Name: 3218-02-8|Cyclohexylmethanamine|98%
Brand: Ambeed
SKU: A684885
Rating: 92 (29 reviews)

1
[ 766-05-2 ]
[ 3218-02-8 ]

Yield	Reaction Conditions	Operation in experiment
99%	With [Ru(H)(BH₄)(CO)(PPh₃)(3-(di-tert-butylphosphino)-N-((1-methyl-1H-imidazol-2 yl)methyl)propylamine)]; hydrogen In isopropyl alcohol at 70℃; for 3h; Inert atmosphere; Autoclave;
92%	With ammonia; hydrogen In toluene at 120℃; for 16h; Autoclave;
91%	With hydrogen In ethanol at 88℃; for 0.5h;	1 Amines Preparation Examples In the 1L hydrogenation kettle, add 100 g of cyclohexanecarbonitrile and 3 g of Raney-Ni, 400 mL of ethanol, and continuously charged with H2, so that the pressure of the system during the reaction was always maintained at 5 MPa. After reaction at a reaction temperature of 88 ° C for 0.5 h, then the temperature was lowered. When the temperature in the reaction vessel was lowered to room temperature, the gas was vented, and c cyclohexanemethylamine (purity: 99% or more) was obtained by filtration and recrystallization in a yield of 91 wt%.

90%	With C₁₉H₃₄Cl₂CoN₂P; hydrogen; sodium ethanolate; sodium triethylborohydride In benzene at 135℃; for 60h; Autoclave;
81%	With ammonia borane In methanol at 50℃; for 12h; Inert atmosphere;	13 Add PdNPore (2.7mg, 5mol%) catalyst into the mesoporous reactorAnd ammonia borane complex (30.86mg, 1mmol),Add methanol (3mL) under nitrogen,Adding substrate cyclohexanecarbonitrile (54.6mg, 0.5mmol),Put it in an oil bath and react at 50 for 12h,After that, it was separated and purified by column chromatography (silica gel, 200-300 mesh; the developing solvent was ethyl acetate: methanol = 10:1),45.8 mg of cyclohexylmethylamine was obtained, with a yield of 81%.
73%	With copper(l) iodide; borane-THF; ethanolamine In tetrahydrofuran at 0 - 20℃; for 24h; Inert atmosphere;	9 Embodiment 9: cyclohexylamine preparation Weighing ethanolamine (61.08 mg, 1.0 mmol) is added in the history leica tube, under protection of inert gas, cooling to 0 °C, adding borane tetrahydrofuran complex (1 M, 2.0 mmol), stirring at the room temperature reaction 24 h, the solvent under vacuum to obtain pumping of the oxazole borane directly used for the next step. In the oxazole borane with electrifying thrill tube still under protection of inert gas into the separation azepine derivative (64.6 mg, 0.5 mmol), tetrahydrofuran (1.0 ml), cuprous iodide (1 mg, 0 . 01 equiv). Stir at room temperature reaction 24 h. The resulting reactant silica gel column (petroleum ether/ethyl acetate=20:1 - 1:1) to obtain the trimethylcyclohexylamine (41.3 mg) yield 73%.
72%	With indium(III) chloride; sodium tetrahydroborate In tetrahydrofuran at 25℃; for 4h; Inert atmosphere;
70%	With ammonia; hydrogen In water; isopropyl alcohol at 80℃; for 24h; Autoclave;
69%	With hydrogen; acetic acid at 20℃; for 6h; Sealed tube; chemoselective reaction;
68%	With methanol; sodium tetrahydroborate at 20℃; for 3h;
	With ammonium hydroxide; nickel Hydrogenation;
	With ethanol; sodium
	With hydrogen In carbon dioxide at 50℃; for 4h; chemoselective reaction;
93 %Chromat.	With [Ru(H₂)H₂(NC₅H₃(CH₂P(C(CH₃)3)2)2)]; water; hydrogen In toluene at 135℃; for 24h; Autoclave;
42 %Chromat.	With [ruthenium(II)(η⁶-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]₂; 1,4-di(diphenylphosphino)-butane; iso-butanol; sodium hydroxide at 120℃; for 0.333333h; Inert atmosphere;
86 %Chromat.	With [bis(2-methylallyl)cycloocta-1,5-diene]ruthenium(II); 2-((dicyclohexylphosphino)methyl)-1-methyl-1H-imidazolin; potassium <i>tert</i>-butylate; hydrogen bromide; hydrogen In tetrahydrofuran; water; acetone; toluene at 100℃; for 5.5h; Inert atmosphere; Schlenk technique; Autoclave;
	With carbonylhydrido(tetrahydroborato)[bis(2-diphenylphosphinoethyl)amino]ruthenium(II); hydrogen In isopropyl alcohol at 100℃; for 3h; Autoclave; chemoselective reaction;
99 %Chromat.	With C₂₆H₄₁Br₂FeNP₂; hydrogen; potassium hexamethylsilazane; sodium triethylborohydride In tetrahydrofuran at 140℃; for 36h; High pressure; Autoclave;
66 %Chromat.	With Fe-<SUP>Cy</SUP>MACHO; hydrogen In isopropyl alcohol at 70℃; for 3h; Autoclave;
99 %Chromat.	With ammonium hydroxide; hydrogen In water; isopropyl alcohol at 130℃; for 2h; Autoclave;
87 %Chromat.	With MnBr(CO)2[NH(CH₂CH₂P(iPr)2)2]; hydrogen; sodium t-butanolate In toluene at 120℃; for 36h; Autoclave;
95 %Chromat.	With [bis(2-methylallyl)cycloocta-1,5-diene]ruthenium(II); [(phenylphosphinediyl)bis(2,1-phenylene)]bis(methylene)}bis(di-tert-butylphosphine); hydrogen In isopropyl alcohol at 50℃; for 17h; Inert atmosphere; Autoclave;
99 %Chromat.	Stage #1: cyclohexane carbonitrile With cobalt(III) acetylacetonate; tris(2-(dicyclohexylphosphanyl)ethyl)phosphane In <i>tert</i>-butyl alcohol Sealed tube; Inert atmosphere; Stage #2: With potassium <i>tert</i>-butylate In <i>tert</i>-butyl alcohol Sealed tube; Inert atmosphere; Stage #3: With hydrogen In <i>tert</i>-butyl alcohol at 140℃; for 24h; Autoclave;
	With C₄₃H₃₈Cl₂CoN₅; potassium <i>tert</i>-butylate; hydrogen; sodium triethylborohydride In toluene at -196.16 - 115℃; for 8h;
99 %Chromat.	With ammonium hydroxide; hydrogen In isopropyl alcohol at 120℃; for 15h; Autoclave;
	With hydrogen In 1,4-dioxane at 120℃; for 18h; Flow reactor;
	With hydrogen In ethyl acetate at 60℃; Flow reactor;
10 %Chromat.	With bis(1,5-cyclooctadiene)nickel ⁽⁰⁾; hydrogen In tetrahydrofuran at 80℃; for 24h; Glovebox; Autoclave;
87 %Chromat.	With ammonium hydroxide; hydrogen; nano-dicobalt phosphide on hydrotalcite In isopropyl alcohol at 150℃; for 20h; Autoclave;

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]Murugesan, Kathiravan; Senthamarai, Thirusangumurugan; Sohail, Manzar; Alshammari, Ahmad S.; Pohl, Marga-Martina; Beller, Matthias; Jagadeesh, Rajenahally V. [Chemical Science, 2018, vol. 9, # 45, p. 8553 - 8560]
[3]Current Patent Assignee: CHINA PETROCHEMICAL CORPORATION - CN104557356, 2017, B Location in patent: Paragraph 0231; 0232
[4]Mukherjee, Arup; Srimani, Dipankar; Chakraborty, Subrata; Ben-David, Yehoshoa; Milstein, David [Journal of the American Chemical Society, 2015, vol. 137, # 28, p. 8888 - 8891]
[5]Current Patent Assignee: DALIAN UNIVERSITY OF TECHNOLOGY - CN112851521, 2021, A Location in patent: Paragraph 0097-0100
[6]Current Patent Assignee: SOUTHWEST PETROLEUM UNIVERSITY - CN109651159, 2019, A Location in patent: Paragraph 0062-0066
[7]Location in patent: experimental part Saavedra, Jaime Z.; Resendez, Angel; Rovira, Alexander; Eagon, Scott; Haddenham, Dustin; Singaram, Bakthan [Journal of Organic Chemistry, 2012, vol. 77, # 1, p. 221 - 228]
[8]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]
[9]Yoshimura, Masatoshi; Komatsu, Akira; Niimura, Masaru; Takagi, Yukio; Takahashi, Tohru; Ueda, Shun; Ichikawa, Tomohiro; Kobayashi, Yutaka; Okami, Hiroki; Hattori, Tomohiro; Sawama, Yoshinari; Monguchi, Yasunari; Sajiki, Hironao [Advanced Synthesis and Catalysis, 2018, vol. 360, # 8, p. 1726 - 1732]
[10]Mullangi, Dinesh; Chakraborty, Debanjan; Pradeep, Anu; Koshti, Vijay; Vinod, Chathakudath P.; Panja, Soumendranath; Nair, Sunil; Vaidhyanathan, Ramanathan [Small, 2018, vol. 14, # 37]
[11]Skinner et al. [Journal of the American Chemical Society, vol. 79, p. 1957,2843,2845]
[12]Demjanow [Zhurnal Russkago Fiziko-Khimicheskago Obshchestva, 1904, vol. 36, p. 172][Chemisches Zentralblatt, 1904, vol. 75, # I, p. 1214]
[13]Location in patent: scheme or table Chatterjee, Maya; Kawanami, Hajime; Sato, Masahiro; Ishizaka, Takayuki; Yokoyama, Toshirou; Suzuki, Toshishige [Green Chemistry, 2010, vol. 12, # 1, p. 87 - 93]
[14]Location in patent: experimental part Gunanathan, Chidambaram; Hoelscher, Markus; Leitner, Walter [European Journal of Inorganic Chemistry, 2011, # 22, p. 3381 - 3386]
[15]Werkmeister, Svenja; Bornschein, Christoph; Junge, Kathrin; Beller, Matthias [Chemistry - A European Journal, 2013, vol. 19, # 14, p. 4437 - 4440]
[16]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]
[17]Neumann, Jacob; Bornschein, Christoph; Jiao, Haijun; Junge, Kathrin; Beller, Matthias [European Journal of Organic Chemistry, 2015, vol. 2015, # 27, p. 5944 - 5948]
[18]Chakraborty, Subrata; Leitus, Gregory; Milstein, David [Chemical Communications, 2016, vol. 52, # 9, p. 1812 - 1815]
[19]Lange; Elangovan; Cordes; Spannenberg; Jiao; Junge; Bachmann; Scalone; Topf; Junge; Beller [Catalysis science and technology, 2016, vol. 6, # 13, p. 4768 - 4772]
[20]Chen, Feng; Topf, Christoph; Radnik, Jörg; Kreyenschulte, Carsten; Lund, Henrik; Schneider, Matthias; Surkus, Annette-Enrica; He, Lin; Junge, Kathrin; Beller, Matthias [Journal of the American Chemical Society, 2016, vol. 138, # 28, p. 8781 - 8788]
[21]Elangovan, Saravanakumar; Topf, Christoph; Fischer, Steffen; Jiao, Haijun; Spannenberg, Anke; Baumann, Wolfgang; Ludwig, Ralf; Junge, Kathrin; Beller, Matthias [Journal of the American Chemical Society, 2016, vol. 138, # 28, p. 8809 - 8814]
[22]Adam, Rosa; Bheeter, Charles Beromeo; Jackstell, Ralf; Beller, Matthias [ChemCatChem, 2016, vol. 8, # 7, p. 1329 - 1334]
[23]Adam, Rosa; Bheeter, Charles Beromeo; Cabrero-Antonino, Jose R.; Junge, Kathrin; Jackstell, Ralf; Beller, Matthias [ChemSusChem, 2017, vol. 10, # 5, p. 842 - 846]
[24]Tokmic, Kenan; Jackson, Bailey J.; Salazar, Andrea; Woods, Toby J.; Fout, Alison R. [Journal of the American Chemical Society, 2017, vol. 139, # 38, p. 13554 - 13561]
[25]Ferraccioli, Raffaella; Borovika, Diana; Surkus, Annette-Enrica; Kreyenschulte, Carsten; Topf, Christoph; Beller, Matthias [Catalysis science and technology, 2018, vol. 8, # 2, p. 499 - 507]
[26]Konrath, Robert; Heutz, Frank J.L.; Steinfeldt, Norbert; Rockstroh, Nils; Kamer, Paul C.J. [Chemical Science, 2019, vol. 10, # 35, p. 8195 - 8201]
[27]Mészáros, Rebeka; Peng, Bai-Jing; Ötvös, Sándor B.; Yang, Shyh-Chyun; Fülöp, Ferenc [ChemPlusChem, 2019, vol. 84, # 10, p. 1508 - 1511]
[28]Rodríguez, Alejandro A.; Garduño, Jorge A.; García, Juventino J. [New Journal of Chemistry, 2020, vol. 44, # 3, p. 1082 - 1089]
[29]Jitsukawa, Koichiro; Mitsudome, Takato; Mizugaki, Tomoo; Nakata, Ayako; Sheng, Min; Yamasaki, Jun [Chemical Science, 2020, vol. 11, # 26, p. 6682 - 6689]

2
[ 14527-26-5 ]
[ 3218-02-8 ]
[ 45957-30-0 ]

Reference： [1]Journal of the American Chemical Society,1934,vol. 56,p. 2134

3
[ 100-49-2 ]
[ 3218-02-8 ]

Reference： [1]Zhurnal Obshchei Khimii,1939,vol. 9,p. 99,101, 102
Chemisches Zentralblatt,1939,vol. 110,p. 1266
[2]Tetrahedron,2011,vol. 67,p. 3140 - 3149
[3]Patent: WO2006/138350,2006,A2

4
[ 1194-21-4 ]
[ 3218-02-8 ]
[ 146203-13-6 ]

Reference： [1]Organic Letters,2009,vol. 11,p. 61 - 64
[2]Journal of Medicinal Chemistry,1993,vol. 36,p. 1024 - 1031

5
[ 5241-64-5 ]
[ 3218-02-8 ]
[1-(Cyclohexylmethyl-carbamoyl)-2-(1H-indol-3-yl)-ethyl]-carbamic acid tert-butyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1996,vol. 39,p. 736 - 748

6
[ 924-44-7 ]
[ 931-53-3 ]
[ 141871-02-5 ]
[ 3218-02-8 ]
2-[2-(tert-butoxycarbonyl-methyl-amino)-benzoyl]-cyclohexylmethyl-amino}-N-cyclohexyl-malonamic acid ethyl ester [ No CAS ]

Reference： [1]Tetrahedron Letters,1999,vol. 40,p. 5295 - 5299

7
[ 7782-77-6 ]
[ 3218-02-8 ]
[ 590-67-0 ]
[ 502-41-0 ]
[ 100-49-2 ]

Reference： [1]Journal of the American Chemical Society,1952,vol. 74,p. 6135

8
[ 2004-07-1 ]
[ 3218-02-8 ]
2-amino-N⁶-(cyclohexylmethyl)adenosine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2000,vol. 43,p. 4135 - 4150

9
[ 69812-29-9 ]
[ 16590-41-3 ]
[ 3218-02-8 ]
C₃₃H₄₄N₄O₆S₂ [ No CAS ]

Reference： [1]Synlett,2002,p. 92 - 96

10
[ 104-03-0 ]
[ 136030-33-6 ]
[ 18637-83-7 ]
[ 3218-02-8 ]
N-cyclohexylmethyl-2-[4-(1,3,4-trioxo-1,3,4,6,11,11a-hexahydro-pyrazino[1,2-b]isoquinolin-2-yl)-phenyl]-acetamide [ No CAS ]

Reference： [1]Synlett,2003,p. 817 - 820

11
[ 3218-02-8 ]
[ 216699-86-4 ]
cyclohexylmethyl-(6,7-dimethoxy-quinoxalin-2-yl)-amine [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 3091 - 3095

12
[ 132684-59-4 ]
[ 3218-02-8 ]
[ 345347-68-4 ]
5-(4-formyl-3,5-dimethoxyphenoxy)valeric aldehyde linker on a polyethylene glycol resin [ No CAS ]
2-butyl-N¹-[1-(cyclohexylmethyl-carbamoyl)-3-phenyl-propyl]-N⁴-hydroxy-succinamide [ No CAS ]

Reference： [1]Antimicrobial Agents and Chemotherapy,2004,vol. 48,p. 250 - 261

13
[ 3218-02-8 ]
[ 153463-65-1 ]
3-cyclohexylmethylamino-5-chloro-4-pyridinecarbonitrile [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 664 - 670

14
[ 841276-88-8 ]
[ 6342-77-4 ]
[ 3218-02-8 ]
N-(1-cyclohexylmethyl-6-nitro-2-oxo-1,2,3,4-tetrahydro-quinolin-4-yl)-3-(2-methoxy-phenyl)-propionamide [ No CAS ]

Reference： [1]Tetrahedron Letters,2005,vol. 46,p. 5361 - 5364

15
[ 3218-02-8 ]
[ 766-05-2 ]

Yield	Reaction Conditions	Operation in experiment
97%	With pyridine; Oxone; 4-acetylamino-2,2,6,6-tetramethyl-1-piperidinoxy; Pyridine hydrobromide In dichloromethane at 20℃; for 12h; Green chemistry;
95%	With pyridine; N-(2,2,6,6-tetramethyl-1-oxopiperidin-1-ium-4-yl)acetamide tetrafluoroborate In dichloromethane at 20℃; for 12h; Inert atmosphere;
95%	With water; potassium hydroxide at 25℃; Electrochemical reaction;

81.6%	With 5% active carbon-supported ruthenium; oxygen In toluene at 150℃; for 4h; Autoclave;	General procedure: In a typical process, into a 25 ml autoclave equipped with a magnetic stirrer were added 5%Ru/AC (0.03 mmol, 3 mol%), benzylamine (1 mmol), 5 mL toluene at room temperature successively. After which the resulting reaction mixture was heated at 150 °C for 4 h under 0.5 MPa of oxygen atmosphere. The final reaction conversion and selectivity towards the corresponding nitriles were determined by Gas Chromatograph. After reaction, the product was purified by column chromatography of the reaction mixture on neutral alumina using hexanes/dichloromethane (80:20) or hexanes/EtOAc (30:1) as eluent.
75%	With aluminum oxide In N,N-dimethyl-formamide at 120℃; for 12h; Inert atmosphere;
60%	With HRu(1,3-bis(6'-methyl-2'-pyridylimino)isoindoline)(PPh<SUB>3</SUB>)<SUB>2</SUB> In toluene at 110℃; for 24h; Inert atmosphere; Glovebox; chemoselective reaction;
100 % Chromat.	With sodium hydroxide; dipotassium peroxodisulfate; dodecyl-N,N-dimethylamine N-oxide In water at 20℃; for 2h;
95 %Chromat.	With ammonium hydroxide; oxygen In tert-Amyl alcohol at 110℃; for 15h; Autoclave; Green chemistry;
80 %Chromat.	With ammonium hydroxide; oxygen at 110℃; Autoclave; Green chemistry;
96 %Spectr.	With copper(l) iodide; oxygen In dichloromethane at 20℃; for 6h; Sealed tube;
75 %Chromat.	With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; C₆₃H₅₁N₂O₃P₂Ru⁽¹⁺⁾*ClO₄^(1-); oxygen In toluene at 90℃; for 20h;
81 %Chromat.	With [Ru(p-cymene)(pzH-NP)(Cl)]Cl; potassium <i>tert</i>-butylate In toluene at 70℃; for 24h; Schlenk technique; Inert atmosphere;
96.1 %Chromat.	With C₆₈H₆₄Cl₂N₆P₂Ru₂⁽⁴⁺⁾2F₆P^(1-)2Cl^(1-); caesium carbonate In N,N-dimethyl-formamide at 100℃; for 24h; Inert atmosphere; Green chemistry;
	With sodium periodate; C₃₁H₂₉Br₂N₃Ru In water; ethyl acetate at 80℃; for 24h;

Reference： [1]Lambert, Kyle M.; Bobbitt, James M.; Eldirany, Sherif A.; Kissane, Liam E.; Sheridan, Rose K.; Stempel, Zachary D.; Sternberg, Francis H.; Bailey, William F. [Chemistry - A European Journal, 2016, vol. 22, # 15, p. 5156 - 5159]
[2]Lambert, Kyle M.; Bobbitt, James M.; Eldirany, Sherif A.; Wiberg, Kenneth B.; Bailey, William F. [Organic Letters, 2014, vol. 16, # 24, p. 6484 - 6487]
[3]Chong, Xiaodan; Huang, Yi; Liang, Yu; Liu, Cuibo; Zhang, Bin [Angewandte Chemie - International Edition, 2018, vol. 57, # 40, p. 13163 - 13166][Angew. Chem., 2018, vol. 130, # 40, p. 13347 - 13350,4]
[4]Niu, Baoqiang; Lu, Fei; Zhang, Hong-Yu; Zhang, Yuecheng; Zhao, Jiquan [Chemistry Letters, 2017, vol. 46, # 3, p. 330 - 333]
[5]Damodara, Dandu; Arundhathi, Racha; Likhar, Pravin R. [Advanced Synthesis and Catalysis, 2014, vol. 356, # 1, p. 189 - 198]
[6]Tseng, Kuei-Nin T.; Rizzi, Andrew M.; Szymczak, Nathaniel K. [Journal of the American Chemical Society, 2013, vol. 135, # 44, p. 16352 - 16355]
[7]Biondini, Daniele; Brinchi, Lucia; Germani, Raimondo; Goracci, Laura; Savelli, Gianfranco [European Journal of Organic Chemistry, 2005, # 14, p. 3060 - 3063]
[8]Jagadeesh, Rajenahally V.; Junge, Henrik; Beller, Matthias [ChemSusChem, 2015, vol. 8, # 1, p. 92 - 96]
[9]Natte, Kishore; Jagadeesh, Rajenahally V.; Sharif, Muhammad; Neumann, Helfried; Beller, Matthias [Organic and Biomolecular Chemistry, 2016, vol. 14, # 13, p. 3356 - 3359]
[10]Xu, Boran; Hartigan, Elizabeth M.; Feula, Giancarlo; Huang, Zheng; Lumb, Jean-Philip; Arndtsen, Bruce A. [Angewandte Chemie - International Edition, 2016, vol. 55, # 51, p. 15802 - 15806][Angew. Chem., 2016, vol. 128, p. 16034 - 16038,5]
[11]Ray, Ritwika; Chandra, Shubhadeep; Yadav, Vishal; Mondal, Prasenjit; Maiti, Debabrata; Lahiri, Goutam Kumar [Chemical Communications, 2017, vol. 53, # 28, p. 4006 - 4009]
[12]Dutta, Indranil; Yadav, Sudhir; Sarbajna, Abir; De, Subhabrata; Hölscher, Markus; Leitner, Walter; Bera, Jitendra K. [Journal of the American Chemical Society, 2018, vol. 140, # 28, p. 8662 - 8666]
[13]Chen, Hua; Fu, Haiyan; Ji, Li; Li, Ruixiang; Nie, Xufeng; Zheng, Yanling [Journal of Catalysis, 2020, vol. 391, p. 378 - 385]
[14]Bera, Jitendra K.; Din Reshi, Noor U; Pal, Nilay Kumar; Pal, Saikat; Pal, Sourav; Yadav, Suman [Applied Organometallic Chemistry, 2022]

16
[ 35998-96-0 ]
[ 98-88-4 ]
[ 75318-43-3 ]
[ 3218-02-8 ]
6-benzamido-2-cyano-3-cyclohexanemethylquinazolin-4(3H)-one [ No CAS ]

Reference： [1]Tetrahedron Letters,2005,vol. 46,p. 7477 - 7481

17
[ 27329-27-7 ]
[ 75318-43-3 ]
[ 3218-02-8 ]
2-cyano-3-cyclohexanemethyl-7-methylquinazolin-4(3H)-one [ No CAS ]

Reference： [1]Tetrahedron Letters,2005,vol. 46,p. 7477 - 7481

18
[ 1070-70-8 ]
[ 3218-02-8 ]
polymer, Mw = 16380, PDI = 2.60; monomer(s): 1,4-butanediol diacrylate; 2-cyclohexyl-methylamine [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2001,vol. 123,p. 8155 - 8156

19
[ 56107-02-9 ]
[ 3218-02-8 ]
[ 917953-84-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 6316 - 6320

20
[ 3218-02-8 ]
[ 61940-21-4 ]
[ 959737-79-2 ]

Yield	Reaction Conditions	Operation in experiment
75%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 80℃; for 3h;	Step B: 2-(Cyclohexylmethyl)-7-nitroisoindolialpha-l-one; Cyclohexylmethylamine (1.63 mL, 12.5 mmol), followed by DIPEA (4.4 mL, 25 mmol) were added to a stirred solution of methyl-2-bromomethyl-6-nitro-benzoate (3.43 g, 12.5 mmol) in DMF (50 mL). The mixture was stirred at 80 0C for 3 h, concentrated in vacuo, diluted with CH2Cl2 (150 mL), washed with saturated NaHCC>3 solution (2x50 mL), brine (50 mL), dried over Na2SO4, filtered and evaporated. Flash chromatography of the residue over silica gel, using EtOAc/hexanes (1:5 to 1:2) gave the title compound, 2.6 g (75%) as a brown solid. 1H NMR (400 MHz, CHLOROFORM-D) delta 0.94 - 1.12 (m, 2 H), 1.13 - 1.30 (m, 3 H), 1.62 - 1.82 (m, 6 H), 3.44 (d, 2 H), 4.42 (s, 2 H), 7.60 - 7.71 (m, 3 H).

Reference： [1]Patent: WO2007/139464,2007,A1 .Location in patent: Page/Page column 50

21
[ 2605-14-3 ]
[ 3218-02-8 ]
[ 953771-32-9 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In 1-methyl-pyrrolidin-2-one; at 105 - 110℃; for 66h;	Step 1. Preparation of N-(cyclohexylmethyl)-6-methoxybenzo[d]thiazol-2-amine To the solution of <strong>[2605-14-3]2-chloro-6-methoxybenzo[d]thiazole</strong> (900 mg, 4.5 mmol) in 4.5 ml of NMP was added cyclohexylmethanamine (865 mg, 7.65 mmol) and DIPEA (1.57 ml, 9.0 mmol). The reaction solution was stirred at 105-110 C. for 66 hours. The reaction was worked up by adding 250 ml ethyl acetate and washed with 260 ml of saturated NaHCO3, 360 ml water, 1*60 ml saturated NaCl, dried with sodium sulfate, filtered and concentrated in vacuo to give N-(cyclohexylmethyl)-6-methoxybenzo[d]thiazol-2-amine as solid (1.18 grams). ES/MS m/z 277.1 (MH+).
	With N-ethyl-N,N-diisopropylamine; In 1-methyl-pyrrolidin-2-one; at 105 - 110℃; for 66h;	To a solution of <strong>[2605-14-3]2-chloro-6-methoxybenzo[d]thiazole</strong> (900 mg, 4.5 mmol) in 4.5 mL of NMP was added cyclohexylmethanamine (865 mg, 7.65 mmol) and DIPEA (1.57 mL, 9.0 mmol). The reaction solution was stirred at 105-110 C for 66 hours. The reaction was diluted with EtOAc (250 mL) and washed with saturated NaHCO3 (2x 60 mL), water (3x 60 mL), saturated NaCl (60 mL), dried with sodium sulfate, filtered and concentrated in vacuo to give N-(cyclohexylmethyl)-6-methoxybenzo[d]thiazol-2-amine as a solid (1.18 grams). ES/MS m/z 277.1 (MH+).

Reference： [1]Patent: US2008/45528,2008,A1 .Location in patent: Page/Page column 86
[2]Patent: WO2008/144062,2008,A1 .Location in patent: Page/Page column 81

22
[ 723280-98-6 ]
[ 3218-02-8 ]
[ 723283-76-9 ]

Yield	Reaction Conditions	Operation in experiment
	In dichloromethane; at 20℃; for 18h;	Under a nitrogen atmosphere, cyclohexylmethylamine (40.9 ML, 315 mmol) was added dropwise to a solution of <strong>[723280-98-6]7-bromo-4-chloro-3-nitroquinoline</strong> (30.0 g, 105 mmol) in dichloromethane (524 mL). The reaction was stirred for 18 hours at ambient temperature and then concentrated under reduced pressure. Water (200 mL) was added to the residue, and the mixture was stirred for three hours. Acetonitrile was added; a precipitate formed. The solid was isolated by filtration, dried under a flow of air for two hours, and recrystallized from acetonitrile to provide 24.0 g of (7-bromo-3-nitroquinolin-4- yl) cyclohexylmethylamine as a yellow solid.

Reference： [1]Patent: WO2004/58759,2004,A1 .Location in patent: Page 265

23
[ 189321-66-2 ]
[ 3218-02-8 ]
[ 878010-29-8 ]

Yield	Reaction Conditions	Operation in experiment
		To a 20 mL tube was placed PS-DCC (832 mg, 0. 018 mmol, 1.38 [MMOL/G),] HOBt (109 mg, 0.81 [MMOL),] and a 5: 1: 1 mixture of CHC13 : CH3CN: tBuOH. Then, cyclohexylmethyl amine [(65] [UL,] 0.5 mmol) and (R, S)-Boc-2- carboxymorpholine (125 mg, 0.54 mmol) were added, and the vial was placed on a GlasCol orbital rotator for 16 hours. After this time, [MP-CARBONATE] (480 mg, 1.62 mmol, 3.38 mmol/g) was added to scavenge the HOBt and excess (R, S)-Boc-2- carboxymorpholine. Three hours later, the vial's contents were filtered through an Applied Separations filter tube, washed with DCM (3 x 3 mL) and concentrated in an HTII-12 Genevac unit to afford an yellow oil. This material was then dissolved in DCM (2 [ML)] and 4 N HCl/dioxane (2 [ML)] added. After 10 minutes, the solvent was evapoarted under a stream of nitrogen gas and purified/free-based by standard SCX SPE. Concentration provided a colorless oil, N- (cyclohexylmethyl) morpholine-2-carboxamide, 102 mg (90%) -a single peak (214 nm and ELSD) at 2.06 min [(CH3CN/H20/1%] TFA, 4 min gradient). To an 8 mL vial was placed ethyl [5-BROMO-3-(CHLOROSULFONYL)-1-(PHENYLSULFONYL)-LH-INDOLE-2-] carboxylate (50 mg, 0.099 mmol), PS-NMM (58 mg, 0.216 mmol, 3.72 mmol/g), PS- DMAP (37 mg, 0.05 mmol, 1.48 mmol/g) and DCM. Then, N- (cyclohexylmethyl) [MORPHOLINE-2-CARBOXAMIDE] [(18] mg, 0. 08 mmol) was added, and the vial placed on a GlasCol orbital rotator for 16 hours. After this time, PS- triamine resin (75 mg, 0. [108] mmol, 1.44 mmol/g) was added to the vial to scavenge excess sulfonyl chloride. Three hours later, the vial's contents were filtered through an Applied Separations filter tube, washed with DCM (3 x 3 mL) and concentrated in an HTII-12 Genevac unit to afford an yellow solid. This material was then dissolved in 2 M NH3/EtOH, sealed in a scintillation vial and heated to 90 degrees on a J-KEM heater/shaker block for 3 hours. The vial was then dried in an HTII-12 Genevac unit to afford a brown solid. This material was then purified by Mass Guided HPLC on an Agilent 1100 Purification unit to afford a white crystalline solid. Analytical LCMS: single peak (214 nm and ELSD) at 3.35 min [(CH3CN/H20/1%] TFA, 4 min gradient). IH NMR (300 MHz, DMSO-d6) : [8] 8.2 (s, 2H), 7.99 (s, 1H), 7.39 [(M,] 2H), 7.48 [(M,] 2H), 3.95 [(T,] J=11 Hz, 2H), 3.63 [(M,] 2H), 3.44 (d, [J=11.] 4 Hz, [1H),] 2.48 [(M,] 2H), 2.3 (t, [J=18] Hz, 1H), 1.56 [(M,] 6H), 1.34 [(M,] 2H), 1.08 [(M,] 2H), 0.77 [(M,] [2H)] ppm. HRMS calc'd for [C21H27BRN405S,] 527. [0958] ; found, 527.0940.

Reference： [1]Patent: WO2004/14851,2004,A2 .Location in patent: Page 156-157

24
[ 351-32-6 ]
[ 3218-02-8 ]
[ 809237-74-9 ]

Yield	Reaction Conditions	Operation in experiment
100%	With sodium carbonate; In ethanol; at 60℃; for 48h;Heating;	Cyclohexylmethylamine (2.86 mL, 2.49 g, 22.0 mmol ) was added to a mixture of <strong>[351-32-6]N-(4-fluoro-3-nitrophenyl)acetamide</strong> (3.96 g, 20.0 mmol) and sodium carbonate (4.66 g, 44 mmol) in EtOH (50 mL) at room temperature. The reaction mixture was heated for 48 h at 60 C, and diluted with H2O (800 mL). The orange solid was precipitated out and collected to give the desired title product (6.60 g, 100%). MS (ESI) (M+H)+: 292.32.
100%	With sodium carbonate; In ethanol; at 20 - 60℃; for 48h;	Step C. N-{4-[(CYCLOHEXYLMETHYL) AMINO]-3-NITROPHENYL} ACETAMIDE; Cyclohexylmethylamine (2.86 mL, 2.49 g, 22.0 mmol) was added to a mixture OF N- (4-fluoro-3-nitrophenyl) acetamide (3.96 g, 20.0 mmol) and sodium carbonate (4.66 g, 44 mmol) in ETOH (50 mL) at room temperature. The reaction mixture was heated for 48 h at 60 C, and diluted with H20 (800 mL). The orange solid was precipitated out and collected to give the desired product (6.60 g, 100%). MS (ESI) (M+H) + : 292.32.
100%	With sodium carbonate; In ethanol; at 20 - 60℃; for 48h;	Cyclohexylmethylamine (2.86 mL, 2.49 g, 22.0 mmol) was added to a mixture of <strong>[351-32-6]N-(4-fluoro-3-nitrophenyl)acetamide</strong> (3.96 g, 20.0 mmol) and sodium carbonate (4.66 g, 44 mmol) in EtOH (50 mL) at room temperature. The reaction mixture was heated for 48 h at 60 C., and diluted with H2O (800 mL). The orange solid was precipitated out and collected to give the desired product (6.60 g, 100%). MS (ESI) (M+H)+: 292.32.

100%	With sodium carbonate; In ethanol; at 20 - 60℃; for 48h;Product distribution / selectivity;	Step B. N-{4-[(CYCLOHEXYLMETHYL) AMINO]-3-NITROPHENYL} ACETAMIDE; CYCLOHEXYLMETHYLAMINE (2. 86 mL, 2.49 g, 22.0 mmol) was added to a mixture OF N- (4-fluoro-3-nitrophenyl) acetamide (3.96 g, 20.0 mmol) (for preparation, see Example 33, Step B) and sodium carbonate (4.66 g, 44 mmol) in EtOH (50 mL) at room temperature. The reaction mixture was heated for 48 h at 60 C, and diluted with H20 (800 mL). The orange solid was precipitated out and collected to give the title product (6.60 g, 100%). MS (ESI) (M+H) + : 292.3.
100%	With sodium carbonate; In ethanol; at 20 - 60℃; for 48h;Product distribution / selectivity;	Step C. N-{4-[(cyclohexylmethyl)amino]-3-nitrophenyl} acetamide; Cyclohexylmethylamine (2.86 mL, 2.49 g, 22.0 mmol) was added to a mixture OF AT- (4-fluoro-3-nitrophenyl) acetamide (3.96 g, 20.0 mmol) and sodium carbonate (4.66 g, 44 mmol) in EtOH (50 mL) at room temperature. The reaction mixture was heated for 48 h at 60 C, and diluted with H20 (800 mL). The orange solid was precipitated out and collected to give the title product (6. 60 g, 100%). MS (ESI) (M+H) + : 292.3.
99%	With triethylamine; In ethanol; at 75℃;Product distribution / selectivity;	Step B. N-{4-[(CYCLOHESYLMETHYL) AMINO]-3-NITROPHENYL} ACETAMIDE; N-(4-Fluoro-3-nitrophenyl) acetamide (500 mg, 2.52 mmol) and cyclohexanemethylamine (0.400 mL, 3.02 mmol) were stirred in 15 mL OF ETOH containing TEA (0.525 mL, 3. 78 mmol) at 75C overnight. The solvent was concentrated. The residue was dissolved in EtOAc and washed with aqueous 5% KHS04, saturated aqueous NAHC03 solution, brine and dried over anhydrous MGS04. The solvent was evaporated. Yield : 735 mg (99%) ;'H NMR (400 MHz, CHLOROFORM-D): 8 1.03 (m, 2 H), 1.25 (m, 3 H), 1.62 (m, 1 H), 1.69 (m, 1 H), 1.76 (m, 1 H), 1.79 (m, 1 H), 1.82 (m, 1 H), 1.86 (m, 1 H), 2.17 (s, 3 H), 3.14 (dd, J=6. 25, 4.30 Hz, 2 H), 6.83 (d, J=9.37 Hz, 1 H), 7.20 (m, 1 H), 7.78 (dd, J=9.28, 2.64 Hz, 1 H), 8.07 (d, J=2.54 Hz, 1 H), 8.12 (m, 1 H).
99%	With triethylamine; In ethanol; at 75℃;Product distribution / selectivity;	Step B. N-{4-[(Cyclohexylmethyl)amino]-3-nitrophenyl}acetamide; N- (4-FLUORO-3-NITROPHENYL) acetamide (500 mg, 2. 52 mmol) and CYCLOHEXANEMETHYLAMINE (0.400 mL, 3.02 mmol) were stirred in 15 mL OF ETOH containing TEA (0.525 mL, 3. 78 mmol) at 75C overnight. The solvent was concentrated. The residue was dissolved in EtOAc and washed with aqueous 5% KHS04, saturated aqueous NAHC03 solution, brine and dried over anhydrous MGS04. The solvent was evaporated. Yield: 735 mg (99%) ; LH NMR (400 MHz, CHLOROFORM-D): 8 1.03 (m, 2 H), 1.25 (M, 3 H), 1.62 (M, 1 H), 1.69 (m, 1 H), 1.76 (m, 1 H), 1.79 (m, 1 H), 1. 82 (m, 1 H), 1.86 (m, 1 H), 2. 17 (s, 3 H), 3.14 (dd, J=6.25, 4.30 Hz, 2 H), 6.83 (d, J=9.37 Hz, 1 H), 7.20 (m, 1 H), 7. 78 (dd, J=9.28, 2.64 Hz, 1 H), 8. 07 (d, J=2.54 Hz, 1 H), 8.12 (m, 1 H).

Reference： [1]Patent: WO2004/108712,2004,A1 .Location in patent: Page 30-31
[2]Patent: WO2005/30732,2005,A1 .Location in patent: Page/Page column 28-29
[3]Patent: US2008/207612,2008,A1 .Location in patent: Page/Page column 12
[4]Patent: WO2005/30733,2005,A1 .Location in patent: Page/Page column 90
[5]Patent: WO2005/30761,2005,A1 .Location in patent: Page/Page column 77-78
[6]Patent: WO2005/30733,2005,A1 .Location in patent: Page/Page column 71
[7]Patent: WO2005/30761,2005,A1 .Location in patent: Page/Page column 150-151

25
[ 22280-56-4 ]
[ 3218-02-8 ]
[ 773147-98-1 ]

Yield	Reaction Conditions	Operation in experiment
98%	With triethylamine; In ethanol; for 12h;Heating / reflux;	To a solution of <strong>[22280-56-4]2-chloro-3-methyl-5-nitropyridine</strong> (3.45 g, 20 mmol) in ETOH (100 mL) and triethylamine (5 ML) was added cyclohexylmethylamine (4.52 g, 40 mmol) at room temperature. The reaction mixture was refluxed for 12 hr, allowed to cool down to room temperature. After condensation, the residue was diluted with AcOEt, washed with 1 N NH40H and brine, dried over MGS04. Removal of solvents provided the desired product (4.90 g, 98 %), which was used directly in the next STEP. H-NMR (CDCI3) : 8 1.02 (m, 2H), 1.23 (m, 3H), 1.75 (m, 6H), 2.16 (s, 3H), 3.46 (m, 2H), 4.98 (brs, 1H), 8. 00 (s, 1H), 8. 96 (s, 1H). MS (ESI) (M+H) + 250.31

Reference： [1]Patent: WO2004/87704,2004,A1 .Location in patent: Page 27

26
1-(3-dimethylaminopropyl)-3-ethylcarboiimide hydrochloride [ No CAS ]
[ 80029-43-2 ]
[ 3218-02-8 ]
[ 197507-59-8 ]
[1,6]naphthyridine-2-carboxylic acid cyclohexyl-methylamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%	In N,N-dimethyl-formamide;	Compound #19 <strong>[197507-59-8][1,6]naphthyridine-2-carboxylic acid</strong> cyclohexyl-methylamide To a stirring mixture of 2-[1,6]naphthyridinecarboxylic acid (50 mg, 0.287 mmol) in anhydrous DMF (1.0 mL) at room temperature was added sequentially 1-hydroxybenzotriazole hydrate (42.7 mg, 0.316 mmol), cyclohexanemethylamine (57.2 muL, 0.431 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarboiimide hydrochloride (61.8 mg, 0.316 mmol). The resulting mixture was allowed to stir at room temperature overnight and it was found to be clear. The solvent was removed under vacuum. Flash column chromatography of the residue (100% ethyl acetate) afforded the desired product as a white solid (74.9 mg, 97%): m.p. 62-63 C.

Reference： [1]Patent: US6255318,2001,B1

27
[ 3017-32-1 ]
[ 525-03-1 ]
[ 3218-02-8 ]
[ 294181-72-9 ]
[ 762241-25-8 ]

Yield	Reaction Conditions	Operation in experiment
		It is disclosed herein that the display of side chains identified as activein galanin or those of the nonpeptide galanin receptor agonist galnon on arigid platform creates a compound capable of recognition by the receptorGalR1. Mixtures of 3 to 4 amines were coupled to the triacid platform (D. Mink,et al., Tetrahedron Lett, (1998) 39, 5709-5712; G. Haberhauer, et al.,Tetrahedron Lett, (2000) 41, 5013-5016; and L. Somogyi, et al., Tetrahedron,(2001) 57, 1699-1708) and obtained small combinatorial libraries. Activemixtures were obtained (after deblocking with trifluoroacetic acid) from theamines shown: cyclohexylmethyl amine, 2; fluorenyl amine 3 ande-t-BOC-/-lysine methyl ester 4. This mixture (11 compounds) was fractionatedby HPLC and the most active compound (structure 5, Galmic, or itscyclodiastereomer) was identified by mass spectrometry. The individualmolecule was prepared by total synthesis which will be described elsewhere. Physical Characterization of Galmic:1H NMR-300 MHz (CDCIs): 9.01 (s, NH); 8.94 (s, NH); 8.89 (s, NH); 7.97 (sbroad, 3H); 7.65 (d, J=7.5 Hz, 2H); 7.55 (d, J=7.2 Hz, 1H); 7.42-7.19 (m, 5H);6.87 (pseudo t, J=5.4 Hz, 1H); 6.15 (d, J=8.4 Hz, 1H); 4.55 (m broad, 1H); 3.61(s, 3H); 3.38 (s broad, 1H); 3.12 (m, 1H); 2.90 (m, 3H); 2.70 (s, 3H); 2.65 (s,6H); 2.19 (s, 3H); 2.09 (s, 3H); 2.04 (s, 3H); 2.00-1.28 (m, 14H); 1.20-1.04 (m,3H); 0.92-0.76 (m, 2H).13C NMR-75 (CDCIs): 171.61; 168.81; 167.39; 160.44;160.41; 160.11; 159.97; 159.17; 156.09; 156.03; 155.91; 143.62; 143.39;140.50; 140.43; 128.67 (CH); 128.58 (CH); 127.85 (CH); 127.65 (CH); 124.97(CH); 124.72 (CH); 119.87 (CH); 60.68; 60.45; 59.90; 55.34 (CH); 52.46 (CHs);52.16 (CH); 46.27 (CHa); 39.55 (CHa); 37.74 (CH); 30.63 (CHa); 26.43 (CHa);26.23 (CHa); 25.80 (CHa); 21.69 (CHs); 21.50 (CHs); 21.44 (CHs); 11.89 (3CHs). MALDI-FTMS [M+H]+: expected: 989.4510; observed: 989.4508.

Reference： [1]Patent: WO2006/4841,2006,A2 .Location in patent: Page/Page column 17; 2/9

28
[ 10130-87-7 ]
[ 3218-02-8 ]
[ 874569-02-5 ]

Yield	Reaction Conditions	Operation in experiment
94%	With N-ethyl-N,N-diisopropylamine; In dichloromethane;	(cyclohexyl methyl)[(2- methoxyphenyl)sulfonyl]amine was prepared by treating cyclohexylmethyl amine (0.23 g, 2mmols) with 2-methoxybenzenesulfonylchloride (0.41 g, 2 mmols) in dichloromethane (10 ml) in presence of diisopropylethylamine (0.7 ml 4 mmols). Yield: 0.53 g (94%). MH+: 284

Reference： [1]Patent: WO2006/9876,2006,A2 .Location in patent: Page/Page column 162

29
[ 43207-78-9 ]
[ 508240-54-8 ]
[ 3218-02-8 ]
[ 508239-44-9 ]

Yield	Reaction Conditions	Operation in experiment
31%		EXAMPLE 427 5-Cyclohexylmethylamino-2-(2-furyl)-8-(7-methoxy-1,2,3,4-tetrahydroisoquinolin-2-ylmethyl)[1,2,4]triazolo[1,5-c]pyrimidine (Compound 428) The subject compound (31%) was obtained as a pale brown oily matter from 8-formyl-2-(2-furyl)-5-methylthio[1,2,4]triazolo[1,5-c]pyrimidine, cyclohexanemethylamine and <strong>[43207-78-9]7-methoxy-<strong>[43207-78-9]1,2,3,4-tetrahydroisoquinoline</strong></strong> in a manner similar to that in Example 315. APCIMS m/z: [M+H]+ 473

Reference： [1]Patent: US2004/110826,2004,A1

30
[ 3218-02-8 ]
[ 102-83-0 ]
[ 245421-04-9 ]
[ 1018478-87-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 1308 - 1311

31
[ 108-77-0 ]
[ 366-99-4 ]
[ 22795-99-9 ]
[ 3218-02-8 ]
[ 502767-57-9 ]

Yield	Reaction Conditions	Operation in experiment
43.7%		Example 43 Synthesis of N2-cyclohexylmethyl-N4-((S)-1-ethyl-pyrrolidin-2-ylmethyl)-N6-(3-fluoro-4-methoxphenyl)-1,3,5-triazine-2,4,6-triamine (141) To a mixture of cyanuric chloride (0.368 g, 2 mmol) in CH3CN at about -20° C. was added 3-fluoro-p-anisidine (0.28 g, 2 mmol) in CH3CN followed by the addition of N,N-diisopropylethylamine (DIEA) (0.35 mL, 2 mmol) and stirred for about 1 hour. The reaction mixture was then stirred at room temperature for about 1 hour. Then, cyclohexylmethyl amine (0.26 mL, 2 mmol) and DIEA (0.35 mL, 2 mmol) were added and the reaction mixture was stirred overnight at RT. Then, S-(-)-2-aminomethyl-N-ethyl pyrrolidine (0.29 mL, 2 mmol) and DIEA (0.35 mL, 2 mmol) were added and the reaction mixture was refluxed overnight. The reaction mixture was diluted with ethyl acetate and washed with brine. The organic layer was separated and dried over sodium sulfate, filtered, and concentrated under reduced. The crude material was purified by column chromatography eluding with 96:3:1 methylene chloride:methanol:conc. ammonium hydroxide to yield a white solid 141 (0.400 g, 43.7percent), mp 68-69° C.; HPLC: Inertsil ODS-3V C18, 40:30:30 [KH2PO4 (0.01 M, pH 3.2): CH3OH: CH3CN], 264 nm, Rt 8.2 min, 97.1percent purity; MS (ESI): m/z 458 (M+H, 100), 362 (2.8), 230 (85.4).
43.7%		To a mixture of cyanuric chloride (0.368 g, 2 mmol) inCH3CN atabout-20 C was added3-fluoro-p-anisidine (0.28 g, 2 mmol) inCH3CN followed by the additionof N, N-diisopropylethylamine (DIEA) (0.35 mL, 2 mmol) and stirred for about 1 hour. The reaction mixture was then stirred at room temperature for about 1 hour. Then, cyclohexylmethyl amine (0.26mL, 2 mmol) and DIEA (0.35 mL, 2 mmol) were added and the reaction mixture was stirred overnight at RT. Then, S-(-)- 2-aminomethyl-N-ethyl pyrrolidine (0.29 mL, 2 mmol) and DIEA (0.35 mL, 2 mmol) were added and the reaction mixture was refluxed overnight. The reaction mixture was diluted with ethyl acetate and washed with brine. The organic layer was separated and dried over sodium sulfate, filtered, and concentrated under reduced. The crude material was purified by column chromatography eluting with 96: 3: 1 methylene chloride: methanol: cone. ammonium hydroxide to yield a white solid 141 (0.400 g, 43.7percent), mp68-69 OC ; HPLC: Inertsil ODS-3V C18, 40: 30: 30[KH2P04(0. 01 M, pH3. 2) :CH30H : CH3CN], 264nm, Rt 8.2 min, 97.1percent purity ; MS (ESI):lnlz 458 (M+H, 100), 362 (2.8), 230(85. 4).

Reference： [1]Patent: US2004/209880,2004,A1 .Location in patent: Page/Page column 81
[2]Patent: WO2004/26844,2004,A1 .Location in patent: Page 325

32
[ 213598-05-1 ]
[ 3218-02-8 ]
[ 1042391-74-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 3456 - 3461

33
[ 100-49-2 ]
[ 3218-02-8 ]
N-cyclohexylmethylidene-1-cyclohexylmethanamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With ammonia;carbonylchlorohydrido(4,5-bis((diisopropylphosphino)methyl)acridine)ruthenium(II); In toluene; under 5700.38 Torr; for 25h;Reflux;Product distribution / selectivity;	Complex 1 (0.01 mmol), alcohol (10 mmol ), and a solvent (3 mL, if applicable) were added to a 90 mL Fischer-Porter tube under an atmosphere of purified nitrogen in a Vacuum Atmospheres glovebox. The tube was taken out of the box and ammonia (7.5 atm) was charged into the Fischer-Porter tube and the reaction mixture was refluxed in an oil bath covered by a protective shield for the specified time (Tables 1-3 in the reports). After cooling to room temperature, the products were analyzed by GC with toluene or mesitylene as an internal standard, using a HP-5 cross linked 5% PH ME Siloxane column (30m x 0.32mm x 0.25 mum film thickness) on a HP 6890 series GC system.

Reference： [1]Angewandte Chemie - International Edition,2008,vol. 47,p. 8661 - 8664
[2]Patent: WO2010/18570,2010,A1 .Location in patent: Page/Page column 24; 25; 31; 32

34
[ 3218-02-8 ]
[ 766-05-2 ]
[ 1122-56-1 ]
[ 98-89-5 ]

Reference： [1]Angewandte Chemie - International Edition,2008,vol. 47,p. 9249 - 9251

35
[ 67899-00-7 ]
[ 3218-02-8 ]
[ 1152209-90-9 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 100℃; for 2h;	To 4 mL of DMF were added 0.50 g of 2-amino-4- methylthiazole-5-carboxylic acid, 0.56 g of 1- hydroxybenzotriazole, 0.80 g of WSC and 0.47 g of cyclohexylmethylamine, and the mixture was stirred at 1000C for 2 hours. The reaction mixture was allowed to stand and cooled to about room temperature, added to an aqueous saturated sodium bicarbonate solution, and extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, then dried over magnesium sulfate, and concentrated under reduced pressure. The resultant residue was subjected to silica gel column chromatography to obtain 0.58 g of N-cyclohexylmethyl-2- amino-4-methylthiazole-5-carboxamide (hereinafter referred to as "the present compound (2)") . The present compound (2) <n="37"/>1H-NMR (CDCl3) delta: 0.91-1.30 (5H, m) , 1.49-1.76 (6H, m) , 2.49 (3H, s), 3.22 (2H, t, J = 6.4 Hz), 5.28 (2H, br s), 5.54 (IH, br s) .

Reference： [1]Patent: WO2009/66790,2009,A1 .Location in patent: Page/Page column 35-36

36
[ 50916-55-7 ]
[ 3282-30-2 ]
[ 3218-02-8 ]
[ 1010833-26-7 ]

Yield	Reaction Conditions	Operation in experiment
35%	Stage #1: 3-(2-bromoacetyl)benzonitrile; cyclohexylmethylamine With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at -20℃; Cooling with ice; Inert atmosphere; Stage #2: pivaloyl chloride In tetrahydrofuran for 1h; Stage #3: With 2,2,2-trifluoroacetic acid ammonia at 140℃; for 0.25h; Inert atmosphere;	1 EXAMPLE 1 3-(2-tert-Butyl-1-cyclohexylmethyl-1H-imidazol-4-yl)benzonitrile (Compound 1) ; Under a nitrogen atmosphere, cyclohexanemethylamine (1.04 mL, 8.03 mmol) was dissolved in THF (15 mL), and diisopropylethylamine (2.8 mL, 16.06 mmol) was added thereto at - 20°C, and then, a solution obtained by dissolving 3-(2-bromoacetyl)benzonitrile (1.50 g, 6.69 mmol) in THF (5 mL) was slowly added dropwise thereto. After the mixture was stirred for 1 hour under ice-cooling, pivaloyl chloride (2.03 mL, 16.46 mmol) was added thereto, and the mixture was further stirred for 1 hour. Water was added to the mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. To the residue, ammonium trifluoroacetate (2.70 g, 23.7 mmol) was added under an argon atmosphere, and the mixture was stirred at 140°C for 15 minutes. After the mixture was left to cool to room temperature, water and an aqueous sodium hydrogen carbonate solution were added thereto, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate = 99/1 to 25/5) to give the title compound 1 (745 mg, 2.31 mmol, yield: 35%). 1H-NMR (dppm, CDCl3): 8.07-8.03 (m, 1H), 7.97 (dt, J = 6.7, 2.1 Hz, 1H), 7.46-7.38 (m, 2H), 7.17 (s, 1H), 3.87 (d, J = 7.1 Hz, 2H), 1.85-1.70 (m, 6H), 1.47 (s, 9H), 1.28-1.20 (m, 3H), 1.08-1.00 (m, 2H). Mass (m/e): 322 (M+H)+.

Reference： [1]Current Patent Assignee: Kyowa Kirin (in: Kirin Holdings); KIRIN HOLDINGS CO., LTD. - EP2090570, 2009, A1 Location in patent: Page/Page column 46

37
[ 20028-68-6 ]
[ 3218-02-8 ]
C₁₅H₁₇Cl₂N₃ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2008,vol. 51,p. 7855 - 7865
[2]Journal of Medicinal Chemistry,2012,vol. 55,p. 8603 - 8614

38
[ 933-20-0 ]
[ 3218-02-8 ]
[ 1189819-45-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 5229 - 5232

39
[ 76903-88-3 ]
[ 3218-02-8 ]
[ 1065129-88-5 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In tetrahydrofuran at 20℃; for 2h;	7 Synthesis Example 7 To 5 ml of THF were added 0.40 g of 3,4-difluorobenzoyl chloride, 0.22 g of cyclohexylmethylamine and 0.40 g of triethylamine, followed by stirring at room temperature for 2 hours. To the reaction mixture, ethyl acetate was added and insolubles were filtered off through Celite. The filtrate was concentrated under reduced pressure. The residue was washed with MTBE, and 0.46 g of N-(cyclohexylmethyl)-3,4-difluorobenzamide was obtained. N-(cyclohexylmethyl)-3,4-difluorobenzamide [Show Image] 1H-NMR (CDCl3) δ: 0.93-1.32 (5H, m), 1.52-1.80 (6H, m), 3.28 (2H, dd, J = 6.5, 6.5 Hz), 6.17 (1H, br s), 7.17-7.24 (1H, m), 7.48-7.52 (1H, m), 7.63 (1H, ddd, J = 10.7, 7.6, 2.3 Hz).

Reference： [1]Current Patent Assignee: Sumitomo Chemical (w/o Dongwoo Fine-Chem); SUMITOMO CHEMICAL COMPANY LIMITED - EP2179651, 2010, A1 Location in patent: Page/Page column 38-39

40
[ 390816-44-1 ]
[ 3218-02-8 ]
[ 1202159-08-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 6507 - 6514

41
[ 1122-56-1 ]
[ 3309-27-1 ]
[ 3218-02-8 ]
[ 100-49-2 ]

Reference： [1]Journal of Catalysis,2011,vol. 278,p. 228 - 238
[2]Advanced Synthesis and Catalysis,2010,vol. 352,p. 869 - 883
[3]Journal of Catalysis,2010,vol. 269,p. 93 - 102

42
[ 1122-56-1 ]
[ 3218-02-8 ]
[ 100-49-2 ]

Reference： [1]Journal of Catalysis,2011,vol. 278,p. 228 - 238
[2]Advanced Synthesis and Catalysis,2010,vol. 352,p. 869 - 883
[3]Journal of Catalysis,2010,vol. 269,p. 93 - 102
[4]Chemical Communications,2018,vol. 54,p. 7503 - 7506

43
[ 55-21-0 ]
[ 3309-27-1 ]
[ 1122-56-1 ]
[ 3218-02-8 ]
[ 100-49-2 ]

Reference： [1]Journal of Catalysis,2010,vol. 269,p. 93 - 102

44
[ 1694-31-1 ]
[ 1204-21-3 ]
[ 3218-02-8 ]
1-cyclohexylmethyl-5-(2,5-dimethoxy-phenyl)-2-methyl-1H-pyrrole-3-carboxylic acid [ No CAS ]

Reference： [1]Organic Letters,2010,vol. 12,p. 5182 - 5185

45
[ 1694-31-1 ]
[ 131805-94-2 ]
[ 3218-02-8 ]
C₂₁H₂₁F₆NO₂ [ No CAS ]

Reference： [1]Organic Letters,2010,vol. 12,p. 5182 - 5185

46
[ 615-20-3 ]
[ 3218-02-8 ]
[ 77414-69-8 ]

Yield	Reaction Conditions	Operation in experiment
92%	With sodium hydrogencarbonate; 1,8-diazabicyclo[5.4.0]undec-7-ene In neat (no solvent) at 20℃; Green chemistry;
88%	Stage #1: cyclohexylmethylamine With copper(l) iodide for 0.5h; Stage #2: With potassium hydroxide In water for 1h; Stage #3: 2-chlorobenzo[d][1,3]thiazole With benzyl tri-n-butylammonium bromide In chloroform; water at 20℃; for 6h; chemoselective reaction;
80%	With 1H-imidazole; sodium chloride In water for 6h; Reflux; Green chemistry;	Synthesis of Benzothiazol-2-yl-morpholine (General Procedure 1) General procedure: In a 50-mL, round-bottom flask, 0.87 g (0.01 mol) of morpholine, 0.68 g(0.01 mol) of imidazole, 0.274 g (0.001 mol) of tributylbenzyl ammonium choride,and 1.69 g (0.01 mol) 2-chlorobenzothiazole were added to 20mL of 5% NaCl (aqueous)solution. The reaction mixture was refluxed for 6 h. The progress of the reactionwas monitored by thin-layer chromatography (TLC). After completion of the reaction,the aqueous layer was washed with ethyl acetate (310 mL). The combinedorganic layer was dried over anhydrous Na2SO4 and concentrated at reduced pressure.Products were purified either by crystallizing or by flash chromatography. Whitecrystalline solid

Reference： [1]Verma, Sanjeev K.; Acharya; Ghorpade, Ramarao; Pratap, Ajay; Kaushik [RSC Advances, 2013, vol. 3, # 41, p. 18783 - 18786]
[2]Verma, Sanjeev K.; Acharya; Kaushik [Organic and Biomolecular Chemistry, 2011, vol. 9, # 5, p. 1324 - 1327]
[3]Verma, Sanjeev K.; Ghorpade, Ramarao; Kaushik [Synthetic Communications, 2014, vol. 44, # 18, p. 2645 - 2655]

47
[ 303-38-8 ]
[ 3218-02-8 ]
[ 1332325-16-2 ]

Yield	Reaction Conditions	Operation in experiment
31%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃; for 6.5h; Inert atmosphere;	5.2.18. N-(4-Fluorobenzyl)-2,3-dihydroxybenzamide (5a) General procedure: A solution of 2,3-dihydroxybenzoic acid (154 mg, 1 mmol), EDCI (380 mg, 2 mmol), DIPEA (2 mmol), and HOBt (290 mg, 2 mmol) in dry THF (15 mL) was stirred at rt under N2. To this solution was added 90% (4-fluorophenyl)methanamine (0.152 mL, 1.2 mmol). The reaction mixture was stirred for 6.5 h at rt. After removal of most of THF, 20 mL of EtOAc was added to the residue. The solution was washed by 1 N HCl, satd NH4Cl and dried over Na2SO4. The concentration provided the residue which was purified by chromatography using petroleum ether/ethyl acetate (1:1) as eluent to give compound 5a as a white solid (51 mg, 57% yield).

Reference： [1]Location in patent: experimental part Fan, Xing; Zhang, Feng-Hua; Al-Safi, Rasha I.; Zeng, Li-Fan; Shabaik, Yumna; Debnath, Bikash; Sanchez, Tino W.; Odde, Srinivas; Neamati, Nouri; Long, Ya-Qiu [Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 16, p. 4935 - 4952]

48
[ 101774-27-0 ]
[ 3218-02-8 ]
[ 1296202-02-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 7107 - 7112

49
[ 5926-51-2 ]
[ 3218-02-8 ]
[ 1266664-85-0 ]

Reference： [1]Organic and Biomolecular Chemistry,2013,vol. 11,p. 2408 - 2411
[2]Chemical Communications,2012,vol. 48,p. 4725 - 4727

50
[ 20028-68-6 ]
[ 3218-02-8 ]
[ 1219456-96-8 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 8603 - 8614

51
[ 2065-37-4 ]
[ 3218-02-8 ]
[ 1421609-32-6 ]

Yield	Reaction Conditions	Operation in experiment
38%	In ethanol;	2-((cyclohexylmethyl)amino)naphthalene- 1,4-dione (2g). To a solution of 2-bromo-l,4-napthoquinone (283 mg, 1.2 mmol) in abs EtOH (40 mL) was added an excess of cyclohexanemethylamine (312 uL, 2.4 mmol). Progress of the reaction was monitored with TLC. Compound was purified using chromatography on silica gel to yield 124 mg orange powder (38% yield). ). MS m/z calcd (M+) 270.34, found 270.1. 1H NMR (400 MHz, DMSO-d6) Shift 7.97 (dd, J = 7.03, 17.57 Hz, 2H), 7.83 (dt, J = 1.00, 7.53 Hz, 1H), 7.70 - 7.77 (m, 1H), 7.64 (t, J = 6.15 Hz, 1H), 5.68 (s, 1H), 3.04 (t, J = 6.53 Hz, 2H), 1.50 - 1.81 (m, 6H), 1.05 - 1.32 (m, 3H), 0.81 - 1.03 (m, 2H). C13-HSQC (400 MHz, DMSO-d6) Shift (ppm) 30.82, 25.66, 26.58, 25.66, 30.82, 6.40, 40.14, 48.34, 99.47, 132.52, 135.19, 125.62, 126.34.

Reference： [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 1007 - 1022
[2]Patent: WO2014/74976,2014,A1 .Location in patent: Paragraph 00215

52
[ 41972-62-7 ]
[ 3218-02-8 ]
[ 530-62-1 ]
[ 1426152-59-1 ]

Reference： [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 2110 - 2124

53
[ 21906-31-0 ]
[ 3218-02-8 ]
[ 1426915-56-1 ]

Reference： [1]Organic Letters,2013,vol. 15,p. 1666 - 1669

54
[ 21906-31-0 ]
[ 3218-02-8 ]
C₁₆H₂₂BrN [ No CAS ]

Reference： [1]Organic Letters,2013,vol. 15,p. 1666 - 1669

55
[ 383132-27-2 ]
[ 3218-02-8 ]
[ 1432641-94-5 ]

Yield	Reaction Conditions	Operation in experiment
80%	Stage #1: 4,6-dimethyl-1H-indole-2-carboxylic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 0.166667h; Inert atmosphere; Stage #2: cyclohexylmethylamine With triethylamine In dichloromethane at 20℃;

Reference： [1]Onajole, Oluseye K.; Pieroni, Marco; Tipparaju, Suresh K.; Lun, Shichun; Stec, Jozef; Chen, Gang; Gunosewoyo, Hendra; Guo, Haidan; Ammerman, Nicole C.; Bishai, William R.; Kozikowski, Alan P. [Journal of Medicinal Chemistry, 2013, vol. 56, # 10, p. 4093 - 4103]

56
[ 6307-87-5 ]
[ 3218-02-8 ]
[ 1445788-75-9 ]

Yield	Reaction Conditions	Operation in experiment
	With tri-tert-butyl phosphine; palladium diacetate; caesium carbonate; In hexane; toluene; at 80℃;Inert atmosphere; Microwave irradiation; Sealed tube;	Example 7 3-((3-carbamoyl-7-(2,4-dimethoxypyrimidin-5-yl)quinolin-4-yl)amino)-5- ((cvclohexylmethyl)amino)benzoic acid 3-amino-5-[(cvclohexylmethyl)aminolbenzoic acid. Under nitrogen atmosphere in a sealed microwave vial, <strong>[6307-87-5]methyl 3-bromo-5-nitrobenzoate</strong> (250 mg, 0.961 mmol), (aminomethyl)cyclohexane (0.312 mL, 2.403 mmol), cesium carbonate (470 mg, 1.442 mmol), tri-tertbutylphosphine 1 M in hexane (0.096 mL, 0.096 mmol), and palladium(ll) acetate (21.58 mg, 0.096 mmol) in toluene (5 mL) were mixed. The reaction was stirred at 80C overnight, before being concentrated and purified by reverse-phase preparative HPLC ( 30-90% acetonitrile/water + 0.1 % trifluoroacetic acid) to give the intermediate nitro compound. 1H NMR (METHANOLS) d: 7.82 - 7.95 (m, 1 H), 7.43 - 7.58 (m, 2H), 3.94 (s, 3H), 2.99 (d, J = 6.8 Hz, 2H), 1 .88 (d, J = 13.1 Hz, 2H), 1 .75 - 1 .83 (m, 2H), 1.72 (d, J = 10.4 Hz, 1 H), 1.56 - 1.67 (m, 1 H), 1.17 - 1.40 (m, 3H), 0.93 - 1.12 (m, 2H). The intermediate nitro compound, 5% palladium-on-charcoal (102 mg, 0.048 mmol) and methanol (3 ml.) were stirred under hydrogen at room temperature overnight. The catalyst was filtered and 6N sodium hydroxide (0.080 ml_, 0.481 mmol) was added. Upon completion, the mixture was concentrated and taken directly to the next step as-is. LCMS (ES+) m/z 249 [M+H]+.

Reference： [1]Patent: WO2013/96151,2013,A1 .Location in patent: Page/Page column 62; 63

57
[ 615-42-9 ]
[ 201230-82-2 ]
[ 3218-02-8 ]
[ 41763-91-1 ]

Yield	Reaction Conditions	Operation in experiment
96%	With triethylamine In toluene at 100℃; for 6h; Autoclave;	General procedure carbonylative cyclization ofmethyl-2-iodobenoate/1,2-diiodo benzene for the synthesis ofN-substituted isoindole-1,3-diones using ImmPd-IL as a catalyst General procedure: General procedure carbonylative cyclization ofmethyl-2-iodobenoate/1,2-diiodo benzene for the synthesis ofN-substituted isoindole-1,3-diones using ImmPd-IL as a catalystIn a 100 mL stainless steel autoclave, methyl-2-iodobenoate/1,2-diiodobenzene (1 mmol), aryl amine (2 mmol), ImmPd-IL(2 mol%), toluene (10 mL) and Et3N (2.5 mmol) were added. Theautoclave was closed, purged three times with nitrogen followedwith carbon monoxide, and then pressurized with 1 atm of CO andheated at 100C for 6 h. After completion of reaction the reac-tor was cooled to room temperature, the remaining CO gas wascarefully vented, and the reactor was opened. The reactor vesselwas thoroughly washed with ethyl acetate (10-15 mL) to removeany traces of product and catalyst if present. The catalyst was fil-tered and the reaction mixture was evaporated under vacuum. Theresidue obtained was purified by column chromatography (silicagel, 60-120 mesh; petroleum ether/ethyl acetate, 95:05) to affordthe desired product. The products were confirmed by GC, GC-MS,1H NMR and13C NMR spectroscopic techniques. The purity of com-pounds was determined by GC-MS analysis.

Reference： [1]Khedkar, Mayur V.; Shinde, Ajinkya R.; Sasaki, Takehiko; Bhanage, Bhalchandra M. [Journal of Molecular Catalysis A: Chemical, 2014, vol. 385, p. 91 - 97]

58
[ 329-98-6 ]
[ 3218-02-8 ]
[ 885373-76-2 ]

Reference： [1]ACS Combinatorial Science,2014,vol. 16,p. 192 - 197

59
[ 51517-01-2 ]
[ 3218-02-8 ]
[ 1375976-45-6 ]

Reference： [1]ACS Combinatorial Science,2014,vol. 16,p. 192 - 197

60
[ 1120-82-7 ]
[ 3218-02-8 ]
[ 1609253-73-7 ]

Yield	Reaction Conditions	Operation in experiment
80.2%	With magnesium sulfate; In dichloromethane; at 20℃; for 72h;Reflux;	LA was prepared by a similar procedure as described in the literature [44]. The CH2Cl2 solution (10.0mL) of cyclohexylmethanamine (2.26g, 0.0200mol) was added to CH2Cl2 solution (30.0mL) of <strong>[1120-82-7]1H-1-pyrazolyl-1-methanol</strong> (3.92g, 0.0400mol). The reaction solution was dried over MgSO4 after stirring at room temperature for 3days. The filtrate solvent under reduced pressure to give a colorless and transparent oil product was obtained (4.38g, 80.2%). Anal. Calc. for C15H23N5: C, 65.9, H, 8.48, N, 25.6. Found: C, 65.8, H, 8.62, N, 25.0%. 1H NMR (CDCl3, 400MHz): delta 7.51 (d, 2H, J=1.2Hz, -N=CH-CH=CH-N-), 7.50 (d, 2H, J=2.4Hz, -N=CH-CH=CH-N-), 6.26 (dd, 2H, J=1.2Hz, J=2.0Hz, -=CH-CH=CH-N-), 4.97 (s, 4H, -N-CH2-N-), 2.45 (d, 2H, J=2.8Hz, -C6H11-CH2-N-), 1.72-1.65 (m, 5H, -C6H11-), 1.53-1.50 (m, 1H, ipso-C6H11-), 1.24-1.07 (m, 3H, -C6H11-), 0.81-0.73 (m, 2H, -C6H11-). 13C NMR (CDCl3, 100MHz): delta 140.69 (d, 2C, J=176Hz, -N=CH-CH=CH-N-), 130.92 (d, 2C, J=177Hz, -N=CH-CH=CH-N-), 107.13 (d, 2C, J=185Hz, -N=CH-CH=CH-N-), 68.62 (t, 2C, J=150Hz, -N-CH2-N-), 56.97 (t, 1C, J=132Hz, -C6H11-CH2-N-), 36.64 (d, 1C, J=123Hz, ipso-C6H11-), 31.60 (t, 2C, J=123Hz, o-C6H11-), 27.06 (t, 1C, J=124Hz, p-C6H11-), 26.32 (t, 2C, J=125Hz, m-C6H11-). IR (liquid neat; cm-1): 3110 (w), 2922 (s), 2850 (m), 1512 (m), 1387 (m), 1251 (m), 1124 (w), 1084 (m), 1044 (s), 962 (m), 859 (w), 746 (s), 614 (m).
80.2%	In dichloromethane; at 20℃; for 24h;	First, cyclohexylmethanamine (2.26 g, 0.0200 mol) was dissolved in a CH2Cl2 solvent (30.0 mL) and <strong>[1120-82-7]1H-1-pyrazolyl-1-methanol</strong> (3.92 g, 0.0400 mol) was dissolved in a CH2Cl2 solvent (20.0 mL) and added. The reaction was carried out at room temperature for 24 hours, the water was removed by solution reaction with MgSO4, and the solution was removed by pressure. A colorless oil was obtained after distillation under reduced pressure. (5.28 g, 80.2%).

Reference： [1]Inorganica Chimica Acta,2015,vol. 438,p. 118 - 127
[2]Patent: KR2017/51867,2017,A .Location in patent: Paragraph 0083-0085
[3]Inorganic Chemistry Communications,2014,vol. 44,p. 164 - 168

61
[ 3218-02-8 ]
[ 231278-84-5 ]
[ 1421356-33-3 ]

Yield	Reaction Conditions	Operation in experiment
73.5%	Stage #1: cyclohexylmethylamine; 5-(4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)quinazolin-6-yl)furan-2-carbaldehyde In tetrahydrofuran at 20℃; for 6h; Inert atmosphere; Stage #2: With sodium tris(acetoxy)borohydride In tetrahydrofuran at 20℃; for 24h;	9 Example 9 Preparation of N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-6-((5-((cyclohexylmethyl)amino)methyl)-2-furyl) -4-quinazolinamine (MS7) Example 9 Preparation of N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-6-((5-((cyclohexylmethyl)amino)methyl)-2-furyl) -4-quinazolinamine (MS7) Under nitrogen, N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-6-(5-formyl-2-furyl)-4-quinazolinamine (0.47g, 1mmol) obtained from Example 1 was dissolved in anhydrous tetrahydrofuran (10ml), followed by the addition of cyclohexyl-methylamine (0.23g, 2 mmol), and stirred at room temperature for 6 h. Sodium triacetoxy borohydride (0.42g, 2 mmol) was added, and then the mixture was stirred at room temperature for 24 h. A saturated aqueous solution of sodium carbonate (10 ml) was added, and then the mixure was stirred for 15 min to be layered. The organic layer was washed with saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate, filtered, and rotary evaporated to give a yellow solid. The solid was separated by column chromatography on silica gel (200-300 mesh) (eluted with a gradient of ethyl acetate/methanol) to give a yellow solid (0.42g, 73.5%), i.e. the compound of Number MS7. 1H NMR(DMSO-d6)δ: 9.87(s, 1H), 8.74(s, 1H), 8.56(s, 1H), 8.16(d, J=8.3 Hz, 1H), 8.01(d, J=2.6 Hz, 1H), 7.79(d, J=8.8 Hz, 1H), 7.74(m, 1H), 7.46- 7.49(m, 1H), 7.27- 47.35(m, 3H), 7.18(t, 1H), 7.05(d, J=3.2 Hz, 1H), 6.49(d, J=3.3 Hz, 1H), 5.26(s, 2H), 3.99- 4.04(m, 1H), 3.66(s, 2H), 2.51(d, 2H), 1.49- 1.67(m, 11H); ESI-MS m/z: 571[M+H]+.
73.5%	Stage #1: cyclohexylmethylamine; 5-(4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)quinazolin-6-yl)furan-2-carbaldehyde In tetrahydrofuran at 20℃; for 6h; Inert atmosphere; Stage #2: With sodium tris(acetoxy)borohydride In tetrahydrofuran at 20℃; for 24h;	9 Preparation of N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-6-((5-((cyclohexylmethyl)amino)methyl)-2-furyl)-4-quinazolinamine (MS7) Example 9 Preparation of N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-6-((5-((cyclohexylmethyl)amino)methyl)-2-furyl)-4-quinazolinamine (MS7) Under nitrogen, N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-6-(5-formyl-2-furyl)-4-quinazolinamine (0.47 g, 1 mmol) obtained from Example 1 was dissolved in anhydrous tetrahydrofuran (10 ml), followed by the addition of cyclohexyl-methylamine (0.23 g, 2 mmol), and stirred at room temperature for 6 h. Sodium triacetoxy borohydride (0.42 g, 2 mmol) was added, and then the mixture was stirred at room temperature for 24 h. A saturated aqueous solution of sodium carbonate (10 ml) was added, and then the mixture was stirred for 15 min to be layered. The organic layer was washed with saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate, filtered, and rotary evaporated to give a yellow solid. The solid was separated by column chromatography on silica gel (200-300 mesh) (eluted with a gradient of ethyl acetate/methanol) to give a yellow solid (0.42 g, 73.5%), i.e. the compound of Number MS7. 1H NMR (DMSO-d6) δ: 9.87 (s, 1H), 8.74 (s, 1H), 8.56 (s, 1H), 8.16 (d, J=8.3 Hz, 1H), 8.01 (d, J=2.6 Hz, 1H), 7.79 (d, J=8.8 Hz, 1H), 7.74 (m, 1H), 7.46-7.49 (m, 1H), 7.27-47.35 (m, 3H), 7.18 (t, 1H), 7.05 (d, J=3.2 Hz, 1H), 6.49 (d, J=3.3 Hz, 1H), 5.26 (s, 2H), 3.99-4.04 (m, 1H), 3.66 (s, 2H), 2.51 (d, 2H), 1.49-1.67 (m, 11H); ESI-MS m/z: 571[M+H]+.

Reference： [1]Current Patent Assignee: HANGZHOU MINSHENG PHARMACEUTICAL CO., LTD. - EP2740729, 2014, A1 Location in patent: Paragraph 0065; 0066
[2]Current Patent Assignee: HANGZHOU MINSHENG PHARMACEUTICAL CO., LTD. - US2015/80392, 2015, A1 Location in patent: Paragraph 0227

62
[ 82437-64-7 ]
[ 122-51-0 ]
[ 3218-02-8 ]
[ 1621968-06-6 ]

Yield	Reaction Conditions	Operation in experiment
73%	With acetic acid; at 160℃;Inert atmosphere; Autoclave;	General procedure: To a pressure bottle containing <strong>[82437-64-7]methyl 3-amino-4-phenylthiophene-2-carboxylate</strong> (100 mg, 0.43 mmol), CH(OEt)3 (1 mL) was added, followed by allylamine hydrochloride (93 mg, 0.99 mmol) and AcOH (0.1 mL). The reaction mixture was stirred and refluxed at 160 C overnight. After the reaction, the mixture was evaporated then solidified with ether. The produced white crystals were filtered and dried in vacuo to give the title compound 4-1 (66 mg, 0.25 mmol, 58 % yield): 1HNMR (300 MHz, CDCl3) delta 8.11 (s, 1H), 7.84-7.79 (m, 3H), 7.50-7.44 (m, 2H), 7.41-7.36 (m, 1H), 6.08-5.95 (m, 1H), 5.34-5.24 (m, 2H), 4.72-4.67 (m, 2H); 13C NMR (100 MHz, CDCl3) delta 157.3, 154.3, 147.3, 138.1, 133.7, 131.9, 130.5,128.7, 128.3, 128.0, 124.9, 119.1, 48.0; LC/MS (ESI+): m/z: calcd for C15H12N2OS: 268.34, [M + H]+; found: 269.05

Reference： [1]Bulletin of the Korean Chemical Society,2015,vol. 36,p. 1439 - 1451

63
[ 16590-41-3 ]
[ 3218-02-8 ]
[ 140-88-5 ]
1'-cyclohexylmethyl-17-cyclopropylmethyl-6,7-didehydro-4,5-epoxy-4',5'-dihydro-3,14-dihydroxy-pyrido[2,3:6,7]morphinan-6(1H)-one hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50%	Stage #1: Naltrexone; cyclohexylmethylamine With toluene-4-sulfonic acid In ethanol for 5h; Inert atmosphere; Molecular sieve; Reflux; Stage #2: ethyl acrylate In ethanol for 18h; Inert atmosphere; Molecular sieve; Reflux; Stage #3: With hydrogenchloride In methanol; diethyl ether Inert atmosphere;	General procedure General procedure: Naltrexone (0.80 g, 2.35 mmol) was dissolved in 2ml of anhydrous ethanol under a nitrogen atmosphere. Catalytic p-toluene sulfonic acid (10mg) and activated molecular sieves (50 mg) were added. The reaction mixture was stirred for 10min and the appropriate amine (RNH2; 2.35 mmol) was added. The reaction mixture was refluxed for 5 h before adding ethyl acrylate (0.26 ml, 2.35 mmol) and again refluxing for 18h. After completion, the reaction mixture was cooled to room temperature, filtered and washed with dichloromethane (50 ml) and the organic layer was washed with water (2×20 ml) and brine (20 ml). The organic layer was dried over magnesium sulfate, concentrated under reduced pressure to obtain crude product which was purified by flash chromatography using methanol/dichloromethane/ammonium hydroxide (1:98.5:0.5). Yield (20-50%).

Reference： [1]Kumar; Clark; Traynor; Lewis; Husbands [Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 15, p. 4067 - 4072]

64
[ 885500-55-0 ]
[ 3218-02-8 ]
ethyl 4-[(cyclohexylmethyl)amino]-1H-pyrrolo[2,3-b]pyridine-5-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62%	With triethylamine; In 1-methyl-pyrrolidin-2-one; at 180℃; for 1h;Microwave irradiation;	General procedure: 5.1.3 Ethyl 4-(cycloheptylamino)-1H-pyrrolo[2,3-b]pyridine-5-carboxylate (5c) A mixture of 4 (112 mg, 0.50 mmol), cycloheptanamine (76 muL, 0.60 mmol), and Et3N (209 muL, 1.5 mmol) in NMP (3.0 mL) was heated in a microwave reactor at 180 C for 1 h. After cooling to room temperature, the reaction mixture was quenched with water, extracted with EtOAc, dried over MgSO4, and evaporated in vacuo. The crude mixture was purified by column chromatography on silica gel (CHCl3/MeOH = 100:0 to 90:10) to give the product (135 mg, 90%). 5.1.4 Ethyl 4-[(cyclohexylmethyl)amino]-1H-pyrrolo[2,3-b]pyridine-5-carboxylate (5d) Compound 5d was prepared in 62% yield as a white solid by a method similar to that described for 5c. 1H NMR (DMSO-d6) delta 1.01-1.33 (m, 5H), 1.31 (t, J = 7.1 Hz, 3H), 1.61-1.86 (m, 6H), 3.52 (t, J = 6.1 Hz, 2H), 4.26 (q, J = 7.1 Hz, 2H), 6.66 (d, J = 3.6 Hz, 1H), 7.15 (d, J = 3.6 Hz, 1H), 8.53 (s, 1H), 8.81 (t, J = 5.4 Hz, 1H), 11.67 (br s, 1H); MS (ESI) m/z 302 [M+H]+.

Reference： [1]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 4846 - 4859

65
[ 1201-07-6 ]
[ 3218-02-8 ]
8-bromo-N-(cyclohexylmethyl)-2-methyl-4-quinolinamine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2015,vol. 58,p. 7021 - 7056

66
[ 1201-07-6 ]
[ 3218-02-8 ]
4-[(cyclohexylmethyl)amino]-2-methyl-8-quinolinecarboxamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2015,vol. 58,p. 7021 - 7056

67
[ 6141-13-5 ]
[ 3218-02-8 ]
[ 1380234-93-4 ]

Reference： [1]Tetrahedron Letters,2016,vol. 57,p. 1035 - 1039

68
[ 3218-02-8 ]
[ 4760-34-3 ]
[ 2876-08-6 ]
[ 106380-62-5 ]

Yield	Reaction Conditions	Operation in experiment
1: 47% 2: 37%	With C₈H₇NO₃; copper(ll) bromide In ethanol at 60℃; for 24h; Green chemistry;

Reference： [1]Nguyen, Khac Minh Huy; Largeron, Martine [European Journal of Organic Chemistry, 2016, vol. 2016, # 5, p. 1025 - 1032]

69
[ 1194-02-1 ]
[ 3218-02-8 ]
[ 100-49-2 ]

Yield	Reaction Conditions	Operation in experiment
35%; 63%	With water; In aq. phosphate buffer; at 25℃; for 6h;pH 2.7 - 3.2;Electrochemical reaction;	General procedure: A conventional two compartment glass or PTFE H-cell separated by a Nafion-117 membrane was used for electrochemical HDF experiments. The cathode was fabricated from a piece of Rh/Ni foam, Rh/Agmesh, Rh/Cu foam, or Rh/carbon felt (projected area: 2 × 3 cm2), whereas the anode was fashioned from a graphite sheet (2 × 3 cm2). 30 mL phosphate buffer solutions (20 mM) served as both the catholyte and the anolyte. Unless otherwise noted, the catholyte was stirred with a stirring velocity of 350 rpm during electrolysis. The concentrations of reactants and their products were determined by an Agilent 7890 A gas chromatograph (GC) and a Waters HPLC system, using standard calibration curves. The fluoride ion (F-) concentration was determined by a REX PHSJ-4F pH/mV meter combined with F- selective electrode (REXPF-202-C). The specific electric energy consumption (SEEC, kW h m-3catholyte) of the HDF process was calculated from the following equation: SEEC I Ut/1000*V where I is the applied current (A), U is the average cell voltage (3 V), t is HDF time (h), and V is the volume of the catholyte (3 × 10-5 m3). Unless otherwise noted, all of the above-mentioned experimentswere performed under air atmosphere, at 25C.

Reference： [1]Electrochemistry Communications,2016,vol. 66,p. 16 - 20

70
[ 773-82-0 ]
[ 3218-02-8 ]
[ 100-49-2 ]

Yield	Reaction Conditions	Operation in experiment
33%; 65%	With water; In aq. phosphate buffer; at 25℃; for 18h;pH 2.7 - 3.2;Electrochemical reaction;	General procedure: A conventional two compartment glass or PTFE H-cell separated by a Nafion-117 membrane was used for electrochemical HDF experiments. The cathode was fabricated from a piece of Rh/Ni foam, Rh/Agmesh, Rh/Cu foam, or Rh/carbon felt (projected area: 2 × 3 cm2), whereas the anode was fashioned from a graphite sheet (2 × 3 cm2). 30 mL phosphate buffer solutions (20 mM) served as both the catholyte and the anolyte. Unless otherwise noted, the catholyte was stirred with a stirring velocity of 350 rpm during electrolysis. The concentrations of reactants and their products were determined by an Agilent 7890 A gas chromatograph (GC) and a Waters HPLC system, using standard calibration curves. The fluoride ion (F-) concentration was determined by a REX PHSJ-4F pH/mV meter combined with F- selective electrode (REXPF-202-C). The specific electric energy consumption (SEEC, kW h m-3catholyte) of the HDF process was calculated from the following equation: SEEC I Ut/1000*V where I is the applied current (A), U is the average cell voltage (3 V), t is HDF time (h), and V is the volume of the catholyte (3 × 10-5 m3). Unless otherwise noted, all of the above-mentioned experimentswere performed under air atmosphere, at 25C.

Reference： [1]Electrochemistry Communications,2016,vol. 66,p. 16 - 20

71
[ 3218-02-8 ]
[ 18480-53-0 ]
3,4-dichloro-N-(cyclohexylmethyl)isothiazole-5-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%		1.1. Synthesis of 3,4-dichloro-N-(cyclohexylmethyl)isothiazole-5-carboxamide: 730 mg of <strong>[18480-53-0]3,4-dichloroisothiazole-5-carboxylic acid</strong> (3.7 mmol) were dissolved in 10 ml of dichloromethane and a drop of dimethylformamide was added. 1.4 g of oxalyl chloride (11.1 - - mmol) were added dropwise at room temperature. After stirring for 1 h at room temperature, the solution was evaporated to dryness on a rotary evaporator. The residue was taken up in 3 ml of dichloromethane and slowly added dropwise to a solution of 626 mg of 1 - cyclohexylmethanamine (5.5 mmol) and 746 mg of triethylamine (7.4 mmol) in 10 ml of dichloromethane. The mixture was stirred at room temperature for 1 h. The reaction mixture was then added to water and extracted repeatedly with dichloromethane. The concentrated extracts were dried over MgS04, concentrated and purified by column chromatography. Yield: 1.05 g (97percent of theory).'H-NMR (400 MHz, CDC13delta, ppm) 6.86 (br,lH), 3.34 (tr,2H), 1.77 (m,4H), 1.66 (m,lH), 1.58 (m,lH), 1.3-1.15 (m,3H), 1.0 (m,2H).
97%		730mg of <strong>[18480-53-0]3,4-dichloroisothiazole-5-carboxylic acid</strong> (3.7 mmol) were dissolved in 10 ml of dichloromethane and a drop of dimethylformamide was added. 1.4 g of oxalyl chloride (11.1 mmol) were added dropwise at room temperature. After stirring for 1 h at room temperature, the solution was evaporated to dryness on a rotary evaporator. The residue was taken up in 3 ml ofdichloromethane and slowly added dropwise to a solution of 626 mg of 1- cyclohexylmethanamine (5.5 mmol) and 746 mg of triethylamine (7.4 mmol) in 10 ml of dichloromethane. The mixture was stirred at room temperature for 1 h. The reaction mixture was then added to water and extracted repeatedly with dichloromethane. The concentrated extracts were dried over MgSO4, concentrated and purified by column chromatography. Yield:1.05 g (97percent of theory).?H-NMR (400 MHz, CDC13 , ppm) 6.86 (br, 1H), 3.34 (tr, 2H), 1.77 (m, 4H), 1.66 (m, 1H), 1.58 (m, 1H), 1.3-1.15 (m, 3H), 1.0 (m, 2H).

Reference： [1]Patent: WO2016/102420,2016,A2 .Location in patent: Page/Page column 100; 101
[2]Patent: WO2016/102435,2016,A2 .Location in patent: Page/Page column 160; 161

72
[ 16523-31-2 ]
[ 3218-02-8 ]
(6Z)-4-(hexahydrobenzylamino)-6-(hexahydrobenzyliminio)-3-oxocyclohexa-1,4-dien-1-olate [ No CAS ]

Reference： [1]New Journal of Chemistry,2016,vol. 40,p. 5782 - 5796

73
[ 3218-02-8 ]
[ 123577-99-1 ]
C₁₅H₂₁F₂N [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
4.4 g		A solution of commercial <strong>[123577-99-1]1-(3,5-difluorophenyl)ethanone</strong> (5 g, 32 mmoles) and cyclohexanemethylamine (3.6 g, 32 mmoles) in toluene (50 mL) is heated for 40 hours at reflux in an azeotropic assembly. The toluene is evaporated off and the residue is dissolved in ethanol (40 mL). The solution is cooled to 10 C., and then NaBH4 (1.2 g, 32 mmoles) is added in portions; the reaction mixture is stirred for 2 hours, and NaBH4 (0.12 g) is again added. After stirring for 30 minutes, a 3N aqueous HCl solution is added carefully, and the ethanol is evaporated off in vacuo. The residue is taken up in toluene (200 mL) and washed with a 40% aqueous NaOH solution. The organic phase is dried over MgSO4, and evaporation under reduced pressure yields intermediate 705 (4.4 g), which is used without additional treatment in the following step.1H NMR (300 MHz, DMSO-d6): delta 7.00 (m, 3H), 3.70 (quad, 1H), 2.20 (dd, 1H), 2.05 (dd, 1H), 1.80-1.70 (3m, 10H), 1.30 (m, 1H), 1.20 (d, 3H) IR (cm-1): 2922-2850, 1114

Reference： [1]Patent: US2017/137385,2017,A1 .Location in patent: Paragraph 0881; 0882; 0883

74
[ 579514-75-3 ]
[ 3218-02-8 ]
C₁₈H₂₆N₂O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In ethanol;	General procedure: To a solution fo <strong>[579514-75-3]tert-butyl 4-fluoro-3-nitrobenzoate</strong> (560 mg, 2.3 mmol) in 20mL of EtOH were added butan-1-amine (853 mg, 11.6 mmol) and stirred at rt for 2 h.The reaction mixture was concentrated to dryness, and the residue was dissolved inEtOAc (10 x 3 mL) and washed with brine (10 mL). The combined organic layerswere dried over MgSO4, and concentrated in vacuo to afford the product tert-butyl 4-(butylamino)-3-nitrobenzoate (35b) as yellow-orange solid (490 g, 72% yield).

Reference： [1]European Journal of Medicinal Chemistry,2018,vol. 147,p. 238 - 252

75
[ 107-94-8 ]
[ 593-75-9 ]
[ 74965-38-1 ]
[ 3218-02-8 ]
C₂₄H₃₆ClN₃O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In methanol; at 20℃; for 24h;	General procedure: Into a clear solution of 2-(Boc-amino)benzaldehyde 1 (1 mmol) in methanol (5 mL) was added amine 2 (1 mmol) and stirred for 5 minutes at room temperature. Then, 3-chloropropanoic acid (3, 1 mmol) and methylisocyanide (4, 1 mmol) were added to the reaction pot. The reaction was allowed to stir until no noticeable amounts of starting material were visible using TLC. Upon completion ofthe reaction, methanol was evaporated under reduced pressure and the crude Ugi products, without any purification, was dissolved in a CH2Cl2 and trifluoroacetic acid mixture(1:1, 2 mL). The reaction was then allowed to stir at room temperature for 5 h and monitored by TLC. Upon completion of the reaction, the solvent was evaporated under reduced pressure and the crude compound, without any purification, was dissolvedin acetonitrile (2 mL) and K2CO3 (2 mmol) was added. The reaction was then allowed to stir under refluxing conditions for 1 h and reaction completion was monitored usingTLC. The reaction mixture was then allowed to cool to room temperature and the solvent evaporated under reduced pressure. The crude products were subjected to flash column chromatography (EtOAc/hexanes) to yield pure compounds 8a-j.

Reference： [1]Beilstein Journal of Organic Chemistry,2018,vol. 14,p. 875 - 883

76
C₁₈H₂₁NO [ No CAS ]
[ 1096-84-0 ]
[ 3218-02-8 ]

Reference： [1]Inorganic Chemistry,2018,vol. 57,p. 7558 - 7567
[2]Inorganic Chemistry,2018,vol. 57,p. 7558 - 7567

77
C₁₈H₂₃NO [ No CAS ]
[ 1096-84-0 ]
[ 3218-02-8 ]

Reference： [1]Inorganic Chemistry,2018,vol. 57,p. 7558 - 7567

78
[ 14418-84-9 ]
[ 3218-02-8 ]
N-(cyclohexylmethyl)prop-2-ene-1-sulfonamide [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2018,vol. 57,p. 12940 - 12944
Angew. Chem.,2018,vol. 130,p. 13122 - 13126,5

79
[ 3218-02-8 ]
[ 886762-70-5 ]
C₁₃H₁₇BrN₂O₂ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2019,vol. 62,p. 234 - 246

80
[ 1882-71-9 ]
[ 3218-02-8 ]
2-cyclohexyl-6-methoxyquinazolin-4(3H)-one [ No CAS ]

Reference： [1]Organic Letters,2019

81
[ 51940-64-8 ]
[ 3218-02-8 ]
ethyl 2-chloro-4-(cyclohexylmethylamino)pyrimidine-5-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 0 - 20℃; for 1h;	A solution of <strong>[51940-64-8]ethyl 2,4-dichloropyrimidine-5-carboxylate</strong> 1 (5.00 g, 22.7 mmol) in acetonitrile (100 mL) was mixed with diisopropyl ethyl amine (3.95 mL, 22.7 mmol) and cyclohexylmethanamine (2.0, 2.95 mL, 22.7 mmol) at 0C. The reaction mixture was stirred at room temperature for 1 h, then diluted with water (50.0 mL) and extracted with EtOAC (250.0 mL). The combined organic layers were dried over NaSO4 and concentrated under reduced pressure. The residue was purified by flash column chromatography (ethyl acetate-hexane) to afford compound 3. Yield 86%, mp 156-158C. 1H NMR spectrum, delta, ppm: 8.63 s (1H), 8.45 br.s (1H), 4.36 q (2H, J = 7.2 Hz), 3.39 t (2H, J = 6.4 Hz), 1.80- 1.57 m (6H), 1.39 t (3H, J = 6.8 Hz), 1.28-1.19 m (3H), 1.07-0.97 m (2H). 13C NMR spectrum, delta, ppm: 166.3, 163.8, 162.0, 160.2, 103.6, 61.34, 46.95, 37.55, 30.80, 26.28, 25.77, 14.15. MS (MM): m/z: 298.0 [M + H]+. Found, %: C 56.37; H 6.68; N 14.20. C14H2OClN3O2. Calculated, %: C 56.47; H 6.77; N 14.11.

Reference： [1]Russian Journal of General Chemistry,2019,vol. 89,p. 836 - 843
Zh. Obshch. Khim.,

82
[ 3622-04-6 ]
[ 3218-02-8 ]
N-(cyclohexylmethyl)benzo[d]thiazole-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91.5%		General procedure: To a magnetically stirred suspension of the carboxylic acid 4b(1.6 mmol) in anhydrous DCM were successively added tributylamine(Hunig's base) (6 equiv.) and N,N,N0,N0-Tetramethyl-O-(1Hbenzotriazol-1-yl)uroniumhexafluorophosphate (HBTU) (1.2equiv.) and the mixturewas allowed to stir at room temperature for30 min. The appropriate amine (1.2 equiv.) was then added, and thesolution was stirred at room temperature for 4e5 h. The solventwas then evaporated under reduced pressure and the resultingcrude product was dissolved in EtOAc, washed with aqueousNaHCO3 solution, 1 N HCl and brine, dried over anhydrous MgSO4and concentrated to give a crude resin. The crude product wasfurther purified using column chromatography. N-(cyclohexylmethyl)benzo[d]thiazole-2-carboxamide (4c).Prepared from cyclohexylmethyl amine. Column chromatographyon silica gel (DCM:Hexane, 6.5:3.5) afforded 4c as a white solid(91.5%); mp: 106e107 C; 1H NMR (d): (400 MHz, CDCl3) d 8.06 (dd,J 7.6, 0.7 Hz, 1H), 7.99e7.94 (m, 1H), 7.57e7.45 (m, 3H), 3.35 (t,J 6.6 Hz, 2H), 1.89e1.71 (m, 4H), 1.72e1.58 (m, 2H), 1.34e1.18 (m,3H), 1.09e0.97 (m, 2H); 13C NMR (d): (101 MHz, CDCl3) d 164.43,160.03, 153.04, 137.28, 126.88, 126.73, 124.33, 122.55, 46.17, 38.20,31.00, 26.48, 25.94; MS (ESI): m/z 275.07 [M H]

Reference： [1]European Journal of Medicinal Chemistry,2019,vol. 180,p. 154 - 170

83
[ 728034-12-6 ]
[ 3218-02-8 ]
[ 165806-95-1 ]
4-(1-(cyclohexylmethyl)-4-(4-fluorophenyl)imidazol-5-yl)-1H-pyrrolo[2,3-b]pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
28%		General procedure: To a solutionof the corresponding aldehyde (1.2 eq.; unless stated otherwise) in DMF (2 inL per 0.3 mmol of aldehyde; unless stated otherwise) was added the corresponding amine (2.5 eq.; unless stated otherwise) and the resulting solution was stirred at 25 C to form the corresponding inline. Then, the corresponding isocyano(tosyl)methyl)arene reagent (1 eq.; unless stated otherwise) and K2CO3 (1.5 eq.; unless stated otherwise) were added and the reaction mixture was stirred at 25 C (unless stated otherwise). The reaction was stopped after the time indicated for each particular reaction. The reaction progress was monitored by TLC. (0083) A saturated aqueous solution of NH4CI (10 mL per 1 mmol of aldehyde) was added to the reaction mixture, which was then extracted with EtOAc (2 x 30 mL per 1 mmol of aldehyde). The combined organic extracts were washed with H2O (2 x 25 mL per 1 mmol of aldehyde), dried over MgSCC, filtered, and the solvent was evaporated in vacuo to provide the crude product. The residue obtained after the workup was purified using column chromatography or preparative TLC (unless stated otherwise). (0084) note: in cases when the amine was used as HC1 salt, 4 eq. of K2CO3 were used

Reference： [1]Patent: WO2019/185631,2019,A1 .Location in patent: Page/Page column 14; 67-68

84
[ 2745-26-8 ]
[ 3218-02-8 ]
C₁₃H₁₉NO₂ [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2019,vol. 141,p. 18926 - 18931

85
[ 3218-02-8 ]
[ 1074-68-6 ]
N-(cyclohexylmethyl)-1-(2-(methylsulfanyl)pyrimidin-4-yl)methanimine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; potassium hydroxide In dichloromethane at 20℃;	A/-(Cyclohexylmethyl)-1 -(2-(methylsulfanyl)pyrimidin-4-yl)methanimine (7) Cyclohexylmethylamine (356 mI_, 2.74 mmol) and K2CO3 (0.227 g, 1 .64 mmol) were added to a solution of the crude aldehyde 1 (0.21 1 g, 1 .37 mmol) in CH2CI2 (5 ml_). The reaction mixture was stirred at r.t. overnight. 1 H NMR analysis indicated complete consumption of the aldehyde. The reaction mixture containing the imine was used directly in the next step without isolation.

Reference： [1]Current Patent Assignee: UNIVERSITY OF MELBOURNE - WO2020/93097, 2020, A1 Location in patent: Page/Page column 78

86
[ 141-97-9 ]
[ 3218-02-8 ]
[ 456-04-2 ]
ethyl 1-(cyclohexylmethyl)-5-(4-fluorophenyl)-2-methyl-1H-pyrrole-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%	Stage #1: ethyl acetoacetate With sodium hydride In tetrahydrofuran; paraffin oil at 0℃; for 0.5h; Stage #2: 2-Chloro-4'-fluoroacetophenone With potassium iodide In tetrahydrofuran; paraffin oil at 20℃; for 2h; Stage #3: cyclohexylmethylamine In acetic acid at 80℃; for 18h;

Reference： [1]Gerndt, Susanne; Chen, Cheng-Chang; Chao, Yu-Kai; Yuan, Yu; Burgstaller, Sandra; Rosato, Anna Scotto; Krogsaeter, Einar; Urban, Nicole; Jacob, Katharina; Nguyen, Ong Nam Phuong; Miller, Meghan T.; Keller, Marco; Vollmar, Angelika M.; Gudermann, Thomas; Zierler, Susanna; Schredelseker, Johann; Schaefer, Michael; Biel, Martin; Malli, Roland; Wahl-Schott, Christian; Bracher, Franz; Patel, Sandip; Grimm, Christian [eLife, 2020, vol. 9]

87
[ 3218-02-8 ]
[ 76-05-1 ]
[ 849475-89-4 ]
(x)C₂HF₃O₂*C₁₇H₂₀N₄O₃ [ No CAS ]

Reference： [1]ACS Medicinal Chemistry Letters,2020,vol. 11,p. 766 - 772

88
[ 331-39-5 ]
[ 3218-02-8 ]
N-(cyclohexylmethyl)-3-(3,4-dihydroxyphenyl)acrylamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With HBTU; benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃;	N-(cyclohexylmethyl)-3-(3,4-dihydroxyphenyl)acrylamide General procedure: To a mixture of the caffeic acid (1 mmol) in dry THF (4 mL) was added HOBt (1.2 mmol), HBTU (1.2 mmol) and DIEA (1.5 mmol). The reaction mixture was stirred at room temperature. The reaction was terminated when the caffeic acid was finished by TLC control. Purified by column chromatography.

Reference： [1]Sucu, Bilgesu Onur; Koc, Elif Beyza; Savlug Ipek, Ozgecan; Mirat, Afranur; Almas, Furkan; Guzel, Melike Aybala; Dogan, Berna; Uludag, Damla; Karakas, Nihal; Durdagi, Serdar; Guzel, Mustafa [Journal of Molecular Graphics and Modelling, 2022, vol. 113]

Type	HazMat fee for 500 gram (Estimated)
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CAS No. :	3218-02-8	MDL No. :	MFCD00001520
Formula :	C₇H₁₅N	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	AVKNGPAMCBSNSO-UHFFFAOYSA-N
M.W :	113.20	Pubchem ID :	76688
Synonyms :

Signal Word:	Danger	Class:	8,3
Precautionary Statements:	P280-P305+P351+P338-P310	UN#:	2734
Hazard Statements:	H225-H314	Packing Group:	Ⅱ
GHS Pictogram:

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P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
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:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
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

[ CAS No. 3218-02-8 ] {[proInfo.proName]}

Quality Control of [ 3218-02-8 ]

Related Doc. of [ 3218-02-8 ]

Product Details of [ 3218-02-8 ]

Safety of [ 3218-02-8 ]

Application In Synthesis of [ 3218-02-8 ]

[ 3218-02-8 ] Synthesis Path-Downstream 1~88

Related Functional Groups of
[ 3218-02-8 ]

Aliphatic Cyclic Hydrocarbons

Amines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

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