuo not exceeding40 C, or recrystallized from ethanol/diethyl ether and suction filteredto obtain a solid [38,51]. DTC-Cu complexes were obtained from a 2:1mixture of DTCs and CuCl2.
	With sodium hydroxide In water; ethyl acetate at 0 - 5℃; for 0.5h;

	With sodium hydroxide In ethanol at 20℃; for 1h; Cooling with ice;	3.1.2. General Procedure for the Synthesis of Sodium N-SubstitutedPiperazine/Morpholine/Piperidine Dithiocarbamates (3a-3u) General procedure: An ethanolic solution (10 mL) of sodium hydroxide (10 mmol, 0.4 g) was added to an ethanolicsolution (10 mL) of the secondary amine (10 mmol). The mixture was cooled in an ice bath; additionally,carbon disulfide (100 mmol, 6.0 mL) was added dropwise with continuous stirring for 1 h at roomtemperature. The precipitates were filtrated and washed with diethyl ether to obtain a white topale-yellow-colored product in 70-90% yield
	With sodium hydroxide In ethanol for 2h; Cooling with ice;	4.1.1.2. Synthesis of dithiocarbamate derivatives (2a-2k). General procedure: For thesynthesis of the dithiocarbamate derivatives (2a-2k), a mixture ofcarbondisulfide in ethanol was added to a mixture of appropriatepiperazine (0.22 mol, 3.73 g) and NaOH in EtOH (30 mL) and stirredin an ice-bath for 2h. After the reaction was complete, the precipitatedproduct was filtered, washed with diethylether and dried

Reference： [1]Amir, Muhammad Kashif; Zia-Ur-Rehman; Hayat, Faisal; Khan, Shahan Zeb; Hogarth, Graeme; Kondratyuk, Tamara; Pezzuto, John M.; Tahir, Muhammad Nawaz [RSC Advances, 2016, vol. 6, # 112, p. 110517 - 110524]
[2]Chen, Cheng; Yang, Ke-Wu; Zhai, Le; Ding, Huan-Huan; Chigan, Jia-Zhu [Bioorganic Chemistry, 2022, vol. 118]
[3]Mandalapu, Dhanaraju; Kushwaha, Bhavana; Gupta, Sonal; Krishna, Shagun; Srivastava, Nidhi; Shukla, Mahendra; Singh, Pratiksha; Chauhan, Bhavana S.; Goyani, Ravi; Maikhuri, Jagdamba P.; Sashidhara, Koneni V.; Kumar, Brijesh; Tripathi, Renu; Shukla, Praveen K.; Siddiqi, Mohammad I.; Lal, Jawahar; Gupta, Gopal; Sharma, Vishnu L. [European Journal of Medicinal Chemistry, 2018, vol. 143, p. 632 - 645]
[4]Hussein, Weiam; Saǧlik, Begüm Nurpelin; Levent, Serkan; Korkut, Büşra; Ilgin, Sinem; Özkay, Yusuf; Kaplancikli, Zafer Asim [Molecules, 2018, vol. 23, # 8]
[5]Çavuşoğlu, Betül Kaya; Çevik, Ulviye Acar; Özkay, Yusuf; Büyükemir, Oya; Beydemir, Şükrü; Kaplancıklı, Zafer Asım; Karaduman, Abdullah Burak; Koparal, Ali Savaş; Levent, Serkan; Nezir, Deniz; Osmaniye, Derya; Sağlık, Begüm Nurpelin [European Journal of Medicinal Chemistry, 2020, vol. 198]

41
C₁₀H₉BrN₄O₈ [ No CAS ]
[ 40172-95-0 ]
2,4,6-trinitrophenyl 3-[4-(2-furoyl)-1-piperazinyl]propylcarbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	Stage #1: N-(furan-2-carbonyl)piperazine With potassium carbonate In acetonitrile for 0.5h; Reflux; Stage #2: C₁₀H₉BrN₄O₈ In acetonitrile Reflux;	3. 5. Synthesis of Different CarbamateDerivatives Bearing 2-Furoyl-1-piperazine Moiety General procedure: 2-Furoyl-1-piperazine (4; 4.5 mmol) dissolved in20-30 mL acetonitrile was taken in a 100 mL round bottomflask, solid K2CO3 (13.5 mmol) was added and thereaction mixture was refluxed for half an hour followedby the addition of respective carbamates (3, 6, 8, 11, 13 or15; one in each case) in equimolar ratio. The mixture wasrefluxed for 4-5 h. TLC was carried out to check the reactioncompletion (20% ethyl acetate: 80% n-hexane). Distilledwater was added to the reaction mixture to acquirethe respective precipitates. On completion, 1-2 drops ofaqueous NaOH were added to the reaction mixture. Precipitateswere filtered, washed and dried to obtain the respectivecarbamates 5, 7, 9, 12, 14 or 16 (one in each case)bearing 2-furoyl-1-piperazine.

Reference： [1]Abbasi, Muhammad Athar; Hussain, Ghulam; Aziz-Ur-Rehman; Siddiqui, Sabahat Zahra; Ali Shah, Syed Adnan; Lodhi, Muhammad Arif; Ali Khan, Farman; Ashraf, Muhammad; Qurat-Ul-Ain; Ahmad, Irshad; Malik, Rabia; Shahid, Muhammad; Mushtaq, Zahid [Acta Chimica Slovenica, 2017, vol. 64, # 1, p. 159 - 169]

42
C₉H₇Br₃ClNO₂ [ No CAS ]
[ 40172-95-0 ]
2,4,6-tribromophenyl 2-[4-(2-furoyl)-1-piperazinyl]ethylcarbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	Stage #1: N-(furan-2-carbonyl)piperazine With potassium carbonate In acetonitrile for 0.5h; Reflux; Stage #2: C₉H₇Br₃ClNO₂ In acetonitrile Reflux;	3. 5. Synthesis of Different CarbamateDerivatives Bearing 2-Furoyl-1-piperazine Moiety General procedure: 2-Furoyl-1-piperazine (4; 4.5 mmol) dissolved in20-30 mL acetonitrile was taken in a 100 mL round bottomflask, solid K2CO3 (13.5 mmol) was added and thereaction mixture was refluxed for half an hour followedby the addition of respective carbamates (3, 6, 8, 11, 13 or15; one in each case) in equimolar ratio. The mixture wasrefluxed for 4-5 h. TLC was carried out to check the reactioncompletion (20% ethyl acetate: 80% n-hexane). Distilledwater was added to the reaction mixture to acquirethe respective precipitates. On completion, 1-2 drops ofaqueous NaOH were added to the reaction mixture. Precipitateswere filtered, washed and dried to obtain the respectivecarbamates 5, 7, 9, 12, 14 or 16 (one in each case)bearing 2-furoyl-1-piperazine.

Reference： [1]Abbasi, Muhammad Athar; Hussain, Ghulam; Aziz-Ur-Rehman; Siddiqui, Sabahat Zahra; Ali Shah, Syed Adnan; Lodhi, Muhammad Arif; Ali Khan, Farman; Ashraf, Muhammad; Qurat-Ul-Ain; Ahmad, Irshad; Malik, Rabia; Shahid, Muhammad; Mushtaq, Zahid [Acta Chimica Slovenica, 2017, vol. 64, # 1, p. 159 - 169]

43
C₁₀H₉Br₄NO₂ [ No CAS ]
[ 40172-95-0 ]
2,4,6-tribromophenyl 3-[4-(2-furoyl)-1-piperazinyl]propylcarbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	Stage #1: N-(furan-2-carbonyl)piperazine With potassium carbonate In acetonitrile for 0.5h; Reflux; Stage #2: C₁₀H₉Br₄NO₂ In acetonitrile Reflux;	3. 5. Synthesis of Different CarbamateDerivatives Bearing 2-Furoyl-1-piperazine Moiety General procedure: 2-Furoyl-1-piperazine (4; 4.5 mmol) dissolved in20-30 mL acetonitrile was taken in a 100 mL round bottomflask, solid K2CO3 (13.5 mmol) was added and thereaction mixture was refluxed for half an hour followedby the addition of respective carbamates (3, 6, 8, 11, 13 or15; one in each case) in equimolar ratio. The mixture wasrefluxed for 4-5 h. TLC was carried out to check the reactioncompletion (20% ethyl acetate: 80% n-hexane). Distilledwater was added to the reaction mixture to acquirethe respective precipitates. On completion, 1-2 drops ofaqueous NaOH were added to the reaction mixture. Precipitateswere filtered, washed and dried to obtain the respectivecarbamates 5, 7, 9, 12, 14 or 16 (one in each case)bearing 2-furoyl-1-piperazine.

Reference： [1]Abbasi, Muhammad Athar; Hussain, Ghulam; Aziz-Ur-Rehman; Siddiqui, Sabahat Zahra; Ali Shah, Syed Adnan; Lodhi, Muhammad Arif; Ali Khan, Farman; Ashraf, Muhammad; Qurat-Ul-Ain; Ahmad, Irshad; Malik, Rabia; Shahid, Muhammad; Mushtaq, Zahid [Acta Chimica Slovenica, 2017, vol. 64, # 1, p. 159 - 169]

44
[ 96783-89-0 ]
[ 40172-95-0 ]
phenyl 2-[4-(2-furoyl)-1-piperazinyl]ethylcarbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	Stage #1: N-(furan-2-carbonyl)piperazine With potassium carbonate In acetonitrile for 0.5h; Reflux; Stage #2: O-phenyl N-(2-chloroethyl)-carbamate In acetonitrile Reflux;	3. 5. Synthesis of Different CarbamateDerivatives Bearing 2-Furoyl-1-piperazine Moiety General procedure: 2-Furoyl-1-piperazine (4; 4.5 mmol) dissolved in20-30 mL acetonitrile was taken in a 100 mL round bottomflask, solid K2CO3 (13.5 mmol) was added and thereaction mixture was refluxed for half an hour followedby the addition of respective carbamates (3, 6, 8, 11, 13 or15; one in each case) in equimolar ratio. The mixture wasrefluxed for 4-5 h. TLC was carried out to check the reactioncompletion (20% ethyl acetate: 80% n-hexane). Distilledwater was added to the reaction mixture to acquirethe respective precipitates. On completion, 1-2 drops ofaqueous NaOH were added to the reaction mixture. Precipitateswere filtered, washed and dried to obtain the respectivecarbamates 5, 7, 9, 12, 14 or 16 (one in each case)bearing 2-furoyl-1-piperazine. 3. 5. 1. Phenyl 2-[4-(2-furoyl)-1-piperazinyl]ethylcarbamate (5)Sticky brown liquid; Yield: 90%; Mol. F.:C18H21N3O4; Mol. Mass.: 343 g/mol; IR (KBr, cm-1) νmax:3406 (N-H), 3086 (Ar C-H), 2882 (R C-H), 1657 (C=O),1582 (Ar C=C), 1498 (N=O), 1197 (C-O-C), 1110(C-N-C), 853 (C-N); 1H-NMR (500 MHz, CDCl3, ppm):δ 7.49 (brs, 1H, H-5’’’), 7.45 (brt, J = 7.2 Hz, 2H, H-3 andH-5), 7.15 (brt, J = 7.3 Hz, 1H, H-4), 7.07 (brd, J = 7.7Hz, 2H, H-2 and H-6), 7.01 (d, J = 4.1 Hz, 1H, H-3’’’),6.50 (dd, J = 1.9, 3.2 Hz, 1H, H-4’’’), 5.19 (s, 1H, NH),3.84 (brs, 4H, CH2-3’’ and CH2-5’’), 3.39 (t, J = 6.2 Hz,2H, CH2-1’), 2.56 (brt, J = 6.0 Hz, 4H, CH2-2’’ and CH2-6’’), 2.42 (t, J = 6.8 Hz, 2H, CH2-2’); EI-MS m/z 343[M]+, 207 [C11H15N2O2]+, 165 [C9H11NO2]•+, 163[C9H9NO2]•+, 95 [C5H3O2]+, 94 [C6H5O]+, 93 [C5HO2]+.Anal. Calc. for C18H21N3O4 (343.15): C, 62.96; H, 6.16;N, 12.24. Found: C, 62.84; H, 6.25; N, 12.37.

Reference： [1]Abbasi, Muhammad Athar; Hussain, Ghulam; Aziz-Ur-Rehman; Siddiqui, Sabahat Zahra; Ali Shah, Syed Adnan; Lodhi, Muhammad Arif; Ali Khan, Farman; Ashraf, Muhammad; Qurat-Ul-Ain; Ahmad, Irshad; Malik, Rabia; Shahid, Muhammad; Mushtaq, Zahid [Acta Chimica Slovenica, 2017, vol. 64, # 1, p. 159 - 169]

45
Phenyl-(β-brom-propyl)-carbamat [ No CAS ]
[ 40172-95-0 ]
phenyl 3-[4-(2-furoyl)-1-piperazinyl]propylcarbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	Stage #1: N-(furan-2-carbonyl)piperazine With potassium carbonate In acetonitrile for 0.5h; Reflux; Stage #2: Phenyl-(β-brom-propyl)-carbamat In acetonitrile Reflux;	3. 5. Synthesis of Different CarbamateDerivatives Bearing 2-Furoyl-1-piperazine Moiety General procedure: 2-Furoyl-1-piperazine (4; 4.5 mmol) dissolved in20-30 mL acetonitrile was taken in a 100 mL round bottomflask, solid K2CO3 (13.5 mmol) was added and thereaction mixture was refluxed for half an hour followedby the addition of respective carbamates (3, 6, 8, 11, 13 or15; one in each case) in equimolar ratio. The mixture wasrefluxed for 4-5 h. TLC was carried out to check the reactioncompletion (20% ethyl acetate: 80% n-hexane). Distilledwater was added to the reaction mixture to acquirethe respective precipitates. On completion, 1-2 drops ofaqueous NaOH were added to the reaction mixture. Precipitateswere filtered, washed and dried to obtain the respectivecarbamates 5, 7, 9, 12, 14 or 16 (one in each case)bearing 2-furoyl-1-piperazine.

Reference： [1]Abbasi, Muhammad Athar; Hussain, Ghulam; Aziz-Ur-Rehman; Siddiqui, Sabahat Zahra; Ali Shah, Syed Adnan; Lodhi, Muhammad Arif; Ali Khan, Farman; Ashraf, Muhammad; Qurat-Ul-Ain; Ahmad, Irshad; Malik, Rabia; Shahid, Muhammad; Mushtaq, Zahid [Acta Chimica Slovenica, 2017, vol. 64, # 1, p. 159 - 169]

46
C₉H₇ClN₄O₈ [ No CAS ]
[ 40172-95-0 ]
2,4,6-trinitrophenyl 2-[4-(2-furoyl)-1-piperazinyl]ethylcarbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	Stage #1: N-(furan-2-carbonyl)piperazine With potassium carbonate In acetonitrile for 0.5h; Reflux; Stage #2: C₉H₇ClN₄O₈ In acetonitrile Reflux;	3. 5. Synthesis of Different CarbamateDerivatives Bearing 2-Furoyl-1-piperazine Moiety General procedure: 2-Furoyl-1-piperazine (4; 4.5 mmol) dissolved in20-30 mL acetonitrile was taken in a 100 mL round bottomflask, solid K2CO3 (13.5 mmol) was added and thereaction mixture was refluxed for half an hour followedby the addition of respective carbamates (3, 6, 8, 11, 13 or15; one in each case) in equimolar ratio. The mixture wasrefluxed for 4-5 h. TLC was carried out to check the reactioncompletion (20% ethyl acetate: 80% n-hexane). Distilledwater was added to the reaction mixture to acquirethe respective precipitates. On completion, 1-2 drops ofaqueous NaOH were added to the reaction mixture. Precipitateswere filtered, washed and dried to obtain the respectivecarbamates 5, 7, 9, 12, 14 or 16 (one in each case)bearing 2-furoyl-1-piperazine.

Reference： [1]Abbasi, Muhammad Athar; Hussain, Ghulam; Aziz-Ur-Rehman; Siddiqui, Sabahat Zahra; Ali Shah, Syed Adnan; Lodhi, Muhammad Arif; Ali Khan, Farman; Ashraf, Muhammad; Qurat-Ul-Ain; Ahmad, Irshad; Malik, Rabia; Shahid, Muhammad; Mushtaq, Zahid [Acta Chimica Slovenica, 2017, vol. 64, # 1, p. 159 - 169]

47
[ 134-85-0 ]
[ 40172-95-0 ]
(4-(4-benzoylphenyl)piperazin-1-yl)(furan-2-yl)methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	With C₄₅H₃₉BrNiOP₂; lithium tert-butoxide; phenylboronic acid In toluene at 110℃; for 16h; Inert atmosphere; Glovebox; Sealed tube;	(22) General Catalytic Procedure (Scheme 4) General procedure: In a nitrogen atmosphere glove box C1 (5 mol%, 0.05 mmol),phenylboronic acid (5 mol%, 0.015 mmol), LiOt-Bu (1.5 mmol),(hetero)aryl chloride (1 mmol), amine/azole (1.1 mmol), anddry, degassed toluene (10 mL) were added to an oven-dried 4dram vial containing a magnetic stir bar. The vial was sealedwith a screw cap featuring a PTFE/silicone septum and removedfrom the glove box. The reaction mixture was magneticallystirred in a temperature-controlled aluminum heating block setto 110 °C for 16 h (unoptimized). The reaction mixture was thencooled to r.t., taken up in EtOAc (ca. 30 mL) and washed withbrine (3 × 50 mL). The organic layer was separated, dried overNa2SO4, filtered, and concentrated with the aid of a rotary evaporatorto afford the crude product, which was purified via chromatographicmethods (see the Supporting Information for completedetails).

Reference： [1]Sawatzky, Ryan S.; Ferguson, Michael J.; Stradiotto, Mark [Synlett, 2017, vol. 28, # 13, p. 1586 - 1591]

48
N-(2-chloroethyl)picolinamide [ No CAS ]
[ 40172-95-0 ]
N-(2-(4-(furoyl)piperazin-1-yl)ethyl)picolinamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
36%	Stage #1: N-(2-chloroethyl)picolinamide With sodium iodide In acetonitrile at 70℃; for 0.5h; Stage #2: N-(furan-2-carbonyl)piperazine With potassium carbonate In acetonitrile at 70℃; for 24h;	20 4.1.3. General procedure for the preparation of picolinamidederivatives (3a-t, 4a-t) General procedure: A mixture of N-(2-chloroethyl)picolinamide (2a, 0.500 g, 2.71mmol) or N-(3-chloropropyl)picolinamide (2b, 0.500 g, 2.52 mmol)and NaI (1.1 equiv.) in acetonitrile (30 mL) was stirred under refluxfor 30 min. Then the appropriate 4-substituted arylpiperazine(1.0 equiv.) and anhydrous K2CO3 (1.1 equiv.) were added. Thereaction mixture was stirred under reflux for 24 h. After coolingto room temperature, the mixture was filtered, concentrated todryness and the residue was dissolved in dichloromethane(20 mL) and washed with NaHCO3, water and brine. The combinedorganic layers were dried on anhydrous Na2SO4 and the solventremoved under vacuum. The crude mixture was purified by silicagel column chromatography using dichloromethane/methanol9.5:0.5 (v/v) or ethyl acetate/methanol 9:1 (v/v) as eluent, accordingto the used arylpiperazine. The crude products were crystallizedfrom diethyl ether, affording final compounds 3a-t and 4a-t(yield 11-86%). Final compounds 3s, 4k and 4t were obtained in a pure form after conversion in the corresponding hydrochloridesalts adding HCl ethereal solution to an ethanolic solution of thefree bases. All derivatives were recrystallized by ethanol/diethylether. 1H NMR, and MS data for all final compounds were consistentwith the proposed structures.

Reference： [1]Fiorino, Ferdinando; Magli, Elisa; Kędzierska, Ewa; Ciano, Antonio; Corvino, Angela; Severino, Beatrice; Perissutti, Elisa; Frecentese, Francesco; Di Vaio, Paola; Saccone, Irene; Izzo, Angelo A.; Capasso, Raffaele; Massarelli, Paola; Rossi, Ilaria; Orzelska-Gòrka, Jolanta; Kotlińska, Jolanta Helena; Santagada, Vincenzo; Caliendo, Giuseppe [Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 20, p. 5820 - 5837]

49
[ 947406-38-4 ]
[ 40172-95-0 ]
N-(3-(4-(furoyl)piperazin-1-yl)propyl)picolinamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56%	Stage #1: N-(3-chloropropyl)-pyridine-2-carboxamide With sodium iodide In acetonitrile at 70℃; for 0.5h; Stage #2: N-(furan-2-carbonyl)piperazine With potassium carbonate In acetonitrile at 70℃; for 24h;	40 4.1.3. General procedure for the preparation of picolinamidederivatives (3a-t, 4a-t) General procedure: A mixture of N-(2-chloroethyl)picolinamide (2a, 0.500 g, 2.71mmol) or N-(3-chloropropyl)picolinamide (2b, 0.500 g, 2.52 mmol)and NaI (1.1 equiv.) in acetonitrile (30 mL) was stirred under refluxfor 30 min. Then the appropriate 4-substituted arylpiperazine(1.0 equiv.) and anhydrous K2CO3 (1.1 equiv.) were added. Thereaction mixture was stirred under reflux for 24 h. After coolingto room temperature, the mixture was filtered, concentrated todryness and the residue was dissolved in dichloromethane(20 mL) and washed with NaHCO3, water and brine. The combinedorganic layers were dried on anhydrous Na2SO4 and the solventremoved under vacuum. The crude mixture was purified by silicagel column chromatography using dichloromethane/methanol9.5:0.5 (v/v) or ethyl acetate/methanol 9:1 (v/v) as eluent, accordingto the used arylpiperazine. The crude products were crystallizedfrom diethyl ether, affording final compounds 3a-t and 4a-t(yield 11-86%). Final compounds 3s, 4k and 4t were obtained in a pure form after conversion in the corresponding hydrochloridesalts adding HCl ethereal solution to an ethanolic solution of thefree bases. All derivatives were recrystallized by ethanol/diethylether. 1H NMR, and MS data for all final compounds were consistentwith the proposed structures.

Reference： [1]Fiorino, Ferdinando; Magli, Elisa; Kędzierska, Ewa; Ciano, Antonio; Corvino, Angela; Severino, Beatrice; Perissutti, Elisa; Frecentese, Francesco; Di Vaio, Paola; Saccone, Irene; Izzo, Angelo A.; Capasso, Raffaele; Massarelli, Paola; Rossi, Ilaria; Orzelska-Gòrka, Jolanta; Kotlińska, Jolanta Helena; Santagada, Vincenzo; Caliendo, Giuseppe [Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 20, p. 5820 - 5837]

50
N-(1H-benzo[d]imidazol-2-yl)-2-iodoacetamide [ No CAS ]
[ 40172-95-0 ]
N-(1H-benzo[d]imidazol-2-yl)-2-(4-(furan-2-carbonyl)piperazin-1-yl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72.76%	With potassium carbonate In acetone at 60℃; for 6h;	4.1.3. General procedure for the synthesis of acetamide derivatives 9a-m) General procedure: A solution of N-(1H-benzo[d]imidazol-2-yl)-2-chloracetamide(7) (1.91 mmol) and sodium iodide (1.90 mmol) in dry acetonewas refluxed with stirring at 60 C for 30 min. Anhydrous potassiumcarbonate (0.5 g) was added to the reaction mixture and the mixture was further refluxed for 1 h. Subsequently, varioussubstituted piperazines such as 1-methylpiperazine, 1-ethylpiperazine,1-phenylpiperazine, 1-(2-fluorophenyl)piperazine, 1-pyridylpiperazine,1-pyrimidylpiperazine, 1-benzylpiperazine, 1-benzhydrylpiperazine,1-(4-methoxyphenyl)piperazine, 1-(4-nitrophenyl)piperazine, 1-{4-(furan-2-carbonyl)}piperazine, 1-(2-methoxyphenyl)piperazine and 1-phenethylpiperazine were added in equimolarquantities (1.91 mmol) to the refluxing solution. The slurryobtained was filtered and the filtrate was evaporated underreduced pressure to obtain a solid residue which was recrystallizedfrom appropriate solvent to afford the purified compounds 9a-m.

Reference： [1]Abbhi, Vasudha; Saini, Lovneet; Mishra, Srishti; Sethi, Gautam; Prem Kumar, Alan; Piplani, Poonam [Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 21, p. 6071 - 6085]

51
5α,6β-epoxy-4,8α,7α(H)-eudesm-11(13)-en-8,12-olide [ No CAS ]
[ 40172-95-0 ]
C₂₄H₃₂N₂O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	In methanol at 20℃; for 24h; regioselective reaction;	A General Method for the Synthesis of Amino Derivatives General procedure: A solution of 1.1 mM amine in methanol (2 mL) was added under stirring to a solution of 1 mM lactone (I) in methanol (5 mL) and allowed to stand at room temperature; the degree of conversion of initial lactone was monitored by TLC. If the product did not precipitate from the reaction mixture, the solvent was evaporated in vacuo after the termination of the reaction,and the residue was recrystallized from the appropriate solvent (usually a mixture of benzene with hexane).The following compounds were obtained by this method.

Reference： [1]Pukhov; Afanasyeva; Anikina; Semakov; Dubrovskaya; Klochkov [Russian Journal of Bioorganic Chemistry, 2018, vol. 44, # 5, p. 553 - 561][Bioorg. Khim., 2018, vol. 44, # 5, p. 560 - 569,9]

52
[ 546-43-0 ]
[ 40172-95-0 ]
(3R,3aR,5S,8aR,9aR)-5,8a-dimethyl-3-[4-(2-furylcarbonyl)piperazin-1-yl]methyl}-3a,5,6,7,8,8a,9,9a-octahydronaphtho[2,3-b]furan-2(3H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	In methanol; at 20℃; for 24h;	General procedure: Lactone (1 mmol) in MeOH (5 mL) wasstirred, treated with a solution of piperazine (1 mmol) in MeOH (2 mL), and left at room temperature. The course of thereaction was monitored by TLC. If the product did not precipitate, the solvent was evaporated in vacuo after the reaction wascomplete. The residue was recrystallized from a suitable solvent (usually C6H6-hexane mixtures). Compounds 5a-e, 6a-d,and 7a,d,e were prepared by this method.

Reference： [1]Chemistry of Natural Compounds,2019,vol. 55,p. 41 - 46
Khim. Prir. Soedin.,2019,vol. 1,p. 36 - 41,6

53
[ 470-17-7 ]
[ 40172-95-0 ]
(3R,3aR,4aS,8aR,9aR)-8a-methyl-5-methylidene-3-[4-(2-furylcarbonyl)piperazin-1-yl]methyl}decahydronaphtho[2,3-b]furan-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	In methanol; at 20℃; for 12h;	General procedure: Lactone (1 mmol) in MeOH (5 mL) wasstirred, treated with a solution of piperazine (1 mmol) in MeOH (2 mL), and left at room temperature. The course of thereaction was monitored by TLC. If the product did not precipitate, the solvent was evaporated in vacuo after the reaction wascomplete. The residue was recrystallized from a suitable solvent (usually C6H6-hexane mixtures). Compounds 5a-e, 6a-d,and 7a,d,e were prepared by this method.

Reference： [1]Chemistry of Natural Compounds,2019,vol. 55,p. 41 - 46
Khim. Prir. Soedin.,2019,vol. 1,p. 36 - 41,6

54
[ 814-68-6 ]
[ 40172-95-0 ]
1-(4-(furan-2-carbonyl)piperazin-1-yl)prop-2-en-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With triethylamine In dichloromethane at 0 - 20℃; for 24.3333h; Inert atmosphere;
95%	With triethylamine In dichloromethane at 0 - 20℃; for 24.3333h; Inert atmosphere;	3; 6; 9 1-(4-(furan-2-carbonyl)piperazin-1-yl)prop-2-en-1-one (TRH 1-145). To a solution 1-(2-furoyl)piperazine (362 mg, 2.0 mmol) in dichloromethane (10 mL) was added acryloyl chloride (0.20 mL, 2.4 mmol) followed by triethylamine (0.34 mL, 2.4 mmol) at 0 C under N2 atmosphere. After stirring for 20 minutes, the reaction mixture was allowed to warm to room temperature and was stirred for 24 hours. The solution was washed twice with brine, dried with magnesium sulfate, and the resulting crude was purified by silica gel chromatography (70% to 100% ethyl acetate in hexanes) to yield 446 mg of yellow solid (95% yield).1H NMR (400 MHz, CDCl3): d 7.53 (m, 1H), 7.06 (dd, J = 0.7, 3.5 Hz, 1H), 6.61 (dd, J = 10.5, 16.8 Hz, 1H), 6.52 (dd, J = 1.8, 3.5 Hz, 1H), 6.33 (dd, J = 1.9, 16.8 Hz, 1H), 5.75 (dd, J = 1.9, 10.5 Hz, 1H), 3.84-3.67 (m, 8H).13C NMR (100 MHz, CDCl3): d 165.5, 159.1, 147.5, 144.0, 128.5, 127.1, 117.0, 111.5, 45.6, 41.9. HRMS (+ESI): Calculated: 235.1077 (C12H15N2O3). Observed: 235.1075.

Reference： [1]Berdan, Charles A.; Ho, Raymond; Lehtola, Haley S.; To, Milton; Hu, Xirui; Huffman, Tucker R.; Petri, Yana; Altobelli, Chad R.; Demeulenaere, Sasha G.; Olzmann, James A.; Maimone, Thomas J.; Nomura, Daniel K. [Cell Chemical Biology, 2019, vol. 26, # 7, p. 1027 - 22,1035]
[2]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz); UNIVERSITY OF CALIFORNIA - WO2020/76996, 2020, A1 Location in patent: Paragraph 0591; 0604; 0700; 0727; 0816; 0848-0849

55
[ 5784-45-2 ]
[ 40172-95-0 ]
furan-2-yl-(4-(phthalazin-1-yl)piperazin-1-yl)methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	With potassium carbonate; potassium iodide In ethanol Reflux;

Reference： [1]Elmeligie, Salwa; Aboul-Magd, Asmaa M.; Lasheen, Deena S.; Ibrahim, Tamer M.; Abdelghany, Tamer M.; Khojah, Sohair M.; Abouzid, Khaled A. M. [Journal of Enzyme Inhibition and Medicinal Chemistry, 2019, vol. 34, # 1, p. 1347 - 1367]

56
[ 19064-68-7 ]
[ 40172-95-0 ]
furan-2-yl-(4-(4-methylphthalazin-1-yl)piperazin-1-yl) methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%	With potassium carbonate; potassium iodide In ethanol Reflux;

Reference： [1]Elmeligie, Salwa; Aboul-Magd, Asmaa M.; Lasheen, Deena S.; Ibrahim, Tamer M.; Abdelghany, Tamer M.; Khojah, Sohair M.; Abouzid, Khaled A. M. [Journal of Enzyme Inhibition and Medicinal Chemistry, 2019, vol. 34, # 1, p. 1347 - 1367]

57
[ 672-78-6 ]
[ 40172-95-0 ]
furan-2-yl[4-(p-tolylsulfinyl)piperazin-1-yl]methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	With nickel dichloride; 1,3-bis[2,6-diisopropylphenyl]imidazolium chloride In tetrahydrofuran at 100℃; for 15h; Inert atmosphere;	General Procedure for the synthesis of sulfinamides General procedure: An oven-dried pressure tube (15 mL) was charged with a magnetic stir bar, catalyst (5 mmol%), ligand (20 mmol%). The solvent (1.2 mL) was then added. Afterwards methyl sulfinates (0.30 mmol, 1 equiv) and amine (0.6 mmol, 2 equiv) were subsequently added into the reaction mixture. The reaction was stirred under an argon atmosphere at 100 for 15 h. After cooling to room temperature, the reaction mixture was directly removed under reduced pressure and subjected to flash column chromatography in petroleum ether/ethyl acetate to obtain the desired products.

Reference： [1]Li, Gang-Jian; Pan, You-Lu; Liu, Yan-Ling; Xu, Hai-Feng; Chen, Jian-Zhong [Tetrahedron Letters, 2019, vol. 60, # 46]

58
[ 40172-95-0 ]
[ 421552-12-7 ]
4-fluoro-2-((4-(furan-2-carbonyl)piperazin-1-yl)methyl)benzonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
160 mg	With potassium carbonate; In acetonitrile; at 20℃;	Take furan-2-yl (piperazin-1-yl) methanone (168mg) in 5mL of acetonitrile, add potassium carbonate (195mg), and stir for a while, then add 4-fluoro-2-bromomethyl-benzonitrile (200mg ),Reaction at room temperature for 3-4 hours. After filtering the reaction solution, the filtrate was evaporated under reduced pressure to remove the solvent.The residue was extracted with ethyl acetate and water. The organic phase was dried, concentrated, dispersed with ether, and filtered to obtain 160 mg of intermediate D12.

Reference： [1]Patent: CN110590708,2019,A .Location in patent: Paragraph 0251-0254

59
[ 75-15-0 ]
[ 100-44-7 ]
[ 40172-95-0 ]
C₁₇H₁₈N₂O₂S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	Stage #1: carbon disulfide; N-(furan-2-carbonyl)piperazine With potassium phosphate In acetone at 20℃; for 0.5h; Stage #2: benzyl chloride In acetone at 20℃;	3.1.1. General Method for the Synthesis of SHD-1 to SHD-15 General procedure: A single neck, round bottom flask was charged with amine/aniline (3 mmol), potassium phosphate (1.5 eq) in 15mL of acetone. After dropwise addition of carbon disulfide (3 eq), the mixture was stirred for 30 minutes at ambient temperature and then corresponding benzyl halide/ chloromethylbenzimidazole (1 eq) was gradually introduced and stirring was continued till the completion of the reaction. The reaction mixture was concentrated and purified on silica column to obtain pure products SHD-1 to SHD-15.

Reference： [1]Ahmad, Khalil; Hamdani, Syeda S.; Hameed, Shahid; Iqbal, Jamshed; Khan, Bilal A.; Mughal, Ehsan U.; Rashid, Faisal; Zaib, Sumera [Medicinal Chemistry, 2019, vol. 15, # 8, p. 892 - 902]

60
[ 75-15-0 ]
[ 100-14-1 ]
[ 40172-95-0 ]
C₁₇H₁₇N₃O₄S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	Stage #1: carbon disulfide; N-(furan-2-carbonyl)piperazine With potassium phosphate In acetone at 20℃; for 0.5h; Stage #2: 4-nitrobenzyl chloride In acetone at 20℃;	3.1.1. General Method for the Synthesis of SHD-1 to SHD-15 General procedure: A single neck, round bottom flask was charged with amine/aniline (3 mmol), potassium phosphate (1.5 eq) in 15mL of acetone. After dropwise addition of carbon disulfide (3 eq), the mixture was stirred for 30 minutes at ambient temperature and then corresponding benzyl halide/ chloromethylbenzimidazole (1 eq) was gradually introduced and stirring was continued till the completion of the reaction. The reaction mixture was concentrated and purified on silica column to obtain pure products SHD-1 to SHD-15.

Reference： [1]Ahmad, Khalil; Hamdani, Syeda S.; Hameed, Shahid; Iqbal, Jamshed; Khan, Bilal A.; Mughal, Ehsan U.; Rashid, Faisal; Zaib, Sumera [Medicinal Chemistry, 2019, vol. 15, # 8, p. 892 - 902]

61
C₁₇H₁₈O₂ [ No CAS ]
[ 40172-95-0 ]
1-(2-furoyl)-4-{3-[2-(sec-butyl)phenoxy]benzyl}piperazine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
25%	With sodium tris(acetoxy)borohydride In dichloromethane at 20℃; Inert atmosphere;	General procedure for synthesis of the target 1-(2-furoyl)-4-(3-phenoxybenzyl)piperazine derivatives3a-g General procedure: 1-(2-Furoyl)piperazine (1.1 eq) and sodium acetoxyborohydride(1.2 eq) were added to a solution of 3-phenoxybenzaldehyde derivatives 2a-g (1 eq) in dichloromethane.The reaction mixture was stirred at room temperature.After overnight stirring, the reaction was quenchedby the addition of water and was then extracted withdichloromethane. The organic layer was washed with brineand dried with anhydrous Na2SO4. The organic solvent wasevaporated under reduced pressure to obtain the crudeproducts 3a-g. The spectral data of compounds 3a-g arereported herein in detail.