Name: 4254-02-8|Cyclopentanecarbonitrile|98%
Brand: Ambeed
SKU: A275048
Price: 20.0 USD
Availability: InStock
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1
[ 67-56-1 ]
[ 4254-02-8 ]
[ 109152-86-5 ]

Yield	Reaction Conditions	Operation in experiment
95%	With hydrogenchloride In hexane Cooling with ice;	7 Synthesis of cyclopentanecarboximidic acid methyl ester hydrochloride Cyclopentanenitrile (50.0 g, 0.53 mol) was dissolved in dry methanol (20 mL). Hexanes (125 mL) was added. The reaction mixture was cooled in ice bath and saturated with hydrogen chloride gas (generated from 100 mL of concentrated hydrochloric acid slowly added to 250 mL of concentrated sulfuric acid). The ice bath was removed and the mixture was stirred overnight. The solution was decanted from the formed semi-solid. The semi-solid was suspended in diethyl ether (750 mL). The suspension was stirred for 30 minutes and the solid was filtered, then dried in the funnel by passage of vacuum for 30 minutes to obtain the product as a white solid. Yield 82.0 g, 95%.
91%	With hydrogenchloride In cyclopentyl methyl ether at 0 - 5℃; for 49h;
	With hydrogenchloride; diethyl ether

Reference： [1]Current Patent Assignee: KALA PHARMACEUTICALS, INC. - WO2019/55028, 2019, A1 Location in patent: Paragraph 0187
[2]Location in patent: scheme or table Watanabe, Kiyoshi; Kogoshi, Naoto; Miki, Hideaki; Torisawa, Yasuhiro [Synthetic Communications, 2009, vol. 39, # 11, p. 2008 - 2013]
[3]McElvain; Starn [Journal of the American Chemical Society, 1955, vol. 77, p. 4571,4577]

2
[ 28247-14-5 ]
[ 4254-02-8 ]

Yield	Reaction Conditions	Operation in experiment
	at 510℃;

Reference： [1]Bailey; Daly [Journal of the American Chemical Society, 1959, vol. 81, p. 5397]

3
[ 3047-38-9 ]
[ 4254-02-8 ]

Reference： [1]Bulletin des Societes Chimiques Belges,1951,vol. 60,p. 270,274

4
[ 4254-02-8 ]
[ 5326-50-1 ]
[ 20334-79-6 ]

Reference： [1]Monatshefte fur Chemie,1968,vol. 99,p. 1050 - 1055

5
[ 4254-02-8 ]
[ 925-90-6 ]
[ 6635-67-2 ]

Reference： [1]Crouzet,J. et al. [Bulletin de la Societe Chimique de France, 1967, p. 3722 - 3729]

6
[ 4254-02-8 ]
[ 74-97-5 ]
[ 112906-02-2 ]

Yield	Reaction Conditions	Operation in experiment
24%	With n-butyllithium; diisopropylamine; lithium diisopropyl amide In tetrahydrofuran; hexane at -78℃; for 3h; Inert atmosphere;
	With n-butyllithium; diisopropylamine 1.) hexane, THF, -65 deg C, 1 h, 2.) -65 deg C; Yield given. Multistep reaction;
	With lithium diisopropyl amide In tetrahydrofuran; hexane	1 1-Chloromethylcyclopentanecarbonitrile EXAMPLE 1 1-Chloromethylcyclopentanecarbonitrile A solution of cyclopentanecarbonitrile (14.3 g, 150 mmol) in THF (25 ml) was added dropwise to a stirred solution of lithium diisopropylamide (158 mmol) in THF (150 ml) and hexane (100 ml), under dry nitrogen, keeping the temperature below -65°. After 0.5 h, the solution was warmed to ambient temperature and added to a stirred solution of bromochloromethane (49.4 ml, 750 mmol) in THF (50 ml) keeping the temperature below -65°. The solution was allowed to warm to ambient temperature and, after 18 h, poured into water (500 ml). The aqueous mixture was extracted with CHCl3 (3*250 ml). The extracts were washed with 2N HCl (100 ml) and H2 O (100 ml), dried (MgSO4), and evaporated under reduced pressure to give an oil which was distilled to give a pale yellow oil (8.9 g) b.p. 96° at 10 mmHg. Found: C, 59.0; H, 7.3; N, 9.5%. C7 H10 ClN requires: C, 58.6; H, 7.0; N, 9.75%.

Reference： [1]Udemba; Smith; Nguyen; Kaliszczak; Carroll; Fortt; Fuchter; Aboagye [Organic and Biomolecular Chemistry, 2015, vol. 13, # 19, p. 5418 - 5423]
[2]Cliffe, Ian A.; Todd, Richard S.; White, Alan C. [Synthetic Communications, 1990, vol. 20, # 12, p. 1757 - 1767]
[3]Current Patent Assignee: PFIZER INC - US4760158, 1988, A

7
[ 4254-02-8 ]
[ 3217-94-5 ]

Yield	Reaction Conditions	Operation in experiment
91%	With [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene]gold bis(trifluoromethanesulfonyl)imidate; water In tetrahydrofuran at 140℃; for 6h; Microwave irradiation;
85%	With sodium hydroxide; dihydrogen peroxide In dichloromethane for 1.16667h; Ambient temperature;
	Multi-step reaction with 2 steps 1: HCl; diethyl ether 2: DMF

Reference： [1]Ramon, Ruben S.; Marion, Nicolas; Nolan, Steven P. [Chemistry - A European Journal, 2009, vol. 15, # 35, p. 8695 - 8697]
[2]Cacchi, S.; Misiti, D.; Torre, F. La [Synthesis, 1980, # 3, p. 243 - 244]
[3]McElvain; Starn [Journal of the American Chemical Society, 1955, vol. 77, p. 4571,4577]

8
[ 41857-46-9 ]
[ 4254-02-8 ]

Yield	Reaction Conditions	Operation in experiment
64 % Chromat.	With sodium cyanide In methanol at 17℃; for 4.7h; electrolysis;

Reference： [1]Okimoto; Chiba [Journal of Organic Chemistry, 1990, vol. 55, # 3, p. 1070 - 1076]

9
[ 28766-49-6 ]
[ 4254-02-8 ]

Yield	Reaction Conditions	Operation in experiment
65%	With sodium cyanide In methanol at 17℃; for 4.7h; electrolysis;

Reference： [1]Okimoto; Chiba [Journal of Organic Chemistry, 1990, vol. 55, # 3, p. 1070 - 1076]

10
[ 61540-46-3 ]
[ 4254-02-8 ]

Yield	Reaction Conditions	Operation in experiment
85%	With 2,2'-azobis(isobutyronitrile); tri-n-butyl-tin hydride In benzene at 80℃; for 5h;

Reference： [1]Yanagawa, Makato; Moriya, Osamu; Watanabe, Yoshihiko; Ueno, Yoshio; Endo, Takeshi [Bulletin of the Chemical Society of Japan, 1988, vol. 61, p. 2203 - 2204]

11
[ 14702-41-1 ]
[ 143-33-9 ]
[ 4254-02-8 ]

Yield	Reaction Conditions	Operation in experiment
42%	In methanol at 17℃; for 4.7h; after standing for seven days before electrolysis;

Reference： [1]Okimoto; Chiba [Journal of Organic Chemistry, 1990, vol. 55, # 3, p. 1070 - 1076]

12
[ 124266-40-6 ]
[ 4254-02-8 ]

Yield	Reaction Conditions	Operation in experiment
71%	With sodium cyanide In methanol at 17℃; for 4.7h; electrolysis;

Reference： [1]Okimoto; Chiba [Journal of Organic Chemistry, 1990, vol. 55, # 3, p. 1070 - 1076]

13
[ 102804-63-7 ]
[ 4254-02-8 ]
[ 3047-38-9 ]

Reference： [1]Synthesis,1987,p. 992 - 998

14
[ 4254-02-8 ]
[ 105734-78-9 ]
N-(5-methyl-1,2-benzisothiazol-3-yl)cyclopentanecarboximidamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With tin(IV) chloride at 140℃; for 0.666667h;
80%	With tin(IV) chloride at 120 - 140℃;

Reference： [1]Vicini; Amoretti; Ballabeni; Barocelli; Chiavarini [European Journal of Medicinal Chemistry, 1995, vol. 30, # 10, p. 809 - 814]
[2]Vicini; Zani [Il Farmaco, 1997, vol. 52, # 1, p. 21 - 24]

15
[ 4254-02-8 ]
[ 23031-78-9 ]
N-(1,2-benzisothiazol-3-yl)cyclopentanecarboximidamide [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,1995,vol. 30,p. 809 - 814

16
[ 4254-02-8 ]
[ 105734-78-9 ]
N-(5-Methyl-benzo[d]isothiazol-3-yl)-cyclopentanecarboxamidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	at 60℃; for 2h;

Reference： [1]Sreekumar; Rugmini; Padmakumar, Raghavakaimal [Tetrahedron Letters, 1997, vol. 38, # 18, p. 3179 - 3182]

17
[ 4254-02-8 ]
[ 23031-78-9 ]
N-Benzo[d]isothiazol-3-yl-cyclopentanecarboxamidine [ No CAS ]

Reference： [1]Tetrahedron Letters,1997,vol. 38,p. 3179 - 3182

18
[ 4254-02-8 ]
[ 6053-81-2 ]

Yield	Reaction Conditions	Operation in experiment
84%	With sodium sulfate	13.a 2-[5-(N-Cyclopentylmethylcarbamoyl)-3-[2-methoxy-4-[2-(phenylsulphonyl)acetyl]benzyl]indol-1-yl]-N,N-dimethylpropionamide (a) A solution of cyclopentylnitrile (15 g) in ether (115 ml) was added dropwise, under nitrogen, to a refluxing slurry of lithium aluminum hydride (9 g) in ether (200 ml). The mixture was treated with a saturated aqueous solution of sodium sulfate and filtered. The filtrate was dried (MgSO4) and evaporated to give cyclopentylmethylamine (13 g, 84%) as a yellow liquid; IR (neat): 3300, 3340, 1600 cm-1.
77%	With ammonia; hydrogen In water; isopropyl alcohol at 80℃; for 24h; Autoclave;
54%	With borane-THF In tetrahydrofuran for 18h; Heating;

	With borane In tetrahydrofuran for 18h; Heating;
	With methanol; sodium for 5h;
	With LiAlH₄ In diethyl ether	3.A Synthesis of Compound 116 A. Aminomethylcyclopentane. To a solution of LiAlH4 (38 g, 1.0 mole) in diethyl ether (2 L) was added cyclopentanecarbonitrile (73.2 g, 0.77 mol) as a solution in 250 mL ether. The solution was stirred overnight at ambient temperature and then quenched by addition of the organics to 3 L of a saturated potassium, sodium tartrate solution. The amine was extracted into 3 L of ether, dried over anhydrous K2 CO3 then concentrated by distillation to approximately 400 mL total volume. The crude product was purified via distillation to give 58.2 g of the title compound as a colorless oil. (1 H)-NMR (CDCl3) consistent with structure.
58.2 g	With lithium aluminium tetrahydride In diethyl ether at 20℃;
	With LiAlH₄ In diethyl ether	114.A Aminomethylcyclopentane A. Aminomethylcyclopentane To a solution of LiAlH4 (38 g, 1.0 mole) in diethyl ether (2L) was added cyclopentanecarbonitrile (73.2 g, 0.77 mol) as a solution in 250 mL ether. The solution was stirred overnight at ambient temperature and then quenched by addition of the organics to 3L of a saturated potassium, sodium tartrate solution. The amine was extracted into 3L of ether, dried over anhydrous K2 CO3 then concentrated by distillation to approximately 400 mL total volume. The crude product was purified via distillation to give 58.2 g of the title compound as a colorless oil. (1 H)-NMR (CDCl3) consistent with structure.
	With LiAlH₄ In diethyl ether	114.A A. A. Aminomethylcyclopentane To a solution of LiAlH4 (38 g, 1.0 mole) in diethyl ether (2 L) was added cyclopentanecarbonitrile (73.2 g, 0.77 mol) as a solution in 250 mL ether. The solution was stirred overnight at ambient temperature and then quenched by addition of the organics to 3 L of a saturated potassium, sodium tartrate solution. The amine was extracted into 3 L of ether, dried over anhydrous K2 CO3 then concentrated by distillation to approximately 400 mL total volume. The crude product was purified via distillation to give 58.2 g of the title compound as a colorless oil. (1 H)-NMR (CDCl3) consistent with structure.
	With carbonylhydrido(tetrahydroborato)[bis(2-diphenylphosphinoethyl)amino]ruthenium(II); hydrogen In isopropyl alcohol at 100℃; for 3h; Autoclave; chemoselective reaction;
	Stage #1: cyclopentanecarbonitrile With lithium aluminium tetrahydride In diethyl ether at 20℃; for 24.17h; Stage #2: With sodium hydroxide; water In diethyl ether at 0℃;	Intermediate 104: CvclopentylmethylamineTo a 1.0M solution of lithium aluminium hydride in dry diethyl ether (27 ml) at RT was added a solution of cyclopentanecarbonitrile (2 g) in dry diethyl ether (10 ml) dropwise over 10 minutes. The purple solution was stirred at RT for 24 hours. The resulting pink solution was cooled to O0C and 5.0M sodium hydroxide solution (10 ml) was added slowly until effervescence ceased. The reaction was filtered from the white precipitate that had formed. The filtrate was dried over magnesium sulphate, filtered and concentrated in vacuo (RT, 200 mbar) to afford the title compound as a clear oil (1.6 g).1H NMR ((CDa)2SO): δ 2.63 (2H, d), 1.92 (1 H, m), 1.77 (2H, m), 1.57 (4H, m), 1.18 (2H, m). NH2 protons not observed.

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - US4837235, 1989, A
[2]Formenti, Dario; Mocci, Rita; Atia, Hanan; Dastgir, Sarim; Anwar, Muhammad; Bachmann, Stephan; Scalone, Michelangelo; Junge, Kathrin; Beller, Matthias [Chemistry - A European Journal, 2020, vol. 26, # 67, p. 15589 - 15595]
[3]Flosi, William J.; DeGoey, David A.; Grampovnik, David J.; Chen, Hui-ju; Klein, Larry L.; Dekhtyar, Tatyana; Masse, Sherie; Marsh, Kennan C.; Mo, Hong Mei; Kempf, Dale [Bioorganic and Medicinal Chemistry, 2006, vol. 14, # 19, p. 6695 - 6712]
[4]Kelley, James L.; Morris Bullock; Krochmal, Mark P.; McLean, Ed W.; Linn, James A.; Durcan, Micheal J.; Cooper, Barrett R. [Journal of Medicinal Chemistry, 1997, vol. 40, # 20, p. 3207 - 3216]
[5]Larsen, Janus S.; Pedersen, Erik B.; Nielsen, Claus [Synthesis, 2004, # 11, p. 1874 - 1878]
[6]Current Patent Assignee: VERTEX PHARMACEUTICALS (OLD) - US5723490, 1998, A
[7]Current Patent Assignee: VERTEX PHARMACEUTICALS (OLD) - US6372778, 2002, B1 Location in patent: Example 114
[8]Current Patent Assignee: VERTEX PHARMACEUTICALS (OLD) - US5585397, 1996, A
[9]Current Patent Assignee: VERTEX PHARMACEUTICALS (OLD) - US5783701, 1998, A
[10]Neumann, Jacob; Bornschein, Christoph; Jiao, Haijun; Junge, Kathrin; Beller, Matthias [European Journal of Organic Chemistry, 2015, vol. 2015, # 27, p. 5944 - 5948]
[11]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2008/101867, 2008, A1 Location in patent: Page/Page column 105

19
[ 4254-02-8 ]
[ 24812-90-6 ]
[ 201287-64-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,1998,vol. 8,p. 2737 - 2742
[2]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 1891 - 1894

20
[ 4254-02-8 ]
[ 63104-44-9 ]
3-cyclopentyl-5,7-dihydro[2]pyrindine-6,6-dicarboxylic acid dimethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
25%	With dicarbonylcyclopentadienylcobalt In 1,2-dimethoxyethane for 18h; Heating;

Reference： [1]Bonaga, Llorente V. R.; Zhang, Han-Cheng; Moretto, Alessandro F.; Ye, Hong; Gauthier, Diane A.; Li, Jian; Leo, Gregory C.; Maryanoff, Bruce E. [Journal of the American Chemical Society, 2005, vol. 127, # 10, p. 3473 - 3485]

21
[ 4254-02-8 ]
[ 4229-44-1 ]
N-hydroxy-N-methyl-cyclopentanecarboxamidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate In ethanol; water at 80℃; for 2h;
	With sodium carbonate In ethanol; water

Reference： [1]Naidu, B. Narasimhulu; Sorenson, Margaret E. [Organic Letters, 2005, vol. 7, # 7, p. 1391 - 1393]
[2]Naidu, B. Narasimhulu; Walker, Michael A.; Sorenson, Margaret E.; Ueda, Yasutsugu; Matiskella, John D.; Connolly, Timothy P.; Dicker, Ira B.; Lin, Zeyu; Bollini, Sagarika; Terry, Brian J.; Higley, Helen; Zheng, Ming; Parker, Dawn D.; Wu, Dedong; Adams, Stephen; Krystal, Mark R.; Meanwell, Nicholas A. [Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 12, p. 2124 - 2130]

22
[ 4254-02-8 ]
[ 106-95-6 ]
[ 928312-98-5 ]

Yield	Reaction Conditions	Operation in experiment
84%	Stage #1: cyclopentanecarbonitrile With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 0.75h; Stage #2: allyl bromide In tetrahydrofuran at -78 - 20℃; Further stages.;
77%	Stage #1: cyclopentanecarbonitrile With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -78℃; for 0.833333h; Inert atmosphere; Stage #2: allyl bromide In tetrahydrofuran; hexane at -78 - 20℃; Inert atmosphere;
	Stage #1: cyclopentanecarbonitrile With lithium diisopropyl amide In tetrahydrofuran; hexane at 0℃; for 1h; Stage #2: allyl bromide In tetrahydrofuran; hexane at 0 - 20℃;

	Stage #1: cyclopentanecarbonitrile With lithium diisopropyl amide Inert atmosphere; Stage #2: allyl bromide Inert atmosphere;
	Stage #1: cyclopentanecarbonitrile With n-butyllithium; diisopropylamine; lithium diisopropyl amide In tetrahydrofuran; hexane at -78℃; for 0.75h; Stage #2: allyl bromide In tetrahydrofuran; hexane at 20℃; for 12h;
	Stage #1: cyclopentanecarbonitrile With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 0.5h; Inert atmosphere; Schlenk technique; Stage #2: allyl bromide In tetrahydrofuran at -78 - 20℃; for 16h; Inert atmosphere; Schlenk technique;
	Stage #1: cyclopentanecarbonitrile With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 2h; Stage #2: allyl bromide In tetrahydrofuran at -78℃;
	Stage #1: cyclopentanecarbonitrile With lithium diisopropyl amide In tetrahydrofuran at -78 - 0℃; for 1h; Inert atmosphere; Stage #2: allyl bromide In tetrahydrofuran at -78 - 20℃; Inert atmosphere;

Reference： [1]Liu, Fa; Worthy, Karen M.; Bindu, Lakshman; Giubellino, Alessio; Bottaro, Donald P.; Fisher, Robert J.; Burke Jr., Terrence R. [Organic and Biomolecular Chemistry, 2007, vol. 5, # 2, p. 367 - 372]
[2]Maddocks, Christopher J.; Ermanis, Kristaps; Clarke, Paul A. [Organic Letters, 2020, vol. 22, # 20, p. 8116 - 8121]
[3]Riegert, David; Collin, Jacqueline; Meddour, Abdelkrim; Schulz, Emmanuelle; Trifonov, Alexander [Journal of Organic Chemistry, 2006, vol. 71, # 6, p. 2514 - 2517]
[4]Zhang, Zuxiao; Tang, Xiaojun; Thomoson, Charles S.; Dolbier, William R. [Organic Letters, 2015, vol. 17, # 14, p. 3528 - 3531]
[5]Du, Wei; Gu, Qiangshuai; Li, Yang; Lin, Zhenyang; Yang, Dan [Organic Letters, 2017, vol. 19, # 2, p. 316 - 319]
[6]Wang, Sheng; Zhang, Xiaowei; Cao, Chengyao; Chen, Chao; Xi, Chanjuan [Green Chemistry, 2017, vol. 19, # 19, p. 4515 - 4519]
[7]Qi, Xiaoxu; Chen, Chaohuang; Hou, Chuanqi; Fu, Liang; Chen, Pinhong; Liu, Guosheng [Journal of the American Chemical Society, 2018, vol. 140, # 24, p. 7415 - 7419]
[8]Chen, Chaohuang; Chen, Pinhong; Hou, Chuanqi; Liu, Guosheng [Chinese Journal of Chemistry, 2020, vol. 38, # 4, p. 346 - 350]

23
[ 1749-29-7 ]
[ 4254-02-8 ]
[ 506-87-6 ]
5-cyclopentyl-5-pyridin-2-ylmethyl-imidazolidine-2,4-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50%	Stage #1: 2-pyridylmethyllithium; cyclopentanecarbonitrile In tetrahydrofuran at 0℃; for 0.5h; Stage #2: ammonium carbonate With potassium cyanide In tetrahydrofuran; ethanol; water at 75℃; for 24h;

Reference： [1]Montagne, Cyril; Shipman, Michael [Synlett, 2006, # 14, p. 2203 - 2206]

24
[ 4254-02-8 ]
[ 917-54-4 ]
[ 506-87-6 ]
[ 6969-79-5 ]

Yield	Reaction Conditions	Operation in experiment
75%	Stage #1: cyclopentanecarbonitrile; methyllithium In tetrahydrofuran at 0℃; for 0.5h; Stage #2: ammonium carbonate With potassium cyanide In tetrahydrofuran; ethanol; water at 75℃; for 24h;

Reference： [1]Montagne, Cyril; Shipman, Michael [Synlett, 2006, # 14, p. 2203 - 2206]

25
[ 4254-02-8 ]
[ 506-87-6 ]
[ 5713-61-1 ]
5-cyclopentyl-5-thiophen-2-yl-imidazolidine-2,4-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
58%	Stage #1: cyclopentanecarbonitrile; thiophen-2-yl magnesium bromide With copper(l) iodide In tetrahydrofuran at 70℃; for 24h; Stage #2: ammonium carbonate With potassium cyanide In tetrahydrofuran; ethanol; water at 75℃; for 24h;

Reference： [1]Montagne, Cyril; Shipman, Michael [Synlett, 2006, # 14, p. 2203 - 2206]

26
N'-cyclopentylmethylene-N,N-dimethyl-hydrazine [ No CAS ]
[ 4254-02-8 ]

Yield	Reaction Conditions	Operation in experiment
94%	With HOF* CH₃CN at 0℃;

Reference： [1]Carmeli, Mira; Shefer, Neta; Rozen, Shlomo [Tetrahedron Letters, 2006, vol. 47, # 50, p. 8969 - 8972]

27
[ 4254-02-8 ]
[ 64-17-5 ]
[ 98552-18-2 ]

Yield	Reaction Conditions	Operation in experiment
99%	With hydrogenchloride In 1,4-dioxane at 20℃; for 48h;	279.279a Compound 279a: ethyl cyclopentanecarbimidate hydrochloride A solution of cyclopentanecarbonitrile (2.0 g, 21 mmol) and ethanol (1.47 ml, 25.2 mmol) was treated with 4.0 N HC1 in dioxane (42.0 ml, 168 mmol) at room temperature. The mixture was stirred at room temperature for 48 h. The solvent was removed under reduced pressure and EtOAc/di ethyl ether added to the residue then removed under reduced pressure. The solid was triturated with diethyl ether and left in refrigerator for 14h. Compound 279a was collected by filtration, washed with diethyl ether and dried under vacuum (3.7 g, 99%) as a white solid. 'H NMR (500MHz, chloroFORM-d) 12.10 (br. s., 1H), 11.23 (br. s., 1H), 4.56 (q, J=6.9 Hz, 2H), 3.29 - 3.19 (m, 1H), 2.05 -1.95 (m, 2H), 1.76 -1.65 (m, 4H), 1.64 -1.54 (m, 2H), 1.38 (t, J=7.0 Hz, 3H).
90%	With hydrogenchloride
	With hydrogenchloride In dichloromethane at 20℃;

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2017/218633, 2017, A1 Location in patent: Page/Page column 104
[2]Bach, Andrew; Jiang, Xinglong; McKenna, Joseph; Prasad, Kapa; Repic, Oljan; Shieh, Wen-Chung [Journal of Heterocyclic Chemistry, 2004, vol. 41, # 4, p. 637 - 640]
[3]Wang, Li-Ya; Tsai, Henry J.; Lin, Hui-Yi; Kaneko, Kimiyoshi; Cheng, Fen-Ying; Shih, Hsin-Siao; Wong, Fung Fuh; Huang, Jiann-Jyh [RSC Advances, 2014, vol. 4, # 27, p. 14215 - 14220]

28
[ 1603-41-4 ]
[ 4254-02-8 ]
[ 123-08-0 ]
4-(3-(cyclopentylamino)-5-methylimidazo[1,2-a]pyridin-2-yl)phenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66%	With acetic acid In methanol at 20 - 100℃; for 0.666667h; Irradiation;	1 To a thick-walled microwave vial equipped with a stir-bar were added 2-amino-5-picoline (1.2 equiv), 4-hydroxybenzaldehyde (1.0 equiv) and dry methanol (5 volume equivalents). Cyclopentyl isocyanide (1.0 equiv) and glacial acetic acid (2.0 equiv) were then added to the reaction mixture. The vial was then sealed with a septum and cap and submitted to microwave radiation for 10 min at 100 0 C. Reaction vessel was allowed to stand at room temp for 30 min, after which a white precipitate formed. This solid was filtered, washed with cold methanol, and dried in vacuo to provide the title compound in 66% yield. LCMS m/z (APCI) = 308.2 (M+H)

Reference： [1]Current Patent Assignee: CYTOKINETICS INC - WO2008/16648, 2008, A2 Location in patent: Page/Page column 46

29
[ 504-29-0 ]
[ 4254-02-8 ]
[ 1529-41-5 ]
N-(3-chlorobenzyl)-2-p-tolylimidazo[1,2-a]pyridin-3-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
54%	With acetic acid In methanol at 20 - 100℃; for 0.166667h; Irradiation;	2 To a thick-walled microwave vial equipped with a stir-bar were added 2-aminopyridine (1.0 equiv), 4-methylbenzaldehyde (1.0 equiv) and dry methanol (5 volume equivalents). 3-Chlorobenzyl isocyanide (1.0 equiv) and glacial acetic acid (2.0 equiv) were then added to the reaction mixture. The vial was then sealed with a septum and cap and submitted to microwave radiation for 10 min at 100 0 C. The solution was allowed to cool to room temperature and then diluted with ethyl acetate (50 volume equivalents), washed with saturated aq. sodium bicarbonate, brine, and dried over sodium sulfate. The organic layer was filtered and concentrated in vacuo to provide a brown oil, which was dissolved in an acetonitrile/water solution and purified by preparative reverse phase HPLC/MS to furnish the title compound as an off-white solid in 54% yield. LCMS m/z (APCI) =348.0 (M+H)

Reference： [1]Current Patent Assignee: CYTOKINETICS INC - WO2008/16648, 2008, A2 Location in patent: Page/Page column 46; 47

30
[ 4254-02-8 ]
[ 883724-27-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: lithium diisopropylamide / tetrahydrofuran; hexane / 1 h / 0 °C 1.2: tetrahydrofuran; hexane / 0 - 20 °C 2.1: 0.71 g / lithium aluminium hydride / diethyl ether / 0 - 20 °C
	Multi-step reaction with 2 steps 1.1: diisopropylamine; lithium diisopropyl amide; n-butyllithium / hexane; tetrahydrofuran / 0.75 h / -78 °C 1.2: 12 h / 20 °C 2.1: lithium aluminium tetrahydride / diethyl ether / 0 - 20 °C
	Multi-step reaction with 2 steps 1.1: lithium diisopropyl amide / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere; Schlenk technique 1.2: 16 h / -78 - 20 °C / Inert atmosphere; Schlenk technique 2.1: lithium aluminium tetrahydride / diethyl ether / 12 h / 0 - 30 °C / Inert atmosphere; Schlenk technique

	Multi-step reaction with 2 steps 1.1: lithium diisopropyl amide / tetrahydrofuran / 2 h / -78 °C 1.2: -78 °C 2.1: lithium aluminium tetrahydride / diethyl ether / 2 h / 0 °C / Inert atmosphere
	Multi-step reaction with 2 steps 1.1: lithium diisopropyl amide / tetrahydrofuran / 1 h / -78 - 0 °C / Inert atmosphere 1.2: -78 - 20 °C / Inert atmosphere 2.1: lithium aluminium tetrahydride / diethyl ether / 2 h / 0 - 20 °C / Inert atmosphere
	Multi-step reaction with 2 steps 1.1: n-butyllithium; diisopropylamine / tetrahydrofuran; hexane / 0.83 h / -78 °C / Inert atmosphere 1.2: -78 - 20 °C / Inert atmosphere 2.1: lithium aluminium tetrahydride / diethyl ether / 0 - 20 °C / Inert atmosphere

Reference： [1]Riegert, David; Collin, Jacqueline; Meddour, Abdelkrim; Schulz, Emmanuelle; Trifonov, Alexander [Journal of Organic Chemistry, 2006, vol. 71, # 6, p. 2514 - 2517]
[2]Du, Wei; Gu, Qiangshuai; Li, Yang; Lin, Zhenyang; Yang, Dan [Organic Letters, 2017, vol. 19, # 2, p. 316 - 319]
[3]Wang, Sheng; Zhang, Xiaowei; Cao, Chengyao; Chen, Chao; Xi, Chanjuan [Green Chemistry, 2017, vol. 19, # 19, p. 4515 - 4519]
[4]Qi, Xiaoxu; Chen, Chaohuang; Hou, Chuanqi; Fu, Liang; Chen, Pinhong; Liu, Guosheng [Journal of the American Chemical Society, 2018, vol. 140, # 24, p. 7415 - 7419]
[5]Chen, Chaohuang; Chen, Pinhong; Hou, Chuanqi; Liu, Guosheng [Chinese Journal of Chemistry, 2020, vol. 38, # 4, p. 346 - 350]
[6]Maddocks, Christopher J.; Ermanis, Kristaps; Clarke, Paul A. [Organic Letters, 2020, vol. 22, # 20, p. 8116 - 8121]

31
[ 4254-02-8 ]
[ 6636-80-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 2: (i) THF, (ii) aq. oxalic acid

Reference： [1]Meyers,A.I. et al. [Journal of Organic Chemistry, 1973, vol. 38, p. 2129 - 2136]

32
[ 930-28-9 ]
[ 143-33-9 ]
[ 4254-02-8 ]

Yield	Reaction Conditions	Operation in experiment
82%	With tetrakis[tris(dimethylamino)phosphoranylideneamino]phosphonium chloride; tris<tris(N,N-dimethylamido)phosphazo> phosphate In octane at 110℃; for 6h;	40 EXAMPLE 40 A 50-ml pressure glass vessel equipped with a thermometer was charged with 1.25 g (12.0 mmol) of chlorocyclopentane, 0.88 g (18.0 mmol) of sodium cyanide, 0.93 g (1.20 mmol) of a phosphazenium compound, i.e., tetrakis [tris(dimethylamino)phosphoranylideneamino] phosphonium chloride ([(Me2N)3P=N]4P+, Cl-), thoroughly dried with flowing dry nitrogen at 100°C, 0.10 g (0.17 mmol) of tris[tris(dimethylamino)phosphoranylideneamino]phosphine oxide ([(Me2N)3P=N]3P=O) thoroughly dried with flowing dry nitrogen at 80°C, and 7.03 g of anhydrous n-octane under a nitrogen atmosphere. The temperature of the resulting suspension was increased to 110°C in about 10 minutes while stirring. The reaction was continued for 6 hours at 110°C. Subsequently, a trace amount of the reaction mixture was sampled to conduct quantitative analysis by GC. The yield of cyanopentane was 82%.

Reference： [1]Current Patent Assignee: MITSUI CHEMICALS,INC. - EP1486479, 2004, A1 Location in patent: Page 17

33
[ 4254-02-8 ]
[ 443984-29-0 ]

Yield	Reaction Conditions	Operation in experiment
79%	Stage #1: With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at 0℃; for 0.5h; Stage #2: cyclopentanecarbonitrile In tetrahydrofuran; hexane at -78℃; Cooling with acetone-dry ice; Stage #3: With hexamethylphosphonic amide; Bromoacetaldehyde diethyl acetal more than 3 stages;	18.1 (Reference Example 18); (+/-)-2-Spirocyclopentane-1,2,3,5,6,7,8,8a-octahydroindolizin-7-one1); 1-Cyano-1-formylmethylcyclopentane diethylacetal In 500 ml of tetrahydrofuran was dissolved 22.00 ml (157 mmol) of diisopropylamine and to this solution was added dropwise under ice cooling 100 ml (157 mmol) of 1.57M n-butyl lithium/hexane solution. The mixture was stirred at the same temperature for 30 minutes. The reaction vessel was transferred to a dry ice-acetone bath and 14.89 ml (143 mmol) of cyclopentanecarbonitrile was added dropwise thereto. After the mixture was stirred at -78°C for 15 minutes, a solution of 27.31 ml (157 mmol) of hexamethylphosphonic amide in 50 ml of tetrahydrofuran was added dropwise thereto, and after stirring at the same temperature for 30 minutes, 23.62 ml (157 mmol) of bromoacetaldehyde diethylacetal was added dropwise thereto. The mixture was stirred at -78°C for 2 hours and at room temperature for a further 20 hours. Ice water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (solvent; hexane:ethyl acetate = 19:1) to give 23.92 g of the title compound as a colorless oil (yield: 79%). 1H-NMR Spectrum (400 MHz, CDCl3) δ ppm: 4.75 (1H, t, J = 5Hz), 3.76-3.66 (2H, m), 3.61-3.52 (2H, m), 2.22-2.13 (2H, m), 1.93 (2H, d, J = 5Hz), 1.91-1.63 (6H, m), 1.23 (6H, t, J = 7Hz).

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP1541571, 2005, A1 Location in patent: Page/Page column 91-92

34
[ 4254-02-8 ]
[ 74-88-4 ]
[ 100555-73-5 ]

Yield	Reaction Conditions	Operation in experiment
44%	With hydrogenchloride; sodium hydroxide; BH₃ In tetrahydrofuran	Methyl-(1-methyl-cyclopentylmethyl)-amine Methyl-(1-methyl-cyclopentylmethyl)-amine To a THF solution (5 mL) of cyclopentanecarbonitrile (4.39 mL, 42.0 mmol), 2M NaHMDS (25.0 mL, 50.0 mmol) in THF was added dropwise under argon at 0° C. The reaction was stirred for 15 min and methyl iodide (3.14 mL, 50.4 mmol) was then added dropwise to the solution at 0° C. The reaction was stirred for 2 h at 0° C., and 1M BH3 (126 mL, 126 mmol) in THF was added to the mixture at room temp. The mixture was stirred for 3 h, and 6N HCl was added dropwise to the mixture at 0° C. until pH reached 2. The mixture was stirred for 15 min. The mixture was poured into water and washed with DCM (340 mL). NaOH was added to the aqueous phase to adjust the pH to 11. (1-methyl-dicyclopentylmethyl)-amine was extracted with ethyl acetate (340 mL). The organic phase was dried over Na2SO4. The solvent was removed to afford (1-methyl-cyclopentylmethyl)-amine as yellow oil (2.0 g, 44%). MS (m/z) calced for C7H15N (MH+), 114; found, 227 (dimer), 340 (trimer).
44%	With hydrogenchloride; sodium hydroxide; BH₃ In tetrahydrofuran	Methyl-(1-methyl-cyclopentylmethyl)-amine Methyl-(1-methyl-cyclopentylmethyl)-amine To a THF solution (5 mL) of cyclopentanecarbonitrile (4.39 mL, 42.0 mmol), 2M NaHMDS (25.0 mL, 50.0 mmol) in THF was added dropwise under argon at 0° C. The reaction was stirred for 15 min and methyl iodide (3.14 mL, 50.4 mmol) was then added dropwise to the solution at 0° C. The reaction was stirred for 2 h at 0° C., and 1M BH3 (126 mL, 126 mmol) in THF was added to the mixture at room temp. The mixture was stirred for 3 h, and 6N HCl was added dropwise to the mixture at 0° C. until pH reached 2. The mixture was stirred for 15 min. The mixture was poured into water and washed with DCM (340 mL). NaOH was added to the aqueous phase to adjust the pH to 11. (1-methyl-dicyclopentylmethyl)-amine was extracted with ethyl acetate (340 mL). The organic phase was dried over Na2SO4. The solvent was removed to afford (1-methyl-cyclopentylmethyl)-amine as yellow oil (2.0 g, 44%). MS (m/z) calced for C7H15N (MH+), 114; found, 227 (dimer), 340 (trimer).

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO; LIGAND PHARMACEUTICALS INC - US2002/65270, 2002, A1 Current Patent Assignee: BRISTOL-MYERS SQUIBB CO; LIGAND PHARMACEUTICALS INC - US2002/137747, 2002, A1
[2]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO; LIGAND PHARMACEUTICALS INC - US6906067, 2005, B2

35
[ 80-73-9 ]
[ 4254-02-8 ]
[ 141337-02-2 ]

Yield	Reaction Conditions	Operation in experiment
55.0%	With n-butyllithium; diisopropylamine; In tetrahydrofuran; hexane;	d 1-[[2-(2-Hydroxyethyl)phenyl]methyl]cyclopentanecarbonitrile Obtained by operating as in example 87a, from 7.8 g (77 mmoles) of diisopropylamine, 48.2 ml of a 1.6M solution of n-butyllithium in hexane, 6.7 g (70 mmoles) of commercial cyclopentanecarbonitrile, 18 ml of 1,3-dimethylimidazolidin-2-one and 20.5 g (71.4 mmoles) of the compound prepared in example 92c in 20 ml of tetrahydrofuran. After distillation, there is obtained 8.8 g (yield=55.0%) of a beige viscous liquid. b.p.0.4 =165 C. I.R. (film): nu (OH)=3360cm-1; (C N)=2215 cm-1. N.M.R. (CDCl3): delta=1.4-2.25 (8H,m); 2.8 (1H,s, exchangeable with D2 O); 3.0 (4H,m); 3.8 (2H,t, J=6.75 Hz); 7.15 (4H,m).

Reference： [1]Patent: US5387709,1995,A

36
[ 80-73-9 ]
[ 4254-02-8 ]
[ 141337-07-7 ]

Yield	Reaction Conditions	Operation in experiment
60.0%	With n-butyllithium; diisopropylamine; In tetrahydrofuran; hexane;	d 1-[[3-(2-Hydroxyethyl)phenyl]methyl]cyclopentanecarbonitrile Obtained by operating as in example 87a, from 7.8g (77 mmoles) of diisopropylamine, 48.2 ml of a 1.6M solution of n-butyllithium in hexane, 6.7 g (70 mmoles) of commercial cyclopentanecarbonitrile, 18 ml of 1,3-dimethylimidazolidin-2-one and 20.5 g (71.4 mmoles) of the compound prepared in example 93c, in 110 ml of dry tetrahydrofuran. After distillation, there is obtained 9.6 g (yield=60.0%) of a viscous liquid. b.p.0.4 =160 C. I.R. (film): nu (OH)=3420 cm-1; (C N)=2215 cm-1. N.M.R. (CDCl3): delta=1.5-2.15 (8H,m); 2.4 (1H,s, exchangeable with D2 O); 2.85 (2H,s); 2.85 (2H,t, J=6.75 Hz); 3.8 (2H,t, J=6.75 Hz); 7.0-7.3 (4H,m).

Reference： [1]Patent: US5387709,1995,A

37
[ 4254-02-8 ]
[ 7252-83-7 ]
1-(2,2-Dimethoxyethyl)cyclopentanecarbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With n-butyllithium; diisopropylamine; lithium diisopropyl amide In tetrahydrofuran; hexane; water; ethyl acetate	6 Stage A: 1-(2,2-Dimethoxyethyl)cyclopentanecarbonitrile Stage A: 1-(2,2-Dimethoxyethyl)cyclopentanecarbonitrile 0.1 mol of cyclopentanecarbonitrile in 50 ml of THF is added in a rapid dropwise manner to a solution, stirred at 78° C. under an argon atmosphere, of 0.1 mol of lithium diisopropylamide (prepared from 0.1 mol of diisopropylamine and 63 ml of 1.6M butyllithium in hexane) in 250 ml of anhydrous THF. The mixture is stirred for 5 minutes at this temperature before adding 0.11 mol of 1-bromo-2,2dimethoxyethane. The mixture is allowed to return to room temperature and is hydrolyzed using 150 ml of water. The medium is allowed to settle, and the aqueous phase is separated and extracted twice with 150 ml of ether. The combined organic phases are washed with 100 ml of aqueous saline solution and 100 ml of water and then dried over magnesium sulfate. The solvents are evaporated off under vacuum and the residual oil is distilled. Boiling point: 84° C. (p=0.2 mmHg) Yield: 54% Stage B: 1-(2,2-Dimethoxyethyl)cyclopentanemethylamine 54 mmol of the product obtained in Stage A, in 100 ml of ether, are added dropwise to 109 mmol of lithium aluminum hydride suspended in 200 ml of ether stirred at room temperature under a nitrogen atmosphere. When all the nitrile has disappeared, 10 ml of ethyl acetate are added to the mixture, followed by 10 ml of water. The mixture is stirred for 1 hour, filtered and dried over MgSO4 and the solvent is evaporated off. The expected product is obtained in an 88% yield.

Reference： [1]Current Patent Assignee: SERVIER MONDE - US5436343, 1995, A

38
[ 110-52-1 ]
[ 3218-49-3 ]
[ 4254-02-8 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; N-benzyl-N,N,N-triethylammonium chloride In water	6 EXAMPLE 6 EXAMPLE 6 1,4-Dibromobutane (106 ml) was added dropwise over 1 hour at 70-80° C. under nitrogen to a stirred mixture of 3,4-dichlorophenylacetonitrile (150 g), benzyltriethylammonium chloride (2 g) and 50% aqueous sodium hydroxide solution (300 ml). When the addition was complete the mixture was stirred at 70-80° C. for 2 hours, then it was cooled to ambient temperature. Ether (400 ml) and water (200 ml) were added, and the layers were separated. The aqueous phase was washed with ether (2*200 ml), then the combined ethereal solutions were dried (MgSO4) and the solvent was removed in vacuo. The residue was distilled to give 1-(3,4-ichlorophenyl)cyclopentanecarbonitrile as a pale yellow oil (135 g), b.p. 132-140° C./0.4 mbar.

Reference： [1]Current Patent Assignee: ABBVIE INC - US6187802, 2001, B1

39
[ 4254-02-8 ]
potassium amminetrichloroplatinate [ No CAS ]
cis-amminecyclopentanecarbonitrildichloroeplatinum(II) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In water for 24h; Heating / reflux;	X X. Preparation of cis-amminecyclopentanecarbonitrildichloroeplatinum(II); C6H12Cl2N2Pt; PtCl,(NH3L(C5H9CN) To a solution of K[PtNH3Cl3] (150 mg) in 4 mL of deionized water was added 0.3 mL of cyclopentanecarbonitrile. The resulting mixture was heated and stirred for 24 hours. The pale yellow precipitate was filtered, washed with deionized water and ethyl ether, and dried under high vacuum to give a crude product. Recrystallization from tetrahydrfuran and acetone afforded a pure product (pale yellow solid; 20 mg). 1H NMR in Aceton-d6: δ: 3.96 (br, 3H), 3.31 (m, 1H), 1.70 (m, 8H). 195Pt NMR δ-2227 ppm. Predicted HRMS for C6H12Cl2N2PtNa+: 399.991736 aμ found: 399.989054 amu.

Reference： [1]Current Patent Assignee: BIONUMERIK PHARMACEUTICALS INC - US2007/4798, 2007, A1 Location in patent: Page/Page column 8

40
[ 4254-02-8 ]
[ 17846-68-3 ]
[ 441024-85-7 ]

Yield	Reaction Conditions	Operation in experiment
3.1 g (43.1%)	With hydrogenchloride; sodium hydroxide In diethyl ether; dichloromethane	29.A Preparation of (3S,4aR,6S,8aR)-6-[[(2S,4S)-2-carboxy4(5-cyclopentyltetrazol-2-yl)-1-pyrrolidinyl]methyl]-decahydroisoquinoline-3-carboxylic Acid Dihydrochloride A. Preparation of 5-cyclopentyltetrazole: A mixture of 5.0 g (0.052 mol) of cyclopentylnitrile and 15 g (0.045 mol) of azidotributyltin was heated to 90° C., and stirred for 17 hours. The mixture was allowed to cool to room temperature, and 30 mL of 1.0N HCl was added. The mixture was extracted 325 mL diethyl ether, and the ether layers combined and extracted 325 mL 1.0N NaOH. The base layers were combined and washed 125 mL dichloromethane. The basic layer was acidified to pH=2 using 5N HCl. The resulting acidic layer was extracted 3(3:1) dichloromethane/isopropanol. The organic layers were dried over Na2SO4, and the solvents removed under vacuum to afford 3.1 g (43.1%) of the title compound.

Reference： [1]Current Patent Assignee: ELI LILLY & CO - US2004/63749, 2004, A1

41
[ 4254-02-8 ]
[ 39895-55-1 ]
[ 1039765-80-4 ]

Yield	Reaction Conditions	Operation in experiment
	With dimethylaluminum chloride In toluene at 150℃; for 0.666667h; Microwave irradiation;	52.52a EXAMPLE 52; N-[(2-Cyclopentyl-1-[4-(1,1-dimethylethyl)phenyl]methyl}-4-hydroxy-6-oxo-1,6-dihydro-5-pyrimidinyl)carbonyl]glycine; 52a) 2-Cyclopentyl-3-[4-(1,1-dimethylethyl)phenyl]methyl}-6-hydroxy-4(3H)-pyrimidinone; Dimethylaluminium chloride (1.212 ml, 1.212 mmol) was added to a solution of 2-cyclopentanecarbonitrile (0.138 ml, 1.322 mmol) and 4-t-Butylbenzylamine (0.194 ml, 1.102 mmol) in Toluene (1.8 ml). The resulting mixture was stirred under nitrogen for 10 min. and then at 150° C. for 30 min in a Biotage Initiator microwave synthesizer. The reaction mixture was cooled and the solvent evaporated. The residue was suspended in Methoxyethanol (4.0 ml). Diethylmalonate (0.668 ml, 4.41 mmol) and sodium methoxide (1.008 ml, 4.41 mmol) were added and the mixture was stirred at reflux for 15 h. After cooling, the mixture was poured into water. The pH was adjusted to ca. 5 by te addition of 1 N HCl. The resulting precipitate was collected, washed with water, dried and purified on silica gel (0-9% MeOH in chloroform) to afford 2-cyclopentyl-3-[4-(1,1-dimethylethyl)phenyl]methyl}-6-hydroxy-4(3H)-pyrimidinone (287 mg, 0.671 mmol, 80.1% yield). This product was used in the next step as is. LCMS (ES+) m/z 327 (MH+).

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - US2008/171756, 2008, A1 Location in patent: Page/Page column 35

42
[ 4254-02-8 ]
[ 99623-12-8 ]

Yield	Reaction Conditions	Operation in experiment
	With hydroxylamine hydrochloride; potassium carbonate In methanol at 80℃; for 5h;	45.1 [743] 2.07 g (15.0 mmol) of potassium carbonate and 320 mg (1.66 mmol) of hydroxylam- inehydrochloride dissolved in 12 mL of methanol were gradually added to 1.14 g (10.0 mmol) of cyclopentanecarbonitrile dissolved in 4 mL of methanol. The reaction solution was heated to 8O0C and stirred for 5 hours. After the reaction solution was cooled to room temperature, the methanol was removed. The resulting solution was concentrated, filtered by Cellite, then distilled off under reduced pressure to give 1.06 g of the title compound in a yield of 145% without purification, and the next step was preceded.[744] Mass (m/e) 129 (M+l)
	With hydroxylamine hydrochloride; N-ethyl-N,N-diisopropylamine In ethanol Reflux;
	With hydroxylamine hydrochloride; triethylamine In <i>tert</i>-butyl alcohol at 80℃; for 18h; Schlenk technique;

Reference： [1]Current Patent Assignee: LG CHEM CO.,LTD. - WO2008/93960, 2008, A1 Location in patent: Page/Page column 61
[2]Location in patent: experimental part Flipo, Marion; Desroses, Matthieu; Lecat-Guillet, Nathalie; Villemagne, Baptiste; Blondiaux, Nicolas; Leroux, Florence; Piveteau, Catherine; Mathys, Vanessa; Flament, Marie-Pierre; Siepmann, Juergen; Villeret, Vincent; Wohlkönig, Alexandre; Wintjens, René; Soror, Sameh H.; Christophe, Thierry; Jeon, Hee Kyoung; Locht, Camille; Brodin, Priscille; Déprez, Benoit; Baulard, Alain R.; Willand, Nicolas [Journal of Medicinal Chemistry, 2012, vol. 55, # 1, p. 68 - 83]
[3]Xu, Hao; Ma, Shuang; Xu, Yuanqing; Bian, Longxiang; Ding, Tao; Fang, Xiaomin; Zhang, Wenkai; Ren, Yanrong [Journal of Organic Chemistry, 2015, vol. 80, # 3, p. 1789 - 1794]

43
[ 4254-02-8 ]
[ 2032-35-1 ]
[ 443984-29-0 ]

Yield	Reaction Conditions	Operation in experiment
79%	Stage #1: cyclopentanecarbonitrile With n-butyllithium; diisopropylamine In tetrahydrofuran at -78℃; for 0.25h; Cooling with acetone-dry ice; Stage #2: With N,N,N,N,N,N-hexamethylphosphoric triamide In tetrahydrofuran at -78℃; for 0.5h; Stage #3: Bromoacetaldehyde diethyl acetal In tetrahydrofuran at -78 - 20℃; for 22h;	18.i 18(i) 1-Cyano-1-formylmethylcyclonentane Diethyl Acetal 100 ml (157 mmol) of a 1.57M solution of n-butyllithium in hexane were added dropwise with ice-cooling to a solution of 22.00 ml (157 mmol) of diisopropylamine in 500 ml of tetrahydrofaran, and the resulting mixture was then stirred for 30 minutes at the same temperature.At the end of this time, 14.89 ml (143 mmol) of cyclopentanecarbonitrile were added dropwise to the reaction mixture on a dry ice-acetone bath.The resulting mixture was stirred for 15 minutes at -78° C., at the end of which time a solution of 27.31 ml (157 mmol) of hexamethylphosphoramide in 50 ml of tetrahydrofuran were added dropwise.After stirring the resulting mixture for 30 minutes at -78° C., 23.62 ml (157 mmol) of bromoacetaldehyde diethyl acetal were added dropwise and the resulting mixture was then stirred for 2 hours at -78° C. and for a further 20 hours at room temperature.At the end of this time, ice-water was added to the reaction mixture, which was then extracted with ethyl acetate.The organic extract was washed with water, dried over anhydrous magnesium sulfate and then concentrated by evaporation under reduced pressure.The resulting residue was purified by chromatography on a silica gel column using a 19:1 by volume mixture of hexane and ethyl acetate as the eluant to afford 23.92 g (yield: 79%) of the title compound as a colorless oil. 1H-NMR spectrum (400 MHz CDCl3) δ ppm: 4.75 (1H, triplet, J=5 Hz); 3.76-3.66 (2H, multiplet); 3.61-3.52 (2H, multiplet); 2.22-2.13 (2H, multiplet); 1.93 (2H, doublet, J=5 Hz); 1.91-1.63 (6H, multiplet); 1.23 (6H, triplet, J=7 Hz).
	With lithium diisopropyl amide In tetrahydrofuran; hexane at -78℃; for 0.75h; Inert atmosphere; Schlenk technique;

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - US2004/54173, 2004, A1 Location in patent: Page 213
[2]Lin, Jin-Shun; Li, Tao-Tao; Jiao, Guan-Yuan; Gu, Qiang-Shuai; Cheng, Jiang-Tao; Lv, Ling; Liu, Xin-Yuan [Angewandte Chemie - International Edition, 2019, vol. 58, # 21, p. 7092 - 7096][Angew. Chem., 2019, vol. 131, p. 7166 - 7170,5]

44
[ 872-53-7 ]
[ 4254-02-8 ]

Yield	Reaction Conditions	Operation in experiment
95%	With hydroxylamine hydrochloride; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In ethyl acetate; N,N-dimethyl-formamide at 100℃;

Reference： [1]Location in patent: experimental part Augustine, John Kallikat; Atta, Rajendra Nath; Ramappa, Balakrishna Kolathur; Boodappa, Chandrakantha [Synlett, 2009, # 20, p. 3378 - 3382]

45
[ 625-92-3 ]
[ 4254-02-8 ]
[ 1195178-79-0 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hexamethyldisilazane In tetrahydrofuran at 20℃; for 48h; Inert atmosphere;	182.1 A solution of 3,5-dibromopyridine (14.9 g, 63.1 mmol) and cyclopentanecarbonitrile (3.29 ml, 31.5 mmol) in THF (100 mL) at 00C was added sodium bistrimethylsilyl amide IM in THF (34.7 ml, 34.7 mmol). After addition, the mixture was stirred at room temperature for 48 h under N2. Then, H2O (100 mL) was added slowly and the mixture was extracted with EtOAc (200 mL). The organic layer was collected, dried over MgSO4, and concentrated in vacuo to give l-(5-bromopyridin-3-yl)cyclopentanecarbonitrile as a brown solid which was used without purification. MS (ESI, positive ion) m/z: 251 (M+l).

Reference： [1]Current Patent Assignee: AMGEN INC - WO2009/137404, 2009, A1 Location in patent: Page/Page column 83

46
[ 4254-02-8 ]
[ 34941-91-8 ]
[ 1195178-56-3 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hexamethyldisilazane In tetrahydrofuran; toluene at 0 - 20℃;	174.1 To a solution of cyclopentanecarbonitrile (2.36 ml, 22.6 mmol) and 2-chloro-4- fluoropyridine (2.97 g, 22.6 mmol) in toluene (60 mL) at 00C was added sodium bis(trimethylsilyl)amide 1.0 M in THF (22.6 mL, 22.6 mmol) dropwise. After addition, the mixture was stirred at 00C for 1 h and 3 h at room temperature. Then, H2O (60 mL) was added and the mixture was stirred at room temperature for 15 minutes. Then, the mixture was extracted with EtOAc (2 x 20 mL) and the combined organic extracts were dried over MgSO4 and concentrated. The residue was mixed with silica gel and the solid mixture was then purified by silica gel column chromatography using ISCO instrument (solid loading, 0%-30% EtOAc) to give l-(2-chloropyridin-4-yl)cyclopentanecarbonitrile as a colorless liquid. MS (ESI, positive ion) m/z: 207 (M+l).

Reference： [1]Current Patent Assignee: AMGEN INC - WO2009/137404, 2009, A1 Location in patent: Page/Page column 76-77

47
[ 4254-02-8 ]
[ 20885-12-5 ]
[ 916176-89-1 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hexamethyldisilazane; In tetrahydrofuran; toluene; at 0 - 20℃;	A solution of cyclopentanecarbonitrile (0.7 g, 0.8 ml, 8 mmol) and 2-chloro-6- fluoropyridine (1.0 g, 8 mmol) in toluene (25 mL) at 00C was added sodium <n="75"/>bis(trimethylsilyl)amide (8 mL, 8 mmol) IM in THF dropwise. After addition, the mixture was stirred at 00C for 1 h and 3 h at room temperature. Then, H2O (20 mL) was added and the mixture was stirred at room temperature for 15 minutes. Then, the mixture was extracted with EtOAC (2 x 20 mL) and the combined organic extracts were dried over MgSO4 and concentrated. The residue was mixed with silica gel and the solid mixture was then purified by silica gel column chromatography using ISCO instrument (solid loading, 0%-30% EtOAc/hexane) to give l-(6-chloropyridin-2-yl)cyclopentanecarbonitrile as a colorless oil. MS (ESI, positive ion) m/z: 207 (M+l).

Reference： [1]Patent: WO2009/137404,2009,A1 .Location in patent: Page/Page column 73-74

48
[ 4254-02-8 ]
[ 10472-24-9 ]
[ 1215017-78-9 ]

Yield	Reaction Conditions	Operation in experiment
95.4%	Stage #1: cyclopentanecarbonitrile With ammonium chloride; trimethylaluminum In toluene at 0 - 80℃; Inert atmosphere; Stage #2: With methanol at 15 - 40℃; for 1h; Stage #3: methyl 2-oxocyclopentane-1-carboxylate With potassium carbonate In ethanol Reflux;	1.i A solution of trimethylaluminum in toluene (2M, 25 mL, 50 mmol) was added slowly under nitrogen to a suspension of ammonium chloride (2.9 g, 54 mmol) in anhydrous toluene at 0° C.-5° C. The mixture was then stirred at a temperature in the range of 15° C. to 40° C. for 20 min before addition of a solution of cyclopentanecarbonitrile (3.13 mL, 30 mmol) in toluene. The resulting mixture was then heated at 80° C. under stirring for 10 hours. Thereafter, the mixture was cooled to a temperature in the range of 15° C. to 40° C. MeOH was slowly added to quench the reaction and stirred at a temperature in the range of 15° C. to 40° C. for 1 hour. Thereafter, the precipitate was filtered and washed with MeOH (3×30 mL). The filtrate and the washings were combined and concentrated under reduced pressure. After drying under vacuum, the crude solid (3.5 g) was dissolved in anhydrous EtOH (20 mL). Methyl-2-oxo-cyclopentanecarboxylate (3.1 mL, 25 mmol) and K2CO3 (4.14 g, 30 mmol) were added sequentially to this solution and the mixture was heated to reflux for a period over 6-15 hours. Thereafter, volatiles were evaporated under reduced pressure and the mixture was diluted with ice-water under stirring. The resultant precipitate was filtered, washed thoroughly with water followed by ether and dried under vacuum (4.6 g, 95.4% yield).1H NMR (CDCl3, 300 MHz): δ 11.58 (bs, 1H), 3.08-2.96 (m, 1H), 2.90-2.76 (m, 4H), 2.14-2.02 (m, 4H), 1.92-1.78 (m, 4H), 1.64-1.74 (m, 2H).LC-MSD (ES+): (m/z) 205 [(M+H)+, 100].

Reference： [1]Current Patent Assignee: DR REDDY'S LABORATORIES LIMITED - US2010/144731, 2010, A1 Location in patent: Page/Page column 17

49
[ 4254-02-8 ]
[ 6940-76-7 ]
[ 148614-13-5 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: cyclopentanecarbonitrile With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; for 0.5h; Stage #2: 1-iodo-3-chloro-propane In tetrahydrofuran at 20℃; for 20h;	1-(3-chloropropyl)cyclopentanecarbonitrile. To a stirred solution of cyclopentanecarbonitrile (1.04 mL, 10 mmol) in THF (20 mL) at -78° C. was added LiHMDS (1M in THF, 11 mL) via syringe. After 30 min, 1-chloro-3-iodopropane (1.6 mL, 15 mmol) was added at once and slowly warmed to room temperature. After 20 h, the reaction mixture was quenched with saturated ammonium chloride (1 mL), diluted with EtOAc (100 mL), dried (MgSO4), filtered and concentrated to give intermediate 28 as yellow oil which was used in the next step without further purification.
	Stage #1: cyclopentanecarbonitrile With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; for 0.5h; Stage #2: 1-iodo-3-chloro-propane In tetrahydrofuran at -78 - 20℃; for 20h;	1 Intermediate 1l-(3-chloropropyl)cyclopentanecarbonitrile. To a stirred solution of cyclopentanecarbonitrile (1.04 mL, 10 mmol) in THF (20 mL) at -78 °C was added LiHMDS (IM in THF, 11 mL) via syringe. After 30 min, l-chloro-3-iodopropane (1.6 mL, 15 mmol) was added at once and slowly warmed to room temperature. After 20 h, the reaction mixture was quenched with saturated ammonium chloride (1 mL), diluted with EtOAc (100 mL), dried (MgSO4), filtered and concentrated to give intermediate 1 as yellow oil which was used in the next step without further purification.
	Stage #1: cyclopentanecarbonitrile With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; Stage #2: 1-iodo-3-chloro-propane

Stage #1: cyclopentanecarbonitrile With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; for 0.5h; Stage #2: 1-iodo-3-chloro-propane In tetrahydrofuran at -78 - 20℃; for 20h;

1-(3-Chloropropyl)cyclopentanecarbonitrile. To a stirred solution of cyclopentanecarbonitrile (1.04 mL, 10 mmol) in THF (20 mL) at -78° C. was added LiHMDS (1M in THF, 11 mL) via syringe. After 30 min, 1-chloro-3-iodopropane (1.6 mL, 15 mmol) was added at once and slowly warmed to room temperature. After 20 h, the reaction mixture was quenched with saturated ammonium chloride (1 mL), diluted with EtOAc (100 mL), dried (MgSO4), filtered and concentrated to give the title compound as a yellow oil which was used in the next step without further purification.

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - US2007/111985, 2007, A1 Location in patent: Page/Page column 39-40
[2]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2007/58646, 2007, A1 Location in patent: Page/Page column 37-38
[3]Naidu, B. Narasimhulu; Walker, Michael A.; Sorenson, Margaret E.; Ueda, Yasutsugu; Matiskella, John D.; Connolly, Timothy P.; Dicker, Ira B.; Lin, Zeyu; Bollini, Sagarika; Terry, Brian J.; Higley, Helen; Zheng, Ming; Parker, Dawn D.; Wu, Dedong; Adams, Stephen; Krystal, Mark R.; Meanwell, Nicholas A. [Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 12, p. 2124 - 2130]
[4]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - US2008/4265, 2008, A1 Location in patent: Page/Page column 17

50
[ 4254-02-8 ]
[ 64871-66-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: lithium diisopropyl amide / tetrahydrofuran / 0.75 h / -78 °C 1.2: 3 h / -78 - 20 °C 2.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.08 h / -78 °C 3.1: isopropylmagnesium chloride / tetrahydrofuran; diethyl ether / 0.08 h / -78 °C 3.2: -78 - 20 °C
	Multi-step reaction with 3 steps 1.1: lithium diisopropyl amide / tetrahydrofuran / 0.75 h / -78 °C 1.2: 3 h / 20 °C 2.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / -78 °C 3.1: isopropylmagnesium chloride / tetrahydrofuran / 0.08 h / -78 °C 3.2: 2 h / 20 °C
	Multi-step reaction with 2 steps 1.1: lithium diisopropyl amide / tetrahydrofuran / 0.75 h / -78 °C 1.2: 3 h / -78 - 20 °C 2.1: n-butyllithium / hexane; tetrahydrofuran / 2 h / -78 - 20 °C

Reference： [1]Nath, Dinesh; Fleming, Fraser F. [Angewandte Chemie - International Edition, 2011, vol. 50, # 49, p. 11790 - 11793]
[2]Nath, Dinesh; Fleming, Fraser F. [Chemistry - A European Journal, 2013, vol. 19, # 6, p. 2023 - 2029]
[3]Nath, Dinesh; Skilbeck, Melanie C.; Coldham, Iain; Fleming, Fraser F. [Organic Letters, 2014, vol. 16, # 1, p. 62 - 65]

51
[ 4254-02-8 ]
[ 882-33-7 ]
[ 36638-54-7 ]

Yield	Reaction Conditions	Operation in experiment
90%	Stage #1: cyclopentanecarbonitrile With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 0.75h; Stage #2: diphenyldisulfane In tetrahydrofuran at -78 - 20℃; for 3h;
90%	Stage #1: cyclopentanecarbonitrile With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 0.75h; Stage #2: diphenyldisulfane In tetrahydrofuran at 20℃; for 3h;
90%	Stage #1: cyclopentanecarbonitrile With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 0.75h; Stage #2: diphenyldisulfane In tetrahydrofuran at -78 - 20℃; for 3h;

Reference： [1]Nath, Dinesh; Fleming, Fraser F. [Angewandte Chemie - International Edition, 2011, vol. 50, # 49, p. 11790 - 11793]
[2]Nath, Dinesh; Fleming, Fraser F. [Chemistry - A European Journal, 2013, vol. 19, # 6, p. 2023 - 2029]
[3]Nath, Dinesh; Skilbeck, Melanie C.; Coldham, Iain; Fleming, Fraser F. [Organic Letters, 2014, vol. 16, # 1, p. 62 - 65]

52
[ 4254-02-8 ]
[ 6140-63-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: lithium hexamethyldisilazane / tetrahydrofuran / 0.58 h / -78 °C 1.2: -78 - 20 °C 2.1: diisobutylaluminium hydride / dichloromethane / 0.5 h / -78 °C
	Multi-step reaction with 2 steps 1.1: lithium hexamethyldisilazane / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 1.2: -78 - 20 °C 2.1: diisobutylaluminium hydride / dichloromethane / 0.25 h / -78 °C / Inert atmosphere 2.2: 1 h
	Multi-step reaction with 2 steps 1.1: lithium hexamethyldisilazane / tetrahydrofuran / 0.58 h / -78 °C 1.2: -78 - 20 °C 2.1: diisobutylaluminium hydride / dichloromethane / 0.5 h / -78 °C

	Multi-step reaction with 2 steps 1.1: lithium hexamethyldisilazane / tetrahydrofuran / 30 ms / -78 °C / Inert atmosphere 1.2: 20 °C 2.1: diisobutylaluminium hydride / dichloromethane / 0.25 h / -78 °C / Inert atmosphere
	Multi-step reaction with 2 steps 1.1: lithium hexamethyldisilazane / tetrahydrofuran / 0.5 h / -70 °C 1.2: 16 h / -70 - 20 °C 2.1: diisobutylaluminium hydride / toluene; dichloromethane / 0.5 h / -65 °C 2.2: 0.17 h / -40 - 25 °C

Reference： [1]Current Patent Assignee: VERTEX PHARMACEUTICALS (OLD) - WO2013/19828, 2013, A1
[2]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2016/20526, 2016, A1
[3]Farmer, Luc J.; Clark, Michael P.; Boyd, Michael J.; Perola, Emanuele; Jones, Steven M.; Tsai, Alice; Jacobs, Marc D.; Bandarage, Upul K.; Ledeboer, Mark W.; Wang, Tiansheng; Deng, Hongbo; Ledford, Brian; Gu, Wenxin; Duffy, John P.; Bethiel, Randy S.; Shannon, Dean; Byrn, Randal A.; Leeman, Joshua R.; Rijnbrand, Rene; Bennett, Hamilton B.; O’Brien, Colleen; Memmott, Christine; Nti-Addae, Kwame; Bennani, Youssef L.; Charifson, Paul S. [ACS Medicinal Chemistry Letters, 2017, vol. 8, # 2, p. 256 - 260]
[4]Current Patent Assignee: JOHNSON & JOHNSON INC - US2017/253600, 2017, A1
[5]Current Patent Assignee: PFIZER INC - US2020/95239, 2020, A1

53
[ 4254-02-8 ]
[ 1422051-86-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: lithium hexamethyldisilazane / tetrahydrofuran / 0.58 h / -78 °C 1.2: -78 - 20 °C 2.1: diisobutylaluminium hydride / dichloromethane / 0.5 h / -78 °C 3.1: ammonium acetate / ethanol / 12 h / Reflux 3.2: 2 h / Reflux
	Multi-step reaction with 3 steps 1.1: lithium hexamethyldisilazane / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 1.2: -78 - 20 °C 2.1: diisobutylaluminium hydride / dichloromethane / 0.25 h / -78 °C / Inert atmosphere 2.2: 1 h 3.1: ammonium acetate / ethanol / 80 °C / Sealed tube 3.2: 2 h / 80 °C
	Multi-step reaction with 4 steps 1.1: lithium hexamethyldisilazane / tetrahydrofuran / 0.58 h / -78 °C 1.2: -78 - 20 °C 2.1: diisobutylaluminium hydride / dichloromethane / 0.5 h / -78 °C 3.1: ammonium acetate / 12 h / 80 °C 4.1: sulfuric acid / 2 h / Reflux

Multi-step reaction with 4 steps 1.1: lithium hexamethyldisilazane / tetrahydrofuran / 30 ms / -78 °C / Inert atmosphere 1.2: 20 °C 2.1: diisobutylaluminium hydride / dichloromethane / 0.25 h / -78 °C / Inert atmosphere 3.1: ammonium acetate / ethanol / 80 °C / Sealed tube 4.1: thionyl chloride / 6 h / 0 °C / Reflux

Reference： [1]Current Patent Assignee: VERTEX PHARMACEUTICALS (OLD) - WO2013/19828, 2013, A1
[2]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2016/20526, 2016, A1
[3]Farmer, Luc J.; Clark, Michael P.; Boyd, Michael J.; Perola, Emanuele; Jones, Steven M.; Tsai, Alice; Jacobs, Marc D.; Bandarage, Upul K.; Ledeboer, Mark W.; Wang, Tiansheng; Deng, Hongbo; Ledford, Brian; Gu, Wenxin; Duffy, John P.; Bethiel, Randy S.; Shannon, Dean; Byrn, Randal A.; Leeman, Joshua R.; Rijnbrand, Rene; Bennett, Hamilton B.; O’Brien, Colleen; Memmott, Christine; Nti-Addae, Kwame; Bennani, Youssef L.; Charifson, Paul S. [ACS Medicinal Chemistry Letters, 2017, vol. 8, # 2, p. 256 - 260]
[4]Current Patent Assignee: JOHNSON & JOHNSON INC - US2017/253600, 2017, A1

54
[ 4254-02-8 ]
[ 74-88-4 ]
[ 64871-70-1 ]

Yield	Reaction Conditions	Operation in experiment
65.4%	Stage #1: cyclopentanecarbonitrile With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 1h; Stage #2: methyl iodide In tetrahydrofuran at -78℃; for 1h;	34.1 Step 1 To a solution of the 529a (4.13 g, 43.5 mmol) in THF (100 mL) was added LDA (1M, 87 ml, 87 mmol) dropwise at -78°C. The mixture was allowed to stir at -78°C for 1 hour, and then to the mixture was added Mel (12.3 g, 87 mmol). The mixture was allowed to stir at -78°C for 1 hour before quenched with NH4CIsolution, extracted with ethyl acetate. The organic layer was washed with water and dried over Na2S04. After concentrated in vacuo, the resulting residue was purified using flash column chromatography on silica gel, eluting with petroleum ether: ethyl acetate (20/1-10/1) to provide 529b (3.1 g, 65.4 %)
65%	Stage #1: cyclopentanecarbonitrile With lithium hexamethyldisilazane In tetrahydrofuran at -70℃; for 0.5h; Stage #2: methyl iodide In tetrahydrofuran at -70 - 20℃; for 16h;	1.1A Step 1A. 1-Methylcyclopentane-1-carbonitrile To a solution of LHMDS (280 mL, 280 mmol, 1 M solution in THF) at -70° C. was added dropwise a solution of cyclopentanecarbonitrile (26.67 g, 280.3 mmol) in THF (20 mL) over 15 min. After stirring for 30 min, iodomethane (59.7 g, 26.2 mL, 420 mmol) was added dropwise, and the reaction was allowed to warm to ambient temperature and stirred for 16 h. The resulting yellow solution was cooled to 0° C. and quenched with saturated aqueous NH4Cl solution (200 mL) and water (100 mL). The mixture was extracted with MTBE (2.5 L*2), and the combined organic extracts were washed with brine (1 L), dried over Na2SO4, and filtered. The filtrate was concentrated in vacuo. The crude product was purified twice using silica gel column chromatography (100% petroleum ether) to afford 60 g (65%) of the title compound as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 2.20-2.10 (m, 2H), 1.90-1.70 (m, 4H), 1.65-1.55 (m, 2H), 1.41 (s, 3H).
4.7 g	Stage #1: cyclopentanecarbonitrile With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; for 0.583333h; Stage #2: methyl iodide In tetrahydrofuran at -78 - 20℃;	1 Formation of 1-methylcyclopentanecarbonitrile (31a) Formation of 1-methylcyclopentanecarbonitrile (31a)To a cold (-78 °C) solution of LiHMDS (48.0 mL of 1 M solution in tetrahydrofuran, 48.0 mmol) in tetrahydrofuran was added dropwise a solution of cyclopentanecarbonitrile (3.81 g, 40.0 mmol) in tetrahydrofuran (10 mL) over a 5 minute period. After stirring at -78 °C for thirty minutes, methyl iodide (3.74 mL, 60.00 mmol) was added in one portion. The reaction was allowed to warm to room temperature overnight. The solution was cooled to 0 °C, ethyl acetate (50 mL) and aqueous saturated ammonium chloride solution (20 mL) was added. Additional water (10 mL) was added to dissolve the solid. The organic layer was separated and washed with aqueous saturated ammonium chloride (20 mL). The aqueous layer was extracted with ethyl acetate (2 X 20 mL). The combined organic phases were washed with brine, dried (MgS04), filtered and concentrated in vacuo to give a 4.7g of a yellow oil that was used without further purification: 1H NMR (400 MHz, CDC13) δ 2.04 - 1.93 (m, 2H), 1.77- 1.65 (m, 2H), 1.66 - 1.55 (m, 2H), 1.54 (m, 2H), 1.25 (s, 3H).

16.8 g	Stage #1: cyclopentanecarbonitrile With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; for 0.5h; Inert atmosphere; Stage #2: methyl iodide In tetrahydrofuran at -78 - 20℃;	1 Step 1 . Under nitrogen, LiHMDS (1 M in THF) (189 mL, 189 mmol) was added dropwise to a solution of cyclopentanecarbonitrile (15 g, 158 mmol) in THF (64 mL) at -78 °C. The mixture was then stirred at 30 min and CH3I (14.7 mL, 240 mmol) was added in one portion and the mixture was slowly warmed to rt overnight. EtOAc (250 mL) was added and NH4CI 10% (200 mL) was slowly added at 0°C. Then water (100 mL) was added to form a solution and the organic layer was separated and washed with brine, dried and concentrated to give 1 - methylcyclopentanecarbonitrile (16.8 g, yellow oil) that was used without purification in the next step.
4.7 g	Stage #1: cyclopentanecarbonitrile With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; for 0.583333h; Stage #2: methyl iodide In tetrahydrofuran at -78 - 20℃;
	Stage #1: cyclopentanecarbonitrile With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; Inert atmosphere; Stage #2: methyl iodide In tetrahydrofuran at 20℃;	Step 1. Under nitrogen, LiHMDS (1M in THF) (189 mL, 189 mmol) was added dropwise to a solution of cyclopentanecarbonitrile (15 g, 158 mmol) in THF (64 mL) at -78° C. The mixture was then stirred at 30 min and CH3I (14.7 mL, 240 mmol) was added in one portion and the mixture was slowly warmed to rt overnight. EtOAc (250 mL) was added and NH4Cl 10% (200 mL) was slowly added at 0° C. Then water (100 mL) was added to form a solution and the organic layer was separated and washed with brine, dried and concentrated to give 1-methylcyclopentanecarbonitrile (16.8 g, yellow oil) that was used without purification in the next step.

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2014/110705, 2014, A1 Location in patent: Page/Page column 147-148
[2]Current Patent Assignee: PFIZER INC - US2020/95239, 2020, A1 Location in patent: Paragraph 0549; 0550
[3]Current Patent Assignee: VERTEX PHARMACEUTICALS (OLD) - WO2013/19828, 2013, A1 Location in patent: Page/Page column 69
[4]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2016/20526, 2016, A1 Location in patent: Page/Page column 69; 70
[5]Farmer, Luc J.; Clark, Michael P.; Boyd, Michael J.; Perola, Emanuele; Jones, Steven M.; Tsai, Alice; Jacobs, Marc D.; Bandarage, Upul K.; Ledeboer, Mark W.; Wang, Tiansheng; Deng, Hongbo; Ledford, Brian; Gu, Wenxin; Duffy, John P.; Bethiel, Randy S.; Shannon, Dean; Byrn, Randal A.; Leeman, Joshua R.; Rijnbrand, Rene; Bennett, Hamilton B.; O’Brien, Colleen; Memmott, Christine; Nti-Addae, Kwame; Bennani, Youssef L.; Charifson, Paul S. [ACS Medicinal Chemistry Letters, 2017, vol. 8, # 2, p. 256 - 260]
[6]Current Patent Assignee: JOHNSON & JOHNSON INC - US2017/253600, 2017, A1 Location in patent: Paragraph 0132

55
[ 4254-02-8 ]
(SS,E)-N-ethylidene-2-methylpropane-2-sulfinamide [ No CAS ]
[ 1426422-20-9 ]

Yield	Reaction Conditions	Operation in experiment
1.96 g	Stage #1: cyclopentanecarbonitrile With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; for 0.5h; Stage #2: (S<SUB>S</SUB>,E)-N-ethylidene-2-methylpropane-2-sulfinamide In tetrahydrofuran at -78℃; for 2h;	100.2 Step 2(S)-2 -Methyl-propane -2-sulfinic acid [(R)-l -(1 -cyano-cyclopentyl)-ethyl]-amide Step 2(S)-2 -Methyl-propane -2-sulfinic acid [(R)-l -(1 -cyano-cyclopentyl)-ethyl]-amideIn a flask, cyclopentanecarbonitrile (3.53 g, 37.1 mmol) was dissolved in THF (40 mL) and cooled at -78°C. LiHMDS (1.0 M in THF, 41 mL, 41 mmol) was added and the mixture stirred for 30 min at -78°C. A solution of (S)-2 -methyl-propane -2-sulfinic acid (E)-ethylideneamide (crude from step 1 , 1.82 g, 12.4 mmol) in THF (10 mL) was slowly added. The mixture was stirred at -78°C for 2 h then allowed to warm to room temperature overnight. The reaction mixture was quenched with saturated aqueous ammonium chloride and extracted with EtOAc. The combined organics were washed with brine, dried over MgS04 and concentrated. The residue was purified by Si02 chromatography (50-100% EtO Ac/heptane) to afford 1.96 g (65%) of (S)-2 -methyl-propane -2-sulfinic acid [(R)-l-(l-cyano-cyclopentyl)-ethyl]-amide as a white solid.

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - WO2013/30138, 2013, A1 Location in patent: Page/Page column 260

56
[ 4254-02-8 ]
[ 60-12-8 ]
[ 1215641-04-5 ]

Yield	Reaction Conditions	Operation in experiment
83%	With carbonyl bis(hydrido)tris(triphenylphosphine)ruthenium(II); sodium hydride; 1,3-di(propan-2-yl)-1H-imidazol-3-ium bromide In toluene at 110℃; for 48h; Sealed tube; Inert atmosphere; Glovebox; Green chemistry;

Reference： [1]Kang, Byungjoon; Fu, Zhenqian; Hong, Soon Hyeok [Journal of the American Chemical Society, 2013, vol. 135, # 32, p. 11704 - 11707]

57
[ 4254-02-8 ]
[ 26759-46-6 ]
[ 1448676-59-2 ]

Yield	Reaction Conditions	Operation in experiment
69%	With hydrogenchloride In 1,4-dioxane at 100℃; for 15h; Inert atmosphere;

Reference： [1]Peddibhotla, Satyamaheshwar; Hedrick, Michael P.; Hershberger, Paul; Maloney, Patrick R.; Li, Yujie; Milewski, Monika; Gosalia, Palak; Gray, Wilson; Mehta, Alka; Sugarman, Eliot; Hood, Becky; Suyama, Eigo; Nguyen, Kevin; Heynen-Genel, Susanne; Vasile, Stefan; Salaniwal, Sumeet; Stonich, Derek; Su, Ying; Mangravita-Novo, Arianna; Vicchiarelli, Michael; Roth, Gregory P.; Smith, Layton H.; Chung, Thomas D. Y.; Hanson, Glen R.; Thomas, James B.; Caron, Marc G.; Barak, Lawrence S.; Pinkerton, Anthony B. [ACS Medicinal Chemistry Letters, 2013, vol. 4, # 9, p. 846 - 851]

58
[ 4254-02-8 ]
[ 3866-16-8 ]
[ 333-27-7 ]
C₁₃H₁₆N₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56%	Stage #1: cyclopentanecarbonitrile With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 0.333333h; Stage #2: 3-methoxyphenyl azide With N,N,N,N,N,N-hexamethylphosphoric triamide In tetrahydrofuran at -78 - 20℃; for 1h; Stage #3: methyl trifluoromethanesulfonate at 20℃; for 1h;

Reference： [1]Huh, Chan Woo; Aube, Jeffrey [Chemical Science, 2014, vol. 5, # 2, p. 699 - 706]

59
[ 4254-02-8 ]
cyclopropylmethyl-amine hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	Stage #1: cyclopentanecarbonitrile With [Ru(H)(BH₄)(CO)(PPh₃)(3-(di-tert-butylphosphino)-N-((1-methyl-1H-imidazol-2 yl)methyl)propylamine)]; hydrogen In isopropanol at 70℃; for 3h; Inert atmosphere; Autoclave; Stage #2: With hydrogenchloride In methanol; isopropanol at 20℃; for 0.5h; Inert atmosphere; Autoclave;
84 %Chromat.	With (Ru(1,2:5,6-η-1,5-cyclooctadiene)(η(3)-methallyl)2); 2-((dicyclohexylphosphino)methyl)-1-methyl-1H-imidazolin; potassium-t-butoxide; hydrogen bromide; hydrogen In tetrahydrofuran; water monomer; acetone; toluene at 100℃; for 5.5h; Inert atmosphere; Schlenk technique; Autoclave;
	Multi-step reaction with 2 steps 1: Ru-MACHO-BH; hydrogen / isopropanol / 3 h / 100 °C / 22502.3 Torr / Autoclave 2: hydrogenchloride / isopropanol; diethyl ether; methanol

	Multi-step reaction with 2 steps 1: Raney nickel / ethanol / 16 h / 20 °C 2: hydrogenchloride / dichloromethane; 1,4-dioxane / 16 h / 20 °C
	Multi-step reaction with 2 steps 1: C₂₂H₃₃N / neat (no solvent) / 16 h / 60 °C / Inert atmosphere; Glovebox; Sealed tube 2: hydrogenchloride / diethyl ether / Inert atmosphere

Reference： [1]Adam, Rosa; Alberico, Elisabetta; Baumann, Wolfgang; Drexler, Hans-Joachim; Jackstell, Ralf; Junge, Henrik; Beller, Matthias [Chemistry - A European Journal, 2016, vol. 22, # 14, p. 4991 - 5002]
[2]Werkmeister, Svenja; Junge, Kathrin; Wendt, Bianca; Spannenberg, Anke; Jiao, Haijun; Bornschein, Christoph; Beller, Matthias [Chemistry - A European Journal, 2014, vol. 20, # 15, p. 4227 - 4231]
[3]Neumann, Jacob; Bornschein, Christoph; Jiao, Haijun; Junge, Kathrin; Beller, Matthias [European Journal of Organic Chemistry, 2015, vol. 2015, # 27, p. 5944 - 5948]
[4]Current Patent Assignee: SUZHOU ABOGEN BIOSCIENCES - CN112979483, 2021, A
[5]Gautam, Nimisha; Logdi, Ratan; Mandal, Swadhin K.; Rajendran, N. M.; Sreejyothi, P.; Tiwari, Ashwani K. [Chemical Communications, 2022, vol. 58, # 18, p. 3047 - 3050]

60
[ 4254-02-8 ]
[ 64-17-5 ]
[ 52186-80-8 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride In 1,4-dioxane at 20℃;	221.1 Step 1. Preparation of ethyl cyclopentanecarbimidate A solution of cyclopentanecarbonitrile (10.0 g, 105.1 mmol) in EtOH (7 mL) was treated with HCl (4.0 M in dioxane, 105 mL, 3.02 mol) and the mixture stirred at rt overnight. After this time, nitrogen gas was passed through the mixture and the mixture was concentrated. The residue was treated with ether and reconcentrated. The residue was again suspended in ether and filtered to afford the title compound (16.0 g, crude) as a white solid. MW = 141.21. ]H NMR (CDC13, 500 MHz) δ 4.79-4.46 (m, 2H), 3.43-3.23 (m, 1H), 2.76 (s, 1H), 2.20-2.00 (m, 2H), 1.86-1.63 (m, 6H), 1.55-1.40 (m, 3H); APCI MS m/z 142 [M + H]+.

Reference： [1]Current Patent Assignee: TETRA DISCOVERY PARTNERS - WO2014/66659, 2014, A1 Location in patent: Page/Page column 0881

61
[ 4254-02-8 ]
[ 124-38-9 ]
[ 625-95-6 ]
[ 1646594-92-4 ]

Yield	Reaction Conditions	Operation in experiment
86%	Stage #1: cyclopentanecarbonitrile With 4,5’-bis(diphenylphosphino)-9,9’-dimethylxanthene; palladium diacetate; sodium hexamethyldisilazane In toluene for 0.0833333h; Glovebox; Inert atmosphere; Stage #2: carbon dioxide; 3-Iodotoluene In toluene at 80℃; for 16h; Glovebox; Inert atmosphere; Autoclave;

Reference： [1]Schranck, Johannes; Burhardt, Mia; Bornschein, Christoph; Neumann, Helfried; Skrydstrup, Troels; Beller, Matthias [Chemistry - A European Journal, 2014, vol. 20, # 31, p. 9534 - 9538]

62
[ 4254-02-8 ]
[ 110-63-4 ]
1-(cyclopentylmethyl)-2,5-pyrrolidinedione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	With dihydridotetrakis(triphenylphosphine)ruthenium; sodium hydride; 1,3-di(propan-2-yl)-1H-imidazol-3-ium bromide In benzene at 80℃; for 18h; Glovebox; Inert atmosphere; Reflux;

Reference： [1]Kim, Jaewoon; Hong, Soon Hyeok [Organic Letters, 2014, vol. 16, # 17, p. 4404 - 4407]

63
[ 164513-32-0 ]
[ 4254-02-8 ]
1-(2-bromo-5-((tert-butyl(dimethyl)silyl)oxy)benzyl)cyclopentanecarbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
471 mg	Stage #1: cyclopentanecarbonitrile With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -78 - 0℃; for 0.5h; Inert atmosphere; Stage #2: (4-bromo-3-(bromomethyl)phenoxy)(tert-butyl)dimethylsilane In tetrahydrofuran; hexane at -78℃; for 4h; Inert atmosphere;	41.A A) 1-(2-bromo-5-((tert-butyl(dimethyl)silyl)oxy)benzyl)cyclopentanecarbonitrile A) 1-(2-bromo-5-((tert-butyl(dimethyl)silyl)oxy)benzyl)cyclopentanecarbonitrile Under a nitrogen atmosphere, to a solution of diisopropylamine (0.36 mL) in THF (7.0 mL) was added a 1.6 M solution of n-butyllithium in hexane (1.6 mL) at 0°C, and the mixture was stirred for 10 min. Cyclopentanecarbonitrile (0.28 mL) was added at -78°C, and the mixture was stirred for 30 min. A solution of (4-bromo-3-(bromomethyl)phenoxy)(tert-butyl)dimethylsilane (503 mg) in THF (3.0 mL) was added, and the mixture was stirred at -78°C for 4 hr. To the reaction mixture was added saturated aqueous ammonium chloride solution, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (471 mg) as a colorless oil. 1H NMR (400 MHz, DMSO-d6) δ 0.20 (6H, s), 0.94 (9H, s), 1.67-1.89 (6H, m), 1.91-2.03 (2H, m), 3.07 (2H, s), 6.75 (1H, dd, J = 8.7, 2.8 Hz), 7.02 (1H, d, J = 2.9 Hz), 7.49 (1H, d, J = 8.7 Hz).

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - EP2816023, 2014, A1 Location in patent: Paragraph 0507; 0508

64
[ 4254-02-8 ]
[ 106-39-8 ]
[ 64399-26-4 ]

Yield	Reaction Conditions	Operation in experiment
71%	With tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; lithium hexamethyldisilazane In tetrahydrofuran at 80℃; for 3h; Inert atmosphere;

Reference： [1]McCabe Dunn, Jamie M.; Kuethe, Jeffrey T.; Orr, Robert K.; Tudge, Matthew; Campeau, Louis-Charles [Organic Letters, 2014, vol. 16, # 24, p. 6314 - 6317]

65
[ 4254-02-8 ]
[ 441024-85-7 ]

Yield	Reaction Conditions	Operation in experiment
84%	With sodium azide; silver(I) triflimide In toluene at 85℃; for 5h;	Synthesis of 5-substituted 1H-tetrazoles; general procedure General procedure: A mixture of the appropriate nitrile (1 mmol), NaN3 (1.5 mmol),toluene (2 mL) and AgNTf2 (5 mol%) was placed in a round bottomed flask and heated at 85 oC. The progress of the reaction was monitored by TLC. After the completion of the reaction, the reaction mixture was cooled and treated with ethyl acetate (15 mL) and 1M HCl (15 mL)and stirred vigorously. The resultant organic layer was separated and the aqueous layer was extracted with ethyl acetate (3 × 10 mL). The combined organic layer was washed with water and concentrated to give the pure tetrazole. All the products are known compounds and the spectral data and melting points were identical to those reported in the literature. The disappearance of one strong and sharp absorption band (CN stretching band), and the appearance of an NH stretching band in the IR spectra, were characteristic of the formation of 5-substituted 1H-tetrazoles.
77%	With sodium azide; tetra(n-butyl)ammonium hydrogensulfate In water at 85℃; for 9h; Green chemistry;	General Procedure for Preparation of Tetrazoles in Water(Method II). General procedure: General Procedure for Preparation of Tetrazoles in Water(Method II). TBAHS (0.25 mmol) was added to a mixture of nitrile (1 mmol), sodium azide (1.5 mmol), and 2 mL H2O in around-bottomed flask. The reaction mixture was heated to 85 °C. After completion of the reaction (as monitored by TLC), the crude reaction mixture was transferred into a separatory funnel, to which was added 1 N HCl (15 mL) extracted by ethylacetate (EtOAc, 10 mL × 5). The combined organic layers were washed with H2O and dried over anhydrous sodium sulfate, and were evaporated under reduced pressure to give pure 5-substituted-1H-tetrazole.

Reference： [1]Wang, Hongshe; Zhao, Weixing [Journal of Chemical Research, 2015, vol. 39, # 6, p. 321 - 323]
[2]Wang, Zengtao; Liu, Zhiguo; Cheon, Seung Hoon [Bulletin of the Korean Chemical Society, 2015, vol. 36, # 1, p. 198 - 202]

66
[ 67-56-1 ]
[ 4254-02-8 ]
N-(cyclopentylmethyl)formamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	With C₄₆H₄₈N₂OP₂Ru In benzene at 90℃; for 10h; Inert atmosphere; Glovebox; Green chemistry;

Reference： [1]Kang, Byungjoon; Hong, Soon Hyeok [Advanced Synthesis and Catalysis, 2015, vol. 357, # 4, p. 834 - 840]

67
[ 4254-02-8 ]
[ 52022-82-9 ]
(E)-1-(penta-2,4-dienyl)cyclopentanecarbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	Stage #1: cyclopentanecarbonitrile With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 1h; Inert atmosphere; Stage #2: (E)-5-bromopenta-1,3-diene In tetrahydrofuran at -78 - 20℃; for 2h; Inert atmosphere; Glovebox;

Reference： [1]Yang, Zehua; Xia, Chao; Liu, Delong; Liu, Yangang; Sugiya, Masashi; Imamoto, Tsuneo; Zhang, Wanbin [Organic and Biomolecular Chemistry, 2015, vol. 13, # 9, p. 2694 - 2702]

68
[ 100-42-5 ]
[ 4254-02-8 ]
2-((trifluoromethyl)thio)benzo[d]isothiazol-3(2H)-one 1,1-dioxide [ No CAS ]
N-(1-phenyl-2-((trifluoromethyl)thio)ethyl)cyclopentanecarboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%	With trifluorormethanesulfonic acid; bis(4-methoxyphenyl)selenide In hexane; water at 20℃; for 24h; Sealed tube;

Reference： [1]Luo, Jie; Zhu, Zechen; Liu, Yannan; Zhao, Xiaodan [Organic Letters, 2015, vol. 17, # 14, p. 3620 - 3623]

69
[ 4254-02-8 ]
[ 130250-58-7 ]
5-(1-cyanocyclopentyl)-N-methoxy-N-methylpentanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	Stage #1: cyclopentanecarbonitrile With lithium diisopropyl amide In tetrahydrofuran at -78 - 20℃; for 1h; Stage #2: 5-bromo-N-methoxy-N-methylpentanamide In tetrahydrofuran at -78 - 20℃; for 12h; chemoselective reaction;

Reference： [1]Yang, Xun; Nath, Dinesh; Fleming, Fraser F. [Organic Letters, 2015, vol. 17, # 19, p. 4906 - 4909]

70
[ 4254-02-8 ]
[ 130250-58-7 ]
1-(5-bromopentanoyl)cyclopentane-1-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%	Stage #1: cyclopentanecarbonitrile With lithium diisopropyl amide In tetrahydrofuran at -78 - 20℃; for 1h; Stage #2: With isopropylmagnesium chloride In tetrahydrofuran for 0.25h; Stage #3: 5-bromo-N-methoxy-N-methylpentanamide In tetrahydrofuran at -78 - 20℃; for 12h; chemoselective reaction;

Reference： [1]Yang, Xun; Nath, Dinesh; Fleming, Fraser F. [Organic Letters, 2015, vol. 17, # 19, p. 4906 - 4909]

71
[ 67-56-1 ]
[ 4254-02-8 ]
[ 75098-42-9 ]

Yield	Reaction Conditions	Operation in experiment
		In 52.7 ml of tetrahydrofuran solution containing 1M boron (52.7 mmol, 1.1 eq), and gradually added dropwise 20 ml cyclopentanecarbonitrile containing 4.56 g (47.9 mmol) in anhydrous tetrahydrofuran is added over 2 hours, after this solution was stirred at reflux for 18 hours, the reaction was cooled to ambient temperature, carefully added to a small portion of methanol diluted (67 ml), and the solution was then placed in an ice bath and hydrogen chloride gas was 0.5 hours, and then the reaction was refluxed for 1.5 hours, manner by vacuum rotary evaporation to remove volatiles, 50 ml of methanol to the residue, the mixture was rotary evaporated in vacuo, methanol was added steps are repeated twice to obtain a white solid was subjected to further purification in ethanol: ethyl ester solvents precipitated 3.62 g of hydrogen chloride (cyclopentyl) methylamine hydrochloride, 56% yield.

Reference： [1]Patent: TWI525093,2016,B .Location in patent: Page/Page column 88; 90

72
[ 4254-02-8 ]
[ 4815-32-1 ]
C₁₂H₁₄N₂OS [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 496 - 500

73
[ 4254-02-8 ]
[ 108-86-1 ]
[ 77-57-6 ]

Reference： [1]Organic Letters,2017,vol. 19,p. 3446 - 3449

74
[ 4254-02-8 ]
[ 99623-12-8 ]

Yield	Reaction Conditions	Operation in experiment
74%	With hydroxylamine hydrochloride; sodium ethanolate In ethanol at 25 - 90℃; for 16h;	N-hydroxy cyclopentane carboximidamide To a solution of cyclopentane carbonitrile (1.00 g, 10.5 mmol) in ethanol (10.0 mL) were added hydroxylamine hydrochloride (803 mg, 11.6 mmol) and sodium ethanolate (858 mg, 12.6 mmol) at 25 °C. The reaction mixture was stirred at 90 °C for 16 hours. The mixture was filtered, and the filtrate was concentrated in vacuo to give N-hydroxy cyclopentane carboximidamide (1.00 g, 74% yield) as light yellow oil. LC-MS (method 4): Rt= 0.149 min; MS (ESIpos): m/z = 129.0 [M+H]+
	With hydroxylamine hydrochloride; triethylamine In ethanol at 75℃; for 14h;	N-hydroxycyclopentanecarboximidamide To a stirred mixture of cyclopentanecarbonitrile (1.00 g, 98 % purity, 10.3 mmol) and hydroxylamine hydrochloride (876 mg, 98 % purity, 12.4 mmol) in ethanol (10 mL) was added triethylamine (2.2 mL, 15 mmol), and the mixture was heated to 75CC for 14 h. The mixture was cooled to r.t., diethyl ether was added and a solid was removed by filtration. The solutionwas concentrated in vacuum. Diethyl ether was added to the residue, the mixture was stirred and again, a solid was removed by filtration. The solution was concentrated in vacuum to give 0.65 g of the title compound as a crude product that was used without further purification. LC-MS (Method 2): R = 0.57 mm; MS (ESipos): m/z = 129 [M+H]1.576 (9.74), 1.583(5.18), 1.611 (4.77),(2.10), 1.646 (2.59),(4.23), 1.679 (3.96),(2.99), 1.718 (3.28),(1.19), 1.743 (0.82),(1.25), 1.920 (1.09),(1.05), 1.943 (1.11),(0.47), 1.976 (0.62),(0.57), 2.368 (3.27),(1.49), 2.409 (2.89),(4.88), 2.872 (0.84),(0.98), 2.926 (1.33), 2.930 (0.88), 2.946 (0.54), 5.241 (9.25), 8.733 (6.43).1.605 (6.46), 1.6091.638 (2.30), 1.6421.669 (6.27), 1.6771.707 (6.87), 1.7151.736 (1.73), 1.7391.914 (1.52), 1.9181.938 (0.90), 1.9411.969 (0.77), 1.9732.355 (0.59), 2.3582.5172.9131H-NMR (400MHz, DMSQ-d6)ö[ppm]:1.405(0.46),1.410(0.50),1.414 (0.67),1.417(0.65),1.421(0.89),1.425 (1.10),1.432(1.65),1.441(2.49),1.445(4.74),1.448 (4.53),1.455(6.07),1.458(6.87),1.462 (4.86),1.465(4.66),1.472(3.11),1.475(2.97),1.481 (2.83),1.483(2.79),1.488(2.65),1.495 (1.88),1.500(1.64),1.505(1.30),1.512(1.03),1.517 (1.26),1.520(1.29),1.526(2.12),1.533 (2.56),1.535(3.01),1.538(3.27),1.541(3.73),1.546 (4.38),1.549(4.07),1.552(4.53),1.554 (5.91),1.557(6.02),1.559(5.09),1.562(5.68),1.566 (7.60),1.571(8.03),(16.00), 1.587 (13.59), 1.591 (13.44), 1.597 (8.52),1.618 (3.33),1.648 (2.59),1.688 (8.76),1.721 (3.66),1.885 (1.39),1.923 (1.34),1.947 (2.19),1.978 (0.66),2.3761.622 (2.81),1.653 (2.33),1.693 (6.26),1.726 (2.39),1.900 (0.48),1.925 (1.60),1.957 (1.48),1.980 (0.65),1.628 (3.65), 1.635 (2.16),1.658 (4.23), 1.663 (7.67),1.703 (7.30), 1.705 (6.79),1.728 (2.29), 1.732 (1.80),1.905 (0.70), 1.908 (1.01),1.928 (2.55), 1.933 (1.93),1.961 (0.96), 1.964 (0.61),2.349 (1.24), 2.351 (0.64),(1.38), 2.380 (1.50), 2.382 (1.58), 2.388 (4.88), 2.396 (2.01), 2.4032.414 (1.03), 2.423 (0.50), 2.430(1.11), 2.496 (1.18), 2.500 (0.79),2.889 (1.64), 2.893 (1.35), 2.895 (0.57), 2.906 (1.23), 2.910 (2.12),

Reference： [1]Current Patent Assignee: Helmholtz Association; BAYER AG - WO2021/214020, 2021, A1 Location in patent: Page/Page column 194
[2]Current Patent Assignee: BAYER AG - WO2017/102091, 2017, A1 Location in patent: Page/Page column 383; 384

75
[ 625-28-5 ]
[ 142-29-0 ]
[ 4254-02-8 ]

Yield	Reaction Conditions	Operation in experiment
83 %Chromat.	With bis(1,5-cyclooctadiene)nickel ⁽⁰⁾; dimethylaluminum chloride; bis[2-(diphenylphosphino)phenyl] ether In hexane; toluene at 100℃; for 16h; Inert atmosphere; Glovebox;	3 Isovaleronitrile 5 (0.26 mL, 2.50 mmol), cyclopentene 33 (44 pL, 0.50 mmol) and 1.OM solution of AIMe2CI in hexane (0.10 mL, 0.10 mmol) were added sequentiallyto a solution of Ni(COD)2 (6.9 mg, 5 mol%) and DPEphos (13.5 mg, 5 mol%) intoluene (1 .0 mL) prepared in a 25 mL pressure tube under an argon atmosphere ina glove box. The pressure tube was taken out of the glove box and heated at 10000 for 16 hours. After that time, the reaction was cooled down to roomtemperature, and n-dodecane (100 pL) as internal standard was added to thesolution. The reaction mixture was analyzed by GO and the yield of 34 determinedby comparing their peak areas to that of the internal standard. (Retention time:6.38 mm, GO yield: 83%)

Reference： [1]Current Patent Assignee: EVONIK INDUSTRIES AG - WO2017/93149, 2017, A1 Location in patent: Page/Page column 15

76
[ 4254-02-8 ]
[ 2227-79-4 ]
3-cyclopentyl-5-phenyl-1,2,4-thiadiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62%	Stage #1: cyclopentanecarbonitrile; benzenecarbothioamide With aluminum (III) chloride In acetic acid butyl ester at 70℃; for 5h; Sealed tube; Stage #2: With water; iodine In acetic acid butyl ester at 20℃; for 24h; Sealed tube; chemoselective reaction;

Reference： [1]Chai, Ling; Xu, Yuanqing; Ding, Tao; Fang, Xiaomin; Zhang, Wenkai; Wang, Yanpeng; Lu, Minghua; Xu, Hao; Yang, Xiaobo [Organic and Biomolecular Chemistry, 2017, vol. 15, # 39, p. 8410 - 8417]

77
[ 4254-02-8 ]
[ 80-17-1 ]
[ 5422-88-8 ]

Yield	Reaction Conditions	Operation in experiment
83%	With 1,10-Phenanthroline; water; palladium diacetate In N,N-dimethyl-formamide at 100℃; for 6h;

Reference： [1]Meng, Mengting; Yang, Liangfeng; Cheng, Kai; Qi, Chenze [Journal of Organic Chemistry, 2018, vol. 83, # 6, p. 3275 - 3284]

78
[ 4254-02-8 ]
[ 541-16-2 ]
[ 544435-71-4 ]

Yield	Reaction Conditions	Operation in experiment
97%	In neat (no solvent) at 80℃; for 2h;	Typical Experimental Procedure for the Reaction of Nitrilesand di-tert-Butyl Malonate General procedure: A mixture of 2-(3, 4-dichlorophenyl)acetonitrile (5 mmol), ditert-butyl malonate (3 mmol), and Fe(ClO4)3·H2O (5 mol%) wasplaced in a round-bottomed flask. Then, the reaction mixturewas heated at 80 °C for 5 h. After completion of the reactionmonitored by thin layer chromatography (TLC), water (10 mL)was added and the reaction mixture was extracted with ethylacetate (3 × 20 mL). The organic layers were collected, combined,washed with water (3 × 20 ml), dried over anhydrousNa2SO4, and concentrated under vacuum. The pure product wasobtained by directly passing through a silica gel (200-300mesh) column to give a white powder 1m (1.08 g, 84% yield).Compound 1m1H NMR (400 MHz, CDCl3): δ = 7.41-7.35 (m, 2 H), 7.12-7.10 (m,1 H), 5.31 (s, 1 H), 3.40 (s, 2 H), 1.32 (s, 9 H) ppm. 13C NMR (100MHz, CDCl3): δ = 168.9, 135.6, 132.7, 131.2, 131.2, 130.6, 128.6,51.6, 43.5, 28.7 ppm. HRMS: m/z calcd for C12H15Cl2NO [M + H]+:259.0531; found: 259.0533.

Reference： [1]Feng, Chengliang; Yan, Bin; Yin, Guibo; Chen, Junqing; Ji, Min [Synlett, 2018, vol. 29, # 17, p. 2257 - 2264]

79
[ 79762-54-2 ]
[ 4254-02-8 ]
1-(1H-indazol-6-yl)cyclopentane-1-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%	With N-Xantphos Pd G₄; lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 3h; Inert atmosphere; Sealed tube;

Reference： [1]Wright, Brandon A.; Ardolino, Michael J. [Journal of Organic Chemistry, 2019, vol. 84, # 8, p. 4670 - 4679]

80
[ 3637-61-4 ]
[ 4254-02-8 ]

Yield	Reaction Conditions	Operation in experiment
86%	With ammonia at 210℃; Inert atmosphere;
82%	With nitrogen; ammonia at 240℃; Heating;

Reference： [1]Wang, Yunzhu; Furukawa, Shinya; Zhang, Zhang; Torrente-Murciano, Laura; Khan, Saif A.; Yan, Ning [Catalysis science and technology, 2019, vol. 9, # 1, p. 86 - 96]
[2]Wang, Yunzhu; Furukawa, Shinya; Yan, Ning [ACS Catalysis, 2019, vol. 9, # 8, p. 6681 - 6691]

81
[ 4254-02-8 ]
cyclopentylmethanamine-d2 hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	Stage #1: cyclopentanecarbonitrile With ethyl [2]alcohol; sodium In hexane; mineral oil at 0℃; for 0.166667h; Inert atmosphere; Stage #2: With hydrogenchloride In diethyl ether
75%	Stage #1: cyclopentanecarbonitrile With ethyl [2]alcohol; sodium In hexane; mineral oil at 0℃; for 0.166667h; Inert atmosphere; Stage #2: With hydrogenchloride In diethyl ether; water Inert atmosphere;	23 Example 23 In a 10 mL single-necked flask, protected by nitrogen, 47.6 mg (0.50 mmol) of compound 3k, 5.0 mL of n-hexane, 188.3 mg (4.00 mmol) of deuterated ethanol (EtOD), and 317.2 mg (4.00 mmol) of sodium reagent were added. A dispersion system of sodium in mineral oil, in which the mass fraction of sodium is 29% by weight and the particle size is <15 μm. During the reaction, it was stirred at 0 ° C for 10 min. The temperature was raised to room temperature and the reaction was quenched with a saturated aqueous sodium bicarbonate solution. Add ether and saturated brine to extract,The organic phase was dried, concentrated hydrochloric acid was added diethyl ether,65.1 mg of the target compound 6k hydrochloride was obtained in a yield of 75%.

Reference： [1]Ding, Yuxuan; Luo, Shihui; Adijiang, Adila; Zhao, Hongye; An, Jie [Journal of Organic Chemistry, 2018, vol. 83, # 19, p. 12269 - 12274]
[2]Current Patent Assignee: CHINA AGRICULTURAL UNIVERSITY - CN110294660, 2019, A Location in patent: Paragraph 0156-0159

82
[ 4254-02-8 ]
[ 124517-47-1 ]
1-((1R,2R)-2-phenylcyclopropyl)cyclopentane-1-carbonitrile [ No CAS ]
C₁₅H₁₇N [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89 % ee	Stage #1: cyclopentanecarbonitrile With lithium bromide; lithium hexamethyldisilazane In tetrahydrofuran at 0 - 20℃; for 0.5h; Schlenk technique; Inert atmosphere; Stage #2: With bis(η3-allyl-μ-chloropalladium(II)); (4R,5R)-1,3-bis(4-(anthracen-9-yl)-2,6-diisopropylphenyl)-4,5-diphenyl-4,5-dihydro-1H-imidazol-3-ium tetrafluoroborate; potassium <i>tert</i>-butylate In tetrahydrofuran at 0 - 20℃; for 0.5h; Schlenk technique; Inert atmosphere; Stage #3: cinnamyl tert-butyl carbonate Overall yield = 90 %; Overall yield = 35.8 mg; Further stages;
	Stage #1: cyclopentanecarbonitrile With silver(I) bromide; lithium hexamethyldisilazane In tetrahydrofuran at 0 - 20℃; for 0.5h; Inert atmosphere; Stage #2: With (4R,5R)-1,3-bis(4-(anthracen-9-yl)-2,6-diisopropylphenyl)-4,5-diphenyl-4,5-dihydro-1H-imidazol-3-ium tetrafluoroborate; potassium <i>tert</i>-butylate; allylpalladium(II) chloride dimer In tetrahydrofuran at 0 - 20℃; for 0.5h; Stage #3: cinnamyl tert-butyl carbonate In tetrahydrofuran at -30℃; for 48h; Overall yield = 90 percent;	2; 41 Example 41 Under argon conditions, add (1.0mmol), lithium bromide (0.10mmol) and 1.0mL tetrahydrofuran to a 10mL reaction tube, add 2.0mL hexamethyldisilazide lithium (1.0M in THF) at 0°C, Return to room temperature and stir for 30 min. Add allyl palladium (II) chloride dimer (1.9 mg, 0.005 mmol) and nitrogen heterocyclic carbene ligand (system named (4R, 5R)- 1,3-bis(4-(anthracen-9-yl)-2,6-diisopropylphenyl)-4,5-diphenyl-4,5-dihydro-1H-imidazol-3-iumtetrafluoroborate)(9.8mg,0.010mmol) And tetrahydrofuran (1.0mL), add 25μL potassium tert-butoxide (1.0M in THF) at 0, stir at room temperature for 30min, combine the two reaction tubes and add cinnamyl tert-butyl carbonate (0.2mmol), the reaction is at -30 After stirring at for 48h, it was quenched by adding 0.5mL water and dried with anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the ratio of the two products obtained by column chromatography was 94.5:5.5, the total yield was 90%, and the purity of 1H NMR was greater than 95%.

Reference： [1]Zhang, Gao-Peng; Huang, Shuai; Jiang, Yang-Jie; Liu, Xiu-Yan; DIng, Chang-Hua; Wei, Yin; Hou, Xue-Long [Chemical Communications, 2019, vol. 55, # 45, p. 6449 - 6452]
[2]Current Patent Assignee: CHINESE ACADEMY OF SCIENCES - CN111362832, 2020, A Location in patent: Paragraph 0161-0163; 0278-0280

83
[ 4254-02-8 ]
[ 114583-20-9 ]

Yield	Reaction Conditions	Operation in experiment
47%	With bromine; phosphorus tribromide In neat (no solvent) at 60℃; Cooling with ice; Inert atmosphere;

Reference： [1]Dai, Lei; Xia, Zi-Hao; Gao, Yuan-Yuan; Gao, Zhong-Hua; Ye, Song [Angewandte Chemie - International Edition, 2019, vol. 58, # 50, p. 18124 - 18130][Angew. Chem., 2019, vol. 131, # 50, p. 18292 - 18298,7]

84
[ 4254-02-8 ]
[ 79-19-6 ]
[ 57235-54-8 ]

Yield	Reaction Conditions	Operation in experiment
61.8%	With trifluoroacetic acid at 80℃; Reflux;	4.1.4. General procedure C for the synthesis of compounds f1-35 General procedure: Trifluoroacetic acid (4 mL) was added to a mixture of nitrile(1.0 mmol) and thiosemicarbazide (1.1 mmol). The reaction mixturewas stirred and refluxed for 6 h. Then, it was cooled to roomtemperature and aqueous ammonia was added. The precipitatedsolidwas filtered,washed with hot water and air-dried. It should benoted that the compounds f1-f35 were directly used for the nextreaction without further purification.

Reference： [1]Xue, Wenjie; Li, Xueyao; Ma, Guixing; Zhang, Hongmin; Chen, Ya; Kirchmair, Johannes; Xia, Jie; Wu, Song [European Journal of Medicinal Chemistry, 2020, vol. 188]

85
[ 4254-02-8 ]
10H-dibenzo[b,e]iodinin-5-ium trifluoromethanesulfonate [ No CAS ]
acridin-10(9H)-yl(cyclopentyl)methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
67%	With potassium phosphate; 2,2,6,6-tetramethylheptane-3,5-dione; water; copper(l) chloride In 1,2-dichloro-ethane; toluene at 100℃; for 17h; Inert atmosphere; Schlenk technique; Sealed tube;

Reference： [1]Peng, Xiaopeng; Li, Ling; Ren, Yichang; Xue, Huanxin; Liu, Jin; Wen, Shijun; Chen, Jianjun [Advanced Synthesis and Catalysis, 2020, vol. 362, # 10, p. 2030 - 2038]

86
[ 4254-02-8 ]
10H-dibenzo[b,e]iodinin-5-ium trifluoromethanesulfonate [ No CAS ]
N-(2-(2-iodobenzyl)phenyl)cyclopentanecarboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
67%	With water; copper(l) chloride In 1,2-dichloro-ethane at 70℃; for 17h; Inert atmosphere; Sealed tube;

Reference： [1]Peng, Xiaopeng; Sun, Zhiqiang; Kuang, Peihua; Li, Ling; Chen, Jingxuan; Chen, Jianjun [Organic Letters, 2020, vol. 22, # 15, p. 5789 - 5795]

87
[ 4254-02-8 ]
C₁₄H₂₂O₃ [ No CAS ]
C₁₅H₂₁N [ No CAS ]
C₁₅H₂₁N [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: cyclopentanecarbonitrile With silver(I) bromide; N,N,N,N,-tetramethylethylenediamine; lithium hexamethyldisilazane In tetrahydrofuran at 0 - 20℃; for 0.5h; Inert atmosphere; Stage #2: With 1,3-bis[2,6-bis(diphenylmethyl)-4-methylphenyl]imidazol-2-ylidene hydrochloride; potassium <i>tert</i>-butylate; allylpalladium(II) chloride dimer In tetrahydrofuran at 0 - 20℃; for 0.5h; Stage #3: C₁₄H₂₂O₃ In tetrahydrofuran at 20℃; for 12h; Overall yield = 76 percent;	18 Example 18 Under argon conditions, add (0.4mmol), silver bromide (0.10mmol), tetramethylethylenediamine (0.10mmol) and 1.0mL tetrahydrofuran to a 10mL reaction tube, add 0.8mL hexamethyl at 0 Lithium disilazide (1.0M inTHF), return to room temperature and stir for 30min, add allylpalladium(II) chloride dimer (1.9mg, 0.005mmol), IPr*·HCl to another 5mL reaction tube (9.5mg, 0.01mmol) and tetrahydrofuran (1.0mL), add 25μL of potassium tert-butoxide (1.0M in THF) at 0, stir for 30min at room temperature, add the two reaction tubes together (0.2mmol), and react at room temperature After stirring for 12h, it was quenched by adding 0.5mL water and dried with anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the ratio between the product and the two obtained by column chromatography was 1:1, the total yield was 76%, and the purity of 1H NMR was greater than 95%.

Reference： [1]Current Patent Assignee: CHINESE ACADEMY OF SCIENCES - CN111362832, 2020, A Location in patent: Paragraph 0209-0211

Type	HazMat fee for 500 gram (Estimated)
Excepted Quantity	USD 0.00
Limited Quantity	USD 15-60
Inaccessible (Haz class 6.1), Domestic	USD 80+
Inaccessible (Haz class 6.1), International	USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic	USD 100+
Accessible (Haz class 3, 4, 5 or 8), International	USD 200+

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
{[ item.p_purity ]}	{[ item.pr_size ]}	{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]}	{[ getRatePrice(item.pr_usd, 1,1) ]}	Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]}	{[ item.pr_usastock ]}	Inquiry -	{[ item.pr_chinastock ]}	Inquiry -

CAS No. :	4254-02-8	MDL No. :	MFCD00013741
Formula :	C₆H₉N	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	SVPZJHKVRMRREG-UHFFFAOYSA-N
M.W :	95.14	Pubchem ID :	77935
Synonyms :

Num. heavy atoms :	7
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.83
Num. rotatable bonds :	0
Num. H-bond acceptors :	1.0
Num. H-bond donors :	0.0
Molar Refractivity :	28.59
TPSA :	23.79 Å²

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.8 cm/s

[ CAS No. 4254-02-8 ] {[proInfo.proName]}

Quality Control of [ 4254-02-8 ]

Related Doc. of [ 4254-02-8 ]

Product Details of [ 4254-02-8 ]

Calculated chemistry of [ 4254-02-8 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 4254-02-8 ]

Application In Synthesis of [ 4254-02-8 ]

[ 4254-02-8 ] Synthesis Path-Downstream 1~87

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Log Po/w (iLOGP) :	1.61
Log Po/w (XLOGP3) :	1.52
Log Po/w (WLOGP) :	1.7
Log Po/w (MLOGP) :	1.0
Log Po/w (SILICOS-IT) :	1.69
Consensus Log Po/w :	1.5

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	2.0
Bioavailability Score :	0.55

Log S (ESOL) :	-1.39
Solubility :	3.9 mg/ml ; 0.041 mol/l
Class :	Very soluble
Log S (Ali) :	-1.63
Solubility :	2.24 mg/ml ; 0.0235 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-1.03
Solubility :	8.78 mg/ml ; 0.0923 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.41

Signal Word:	Danger	Class:	3,6.1
Precautionary Statements:	P261-P301+P310-P305+P351+P338	UN#:	1992
Hazard Statements:	H225-H301-H315-H319-H335	Packing Group:	Ⅲ
GHS Pictogram:

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
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P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
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P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
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P260	Do not breathe dust/fume/gas/mist/vapours/spray.
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P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
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P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
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P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
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P337	If eye irritation persists:
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P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling