Name: 1196-92-5|4-(Aminomethyl)-2-methoxyphenol|97%
Brand: Ambeed
SKU: A250193
Price: 12.0 USD
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1
[ 764-85-2 ]
[ 1196-92-5 ]
[ 2444-46-4 ]

Yield	Reaction Conditions	Operation in experiment
88.6%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃;	To a solution of the hydrochloride or hydrobromide salt of an amine (1 mmol) in anhydrous N,N- dimethylformamide (DMF) (2 mL) was added N, N- diisopropylethylamine (DIPEA) (2 mmol) to liberate the amine. After stirring at room temperature for 10 min, nonanoyl chloride (1 mmol) was added. The solution was stirred at room temperature for 6 to 24 h. After the reaction, water (40 mL) was added to the solution. The reaction mixture was transferred to a separating funnel and extracted with dichloromethane, CH2Cl2 (3 * 6 mL) . The organic extracts were concentrated under reduced pressure to give a crude product. The crude product was then purified by silica gel column chromatography (using hexane/ethyl acetate, 2:1 v/v, as eluent) or preparative HPLC (using the protocol set out in "Analytical Protocols" above) to give the final product.

Reference： [1]Advanced Synthesis and Catalysis,2014,vol. 356,p. 2113 - 2118
[2]Patent: WO2010/144055,2010,A1 .Location in patent: Page/Page column 45-46; 50
[3]Journal of Medicinal Chemistry,1993,vol. 36,p. 2595 - 2604
[4]Recueil des Travaux Chimiques des Pays-Bas,1934,vol. 53,p. 855
[5]Journal of Medicinal Chemistry,1993,vol. 36,p. 2362 - 2372

2
[ 1196-92-5 ]
[ 121-33-5 ]

Yield	Reaction Conditions	Operation in experiment
90%	With immobilised amine transaminase from the moderate halophilic bacterium Halomonas elongata; sodium pyruvate In aq. phosphate buffer; dimethyl sulfoxide at 37℃; for 2h;
	With potassium phosphate buffer; air; flavoprotein vanillyl alcohol oxidase at 25℃;
	With 4-chloro-3,5-dinitrobenzenesulfonic acid; potassium carbonate und Oxydation der entstandenen 3.5-Dinitro-4-vanillylamino-sulfonsaeure-⁽¹⁾ mit Chromschwefelsaeure;

	Multi-step reaction with 2 steps 1: potassium carbonate
	With 4-ethylphenol oxidase from Gulosibacter chungangensis In aq. phosphate buffer; dimethyl sulfoxide at 25℃; for 24h; Enzymatic reaction;

Reference： [1]Contente, Martina L.; Dall'Oglio, Federica; Tamborini, Lucia; Molinari, Francesco; Paradisi, Francesca [ChemCatChem, 2017, vol. 9, # 20, p. 3843 - 3848]
[2]Van den Heuvel; Fraaije; Laane; Van Berkel [Journal of Agricultural and Food Chemistry, 2001, vol. 49, # 6, p. 2954 - 2958]
[3]Current Patent Assignee: I.G. FARBENINDUSTRIE AG (historic) - DE482837, 1929, C [Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 16, p. 422][Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 16, p. 422]
[4]Current Patent Assignee: I.G. FARBENINDUSTRIE AG (historic) - DE482837, 1929, C [Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 16, p. 422][Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 16, p. 422]
[5]Alvigini, Laura; Fraaije, Marco W.; Gran-Scheuch, Alejandro; Guo, Yiming; Mattevi, Andrea; Saifuddin, Mohammad; Trajkovic, Milos [ChemBioChem, 2021, vol. 22, # 22, p. 3225 - 3233]

3
[ 2874-33-1 ]
[ 1196-92-5 ]

Yield	Reaction Conditions	Operation in experiment
98%	With sodium hydrogensulfate monohydrate; molybdenum(V) chloride; sodium cyanoborohydride In ethanol for 0.8h; Reflux;
94%	With sodium tetrahydroborate at 20℃; for 0.0333333h; neat (no solvent, solid phase);
	With sodium amalgam; ethanol; acetic acid at 50 - 60℃;

	With hydrogenchloride; palladium Hydrogenation;
	With sulfuric acid bei der elektrolytischen Reduktion an einer Bleikathode;
	With ethanol; sodium; acetic acid at 50 - 60℃;
	With ethanol; sodium; acetic acid
	With acetic acid; zinc at 90 - 98℃;
	Multi-step reaction with 2 steps 1: hydrogenchloride; palladium 10% on activated carbon; hydrogen / ethanol / 3 h / 20 °C 2: sodium hydroxide / water
	With palladium on activated charcoal; acetic acid Hydrogenation;

Reference： [1]Location in patent: experimental part Kouhkan, Mehri; Zeynizadeh, Behzad [Bulletin of the Korean Chemical Society, 2011, vol. 32, # 9, p. 3323 - 3326]
[2]Location in patent: experimental part Zeynizadeh, Behzad; Kouhkan, Mehri [Bulletin of the Korean Chemical Society, 2011, vol. 32, # 9, p. 3448 - 3452]
[3]Nelson [Journal of the American Chemical Society, 1919, vol. 41, p. 1118]
[4]Ott; Zimmermann [Justus Liebigs Annalen der Chemie, 1921, vol. 425, p. 328] Current Patent Assignee: ERWIN OTT DR - DE383539, 1923, C [Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 14, p. 1463][Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 14, p. 1463]
[5]Kaplansky [Chemische Berichte, 1927, vol. 60, p. 1843]
[6]Kobayashi [Scientific Papers of the Institute of Physical and Chemical Research (Japan), vol. 6, p. 162][Chemisches Zentralblatt, 1928, vol. 99, # I, p. 1028]
[7]Jones; Pyman [Journal of the Chemical Society, 1925, vol. 127, p. 2597]
[8]Kobayashi [Scientific Papers of the Institute of Physical and Chemical Research (Japan), vol. 6, p. 162][Chemisches Zentralblatt, 1928, vol. 99, # I, p. 1028]
[9]Liu, Hefang; Lepoittevin, Bénédicte; Roddier, Céline; Guerineau, Vincent; Bech, Loïc; Herry, Jean-Marie; Bellon-Fontaine, Marie-Noelle; Roger, Philippe [Polymer, 2011, vol. 52, # 9, p. 1908 - 1916]
[10]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - DE760746, 1941, C [DRP/DRBP Org.Chem.][DRP/DRBP Org.Chem.]

4
[ 1196-92-5 ]
[ 103-71-9 ]
1-(4-hydroxy-3-methoxybenzyl)-3-phenylurea [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
42%	With triethylamine In methanol; dichloromethane at 20℃; for 4h; Inert atmosphere;	4.1.1.2. Synthesis of derivatives 7a-7g and 8a-8f General procedure: Vanillylamine(1.1 mmol) and triethylamine (1 mmol) were diluted in 40 mL ofdichloromethane:methanol (DCM:MeOH - 8:2) in a 100 mL doubleneck round bottom flask coupled with an addition funnel of 50 mL.Isocyanate (1 mmol) or isothiocyanate (1 mmol) was dissolved in DCM(5 mL) and added dropwise to the solution of vanillylamine. Themixture was kept under stirring in nitrogen atmosphere for 4 h. Then,the solvent was evaporated under reduced pressure and the product waspurified by recrystallization.

Reference： [1]Pereira, Gustavo José Vasco; Tavares, Maurício Temotheo; Azevedo, Ricardo Alexandre; Martins, Barbara Behr; Cunha, Micael Rodrigues; Bhardwaj, Rajesh; Cury, Yara; Zambelli, Vanessa Olzon; Barbosa, Euzébio Guimarães; Hediger, Matthias A.; Parise-Filho, Roberto [Bioorganic and Medicinal Chemistry, 2019, vol. 27, # 13, p. 2893 - 2904]
[2]Lange; Ebert; Youse [Journal of the American Chemical Society, 1929, vol. 51, p. 1912]

5
[ 1196-92-5 ]
[ 103-72-0 ]
1-(4-hydroxy-3-methoxybenzyl)-3-phenylthiourea [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
37%	With triethylamine In methanol; dichloromethane at 20℃; for 4h; Inert atmosphere;	4.1.1.2. Synthesis of derivatives 7a-7g and 8a-8f General procedure: Vanillylamine(1.1 mmol) and triethylamine (1 mmol) were diluted in 40 mL ofdichloromethane:methanol (DCM:MeOH - 8:2) in a 100 mL doubleneck round bottom flask coupled with an addition funnel of 50 mL.Isocyanate (1 mmol) or isothiocyanate (1 mmol) was dissolved in DCM(5 mL) and added dropwise to the solution of vanillylamine. Themixture was kept under stirring in nitrogen atmosphere for 4 h. Then,the solvent was evaporated under reduced pressure and the product waspurified by recrystallization.

Reference： [1]Pereira, Gustavo José Vasco; Tavares, Maurício Temotheo; Azevedo, Ricardo Alexandre; Martins, Barbara Behr; Cunha, Micael Rodrigues; Bhardwaj, Rajesh; Cury, Yara; Zambelli, Vanessa Olzon; Barbosa, Euzébio Guimarães; Hediger, Matthias A.; Parise-Filho, Roberto [Bioorganic and Medicinal Chemistry, 2019, vol. 27, # 13, p. 2893 - 2904]
[2]Lange; Ebert; Youse [Journal of the American Chemical Society, 1929, vol. 51, p. 1912]

6
[ 112-77-6 ]
[ 1196-92-5 ]
[ 58493-49-5 ]

Yield	Reaction Conditions	Operation in experiment
89%	With triethylamine In N,N-dimethyl-formamide at 20℃; for 5h; Cooling with ice;	General Procedure for Preparation of N-Acylhistamines (N-Acyl-HAs) General procedure: A solution of fatty acid acyl chloride (1.0 mmol), purchased from Tokyo Chemical Industory (Tokyo, Japan), in N,N-dimethylformamide (DMF) (2 mL) was added dropwise to a suspension of histamine dihydrochlolide (2.0 mmol) and Et3N (8 mmol) in DMF (5 mL) cooled in an ice bath. In some cases (i.e., for the C18:1, C18:2 and C20:4 analogues), the acyl chlorides were prepared by reacting the free fatty acids with oxalyl chloride (5 eq, CH2Cl2, r.t., 3 h). The reaction mixture was stirred for 5 h at room temperature. Ice water was added to the mixture and the reaction mix was extracted with CHCl3. The organic layer was dried over Na2SO4 and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (CHCl3 : MeOH : aq. NH3=20 : 1 : 0.5) to give the corresponding N-acylhistamine.
85%	In diethyl ether; N,N-dimethyl-formamide Ambient temperature;

Reference： [1]Takao, Koichi; Noguchi, Kaori; Hashimoto, Yosuke; Shirahata, Akira; Sugita, Yoshiaki [Chemical and Pharmaceutical Bulletin, 2015, vol. 63, # 4, p. 278 - 285]
[2]Janusz, John M.; Buckwalter, Brian L.; Young, Patricia A.; LaHann, Thomas R.; Farmer, Ralph W.; et al. [Journal of Medicinal Chemistry, 1993, vol. 36, # 18, p. 2595 - 2604]

7
[ 1196-92-5 ]
[ 91702-98-6 ]
Thioacetic acid S-[2-(4-hydroxy-3-methoxy-benzylcarbamoyl)-3-phenyl-propyl] ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1989,vol. 32,p. 2519 - 2526

8
[ 1196-92-5 ]
[ 31467-61-5 ]
[ 25775-90-0 ]

Yield	Reaction Conditions	Operation in experiment
5.42 g	In tert-butyl methyl ether; at 20 - 40℃; for 4h;	Under nitrogen protection,To 10 mL of thionyl chloride, 4.64 g (0.027 mol) of Z-8-methyl-6-ene-nonanoic acid was added.Stir at room temperature for 8 hours, heat to 100 C and stir for 0.5 hours.After concentration in vacuo (temperature: 35 C to 55 C, pressure -0.08 MPa to -0.095 MPa) to dryness, 50 mL of methyl tert-butyl ether and 8.35 g (0.054 mol) of 3-methoxy-4-hydroxybenzylamine were added. Stir at room temperature for 2 hours,Heat to 30 to 40 C and stir for 2 hours. Cool to 0 to 5 C and stir for 1 to 2 hours. Filter, rinse with methyl tert-butyl ether and drain. The organic layer was concentrated in vacuo (temperature 45 C ~ 55 C, pressure -0.085 MPa ~ -0.1 MPa) to dry. Column chromatography separation (silica gel column, mobile phase ethyl acetate: petroleum ether = 1:2) afforded Zucapsaicin I 7.51 g, yield 90.2%. The HPLC purity was 86.74%, the E isomer was 8.17%, and the other largest single impurity was 1.36%. After recrystallization from methyl tert-butyl ether n-heptane three times, Zucapsaicin I 5.42 g was obtained in a yield of 72.2%, and the total yield in three steps was 48.3%. HPLC pureThe degree is 97.38%, the E isomer is 1.94%, and the other largest single impurity is 0.42%.

Reference： [1]Journal of Medicinal Chemistry,1993,vol. 36,p. 2595 - 2604
[2]Journal of Organic Chemistry,1988,vol. 53,p. 1064 - 1071
[3]Journal of Organic Chemistry,1989,vol. 54,p. 3477 - 3478
[4]Patent: CN108947863,2018,A .Location in patent: Paragraph 0091; 0092; 0094

9
[ 1196-92-5 ]
[ 95636-02-5 ]
[ 404-86-4 ]

Yield	Reaction Conditions	Operation in experiment
91%	Stage #1: Vanillylamin With sodium hydrogencarbonate In chloroform; water at 20℃; for 0.75h; Stage #2: (E)-8-Methylnon-6-enoic acid chloride In chloroform; water at 20 - 40℃; for 1h;
	In diethyl ether for 72h; Ambient temperature;
	In diethyl ether 1.) RT, 2 h, 2.) reflux, 2 h; Yield given;

	In diethyl ether Yield given;
	In diethyl ether for 2h; Heating; Yield given;
	With pyridine In diethyl ether; water	10 Example 10 Example 10 By using a similar reaction vessel to that in Example 9, 5.7 parts of 8-methylnon-trans-6-enoyl chloride and 0.2 part of pyridine were added to a solution of 4.7 parts of 4-hydroxy-3-methoxybenzylamine in 25 parts of diethyl ether, and the mixture was stirred at room temperature for 4 hours. After 10 parts of water was added to the mixture and stirred for 5 minutes, the resultant mixture was allowed to stand for 5 minutes. The water layer in the lower layer was discharged. By almost completely removing ether under a reduced pressure, crude (E)-N-(4-hydroxy-3-methoxybenzyl)-8-methylnon-6-enamide was obtained. As a result of quantitative analysis of a slight amount of product by an HPLC, the purity of (E) -N-(4-hydroxy-3-methoxybenzyl)-8-methylnon-6-enamide was determined to be 90.5%.
	With triethylamine In benzene

Reference： [1]Anderson, Mattias; Afewerki, Samson; Berglund, Per; Cordova, Armando [Advanced Synthesis and Catalysis, 2014, vol. 356, # 9, p. 2113 - 2118]
[2]Gannett, Peter M.; Nagel, Donald L.; Reilly, Pam J.; Lawson, Terence; Sharpe, Jody; Toth, Bela [Journal of Organic Chemistry, 1988, vol. 53, # 5, p. 1064 - 1071]
[3]Kaga, Harumi; Miura, Masakatsu; Orito, Kazuhiko [Journal of Organic Chemistry, 1989, vol. 54, p. 3477 - 3478]
[4]Kaga, Harumi; Goto, Kouhei; Fukuda, Takashi; Orito, Kazuhiko [Bioscience, Biotechnology and Biochemistry, 1992, vol. 56, # 6, p. 946 - 948]
[5]Kaga, Harumi; Goto, Kouhei; Takahashi, Tomiki; Hino, Masao; Tokuhashi, Takashi; Orito, Kazuhiko [Tetrahedron, 1996, vol. 52, # 25, p. 8451 - 8470]
[6]Current Patent Assignee: NIPPON KAYAKU CO LTD - US5456916, 1995, A
[7]Location in patent: scheme or table Kananovich, Dzmitry G.; Zubrytski, Dzmitry M.; Kulinkovich, Oleg G. [Synlett, 2010, # 7, p. 1043 - 1046]

10
[ 121-33-5 ]
[ 1196-92-5 ]

Yield	Reaction Conditions	Operation in experiment
95%	With ammonia; hydrogen In methanol at 90℃; for 4h; Autoclave;	7; 8; 34 A method for catalyzing the reductive amination of aldehydes and ketones to prepare primary amines includes the following steps: 1) Same as Example 1; 2) Mix 7mmol of 3-methoxy-4-hydroxybenzaldehyde, 70mL of methanol solution of 2mol/L ammonia and 140mg of ink-coated nickel-nickel oxide catalyst into the autoclave, and then add hydrogen. The hydrogen pressure of the control system was 2MPa, the stirring rate was 800rpm, and the reaction was conducted at 90°C for 4h to obtain 3-methoxy 4-hydroxybenzylamine (yield 95%).
94%	With ammonia; hydrogen at 30℃; for 1h;	1.1; 1.2; 1.3; 1.4; 1.5; 1.6; 1.7; 2; 3 Example 1 General procedure: This embodiment provides a preparation method of vanillin free base, which specifically comprises the following steps1) mixing vanillin with water to form a suspension,Add to a 1L hydrogenation kettle,Then Raney Ni catalyst was added and 25-28% aqueous ammonia was added with stirring.2) The hydrogenation tank is evacuated,Then, nitrogen gas was introduced until the pressure in the autoclave reached 0.5 MPa.Exhaust nitrogen,Repeat 5 times,The hydrogen gas was introduced until the pressure in the autoclave reached 0.8 to 1.2 MPa.3) Turn on the heating and stirring switch,Bring the temperature inside the kettle to the set temperature,The pressure in the kettle began to drop,Replenishing hydrogen to maintain the pressure in the kettle at 0.8-1.2 MPa,Until the pressure in the kettle did not change significantly within 1 hour.4) Cool the hydrogenation vessel to ice at an internal temperature of 5C.Part of the reaction solution was analyzed by HPLC.The remaining material was removed from the Raney Ni catalyst in the reaction solution through a magnetic filter and stored in air.The reaction mixture was then filtered to give a wet vanillamine free base solid.5) Drying the wet vanillin free base solid in step 4) to give the vanillin free base product.
88%	With ammonium hydroxide; hydrogen In ethanol; water at 80℃; for 10h; Autoclave;

87%	With ammonium formate In toluene at 80℃; for 2.5h; Inert atmosphere; chemoselective reaction;	2 example 2 To a microwave-vial containing the Pd°-catalyst (Pd°-AmP-MFC, 13.4 mg, 0.01 mmol, 8.25 wt%, 5 mol%) or (Pd°-CPG, 569A, 74.0 mg, 0.013 mmol, 2.05 wt%, 6.6 mol%) and ammonium formate (37.8 mg, 0.6 mmol, 3.0 equiv.) was added the solid 1 (0.2 mmol, 1.0 equiv.) under N2 atmosphere. Next, toluene (1 mL) was added at room temperature. If the aldehyde substrate was a liquid it was added after the addition of toluene. The temperature was then increased and the reaction mixture was stirred 80°C for the time shown in Table 2 under N2 atmosphere. Before the purification of the products, the crude reaction mixture was filtrated through Celite using CHCI3 (10 mL) as eluent and evaporated. The crude material was purified by silica gel flash column chromatography to give the corresponding amines 2. NMR samples for NMR-yield were prepared by removing 0.05 mL aliquots from the reaction mixtures, filtration through Celite using CDCl3 (1.5 mL) as eluent and mesitylene as the internal standard. The hexan-1-amine 2d, furan-2-ylmethan amine 2h and propan-1- amine 2j were directly acylated by Novozyme 435 to the corresponding amides and then isolated by silica gel column chromatography (See Table 2).
87%	With ammonium formate In toluene at 80℃; for 2.5h; Inert atmosphere; chemoselective reaction;
82%	With ammonium hydroxide; Ni₆AlO(z); hydrogen at 100℃; for 10h; Autoclave;	4 Example 4 General procedure: The reaction was performed in a stainless steel autoclave. 2 mmol first reactant (aldehydes or ketones) , 50 mg Ni6AlOzcatalyst and 3 ml aqueous ammonia (28 wt%) were loaded into the reactor. The autoclave was purged with hydrogen for three times, and charged with H2at 1 bar pressure at room temperature. Then, the autoclave was heated to desired temperature and kept for several hours. The GC-yield was determined by GC-FID (Agilent 7890A) using dioxane as internal standard, and the isolated yields were obtained by flash column chromatography. The yields of amines obtained are shown in Table 3.
	With ammonium formate at 180℃; for 3h;
	Multi-step reaction with 3 steps 1: hydroxylamine hydrochloride; water; acetic acid; sodium hydroxide / 5 h / 20 °C 2: hydrogenchloride; palladium 10% on activated carbon; hydrogen / ethanol / 3 h / 20 °C 3: sodium hydroxide / water
	With glucose dehydrogenase; L-alanin; D-glucose; L-alanine dehydrogenase; amine transaminase; ammonium chloride; NADH; sodium hydroxide In dimethyl sulfoxide at 37℃; for 22h; Darkness; Enzymatic reaction;
	Multi-step reaction with 2 steps 1: rac-Pro-OH / 24 h / 20 °C / Inert atmosphere 2: D-glucose; L-alanin; ammonium chloride; glucose dehydrogenase; amine transaminase; L-alanine dehydrogenase; NADH; sodium hydroxide / dimethyl sulfoxide / 90 h / 37 °C / pH 8.2 / Darkness; Enzymatic reaction
	With (<i>S</i>)-1-phenyl-ethylamine; Halomonas elongata ω-transaminase In aq. phosphate buffer at 37℃; Enzymatic reaction;	2.9 Enzymatic reaction General procedure: The enzymatic reactions were carried out at 37°C in pH 8.0 potassium phosphate buffer 100mM and 15% v/v purified enzyme solution corresponding to 0.89U/mL for the screening of the amino donors, and 0.71U/mL for the screening of the amino acceptor reactions. The reaction mixture contained 10mM enantiopure amino donor (20mM if racemic), 10mM amino acceptor and 0.05mg/mL of HEWT in a reaction volume of 200μL. For the determination of enantioselectivity, reactions were carried out at 37°C in pH 8.0 potassium phosphate buffer 100mM in 1mL, containing 20mM rac-1-phenylethylamine, 10mM pyruvate, 0.1mM PLP with 0.1mg/mL of HEWT. As a control, the reactions were set up as previously described but without the addition of HEWT, in which case only starting material was detected. The activity of the enzyme in the various reaction conditions was established employing (S)-(-)-1-phenylethylamine as amino donor and pyruvate as acceptor. One enzymatic unit was defined as the amount of enzyme that converts 1μmol of (S)-(-)-1-phenylethylamine in 1min. The initial rate was determined by monitoring the decrease of the concentration of (S)-(-)-1-phenylethylamine during the first three minutes. Frozen aliquots of the enzyme at -20°C were used. H. elongata ω-transaminase was stable for several months without evident loss of activity. Data were obtained by averaging the measurements on three independent samples.
	With glucose dehydrogenase; D-Glucose; L-alanin; L-alanine dehydrogenase; chromobacterium violaceum amine transaminase; ammonium chloride; NADH In dimethyl sulfoxide at 37℃; for 17h; Darkness; Enzymatic reaction;	Preparation of vanillylamine from vanillin In the first experiments, 250 mM L-alanine and 5 mM vanillin (2a) were mixed in HEPES buffer 50 mM pH 8.2, together with 0.2 mg/niL ATA. After 23 h, 25 % of the vanillin had been converted into vanillylamine (4a). The same experiment was repeated with the addition of the L-alanine dehydrogenase. Since no NADH regeneration system was used for this ex- periment, an excess (2 eq) of NADH was used. The reaction composition was 250 mM L-alanine, 5 mM vanillin, 100 mM ammonium chloride and 10 mM NADH in HEPES buffer 50 mM pH 8.2, together with 0.2 mg/niL ATA and 7 U/mL L-alanine dehydrogenase. This resulted in a conversion of 70 % after 23 h. The experiment was then repeated with the addition of glucose dehydrogenase to regenerate NADH. With the presence of the regeneration sys- tern, NADH concentration in the reaction was changed from excess to a catalytic amount. The reaction composition was 250 mM L-alanine, 5 mM vanillin, 100 mM ammonium chloride, 100 mM D-glucose and 1 mM NADH in HEPES buffer 50 mM pH 8.2, together with 0.2 mg/niL ATA, 7 U/mL L-alanine dehydrogenase and 10 U/mL glucose dehydrogenase. In 23 h, this system resulted in a conversion of >99%. The starting concentration of vanillin (2a) in the reaction could successfully be increased to 50 mM while maintaining a high conversion. Vanillin was first dissolved in DMSO and then mixed with D-glucose, ammonium chloride and L-alanine in HEPES buffer 50 mM. The pH was adjusted to 8.2 (1 M NaOH) and the solution was mixed with NADH and the enzymes in an eppendorf tube to give the final concentrations 250 mM L-alanine, 50 mM vanillin, 150 mM ammonium chloride, 150 mM D-glucose, 1 mM NADH and 10 % DMSO v/v, together with 0.9 mg/niL ATA, 7 U/mL L-alanine dehydrogenase and 10 U/mL glucose dehydrogenase. This resulted in a conversion of 95 % after 17 h.
	Multi-step reaction with 2 steps 1: rac-Pro-OH / 24 h / 20 °C / Inert atmosphere 2: ammonium chloride; NADH; L-alanine dehydrogenase; glucose dehydrogenase; chromobacterium violaceum amine transaminase; L-alanin; D-Glucose / dimethyl sulfoxide / 92 h / 37 °C / pH 8.2 / Darkness; Enzymatic reaction
	Stage #1: vanillin With hydroxylamine hydrochloride; sodium hydroxide In ethanol; water at 65℃; for 2.5h; Stage #2: With palladium on activated charcoal	the synthesis method of compound I is as follows: Take 1 equivalent of vanillin in absolute ethanol,One equivalent of hydroxylamine hydrochloride dissolved in water,1.1 equivalents of sodium hydroxide are dissolved in water.An aqueous hydroxylamine hydrochloride solution and an aqueous sodium hydroxide solution are added to a solution of vanillin in ethanol.It is refluxed at 65°C for 2.5 hours. After removing the solvent, a milky solid is obtained.Water/ethyl acetate extractionCollect the ethyl acetate layer,After drying to remove the solvent,The resulting compound was reduced with Pd/C.After the reaction is completed, it is filtered, concentrated and purified by column chromatography and dissolved in water.Add NaOH and stir until a lot of white solids appear.The compound I was obtained by suction filtration and vacuum drying.
53 %Spectr.	With ammonia; hydrogen In methanol at 90℃; for 8h; Autoclave;
	With ammonium hydroxide; hydrogen In water at 30℃;	1-3 In the embodiment, the preparation method of vanillyl amine-catalyst-water reaction mixture is: Mix 50g of vanillin with 250g of water to form a suspension,Add to the hydrogenation kettle with a volume of 1L, and then add 5.7g of Raney Ni catalyst,Add 53 g of 25-28% ammonia water under stirring.2) The hydrogenation kettle is evacuated, and then nitrogen is introduced until the pressure in the hydrogenation kettle reaches 0.5 MPa,The nitrogen is discharged, the operation is repeated 5 times, and hydrogen is introduced until the pressure in the kettle reaches 0.8-1.2 MPa.3) Turn on the heating and stirring switch to make the temperature in the kettle reach 30°C, and the pressure in the kettle begins to drop, add hydrogen to keep the pressure in the kettle at 0.81.2MPa.Until the pressure in the kettle does not change significantly within 1 hour,Cool to below 5°C, filter to obtain vanillyl amine-catalyst-water reaction mixture.

Reference： [1]Current Patent Assignee: CHINESE ACADEMY OF SCIENCES - CN111116375, 2020, A Location in patent: Paragraph 0045-0048; 0060-0063
[2]Current Patent Assignee: Liu Xiaozhen - CN110305031, 2019, A Location in patent: Paragraph 0100-0124
[3]Zhang, Jia; Yang, Jian; Tian, Junying; Liu, Hailong; Li, Xuemei; Fang, Weiguo; Hu, Xun; Xia, Chungu; Chen, Jing; Huang, Zhiwei [New Journal of Chemistry, 2021, vol. 45, # 9, p. 4236 - 4245]
[4]Current Patent Assignee: XP CHEMISTRIES - WO2016/96905, 2016, A1 Location in patent: Page/Page column 17
[5]Palo-Nieto, Carlos; Afewerki, Samson; Anderson, Mattias; Tai, Cheuk-Wai; Berglund, Per; Córdova, Armando [ACS Catalysis, 2016, vol. 6, # 6, p. 3932 - 3940]
[6]Current Patent Assignee: CHINESE ACADEMY OF SCIENCES; SOLVAY - WO2019/174221, 2019, A1 Location in patent: Page/Page column 17-18
[7]Kaga, Harumi; Miura, Masakatsu; Orito, Kazuhiko [Journal of Organic Chemistry, 1989, vol. 54, p. 3477 - 3478]
[8]Liu, Hefang; Lepoittevin, Bénédicte; Roddier, Céline; Guerineau, Vincent; Bech, Loïc; Herry, Jean-Marie; Bellon-Fontaine, Marie-Noelle; Roger, Philippe [Polymer, 2011, vol. 52, # 9, p. 1908 - 1916]
[9]Anderson, Mattias; Afewerki, Samson; Berglund, Per; Cordova, Armando [Advanced Synthesis and Catalysis, 2014, vol. 356, # 9, p. 2113 - 2118]
[10]Anderson, Mattias; Afewerki, Samson; Berglund, Per; Cordova, Armando [Advanced Synthesis and Catalysis, 2014, vol. 356, # 9, p. 2113 - 2118]
[11]Cerioli, Lorenzo; Planchestainer, Matteo; Cassidy, Jennifer; Tessaro, Davide; Paradisi, Francesca [Journal of Molecular Catalysis B: Enzymatic, 2015, vol. 120, p. 141 - 150]
[12]Current Patent Assignee: XP CHEMISTRIES - WO2015/144902, 2015, A1 Location in patent: Page/Page column 9
[13]Current Patent Assignee: XP CHEMISTRIES - WO2015/144902, 2015, A1
[14]Current Patent Assignee: ZHEJIANG UNIVERSITY - CN105295896, 2017, B Location in patent: Paragraph 0051; 0052
[15]Cui, Zhibing; Liu, Jianguo; Liu, Qiying; Ma, Longlong; Singh, Thishana; Wang, Chenguang; Wang, Nan; Zhu, Yuting [Green Chemistry, 2020, vol. 22, # 21, p. 7387 - 7397]
[16]Current Patent Assignee: SUINING JINGAN TECH - CN112608247, 2021, A Location in patent: Paragraph 0115-0117

11
[ 1196-92-5 ]
[ 883-55-6 ]
2-(5-Chloro-1H-indol-3-yl)-N-(4-hydroxy-3-methoxy-benzyl)-2-oxo-acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61%	With triethylamine In tetrahydrofuran a) RT, 24 h, b) reflux, 2 h;

Reference： [1]Da Settimo, Antonio; Primofiore, Giampaolo; Da Settimo, Federico; Marini, Anna Maria; Novellino, Ettore; Greco, Giovanni; Martini, Claudia; Giannaccini, Gino; Lucacchini, Antonio [Journal of Medicinal Chemistry, 1996, vol. 39, # 26, p. 5083 - 5091]

12
[ 67-56-1 ]
[ 2444-46-4 ]
[ 1196-92-5 ]
[ 1731-84-6 ]

Reference： [1]Bollettino Chimico Farmaceutico,1997,vol. 136,p. 237 - 243

13
[ 1196-92-5 ]
[ 66753-05-7 ]
N-[5,6,8,9,11,12,14,15-3H₈]arachidonoyl-4-hydroxy-3-methoxybenzylamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	Stage #1: <5,6,8,9,11,12,14,15-3H8>arachidonic acid With triethylamine; isobutyl chloroformate In acetonitrile at 23℃; for 2h; Stage #2: Vanillylamin In N,N-dimethyl-formamide at 23℃; for 20h;

Reference： [1]Shevchenko; Nagaev; Myasoedov; Yudushkin; Gretskaya; Bobrov; Bezuglov [Journal of labelled compounds and radiopharmaceuticals, 2003, vol. 46, # 2, p. 187 - 193]

14
[ 1196-92-5 ]
[ 635325-27-8 ]
N-(4-hydroxy-3-methoxy-benzyl)-3-[6-methyl-3-oxo-4-(3-trifluoromethyl-phenyl)-3,6-dihydro-1H-1,2,5,6,7-pentaaza-as-indacen-2-yl]-benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
45%	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 16h;

Reference： [1]Green, Neal J.; Xiang, Jason; Chen, Jing; Chen, Lihren; Davies, Audrey M.; Erbe, Dave; Tam, Steve; Tobin, James F. [Bioorganic and Medicinal Chemistry, 2003, vol. 11, # 13, p. 2991 - 3013]

15
[ 143-07-7 ]
[ 1196-92-5 ]
[ 69693-11-4 ]

Yield	Reaction Conditions	Operation in experiment
60%	With Streptomyces mobaraensis NBRC 13819 acylase In hexane at 37℃;

Reference： [1]Koreishi, Mayuko; Zhang, Demin; Imanaka, Hiroyuki; Imamura, Koreyoshi; Adachi, Shuji; Matsuno, Ryuichi; Nakanishi, Kazuhiro [Journal of Agricultural and Food Chemistry, 2006, vol. 54, # 1, p. 72 - 78]

16
[ 1196-92-5 ]
[ 124-07-2 ]
[ 58493-47-3 ]

Yield	Reaction Conditions	Operation in experiment
46%	With Streptomyces mobaraensis NBRC 13819 acylase In n-heptan1ol at 37℃; for 96h;

Reference： [1]Koreishi, Mayuko; Zhang, Demin; Imanaka, Hiroyuki; Imamura, Koreyoshi; Adachi, Shuji; Matsuno, Ryuichi; Nakanishi, Kazuhiro [Journal of Agricultural and Food Chemistry, 2006, vol. 54, # 1, p. 72 - 78]

17
[ 1196-92-5 ]
[ 334-48-5 ]
[ 31078-36-1 ]

Yield	Reaction Conditions	Operation in experiment
81%	With Streptomyces mobaraensis NBRC 13819 acylase In hexane at 37℃; for 96h;

Reference： [1]Koreishi, Mayuko; Zhang, Demin; Imanaka, Hiroyuki; Imamura, Koreyoshi; Adachi, Shuji; Matsuno, Ryuichi; Nakanishi, Kazuhiro [Journal of Agricultural and Food Chemistry, 2006, vol. 54, # 1, p. 72 - 78]

18
[ 1196-92-5 ]
[ 6217-54-5 ]
(Z,Z,Z,Z,Z,Z)-N-[(4-hydroxy-3-methoxyphenyl)methyl]-docosa-4,7,10,13,16,19-hexaenamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; 2,6-di-tert-butyl-4-methyl-phenol; dicyclohexyl-carbodiimide In chloroform at 20℃; for 48h;
	Stage #1: docosahexaenoic acid With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; triethylamine In ethyl acetate at 20℃; for 1h; Stage #2: Vanillylamin In ethyl acetate at 20℃; for 12h;	5.2. Synthesis of fatty acid amides General procedure: All fatty acid amides with different acyl chains and amine heads were synthesized using the same procedure but with different precursor compounds. 2-(1H-Benzotriazole-1-yl)-1,2,3,3-tetramethyluronium tetrafluoroborate (TBTU, 1 equiv) was added to a mixture of compound C1 (1 equiv) and triethylamine (TEA, 2 equiv) in EtOAc. After stirring for 1 h at room temperature, isopropylamine (2 equiv) was added and the reaction mixture was stirred for 12 h. The mixture was washed with water, dried and concentrated to give a residue that was purified by reversed-phase HPLC (YMC ODS-H80) eluting with 80% aqueous CH3CN to yield compound 1 (1.5 mg, 63%);

Reference： [1]Tuoya; Baba, Naomichi; Shimoishi, Yasuaki; Murata, Yoshiyuki; Tada, Mikiro; Koseki, Masamichi; Takahata, Kyoya [Life Sciences, 2006, vol. 78, # 13, p. 1515 - 1519]
[2]Location in patent: experimental part Dang, Hung The; Kang, Gyeoung Jin; Yoo, Eun Sook; Hong, Jongki; Choi, Jae Sue; Kim, Hyung Sik; Chung, Hae Young; Jung, Jee H. [Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 4, p. 1520 - 1527]

19
[ 1196-92-5 ]
[ 2459-05-4 ]
[ 7188-38-7 ]
[ 630-19-3 ]
C₂₄H₃₆N₂O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%	In water at 200℃; for 0.333333h; microwave irradiation;

Reference： [1]Santra, Soumava; Andreana, Peter R. [Organic Letters, 2007, vol. 9, # 24, p. 5035 - 5038]

20
[ 1196-92-5 ]
[ 2459-05-4 ]
[ 7188-38-7 ]
[ 630-19-3 ]
(E)-ethyl 3-(N-(1-(tert-butylcarbamoyl)-2,2-dimethylpropyl)-N-(4-hydroxy-3-methoxybenzyl)carbamoyl)acrylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	In dichloromethane at 200℃; for 0.333333h; microwave irradiation;

Reference： [1]Santra, Soumava; Andreana, Peter R. [Organic Letters, 2007, vol. 9, # 24, p. 5035 - 5038]

21
[ 1196-92-5 ]
docosahexa-4,7,10,13,16,19-enoic acid [ No CAS ]
N-vanillyl-4,7,10,13,16,19-docosahexaenamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; dicyclohexyl-carbodiimide In chloroform at 20℃; for 42h;	1 Example 1; Synthesis of N-vanillyl-4,7,10,13,16,19-Docosahexaenamide (Referred to as Dohevanil Herein Below) Dohevanil was synthesised by reacting vanillyl amine with 4,7,10,13,16,19-docosahexaenoic acid (C22:6, DHA) according to the procedure described below. 1.23 g Of vanillyl amine hydrochloride (ALDRICH) was dissolved in 5 ml of tepid water at 42 degrees Celsius, 10% sodium hydroxide (2.62 ml) in an equimolar amount was added and then the mixture was stirred at 40 degrees Celsius for 20 minutes.The deposited precipitate was filtered and washed three times with cold distilled water.The filtered precipitate was dried under reduced pressure at 110 degrees Celsius for three hours and further dried under vacuum at an ambient temperature for 30 minutes to obtain 0.801 g of the vanillyl amine. 0.230 g Of the vanillyl amine and 0.591 g of 4, 7, 10, 13, 16, 19-docosahexaenic acid (DOOSAN SERDARY RESEARCH LABORATORIES) were dissolved in 13.8 ml of chloroform.Then, 0.310 g of dicyclohexylcarbodiimide (DCC) (Tokyo Kasei Kogyo Co., Ltd), 0.037 g of dimethylaminopyridine (DMAP) (Tokyo Kasei Kogyo Co., Ltd), and a very small amount of butylhydoxytoluene were added.The mixture was stirred at an ambient temperature for 42 hours.After the reaction terminated, the reaction mixture was filtered to remove the precipitate and then the filtrate was condensed to about 0.5 ml by rotary evaporator.The condensed filtrate was fractionated by silicagel column chromatography (40 g of silicagel, developing solvent: hexane/ethyl acetate=6/4 (vol/vol)).The fraction of Dohevanil was collected, concentrated and dried to give a solid by rotary evaporator and then further dried under vacuum to give 0.311 g of colorless or citrine amorphous-like solid of Dohevanil. The obtained Dohevanil was analyzed by NMR. The result is as follows: 1H-NMR (200 MHz, CDCl3): δ=0.97 (3H, t, J=7.6 Hz, -C-CH3), 2.1 (2H, m, Me-CH2-C=C-), 2.25 (2H, m, -CH2-CH2-CH =CH-), 2.4 (2H, m, -CO-C2-CH=CH-), 2.83 (10H, m, -C=C -CH2-C=C-5), 3.88 (3H, S, -OCH3), 4.35 (2H, d, J=2.8 Hz, -NH-CH2-), 5.37 (12H, m, -CH=CH-6), 5.6 (1H, d, J=1 Hz, -OH), 6.82 (3H, m, aromatic proton).

Reference： [1]Current Patent Assignee: KUREHA CORP. - US2004/110844, 2004, A1 Location in patent: Page/Page column 4

22
[ 7149-10-2 ]
[ 1196-92-5 ]

Yield	Reaction Conditions	Operation in experiment
92.2%	With sodium hydroxide In water for 0.166667h;	1.3 3) Preparation of vanillin amine 1000ml three-necked flask, fitted with a stirrer, a thermometer, and thereto was added 350mL of water, 34.0g of vanilla hydrochloride, was slowly added dropwise with vigorous stirring 9mL sodium hydroxide solution (2mol / L), a heavy white precipitate appeared, stirring was continued for 10min, the suspension was suction filtered, the solid washed with 100mL, set 50 ~ 60 in a vacuum oven and dried under vacuum to give 25g of white solid amine vanillin, yield 92.2%,
	With sodium hydroxide In water at 40 - 42℃; for 0.333333h;	1 Example 1; Synthesis of N-vanillyl-4,7,10,13,16,19-Docosahexaenamide (Referred to as Dohevanil Herein Below) Dohevanil was synthesised by reacting vanillyl amine with 4,7,10,13,16,19-docosahexaenoic acid (C22:6, DHA) according to the procedure described below. 1.23 g Of vanillyl amine hydrochloride (ALDRICH) was dissolved in 5 ml of tepid water at 42 degrees Celsius, 10% sodium hydroxide (2.62 ml) in an equimolar amount was added and then the mixture was stirred at 40 degrees Celsius for 20 minutes.The deposited precipitate was filtered and washed three times with cold distilled water.The filtered precipitate was dried under reduced pressure at 110 degrees Celsius for three hours and further dried under vacuum at an ambient temperature for 30 minutes to obtain 0.801 g of the vanillyl amine. 0.230 g Of the vanillyl amine and 0.591 g of 4, 7, 10, 13, 16, 19-docosahexaenic acid (DOOSAN SERDARY RESEARCH LABORATORIES) were dissolved in 13.8 ml of chloroform.Then, 0.310 g of dicyclohexylcarbodiimide (DCC) (Tokyo Kasei Kogyo Co., Ltd), 0.037 g of dimethylaminopyridine (DMAP) (Tokyo Kasei Kogyo Co., Ltd), and a very small amount of butylhydoxytoluene were added.The mixture was stirred at an ambient temperature for 42 hours.After the reaction terminated, the reaction mixture was filtered to remove the precipitate and then the filtrate was condensed to about 0.5 ml by rotary evaporator.The condensed filtrate was fractionated by silicagel column chromatography (40 g of silicagel, developing solvent: hexane/ethyl acetate=6/4 (vol/vol)).The fraction of Dohevanil was collected, concentrated and dried to give a solid by rotary evaporator and then further dried under vacuum to give 0.311 g of colorless or citrine amorphous-like solid of Dohevanil. The obtained Dohevanil was analyzed by NMR. The result is as follows: 1H-NMR (200 MHz, CDCl3): δ=0.97 (3H, t, J=7.6 Hz, -C-CH3), 2.1 (2H, m, Me-CH2-C=C-), 2.25 (2H, m, -CH2-CH2-CH =CH-), 2.4 (2H, m, -CO-C2-CH=CH-), 2.83 (10H, m, -C=C -CH2-C=C-5), 3.88 (3H, S, -OCH3), 4.35 (2H, d, J=2.8 Hz, -NH-CH2-), 5.37 (12H, m, -CH=CH-6), 5.6 (1H, d, J=1 Hz, -OH), 6.82 (3H, m, aromatic proton).
	With triethylamine In tert-Amyl alcohol at 30℃; for 0.5h; Molecular sieve;

With sodium hydroxide In water

Reference： [1]Current Patent Assignee: ANHUI YIXINMING PHARMACEUTICAL TECH - CN105439889, 2016, A Location in patent: Paragraph 0033
[2]Current Patent Assignee: KUREHA CORP. - US2004/110844, 2004, A1 Location in patent: Page/Page column 4
[3]Location in patent: experimental part Castillo, Edmundo; Regla, Ignacio; Demare, Patricia; Luviano-Jardón, Axel; López-Munguía, Agustín [Synlett, 2008, # 18, p. 2869 - 2873]
[4]Location in patent: experimental part Liu, Hefang; Lepoittevin, Bénédicte; Roddier, Céline; Guerineau, Vincent; Bech, Loïc; Herry, Jean-Marie; Bellon-Fontaine, Marie-Noelle; Roger, Philippe [Polymer, 2011, vol. 52, # 9, p. 1908 - 1916]

23
[ 1196-92-5 ]
[ 848068-44-0 ]
phenylcapsaicin [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56%	In diethyl ether Heating / reflux;	2 A solution of 7-phenylhept-6-ynoyl chloride (3) (10 mmol, 2,21 g) in dry ET20 (25 mL) was added in drops to a suspen- sion of vanillylamine (2) (3,06 g, 20 mmol) in dry Et20 (75 mL) in an argon atmosphere. The reaction mixture was refluxed until TLC indicated that the base materials had been con- verted. Diethyl ether was removed on a rotary evaporator, yielding 2,9 g (86 %) of a yellow viscous oil which crystal- lized when left to rest. TLC and NMR indicated a pure prod- uct.

Reference： [1]Current Patent Assignee: AXICHEM AB - WO2005/25314, 2005, A1 Location in patent: Page/Page column 17; 21

24
[ 849343-50-6 ]
[ 1196-92-5 ]
[ 849343-53-9 ]

Yield	Reaction Conditions	Operation in experiment
23%	With PPA; triethylamine In ethanol; dichloromethane at 20℃; for 3h;	VI EXAMPLE VI - 12-Phenylacetyl rinvanil; 1.85 g of 12-phenylacetyl ricinoleic acid are dissolved (4.4 mmol) in 15 ml of dry dichloromethane and added with 2 eqmol of vanillamine hydrochloride (835 mg, 4.4 mmol), 4 eqmol of TEA (2.45 ml, 1.78 g, 17.6 mmol) and 1.2 eqmol of polyphosphoric acid (50% EtOH solution, 3.4 ml, 1.68 g, 5.28 mmol). The reaction is left under stirring at room temperature and monitored by TLC (6:4: Rfp= 0.67; Rfa=0.37). After 3 hrs the solvent is evaporated off and the crude is purified by column chromatography (50 g of silica gel, eluted with 7:3 petroleum ether/ethyl acetate, fractions: about 20 ml). The product is further purified by filtration through alumina (6:4 to 4:6 petroleum ether/ethyl acetate). 512 mg of phenylacetyl rinvanil are obtained (23%).

Reference： [1]Current Patent Assignee: DIBIFIN SRL - WO2006/10445, 2006, A1 Location in patent: Page/Page column 12

25
[ 135799-48-3 ]
[ 1196-92-5 ]
benzoylrinvanil [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
38%	With PPA; triethylamine In ethanol; dichloromethane at 20℃; for 2h;	IX EXAMPLE IX - 12-Benzoyl rinvanil; 60 mg of 12-benzoyl ricinoleic acid (M.W.=402.57; 0.15 mmol) are dissolved in 2 ml of dry dichloromethane and added with 2 eqmol of vanillamine hydrochloride (M.W.=189.64; 0.30 mmol; 56.89 mg), 8 eqmol of TEA (M.W.=101; 1.2 mmol; 121 mg; d=0.726; 167 pi) and 3 eqmol of polyphosphoric acid (M.W.=318.19; 0.45 mmol; 34.2 mg; 50% EtOHsolution, 68 \|al). The mixture is left under stirring at room temperature and the reaction is monitored by TLC (8:2 petroleum ether/ethyl acetate; Rfp=0.41; Rfa=0). After 2 hours the reaction solvent is evaporated off and the crude is purified by column chromatography (2.5 g of silica gel, 8:2 petroleum ether/ethyl acetate, fractions: about 5 ml). 31 mg of benzoyl rinvanil (38%) are obtained..H NMR (300 MHz, CDC13): 5 8.02 (Bz AA'), 7.54 (Bz C), 7.42 (Bz BB'), 6.84 (dd, J = 8, 3 Hz, 1H), 6.79 (d, J = 3 Hz, 1H), 6.74 (d, J = 8 Hz, 1H), 5.78 (br s, 1H), 5.41 (m, 2H), 5.11 (quint, J = 6.0 Hz, 1H), 4.33 (d, J - 5.8 Hz, 2H), 3.85 (s, 3H), 3.60 (br t, J = 6.0 Hz, 2H), 2.40 (m, 2H), 2.16 (t, J - 7.4 Hz), 2.01 (m, 2H), about 1.64 (m, 4 H), about 1.26 (br m, 20H), 0.85 (br t, J = 7.1 Hz, 3H).

Reference： [1]Current Patent Assignee: DIBIFIN SRL - WO2006/10445, 2006, A1 Location in patent: Page/Page column 13-14

26
13-cyclohexyl-6-(morpholin-4-ylcarbonyl)-5H-indolo[2,1-a][2]benzazepine-10-carboxylic acid [ No CAS ]
[ 1196-92-5 ]
13-cyclohexyl-N-[4-hydroxy-3-methoxybenzyl]-6-[(N-morpholinyl)carbonyl]-7H-indolo[2,1-a][2]benzazepine-10-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃;	II To 0.05mmol of I in 1.0 mL of anhydrous λζN-Dimethylforaiamide (DMF) in a 3 dram vial equipped with a teflon lined screw cap was added 0.15 mmol (3 eq.) of 2-(l H-Benzotriazole- 1 -yl)- 1 , 1 ,3 ,3 ,-Tetramethyluronium Tetrafluoroborate(TBTU) in 1.0 mL of anhydrous DMF followed by the addition of O.lmmol (2 eq.) of amine 2 in 1.0 mL of anhydrous DMF. The reaction was shaken on an Innova 2000 orbital shaker at 240 rpm overnight at room temperature. The reaction volume was then reduced to a total volume of 2.0 mL in a Savant Speedvac and the crude product was purified using a Dionex ELSD triggered preparative HPLC employing acetonitrile/water and 10 mM ammonium acetate buffer with a Sunfire, Cl 8, 21.2 mm x 150 mm, lOμm column at a focused gradient flow rate of 20 rnL/min. Postpurification LC/MS data was obtained on a Waters analytical LC /Micromass Platform LC (ES 1+) at 220nm using the following set of conditions: Sunfire 5μm Cl 8, 4.6 x 100mm column, with a focused gradient of 50-95%B (B = HPLC grade acetonitrile), (A = HPLC grade water with 0.1% ammonium acetate), in 7 minutes with a 1 minute hold.AU NMR spectra were recorded at room temperature using a Bruker DRX500 spectrometer. The NMR solvent used was 1 : 1 (by volume) methyl alcohol-/4 (CD3OD)/ chloroform-d (CDCl3). Chemical shifts were reported in ppm relative to CD3OD. Coupling constants were reported in hertz. Peak multiplicity was reported using the following abbreviations: s (singlet), d (doublet), t (triplet), m (multiplet), br (broad).7H-indolo[2,l-a] [2]benzazepine~10~carboxamide, 13-cyclohexyl-N- [(dimethylamino)sulfonyl] -6-[(3 ,5-dimethyl-l~pipβrazinyl)carbonyl] -1HNMR: δ 0.84 (m, IH), 1.23 (m, 6H), 1.38 (m, 2H), 1.47 (m, 2H), 1.74 (m, 2H), 1.98 (m, 5H), 2.73 (m, 2H), 2.84 (m, 2H), 3.00 (s, 6H), 3.10 (m, IH), 3.73 (s, IH), 4.44 m, IH), 5.06 (m, IH), 6.91 (br s, IH), 7.46-7.61 (br m, 5H), 7.91 (d, IH, J= 8.48 Hz), 8.07 (br s, IH). LC/MS: m/z 604.26, Rf.% min., 99.4% purity.

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2007/92000, 2007, A1 Location in patent: Page/Page column 175-177

27
[ 1196-92-5 ]
[ 91366-99-3 ]
[ 1144854-50-1 ]

Yield	Reaction Conditions	Operation in experiment
85%	With triethylamine In propan-1-ol; butan-1-ol at 100℃; for 3h;
80%	With triethylamine In propan-1-ol for 3h; Heating / reflux;	11; 69 Example 116-(4-hydroxy-3-methoxybenzylamino)-9-(tetrahydrofuran-2-yl)-purine. A mixture of 10 mmol (2240 mg) of 6-chloro-9-(tetrahydrofuran-2-yl)-purine (prepared from 10 mmol (1546 mg) of 6-chloropurine), 12 mmol (1838 mg) of 4-hydroxy-3-methoxybenzylamine and 5 mL of triethylamine was refluxed in n-propanol for 3 hours. After removal of the n-propanol by vacuum evaporation, the resulting material was treated with water and extracted into ethyl acetate. The ethyl acetate phase was evaporated and the residuum subsequently washed with 30 ml of petroleum ether. The solid residue was filtered off and the crude product crystallized from methanol. Yield 80%, white solid. TLC (EtOAc:hexane) (1:1) (v:v): single spot; HPLC: purity>98%. 1H NMR (400 MHZ, DMSO): 0.90d(3H, J=6.6 Hz); 1.32m(1H); 1.57m(1H); 1.84m(1H); 1.95m(1H); 2.12m(2H); 2.29m(1H); 3.26m(1H); 3.51bs(2H); 3.73m(1H); 3.89m(1H); 4.40t(1H, J=5.1 Hz); 6.12d(1H, J=5.2 Hz); 7.74bs(1H); 8.18s(1H); 8.28s(1H. MS (ES): [M+H]+=342 (100).

Reference： [1]Location in patent: experimental part Szuecova, Lucie; Spichal, Lukas; Dolezal, Karel; Zatloukal, Marek; Greplova, Jarmila; Galuszka, Petr; Krystof, Vladimir; Voller, Jiri; Popa, Igor; Massino, Frank J.; Jorgensen, Jan-Elo; Strnad, Miroslav [Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 5, p. 1938 - 1947]
[2]Current Patent Assignee: INST OF EX BOTANY ACADEMY OF S; INST OF EX BOTANY ACADEMY OF SCIENCES OF THE CZECK; CZECH ACADEMY OF SCIENCES - US2009/170879, 2009, A1 Location in patent: Page/Page column 9-10

28
[ 1196-92-5 ]
[ 7306-68-5 ]
[ 1144854-43-2 ]

Yield	Reaction Conditions	Operation in experiment
85%	With triethylamine In propan-1-ol; butan-1-ol at 100℃; for 3h;

Reference： [1]Location in patent: experimental part Szuecova, Lucie; Spichal, Lukas; Dolezal, Karel; Zatloukal, Marek; Greplova, Jarmila; Galuszka, Petr; Krystof, Vladimir; Voller, Jiri; Popa, Igor; Massino, Frank J.; Jorgensen, Jan-Elo; Strnad, Miroslav [Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 5, p. 1938 - 1947]

29
[ 1196-92-5 ]
[ 24424-99-5 ]
[ 130972-89-3 ]

Yield	Reaction Conditions	Operation in experiment
99%	With triethylamine In 1,4-dioxane; water at 20℃; for 2h;
99%	With triethylamine In 1,4-dioxane; water	70 (4-Hydroxy-3-methoxybenzyl)carbamic Acid t-butyl Ester (30) Example 70 (4-Hydroxy-3-methoxybenzyl)carbamic Acid t-butyl Ester (30) A mixture of 4-hydroxy-3-methoxy benzylamine (29, 0.5 g, 2.64 mmol) and NEt3 (0.054 g, 5.29 rmnol) in H2O (10 mL) was treated dropwise with a solution of di-t-butyl-di-carbonate (1.15 g, 5.29 mmol) in dioxane (1.5 mL) for 20 min. After stimrng for 24 h at room temperature, the reaction mixture was extracted with CH2Cl2 several times. The combined organic layer was dried over MgSO4 and concentrated in vacuo. The residue was purified by flash column chromatography over silica gel using EtOAc:Hex (1:1) as eluant to give 30 as oil (0.663 g, 99%). 1H NMR (CDCl3) δ 6.74-7.00 (m, 3H, Ar), 5.65 (s, 1H, OH), 4.79 (bs, 1H, NH), 4.23 (d, 2H, NHCH2) 3.87 (s, 3H, OCH3), 1.43 (s, 9H, O(CH3)3).
	With N-ethyl-N,N-diisopropylamine at 20℃; for 16h;	44.A Step A: teλt-Butyl(4-hydroxy-3-rnethoxybenzyl)carbamate; To a solution of 4-hydroxy-3-methoxybenzylamine (1.0 g, 5.27 mmol) in acetonitrile (30 mL) was added /erf-butyldicarbonate (1.27 g, 5.80 mmol) and di- isopropylethylamine (1.84 mL, 10.54 mmol). The reaction was stirred at room temperature for 16 h before being partitioned between EtOAc (60 mL) and water (30 mL). The aqueous phase was separated and re-extracted with EtOAc (3 x 25 mL) and the combined organic extracts were washed with brine (60 mL), dried over MgSO4, filtered and concentrated. Purification by flash chromatography (40% EtOAc/hexanes) gave /er/-Butyl(4-hydroxy-3-methoxybenzyl)carbamate. LCMS - 275.9 (M+l)+.

Reference： [1]Location in patent: scheme or table Cho, Yongsung; Kim, Myeong Seop; Kim, Ho Shin; Ann, Jihyae; Lee, Jeewoo; Lee, Jiyoun; Pearce, Larry V.; Pavlyukovets, Vladimir A.; Morgan, Matthew A.; Blumberg, Peter M. [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 16, p. 5227 - 5231]
[2]Current Patent Assignee: MEDIFRON DBT CO.,LTD. - US6476076, 2002, B1
[3]Current Patent Assignee: MERCK & CO INC - WO2010/39474, 2010, A1 Location in patent: Page/Page column 35

30
[ 479636-66-3 ]
[ 1196-92-5 ]
3-(4-hydroxy-3-methoxybenzyl-carbamoyl)-1-oxa-2,8-diazaspiro[4.5]dec-2-en-8-carboxylic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
99%	Stage #1: 8-[(tert-butoxy)carbonyl]-1-oxa-2,8-diazaspiro[4.5]dec-2-ene-3-carboxylic acid With 4-methyl-morpholine; (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 1.5h; Stage #2: Vanillylamin In N,N-dimethyl-formamide at 20℃; for 22.5h;

Reference： [1]Current Patent Assignee: Gruenenthal Pharma GmbH & Co. Kommanditgesellschaft - WO2006/122769, 2006, A2 Location in patent: Page/Page column 68-69

31
[ 1196-92-5 ]
[ 3158-26-7 ]
N-(3-methoxy-4-hydroxybenzyl)-N'-octylurea [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
39%	at 20℃;	3 To a solution of the hydrochloride or hydrobromide salt of an amine (1-2 mmol) in anhydrous dichloromethane, tetrahydrofuran or N,Λ7-dimethylformamide (DMF) (2-4 mL) was added N,N-diisopropylethylamine (DIPEA) (1-2 iranol) to liberate the amine. After stirring at room temperature for 10 min, isocyanate or isothiocyanate (1-2 mmol) was added. The solution was stirred at room temperature for 6 to 24 h. After the reaction, water (20 mL) was added to the solution. The reaction mixture was transferred to a separating funnel and extracted with dichloromethane, CH2CI2 (3 * 10 mL) . The organic extracts were concentrated under reduced pressure to give a crude product, which was purified by silica gel column chromatography (using hexane/ethyl acetate, 2:1 v/v, as eluent) or preparative HPLC (using the protocol set out in "Analytical Protocols" above) to give the final product.For analogues that precipitated during the extraction process with dichloromethane, the suspension containing the precipitated analogues was transferred to a Falcon tube and centrifuged. The supernatant was discarded. The pellet was re-suspended with ethyl acetate(5 mL) and centrifuged. The re-suspension and centrifugation steps were carried out twice. The crude product obtained was further purified by preparative HPLC (using the protocol set out in "Analytical Protocols" above) .

Reference： [1]Current Patent Assignee: NANYANG POLYTECHNIC - WO2010/144055, 2010, A1 Location in patent: Page/Page column 47-48; 50

32
[ 1196-92-5 ]
[ 1202704-74-2 ]
[ 1202699-20-4 ]

Yield	Reaction Conditions	Operation in experiment
49%	Stage #1: Vanillylamin; methyl 5-([2-(ethyloxy)-2-oxoethyl]amino}carbonyl)-1-[2-fluoro-4-(trifluoromethyl)phenyl]methyl}-2.4-dihydroxy-6-oxo-1,6-dihydro-3-pyridinecarboxylate In 1,4-dioxane at 150℃; for 0.5h; Microwave irradiation; Sealed tube; Stage #2: With sodium hydroxide In 1,4-dioxane Stage #3: With hydrogenchloride In 1,4-dioxane; water; ethyl acetate	20 Methyl 5-([2-(ethyloxy)-2-oxoethyl]amino}carbonyl)-l- [2-fluoro-4-(trifluoromethyl)phenyl]methyl} -2,4-dihydroxy-6-oxo- 1 ,6-dihydro-3-pyridinecarboxylate (300 mg, 0.612 mmoles) and 4-(aminomethyl)-2-(methyloxy)phenol (94 mg, 0.612 mmoles) in 1,4-dioxane (3 mL) were sealed in a pressure tube and heated in a microwave reactor at 150 0C for 30 minutes. LCMS indicated the reation was complete. The reaction mixture was treated with 1 molar sodium hydroxide solution (3 mL) and stirred overnight. The mixture was diluted with ethyl acetate and washed with 1 molar hydrochloric acid (x2) and evaporated to a solid that was triturated in diethyl ether, collected, washed with diethyl ether and hexanes and dried to afford the title compound as a tan solid (175 mg, 49%). 1H NMR (400 MHz, DMSO-^6) δ ppm 13.00 (br. s., 1 H), 9.86 (d, J=19.45 Hz, 2 H), 8.96 (br. s., 1 H), 7.68 (d, J=10.36 Hz, 1 H), 7.50 (d, J=7.58 Hz, 1 H), 7.31 (dd, J=7.71 Hz, 1 H), 6.95 (d, J=I.77 Hz, 1 H), 6.65 - 6.80 (m, 2 H), 5.20 (s, 2 H), 4.45 (d, J=5.81 Hz, 2 H), 4.09 (d, J=5.56 Hz, 2 H), 3.75 (s, 3 H).

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2009/158315, 2009, A1 Location in patent: Page/Page column 31

33
[ 1196-92-5 ]
[ 112-80-1 ]
[ 58493-49-5 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: cis-Octadecenoic acid With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; triethylamine In ethyl acetate at 20℃; for 1h; Stage #2: Vanillylamin In ethyl acetate at 20℃; for 12h;	5.2. Synthesis of fatty acid amides General procedure: All fatty acid amides with different acyl chains and amine heads were synthesized using the same procedure but with different precursor compounds. 2-(1H-Benzotriazole-1-yl)-1,2,3,3-tetramethyluronium tetrafluoroborate (TBTU, 1 equiv) was added to a mixture of compound C1 (1 equiv) and triethylamine (TEA, 2 equiv) in EtOAc. After stirring for 1 h at room temperature, isopropylamine (2 equiv) was added and the reaction mixture was stirred for 12 h. The mixture was washed with water, dried and concentrated to give a residue that was purified by reversed-phase HPLC (YMC ODS-H80) eluting with 80% aqueous CH3CN to yield compound 1 (1.5 mg, 63%);

Reference： [1]Location in patent: experimental part Dang, Hung The; Kang, Gyeoung Jin; Yoo, Eun Sook; Hong, Jongki; Choi, Jae Sue; Kim, Hyung Sik; Chung, Hae Young; Jung, Jee H. [Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 4, p. 1520 - 1527]

34
[ 1196-92-5 ]
[ 60-33-3 ]
Livanil [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: linoleic acid With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; triethylamine In ethyl acetate at 20℃; for 1h; Stage #2: Vanillylamin In ethyl acetate at 20℃; for 12h;	5.2. Synthesis of fatty acid amides General procedure: All fatty acid amides with different acyl chains and amine heads were synthesized using the same procedure but with different precursor compounds. 2-(1H-Benzotriazole-1-yl)-1,2,3,3-tetramethyluronium tetrafluoroborate (TBTU, 1 equiv) was added to a mixture of compound C1 (1 equiv) and triethylamine (TEA, 2 equiv) in EtOAc. After stirring for 1 h at room temperature, isopropylamine (2 equiv) was added and the reaction mixture was stirred for 12 h. The mixture was washed with water, dried and concentrated to give a residue that was purified by reversed-phase HPLC (YMC ODS-H80) eluting with 80% aqueous CH3CN to yield compound 1 (1.5 mg, 63%);

Reference： [1]Location in patent: experimental part Dang, Hung The; Kang, Gyeoung Jin; Yoo, Eun Sook; Hong, Jongki; Choi, Jae Sue; Kim, Hyung Sik; Chung, Hae Young; Jung, Jee H. [Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 4, p. 1520 - 1527]

35
[ 1196-92-5 ]
[ 463-40-1 ]
Linvanil [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: All fatty acid amides with different acyl chains and amine heads were synthesized using the same procedure but with different precursor compounds. 2-(1H-Benzotriazole-1-yl)-1,2,3,3-tetramethyluronium tetrafluoroborate (TBTU, 1 equiv) was added to a mixture of compound C1 (1 equiv) and triethylamine (TEA, 2 equiv) in EtOAc. After stirring for 1 h at room temperature, isopropylamine (2 equiv) was added and the reaction mixture was stirred for 12 h. The mixture was washed with water, dried and concentrated to give a residue that was purified by reversed-phase HPLC (YMC ODS-H80) eluting with 80% aqueous CH3CN to yield compound 1 (1.5 mg, 63%);

Reference： [1]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 1520 - 1527

36
[ 1196-92-5 ]
[ 112-86-7 ]
(Z)-N-[(4-hydroxy-3-methoxyphenyl)methyl]-docos-13-enamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: All fatty acid amides with different acyl chains and amine heads were synthesized using the same procedure but with different precursor compounds. 2-(1H-Benzotriazole-1-yl)-1,2,3,3-tetramethyluronium tetrafluoroborate (TBTU, 1 equiv) was added to a mixture of compound C1 (1 equiv) and triethylamine (TEA, 2 equiv) in EtOAc. After stirring for 1 h at room temperature, isopropylamine (2 equiv) was added and the reaction mixture was stirred for 12 h. The mixture was washed with water, dried and concentrated to give a residue that was purified by reversed-phase HPLC (YMC ODS-H80) eluting with 80% aqueous CH3CN to yield compound 1 (1.5 mg, 63%);

Reference： [1]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 1520 - 1527

37
[ 1196-92-5 ]
[ 57-10-3 ]
[ 69693-13-6 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 1-hexadecylcarboxylic acid With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; triethylamine In ethyl acetate at 20℃; for 1h; Stage #2: Vanillylamin In ethyl acetate at 20℃; for 12h;	5.2. Synthesis of fatty acid amides General procedure: All fatty acid amides with different acyl chains and amine heads were synthesized using the same procedure but with different precursor compounds. 2-(1H-Benzotriazole-1-yl)-1,2,3,3-tetramethyluronium tetrafluoroborate (TBTU, 1 equiv) was added to a mixture of compound C1 (1 equiv) and triethylamine (TEA, 2 equiv) in EtOAc. After stirring for 1 h at room temperature, isopropylamine (2 equiv) was added and the reaction mixture was stirred for 12 h. The mixture was washed with water, dried and concentrated to give a residue that was purified by reversed-phase HPLC (YMC ODS-H80) eluting with 80% aqueous CH3CN to yield compound 1 (1.5 mg, 63%);

Reference： [1]Location in patent: experimental part Dang, Hung The; Kang, Gyeoung Jin; Yoo, Eun Sook; Hong, Jongki; Choi, Jae Sue; Kim, Hyung Sik; Chung, Hae Young; Jung, Jee H. [Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 4, p. 1520 - 1527]

38
[ 1196-92-5 ]
[ 1120-07-6 ]
[ 2444-46-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 5227 - 5231

39
[ 1196-92-5 ]
[ 1204-06-4 ]
[ 1610703-53-1 ]

Yield	Reaction Conditions	Operation in experiment
55%		General procedure: To a solution of the acid derivative (1mmol) in CH2Cl2 were added triethylamine (2mmol) and ethyl chloroformate (1mmol), followed by stirring at 0C for 30min. After addition of the appropriate amine derivative (1.2mmol), the mixture was stirred for an additional 1h at 0C. Then, the reaction mixture was warmed to room temperature and stirred overnight. After the solvent was evaporated under reduced pressure, acetone was added, filtered, and evaporated. The residue was dissolved in CH2Cl2, and the organic phase was washed with a 1% NaHCO3 solution and brine, dried over Na2SO4, and evaporated under vacuum. The final residue was purified by flash column chromatography (Combiflash Rf) using CH2Cl2-MeOH (0-5%) as eluents. 4.3.7 (E)-N-(4-Hydroxy-3-methoxybenzyl)-3-(1H-indol-3-yl)acrylamide 3g Yield 55%, mp 213-215 C; IR (FTIR/FTNIR-ATR): 1702 cm-1 (C=O), 3266 cm-1 (N-H). 1H NMR (DMSO-d6) delta: 11.55 (1H, s), 8.87 (1H, s), 8.23 (1H, t, J = 5.6 Hz), 7.89 (1H, d, J = 7.2 Hz), 7.67 (1H, m), 7.63 (1H, d, J = 15.6 Hz), 7.45 (1H, d, J = 7.6 Hz), 7.18 (2H, m), 6.88 (1H, s), 6.72 (1H, m), 6.67 (1H, d, J = 15.6 Hz), 4.29 (2H, d, J = 5.2 Hz), 3.75 (3H, s). The OH-signal was not observed in the spectrum, due to solvent exchange. 13C NMR (DMSO-d6) delta: 166.8, 148.1, 146.1, 138.0, 133.8, 131.0, 130.9, 125.5, 125.2, 122.8, 120.9, 120.7, 116.9, 115.9, 112.9, 112.8, 112.6, 56.2, 42.9; HRMS C19H19N2O3 [M+H]+ Calcd 323.1396, Found m/z 323.1397.

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 3096 - 3104

40
[ 1196-92-5 ]
[ 112-05-0 ]
[ 2444-46-4 ]

Yield	Reaction Conditions	Operation in experiment
91%	With SiO2-H3BO3; In toluene; for 7h;Reflux;	General procedure: This embodiment provides a preparation method of decanoyl vanillamine, which specifically comprises the following steps1) Take a 100ml reactor, install a water separator (with a condenser),Magnetic stirrer and thermometer; in the reactorAdd vanillin free base,nonanoic acid,SiO2-H3BO3 catalyst and toluene.2) Stirring,Heating to reflux water separation reaction 6h~10h,Then cooled to 30 C,Take a small amount of the reaction solution to remove the solvent under reduced pressure.HPLC analysis.3) The remaining reaction solution is sequentially diluted with dilute hydrochloric acid having a mass concentration of 1%.After washing with pure water,The solvent is removed under direct reduced pressure until no liquid flows out.-5C cooled crystals.5) Filtering,A small amount of toluene washed the filter cake to give a white solid.After drying, the decanoyl vanillamine product is obtained.
87.4%	With boric acid; In toluene; at 130℃; for 8h;	In a three-neck 500 mL flask, 30.0 g (0.196 mol) of vanillin was added.31.0 g (0.196 mol) of n-decanoic acid and 300 mL of toluene were added.Boric acid 0.6g (9.8mmol), a three-neck flask fitted with a thermometer,A mouth water separator + reflux condenser (the water separator is loaded into the reaction flask,Then install the reflux condenser above the water separator.)Another mouth is closed, stirring is started, and the temperature is raised to 130C for 8 hours.After the reaction is completed, it is cooled to room temperature.Add 50mL of water twice to wash (extract boric acid),After drying over anhydrous sodium sulfate,Recovery of toluene under reduced pressure at 60 C using a rotary evaporatorTo the distillation of toluene is 2/3 of the original volume, stop decompression recovery,The remaining liquid is transferred to the cryogenic reactor,Stir and crystallize at -20C for 3h, filter,The resulting crystals are washed with toluene.Drained to give 50.3 g of a white powdery solid with a yield of 87.4%.HPLC purity 99.1%.White powder solids analysis:
74%	With Candida antarctica lipase B; In toluene; at 80℃; for 36h;Inert atmosphere; Molecular sieve; Enzymatic reaction;	A microwave-vial containing a solution of 1 (0.2 mmol, 1.0 equiv.), ammonium formiate (37.8 mg, 0.6 mmol, 3.0 equiv.) and Pd-catalyst(Pd-AmP-MFC, 13.4 mg, 0.01 mmol, 8 wt%, 5 mol%) or(Pd-CPG, 569A, 74.0 mg, 0.013 mmol, 6.6 mol%) in toluene (1 mL) under ISfc conditions was stirred at 80C for the time shown in Table 3. Afterwards, molecular sieves 4A, acid 4 (0.2 mmol, 1.0 equiv.) and lipase (120 mg/mmol) were added to reaction mixture and stirred at 80C for 36h. The crude reaction mixture was filtrated through Celite using CHCb(10 mL) as eluent and evaporated. The crude material was purified by silica gel flash column chromatography to afford the corresponding amide 3 as indicated in Table 3. The lipase is preferably Novozyme-435 immobilized on a macroporous anionic resin.

52%

With lipase; In tert-Amyl alcohol; at 45℃; for 48h;Molecular sieve; Enzymatic reaction;

The dried crude reaction mixture from the previous step (containing vanillylamine 94 mg, 0.62 mmol, 1.00 equiv.) was dissolved in 2-methyl-2-butanol (31 mL, 20 mM). To the reaction was added Ms 4A (2 g), compound 5b (98.7 mg, 0.62 mmol, 1.00 equiv.) and lipase (1.9 g, 20 mg/niL). The reaction was stirred at 45C for 48 h. Afterwards the reaction was cooled to room temperature and filtered. The solvent was removed under reduced pressure and the crude material was purified by chromatography to afford nonivamide (7b) (isolated yield 52 %) as light yellow oil.

Reference： [1]Patent: CN110305031,2019,A .Location in patent: Paragraph 0125-0133; 0137-0152; 0168-0175
[2]Patent: CN107793325,2018,A .Location in patent: Paragraph 0027; 0028; 0029; 0030; 0031; 0032; 0033-0040
[3]Patent: WO2016/96905,2016,A1 .Location in patent: Page/Page column 19
[4]ACS Catalysis,2016,vol. 6,p. 3932 - 3940
[5]Patent: WO2015/144902,2015,A1 .Location in patent: Page/Page column 11
[6]Advanced Synthesis and Catalysis,2014,vol. 356,p. 2113 - 2118

41
[ 61152-59-8 ]
[ 1196-92-5 ]

Yield	Reaction Conditions	Operation in experiment
	With glucose dehydrogenase; L-alanin; D-glucose; L-alanine dehydrogenase; amine transaminase; ammonium chloride; NADH; sodium hydroxide In dimethyl sulfoxide at 37℃; for 90h; Darkness; Enzymatic reaction;
	With glucose dehydrogenase; D-Glucose; L-alanin; L-alanine dehydrogenase; chromobacterium violaceum amine transaminase; ammonium chloride; NADH In dimethyl sulfoxide at 37℃; for 92h; Darkness; Enzymatic reaction;	Procedure for synthesis of vanillylamine by a retro-aldol reaction followed by transamination in one pot D-glucose, ammonium chloride and L-alanine were dissolved in HEPES buffer 50 mM and the pH was adjusted to 8.2 (1 M NaOH). The lignin model 3 was dissolved in DMSO and then added to the solution together with NADH and the enzymes to give the final volume 1 mL and concentrations 250 mM L-alanine, 2.5 mM of compound 3, 150 mM ammonium chloride, 150 mM D-glucose, 1 mM NADH and 10 % DMSO v/v, together with 1 mg/niL ATA, 7 U/mL L-alanine dehydrogenase and 10 U/mL glucose dehydrogenase. The reaction was performed in 37°C and darkness with no stirring. This resulted in a conversion to vanillylamine (4a) of 25 % after 92 h as determined by HPLC analysis. The same reaction was repeated but using 100 mM HEPES instead of 50 mM (final volume 1 mL and concentrations 250 mM L-alanine, 2.5 mM of compound 3, 150 mM ammonium chloride, 150 mM D-glucose, 1 mM NADH and 10 % DMSO v/v, together with 0.9 mg/niL ATA, 7 U/mL L-alanine dehydrogenase and 10 U/mL glucose dehydrogenase). The reaction was performed in 37°C and darkness with no stirring. This resulted in a conversion to vanillylamine (4a) of 40 % after 90 h as determined by HPLC analysis. The effect of the higher buffer concentration was investigated on the previously described system for synthesis of vanillylamine (4a) from vanillin (2a). In the same way as earlier, vanillin was dissolved in DMSO and then mixed with D-glucose, ammonium chloride and L-ala- nine in HEPES buffer 100 mM. The pH was adjusted to 8.2 (1 M NaOH) and the solution was mixed with NADH and the enzymes in an eppendorf tube to give the final volume 1 mL and concentrations 250 mM L-alanine, 50 mM vanillin, 150 mM ammonium chloride, 150 mM D- glucose, 1 mM NADH and 10 % DMSO v/v, together with 0.9 mg/niL ATA, 7 U/mL L-alanine dehydrogenase and 10 U/mL glucose dehydrogenase. The reaction was performed in 37°C and darkness with no stirring. This resulted in the reaction ending after 18 h, with a conversion of vanillin to vanillylamine of only 77 %. Since conversions of 95 % (small scale) and >99 % (scale-up) were obtained with the same system with a lower buffer concentration, it was decided to not work further with the 100 mM buffer concentration.
	Multi-step reaction with 2 steps 1: ammonium chloride; NADH; L-alanine dehydrogenase; glucose dehydrogenase; L-alanin; D-Glucose / dimethyl sulfoxide / 70 h / 37 °C / pH 8.2 / Enzymatic reaction 2: ammonium chloride; NADH; L-alanine dehydrogenase; glucose dehydrogenase; chromobacterium violaceum amine transaminase; L-alanin; D-Glucose / dimethyl sulfoxide / 17 h / 37 °C / pH 8.2 / Darkness; Enzymatic reaction

Reference： [1]Anderson, Mattias; Afewerki, Samson; Berglund, Per; Cordova, Armando [Advanced Synthesis and Catalysis, 2014, vol. 356, # 9, p. 2113 - 2118]
[2]Current Patent Assignee: XP CHEMISTRIES - WO2015/144902, 2015, A1 Location in patent: Page/Page column 14
[3]Current Patent Assignee: XP CHEMISTRIES - WO2015/144902, 2015, A1

42
[ 1196-92-5 ]
[ 30562-34-6 ]
[ 1622011-55-5 ]

Yield	Reaction Conditions	Operation in experiment
	In dichloromethane at 20℃; for 24h;	15 4.2 General procedure for preparation of compounds 2-34 General procedure: To geldanamycin (34 mg, 0.06 mmol, 1.0 equiv.) in dichloromethane (8 mL) was added substitutional arylmethylamine (0.12 mmol, 20.0 equiv.). The reaction mixture was stirred for 24 h at room temperature, and the color changed from yellow to purple. TLC was used to monitor the progress of the reaction. After the reaction complete, the mixture was diluted with 20 mL of dichloromethane and washed with 1.5 N HCl (2 x 20 mL) followed by brine (3 x 25 mL). The organic layer was dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. The residue was purified by flash column chromatography (silica gel, ethyl acetate/petroleum ether 1:1) to afford a purple solid.

Reference： [1]Li, Zhenyu; Jia, Lejiao; Wang, Jifeng; Wu, Xingkang; Hao, Huilin; Xu, Hongjiao; Wu, Yunfei; Shi, Guowei; Lu, Chunhua; Shen, Yuemao [European Journal of Medicinal Chemistry, 2014, vol. 85, p. 359 - 370]

43
[ 1196-92-5 ]
[ 4421-08-3 ]

Yield	Reaction Conditions	Operation in experiment
83%	With ammonium hydroxide; oxygen In tert-Amyl alcohol at 110℃; for 15h; Autoclave; Green chemistry;

Reference： [1]Jagadeesh, Rajenahally V.; Junge, Henrik; Beller, Matthias [ChemSusChem, 2015, vol. 8, # 1, p. 92 - 96]

44
[ 1196-92-5 ]
[ 4711-72-2 ]
N-[(4-hydroxy-3-methoxyphenyl)methyl]-5-(3,4-methylenedioxyphenyl)-2E,4E-pentadienamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56%	With triethylamine at 20℃; for 5h; Cooling with ice;	General Procedure for Preparation of Piperic AcidAmides (4-24) General procedure: Oxalyl chloride (1.27 g, 10 mmol) was addedto a mixture of piperic acid (218 mg, 1.0 mmol) in CH2Cl2(5 mL) and the mixture was stirred at room temperature for3 h. The solvent and excess oxalyl chloride was then evaporatedunder reduced pressure. The crude acid chloride generatedwas dissolved in CH2Cl2 or N,N-dimethylformamide(DMF) (2 mL), and was added dropwise to a mixture of theappropriate amine or its hydrochloride salt (1.2 mmol) andEt3N (808 mg, 8 mmol) in CH2Cl2 or DMF (5 mL) under icecooling.The reaction mixture was stirred for 5 h at roomtemperature. Ice-water was added to the mixture, which wassubsequently extracted with CHCl3. The organic layer wasdried over Na2SO4 and the solvent was evaporated under reducedpressure. The residue was purified by silica gel columnchromatography (CHCl3 : MeOH : aq. NH3=100 : 1 : 0.1) to givethe corresponding piperic acid amides.

Reference： [1]Takao, Koichi; Miyashiro, Takaki; Sugita, Yoshiaki [Chemical and Pharmaceutical Bulletin, 2015, vol. 63, # 5, p. 326 - 333]

45
[ 1196-92-5 ]
4-[5-(pyridine-3-yl)thiophen-2-yl]butanoic acid [ No CAS ]
N-(4-hydroxy-3-methoxybenzyl)-4-(5-(pyridin-3-yl)thiophen-2-yl)butanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With benzotriazol-1-ol; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃;	N-(4-hydroxy-3-methoxybenzyl)-4-(5-(pyrid i n-3-yI)thi ophen-2-yI)butanam ide(MSP53) General procedure: Method 0. The 4-(5-(pyridin-3-yl)thiophen-2-yl)butanoic acid (1 .0 eq.) was dissolved in dry DMF (5-7 mL) and HOBt (1.0 eq.) HBTU (2.0 eq.), DIPEA (3.0 eq.) and theappropriate amine (1.4 eq.) were added to the solution. After stirring at room temperature for 30 mm, more DIPEA (3.0 eq.) was added and the reaction mixture was stirred at room temperature overnight. Then the reaction mixture was diluted with saturated NH4CI solution and extracted with ethyl acetate (4 times). The collected organic layers were washed twice with brine, dried over anhydrousNa2SO4, filtered and evaporated to dryness. The crude residue was purified by flash chromatography on silica gel with the appropriate eluent mixtures.; This compound was prepared from 4-[5-(pyridine-3-yl)thiophen-2-yl]butanoic acidand 4-hydroxy-3-methoxybenzylamine, following Method C. Pure compound wasisolated as pasty yellow solid (yield 75.0 %, eluent: CHCI3/MeOH 50/2).Mp < 30 00 1H-NMR (400 MHz) CDCI3 6 (ppm): 8.77 (5, 1 H), 8.45 (5, 1 H), 7.77 (d,1H, J= 7.9 Hz), 7.28-7.25 (m, 1H), 7.14 (d, 1H, J= 3.5 Hz), 6.84 (d, 1H, J= 8.0 Hz),6.78 (5, 1 H), 6.75-6.73 (m, 2H), 5.76 (br s, 1 H), 4.33 (d, 2H, J = 5.6 Hz), 3.84 (5,3H), 2.87 (t, 2H, J= 7.3 Hz), 2.25 (t, 2H, J= 7.3 Hz), 2.09-2.02 (m, 2H). 3C-NMR(400 MHz) CDCI3: 172.0, 147.8, 146.8, 146.3, 145.6, 145.3, 138.0, 132.7, 130.5,130.2, 125.9, 124.1, 123.7, 120.9, 114.5, 110.8, 56.0, 43.6, 35.4, 29.5, 27.2. MS(ESI) m/z: 383 [M+H] (100), 405 [M+Na] (35). Anal. calcd. for 021 H22N2035 (MW382.48): C, 65.95%; H, 5.80%; N, 7.32%. Found: C, 65.87%; H, 5.92%; N, 7.24%.

Reference： [1]Current Patent Assignee: UNIVERSITY OF CALABRIA; UNIV SIENA - WO2015/162216, 2015, A1 Location in patent: Page/Page column 19; 36

46
[ 1196-92-5 ]
C₁₀H₁₇ClO [ No CAS ]
[ 7553-53-9 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate In chloroform; water at 20 - 40℃; for 1h;	2 General procedure for synthesis of capsaicin and nonivamide from vanillyla- mine. General procedure: To a vial (8-mL) containing vanillylamine (4) (81.1 mg, 0.53 mmol, 1.00 equiv.) and NaHC03 (145.6 mg, 1.73 mmol, 3.27 equiv.) was added H20 (1.5 mL) and stirred for 30 minutes at r.t, followed by addition of CHC13 (2 mL) and the reaction kept stirring at r.t. for 15 minutes. Next, a solution of 6a or 6b (0.61 mmol, 1.16 equiv.) in CHCI3 (0.5 mL) was added drop wise and the reaction stirred at r.t. for additional 30 minutes. Afterwards the reaction was heated to 40°C and stirred for 30 minutes (monitored by TLC). The organic layer was separated and the water layer washed with CHC13 (3x15 mL). The combined organic layers were washed with aq. HCl (2%) and then brine followed by drying over Na2S04. The crude material was purified by chromatography to afford the 7a (isolated yield 91 %) and 7b (iso- lated yield 94 %) as light yellow oil.26 7a: IR (neat) λ 3296 (br), 2922 (s), 2853 (m), 1730 (m), 1647 (m), 1515 (m), 1459 (m), 1376 (m), 1272 (m), 1214 (m), 1154 (m), 1123 (w), 1034 (m), 970 (w), 816 (w), 756 (s), 667 (m), 557 (w) cm 1; NMR (500 MHz, CDC13): δ 6.86 (d, J = 8.1 Hz, lH), 6.81 (s, lH), 6.79-6.73 (m, lH), 5.62 (br s, 2H), 5-41-5-27 (m, lH), 4.36 (d, J = 5.7 Hz, 2H), 3.88 (s, 3H), 2.36-2.13 (m, 4H), 1.98 (q, J = 8.3 Hz, lH), 1.83-1.72 (m, lH), 1.72-1.57 (m, 4H), 1.53-1-43 (m, lH), 1.42-1.34 (m, lH), 0.95 (d, J = 7.0 Hz, 2H), 0.93 (d, J = 6.8 Hz, 3H). *3C NMR (125MHz, CDCI3): δ 172.9, 172.5, 146.8, 145-30, 145-27, 138-3, 130-6, 130.5, 126.6, 121.03, 120.97, 114-52, 114-49, no.86, 110.81, 72.1, 63.3, 56.12, 56.09, 43.76, 43-69, 36.9, 36.7, 35-1, 32-4, 31-1, 30.5, 29-4, 25.4, 25.2, 22.8, 21.1, 15.1, 14.4; HRMS (ESI ) [M+Na]+ calcd for Ci8H27N03Na+: 306.2064, found: 306.2059;

Reference： [1]Current Patent Assignee: XP CHEMISTRIES - WO2015/144902, 2015, A1 Location in patent: Page/Page column 10

47
[ 1196-92-5 ]
[ 49769-28-0 ]
phenylcapsaicin [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With Novozyme In tert-Amyl alcohol at 45℃; for 48h; Molecular sieve; Enzymatic reaction;	Synthesis of Phenylcapsaicin To an oven dried vial containing Ms 4A (100 mg), were added 2-methyl-2-butanol (5 niL), 7-phenylhept-6-ynoic acid (20.2 mg, 0.1 mmol, 1.0 equiv.), 4a (15.2 mg, 0.1 mmol, 1.0 equiv.), and Novozyme (100 mg). The reaction was stirred at 45°C for 48I1. Afterwards the reaction was cooled to room temperature and filtered. The solvent was removed under reduced pressure and the crude material was purified by chromatography to afford phenylcapsaicin (isolated yield 95 %) as light yellow oil. IR (neat) λ 3053 (w), 2937 (w), 1645 (m), 1600 (w), 1513 (m), 1461 (w), 1431 (m), 1373 (m), 1264 (m), 1236 (w), 1154 (m), 1123 (m), 1034 (m), 854 (w), 818 (w), 732 (s), 693 (m), 542 (w), 465 (w) cm 1; NMR (500 MHz, CDC13): δ 7·39"7·33 (m, 2H), 7·29"7·24 (m, 3H), 6.85 (d, J = 8.0 Hz, lH), 6.80 (s, lH), 6.75 (d, J = 8.1 Hz, lH), 5.67 (br s, lH), 5.60 (s, lH), 4.36 (d, J = 5.7 Hz, 2H), 3.86 (s, 3H), 2.44 (t, J = 7.0 Hz, 2H), 2.27 (t, J = 7.1 Hz, 2H), 1.88-1.80 (m, 2H), 1.69-1.61 (m, 2H). *3C NMR (125MHz, CDCI3): δ 172.5, 146.8, 145.3, 131-7, 130-5, 128.4, 127.8, 123.9, i2i.o, 114.5, 110.8, 89.8, 8ι.2, 56.1, 43.7, 36.4, 28.4, 25.2, 19.4; HRMS (ESI ) [M+Na]+ calcd for C2iH23N03Na+: 360.1572, found: 360.1570;
78%	With palladium⁽⁰⁾-aminopropyl-mesocellular foam catalyst; Candida antarctica lipase B immobilized on a macroporous resin In toluene at 80℃; for 36h; Molecular sieve; Green chemistry; Enzymatic reaction;

Reference： [1]Current Patent Assignee: XP CHEMISTRIES - WO2015/144902, 2015, A1 Location in patent: Page/Page column 15
[2]Palo-Nieto, Carlos; Afewerki, Samson; Anderson, Mattias; Tai, Cheuk-Wai; Berglund, Per; Córdova, Armando [ACS Catalysis, 2016, vol. 6, # 6, p. 3932 - 3940]

48
[ 121-33-5 ]
[ 1196-92-5 ]
[ 498-00-0 ]

Yield	Reaction Conditions	Operation in experiment
1: 90.8 %Chromat. 2: 9.2 %Chromat.	Stage #1: vanillin With 5wt.% Rh on activated alumina; ammonia In water for 1h; Green chemistry; Stage #2: With hydrogen In water at 80℃; for 2h; Green chemistry;
	With ammonium hydroxide; 5% rhodium on activated aluminium oxide; hydrogen at 80℃; for 3h; Autoclave;	8 General procedure: For the synthesis reaction, a 50 mL stainless steel autoclave was used. Into the autoclave, the raw material furfural (0.2 g, 2 mM), the catalyst 5 wt% Rh / Al 2 O 3 (0.002 g, Rh average particle diameter 40 nm), 28 wt% ammonia water (4.0 mL, 66 mM), finally a magnetic stir bar were put and covered, then the temperature was raised while stirring. After about 1 hour, when the vessel reached the reaction temperature of 80 ° C, hydrogen gas (2 MPa) was introduced to start the reaction. After a reaction time of 2 hours, cooled to 5 ° C or less with ice water, then the remaining hydrogen gas was released by opening the valve slowly, and then after filtering with filter paper (No. 1), Qualitative and quantification were carried out using GC-MS (CP-3800 + 1200 L made by Bruker Daltonics Co) or GC (HP6890 manufactured by Agilent Technologies). As a result, the conversion rate of raw material furfural was 100% and disappeared and the target product methyl amino furan was obtained in a yield of 91.7% (based on mol%, same in the following examples also). Other by-products are 8.3% of N,N-bis(furanyl methyl)amine and no other by-products were detected.The reaction was carried out under the same conditions as in Example 1 except that various kinds of raw materials were used instead of furfural as the aromatic compound or furan derivative having an aldehyde group. The results are summarized in Table 2. In all the raw materials, the structure of the aromatic or furan ring was maintained even after the reaction. In the case of having a nitro group as a substituent, it was found that the nitro group was reduced to be converted to an amino group, but otherwise the aldehyde group was converted to a methyl amino group.

Reference： [1]Chatterjee, Maya; Ishizaka, Takayuki; Kawanami, Hajime [Green Chemistry, 2016, vol. 18, # 2, p. 487 - 496]
[2]Current Patent Assignee: UNITIKA LTD; NATIONAL INSTITUTE OF ADVANCED INDUSTRIAL SCIENCE AND TECHNOLOGY - JP2017/25012, 2017, A Location in patent: Paragraph 0034; 0035

49
[ 4653-11-6 ]
[ 1196-92-5 ]
N-(4-hydroxy-3-methoxybenzyl)-4-(thiophen-2-yl)butanamide [ No CAS ]

Reference： [1]ACS Chemical Neuroscience,2016,vol. 7,p. 737 - 748

50
[ 121-33-5 ]
[ 1196-92-5 ]
[ 93-51-6 ]

Yield	Reaction Conditions	Operation in experiment
	With ammonium formate In toluene at 22℃; for 12h; Inert atmosphere; Overall yield = 90 %Spectr.; chemoselective reaction;	1 example 1 To a microwave-vial containing the Pd°-catalyst (5 mol%) and ammonium formate (37.8 mg, 0.6 mmol, 3.0 equiv.) was added the solid vanillin 1a (0.2 mmol, 1.0 equiv.) under ISb atmosphere. Next, toluene (1 mL) was added at room temperature. The temperature was then set to the one shown in Table 1 and the reaction mixture was stirred under N2 atmosphere. After the time shown in Table 1 , the crude reaction mixture was filtrated through Celite using CHCI3 (10 mL) as eluent and evaporated. The crude material was purified by silica gel flash column chromatography. NMR samples for NMR-yield were prepared by removing 0.05 mL aliquots from the reaction mixtures, filtration through Celite using CDCI3 ( .5 mL) as eluent and mesitylene as the internal standard.
	With ammonium formate In toluene at 80℃; for 2.5h; Inert atmosphere; chemoselective reaction;

Reference： [1]Current Patent Assignee: XP CHEMISTRIES - WO2016/96905, 2016, A1 Location in patent: Page/Page column 15
[2]Palo-Nieto, Carlos; Afewerki, Samson; Anderson, Mattias; Tai, Cheuk-Wai; Berglund, Per; Córdova, Armando [ACS Catalysis, 2016, vol. 6, # 6, p. 3932 - 3940]

51
[ 121-33-5 ]
[ 1196-92-5 ]
[ 93-51-6 ]
[ 498-00-0 ]

Yield	Reaction Conditions	Operation in experiment
	With ammonium formate; palladium diacetate In toluene at 80℃; for 20h; Inert atmosphere; Overall yield = > 99 %Spectr.;	1 example 1 To a microwave-vial containing the Pd°-catalyst (5 mol%) and ammonium formate (37.8 mg, 0.6 mmol, 3.0 equiv.) was added the solid vanillin 1a (0.2 mmol, 1.0 equiv.) under ISb atmosphere. Next, toluene (1 mL) was added at room temperature. The temperature was then set to the one shown in Table 1 and the reaction mixture was stirred under N2 atmosphere. After the time shown in Table 1 , the crude reaction mixture was filtrated through Celite using CHCI3 (10 mL) as eluent and evaporated. The crude material was purified by silica gel flash column chromatography. NMR samples for NMR-yield were prepared by removing 0.05 mL aliquots from the reaction mixtures, filtration through Celite using CDCI3 ( .5 mL) as eluent and mesitylene as the internal standard.
	With palladium on activated charcoal; ammonium formate In toluene at 80℃; for 2.5h; Inert atmosphere; chemoselective reaction;
	With ammonium formate In toluene at 80℃; for 2.5h; Inert atmosphere; chemoselective reaction;

Reference： [1]Current Patent Assignee: XP CHEMISTRIES - WO2016/96905, 2016, A1 Location in patent: Page/Page column 16
[2]Palo-Nieto, Carlos; Afewerki, Samson; Anderson, Mattias; Tai, Cheuk-Wai; Berglund, Per; Córdova, Armando [ACS Catalysis, 2016, vol. 6, # 6, p. 3932 - 3940]
[3]Palo-Nieto, Carlos; Afewerki, Samson; Anderson, Mattias; Tai, Cheuk-Wai; Berglund, Per; Córdova, Armando [ACS Catalysis, 2016, vol. 6, # 6, p. 3932 - 3940]

52
[ 1196-92-5 ]
8-methyl-6-nonenoic acid [ No CAS ]
[ 7553-53-9 ]

Yield	Reaction Conditions	Operation in experiment
73%	With Candida antarctica lipase B In toluene at 80℃; for 36h; Inert atmosphere; Molecular sieve; Enzymatic reaction;	3 example 3 A microwave-vial containing a solution of 1 (0.2 mmol, 1.0 equiv.), ammonium formiate (37.8 mg, 0.6 mmol, 3.0 equiv.) and Pd°-catalyst(Pd°-AmP-MFC, 13.4 mg, 0.01 mmol, 8 wt%, 5 mol%) or(Pd°-CPG, 569A, 74.0 mg, 0.013 mmol, 6.6 mol%) in toluene (1 mL) under ISfc conditions was stirred at 80°C for the time shown in Table 3. Afterwards, molecular sieves 4A, acid 4 (0.2 mmol, 1.0 equiv.) and lipase (120 mg/mmol) were added to reaction mixture and stirred at 80°C for 36h. The crude reaction mixture was filtrated through Celite using CHCb(10 mL) as eluent and evaporated. The crude material was purified by silica gel flash column chromatography to afford the corresponding amide 3 as indicated in Table 3. The lipase is preferably Novozyme-435 immobilized on a macroporous anionic resin.
73%	With palladium⁽⁰⁾-aminopropyl-mesocellular foam catalyst; Candida antarctica lipase B immobilized on a macroporous resin In toluene at 80℃; for 36h; Molecular sieve; Green chemistry; Enzymatic reaction;
72%	With 4-(2-(1,3-dioxa-3a1,8,10-triaza-2,3a,14b-triboradibenzo[fg,op]tetracen-2-yl)phenyl)benzo[c]pyrimido[4,5-e][1,2]azaborinin-6(5H)-ol In fluorobenzene at 85℃; for 16h; Molecular sieve;

Reference： [1]Current Patent Assignee: XP CHEMISTRIES - WO2016/96905, 2016, A1 Location in patent: Page/Page column 19
[2]Palo-Nieto, Carlos; Afewerki, Samson; Anderson, Mattias; Tai, Cheuk-Wai; Berglund, Per; Córdova, Armando [ACS Catalysis, 2016, vol. 6, # 6, p. 3932 - 3940]
[3]Opie, Christopher R.; Noda, Hidetoshi; Shibasaki, Masakatsu; Kumagai, Naoya [Chemistry - A European Journal, 2019, vol. 25, # 18, p. 4648 - 4653]

53
[ 1196-92-5 ]
(4E,8E,12E)-5,9,13-trimethyl-4,8,12-tetradecatrienoic acid chloride [ No CAS ]
C₂₅H₃₇NO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80.2%	In dichloromethane for 4h;	1.4 4) Preparation of Compound I-1 In 1000mL flask equipped with a stirring device, vanilla amine 23g, 400mL methylene chloride, was stirred open, completely dissolved, dropwise addition of 43g (4E, 8E, 12E) -5,9,13- trimethyl -4 , 8,12- tetradecatrienoic acid chloride (dissolved in 80 mL dichloromethane), IH dropwise addition, the reaction temperature 4h, after completion of the reaction the reaction solution was extracted with 100mL water, wherein the acid-soluble, and the organic layer was dried over anhydrous sodium sulfate and spin dry using a mass fraction of 3.0% sodium hydroxide aqueous solution adjusted to pH 13 to 13.5, after stirring sufficiently solid was suction filtered, then diluted hydrochloric acid solution using 2mol / L of adjusting the pH of the filtrate to 9.0 to 9.5, at this time there are a lot of white powder appears, the suspension placed 3h at -5 ~ 0 , filtration, 60 ~ 65 vacuum dried to give a white powder with methyl isobutyl ketone - recrystallized from methanol to give compound I-148.1g, a yield of 80.2%, mp: 105 ~ 107 , HPLC content of 99.4%.

Reference： [1]Current Patent Assignee: ANHUI YIXINMING PHARMACEUTICAL TECH - CN105439889, 2016, A Location in patent: Paragraph 0034; 0035

54
[ 1196-92-5 ]
[ 179128-84-8 ]
C₂₃H₂₅NO₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane; N,N-dimethyl-formamide	Preparation of Caffeoyl Amides (1-4) General procedure: According to the general procedure for the preparation of cinnamic acid amides, 3,4-diallyloxy cinnamic acid (IIa)28) and the biogenic amines (2.0mmol) were treated with EDC (2.1mmol),HOBt (2.1 mmol) and Et3N (2.0 mmol), and then the residue was passed once through a short silica gel column (hexane:AcOEt=1:2) and the solvent was evaporated. The obtained allyl protected compound (1.0mmol) was dissolved in degassed anhydrated tetrahydrofuran (THF) (30 mL) and morpholine (20 mmol), and Pd(PPh3)4 (5mol%) was added. The green mixture was stirred at 50°C (monitored by TLC) and concentrated under reduced pressure.The residue was treated with NH4Cl solution and extracted with AcOEt. The organic layer was dried over Na2SO4 and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography(hexane:AcOEt=1:5)to give the title compound.

Reference： [1]Takao, Koichi; Toda, Kazuhiro; Saito, Takayuki; Sugita, Yoshiaki [Chemical and Pharmaceutical Bulletin, 2017, vol. 65, # 11, p. 1020 - 1027]

55
[ 1196-92-5 ]
[ 7400-08-0 ]
(2E)-N-[(4-hydroxy-3-methoxyphenyl)methyl]-3-(4-hydroxy phenyl)-2-propenamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	Stage #1: p-Coumaric Acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane; N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: Vanillylamin With triethylamine In dichloromethane; N,N-dimethyl-formamide at 20℃; Inert atmosphere;

Reference： [1]Takao, Koichi; Toda, Kazuhiro; Saito, Takayuki; Sugita, Yoshiaki [Chemical and Pharmaceutical Bulletin, 2017, vol. 65, # 11, p. 1020 - 1027]

56
[ 1196-92-5 ]
6-chloro-1-cyclopentyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one [ No CAS ]
1-cyclopentyl-6-((4-hydroxy-3-methoxybenzyl)amino)-1Hpyrazolo[3,4-d]pyrimidin-4(5H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
49%	With triethylamine In isopropyl alcohol at 80℃; for 1h;

Reference： [1]Yu, Yan-Fa; Huang, Ya-Dan; Zhang, Chen; Wu, Xu-Nian; Zhou, Qian; Wu, Deyan; Wu, Yinuo; Luo, Hai-Bin [ACS Chemical Neuroscience, 2017, vol. 8, # 11, p. 2522 - 2534]

57
[ 1196-92-5 ]
(R)-2-(2,4-bis(benzyloxy)-5-chlorobenzoyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid [ No CAS ]
C₃₉H₃₅ClN₂O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃;	1 4.2.1 (R)-2-(5-chloro-2,4-dihydroxybenzoyl)-N-(2-chlorobenzyl)-1,2,3,4-tetrahydro -3-isoquinolinecarboxamide (10) General procedure: The chiral monomer (R)-2-(2,4-bis(benzyloxy)-5-chlorobenzoyl)-1, 2,3,4-tetrahydroisoquinoline-3-carboxylic acid 9 (100 mg, 0.19 mmol), EDCI (43.7 mg, 0.228 mmol), HOBt (30.8 mg, 0.228 mmol) and 2-chloro benzylamine (0.15 mL, 1.2 mmol) in DMF (3 mL) was stirred overnight at room temperature. The organic layer was washed successively with 2 M HCl and 2 M NaOH, then dried over anhydrous/Na2SO4, filtered and evaporated under vacuum to afford a yellowish powder that was used for the next step reaction without further purification. To the anhydrous CH2Cl2 (3 mL) solution of this product cooled to 0 °C under N2 was added BCl3 (1.0 M in CH2Cl2, 0.57 mL, 0.56 mmol). The reaction mixture was allowed to warm to RT and stirred for 1.5 h. Sat. NaHCO3 solution (5 mL) was added and CH2Cl2 was removed under vacuum. The aqueous residue was extracted with EtOAc (4 x 10 mL) and evaporated under vacuum to produce a brown powder. The powder was purified by column chromatography over silica gel eluted with CH2Cl2-MeOH (30: 1, v/v) to give compound 10 (82.8 mg) as a white powder, yield: 91%.

Reference： [1]Liang, Chuanpeng; Wu, Xingkang; Li, Zhenyu; Zhu, Jing; Lu, Chunhua; Shen, Yuemao [European Journal of Medicinal Chemistry, 2018, vol. 143, p. 85 - 96]

58
[ 1196-92-5 ]
[ 88235-25-0 ]
C₂₀H₂₃N₅O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; benzotriazol-1-ol; dicyclohexyl-carbodiimide In N,N-dimethyl-formamide at 20℃; for 24h;	1 Example 1: Take 1 equivalent of compound I and 1 equivalent of R=(CH2)5 compound II,Soluble in DMF,Add 1 equivalent of HOBT,1 equivalent DCC, 0.1 equivalent DMAP,Stir at room temperature for 24 hours. Remove organic solvents,Column chromatography,Elution with dichloromethane:methanol = 10:1,The corresponding compound III is obtained.

Reference： [1]Current Patent Assignee: ZHEJIANG UNIVERSITY - CN105295896, 2017, B Location in patent: Paragraph 0046; 0047

59
[ 1196-92-5 ]
[ 96801-39-7 ]
C₂₆H₃₅N₅O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; benzotriazol-1-ol; dicyclohexyl-carbodiimide In N,N-dimethyl-formamide at 20℃; for 24h;	2 Example 2 One equivalent of compound I and one equivalent of R=(CH2)11 compound II are dissolved in DMF.Add 1 equivalent of HOBT, 1 equivalent of DCC, 0.1 equivalent of DMAP,Stir at room temperature for 24 hours.Remove organic solvents,Column chromatography,With dichloromethane:Methanol = 10:1 elutionThe corresponding compound III is obtained.

Reference： [1]Current Patent Assignee: ZHEJIANG UNIVERSITY - CN105295896, 2017, B Location in patent: Paragraph 0048; 0049

60
[ 1196-92-5 ]
C₁₀H₁₅ClO [ No CAS ]
C₁₈H₂₅NO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92.7%	With N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 30℃; Inert atmosphere; Large scale;	4-6 Example 4: Preparation of Zucapsaicin intermediate IV Under nitrogen protection,Neutralization of diisopropylethylamine 8.29 Kg (64.26 mol) and 3-methoxy-4-hydroxybenzylamine 9.05 Kg (59.08 mol) to 40 L of dichloromethane.Add Zucapsaicin intermediate III 10.0Kg (53.57mol,a mixture of GC purity 97.32%) and dichloromethane 30L,Stir at 20 to 30 ° C for 3 to 4 hours. Cool to 0 ~ 5 ° C under stirring 1~ 2 hours. filter,Rinse with dichloromethane and drain. The mother liquor is sequentially used with a mass concentration of 6% hydrochloric acid aqueous solution (the mass concentration refers to the mass of hydrogen chloride as a percentage of the total mass of the hydrochloric acid aqueous solution), and the mass concentration is 3% aqueous sodium carbonate solution.(The mass concentration refers to the mass of sodium carbonate as a percentage of the total mass of the sodium carbonate aqueous solution),The mass concentration is 7% aqueous solution of sodium hydrogencarbonate (the mass concentration refers to the mass of sodium hydrogencarbonate as a percentage of the total mass of the aqueous solution of sodium hydrogencarbonate),The mass concentration is 10% aqueous sodium chloride solution (the mass concentration refers to the mass of sodium chloride as a percentage of the total mass of the brine), and then stirred and allowed to stand.The water layer is separated. The organic layer is concentrated in vacuo (temperature 25 ° C ~ 45 ° C,Pressure -0.06MPa ~ -0.09MPa) remove most of the solvent,Add 30L of isopropyl ether, heat to 55-65 ° C, slowly add n-heptane 60L,Cool again to 0 to 5 ° C and stir for 2 to 3 hours. Centrifuge and rinse with n-heptane three times.Vacuum drying (vacuum degree -0.01MPa ~ -0.1MPa,Dry at 45-55 ° C for 12 to 16 hours,Obtained 15.08kg of Zucapsaicin intermediate IV, yield 92.7%,The HPLC purity was 99.32%.

Reference： [1]Current Patent Assignee: SHANGHAI BOCIMED PHARMACEUTICAL CO LTD - CN108947863, 2018, A Location in patent: Paragraph 0073-0079

61
[ 4421-08-3 ]
[ 1196-92-5 ]

Yield	Reaction Conditions	Operation in experiment
85%	With sodium tetrahydroborate; copper ferrite In water for 0.0833333h; Reflux; Green chemistry; chemoselective reaction;	General procedure for the reduction of nitriles to primary amines General procedure: As a representative example, in a round-bottom flask (15 mL) equipped with a magnetic stirrer, benzonitrile (1 mmol, 0.103 g) was dissolved in H2O (2 mL). Afterward, CuFe2O4 (0.2 mmol, 0.048 g) was added and the mixture was stirred. Then, NaBH4 (2 mmol, 0.076 g) was also added, and the resulting mixture continued to stir at reflux for 5 min. Upon completion of the reaction (monitored by TLC), the mixture was cooled to room temperature, and the catalyst was separated by an external magnet. The reaction mixture was extracted with ethyl acetate (EtOAc) (2 x 4 mL). The organic layers were combined together and dried over anhydrous sodium sulfate (Na2SO4). The solvent was evaporated under reduced pressure. The pure colorless liquid benzylamine was obtained in 95% yield.
81%	With sodium tetrahydroborate; nickel(II) acetate tetrahydrate In water at 50℃; for 0.2h;	3.2. General procedure for the reduction of arynitriles to corresponding primary amines General procedure: As a representative example, in a round-bottom flask (10 mL) equipped with a magnetic stirrer, benzonitrile (1 mmol) was dissolved in H2O (2 mL). Afterward, Ni(OAc)2•4H2O (50 mol%) was added, and the mixture was stirred. Then, NaBH4 (2 mmol) was added, and the resulting mixture was continued to stirring at 50 C for 12 min. Upon completion of the reaction (monitored by TLC), the mixture was cooled to room temperature, and then 5 mL of water was added to the reaction mixture and was stirred at room temperature for about 5-10 min. The reaction mixture was extracted with ethyl acetate (EtOAc) (2 × 4 mL). The organic layers were combined and dried over anhydrous sodium sulfate (Na2SO4). Next, the solvent was evaporated under reduced pressure, and subsequently, the pure colorless liquid benzylamine was obtained in 89% yield

Reference： [1]Zeynizadeh, Behzad; Mohammad Aminzadeh, Farkhondeh; Mousavi, Hossein [Research on Chemical Intermediates, 2019]
[2]Mohammad Aminzadeh, Farkhondeh; Mousavi, Hossein; Zeynizadeh, Behzad [Journal of Molecular Structure, 2022, vol. 1255]

62
[ 1196-92-5 ]
[ 100-28-7 ]
1-(4-hydroxy-3-methoxybenzyl)-3-(4-nitrophenyl)urea [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
48%	With triethylamine In methanol; dichloromethane at 20℃; for 4h; Inert atmosphere;	4.1.1.2. Synthesis of derivatives 7a-7g and 8a-8f General procedure: Vanillylamine(1.1 mmol) and triethylamine (1 mmol) were diluted in 40 mL ofdichloromethane:methanol (DCM:MeOH - 8:2) in a 100 mL doubleneck round bottom flask coupled with an addition funnel of 50 mL.Isocyanate (1 mmol) or isothiocyanate (1 mmol) was dissolved in DCM(5 mL) and added dropwise to the solution of vanillylamine. Themixture was kept under stirring in nitrogen atmosphere for 4 h. Then,the solvent was evaporated under reduced pressure and the product waspurified by recrystallization.

Reference： [1]Pereira, Gustavo José Vasco; Tavares, Maurício Temotheo; Azevedo, Ricardo Alexandre; Martins, Barbara Behr; Cunha, Micael Rodrigues; Bhardwaj, Rajesh; Cury, Yara; Zambelli, Vanessa Olzon; Barbosa, Euzébio Guimarães; Hediger, Matthias A.; Parise-Filho, Roberto [Bioorganic and Medicinal Chemistry, 2019, vol. 27, # 13, p. 2893 - 2904]

63
[ 1196-92-5 ]
[ 104-12-1 ]
1-(4-chlorophenyl)-3-(4-hydroxy-3-methoxybenzyl)urea [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
59%	With triethylamine In methanol; dichloromethane at 20℃; for 4h; Inert atmosphere;	4.1.1.2. Synthesis of derivatives 7a-7g and 8a-8f General procedure: Vanillylamine(1.1 mmol) and triethylamine (1 mmol) were diluted in 40 mL ofdichloromethane:methanol (DCM:MeOH - 8:2) in a 100 mL doubleneck round bottom flask coupled with an addition funnel of 50 mL.Isocyanate (1 mmol) or isothiocyanate (1 mmol) was dissolved in DCM(5 mL) and added dropwise to the solution of vanillylamine. Themixture was kept under stirring in nitrogen atmosphere for 4 h. Then,the solvent was evaporated under reduced pressure and the product waspurified by recrystallization.

Reference： [1]Pereira, Gustavo José Vasco; Tavares, Maurício Temotheo; Azevedo, Ricardo Alexandre; Martins, Barbara Behr; Cunha, Micael Rodrigues; Bhardwaj, Rajesh; Cury, Yara; Zambelli, Vanessa Olzon; Barbosa, Euzébio Guimarães; Hediger, Matthias A.; Parise-Filho, Roberto [Bioorganic and Medicinal Chemistry, 2019, vol. 27, # 13, p. 2893 - 2904]

64
[ 1196-92-5 ]
[ 5416-93-3 ]
1-(4-hydroxy-3-methoxybenzyl)-3-(4-methoxyphenyl)urea [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%	With triethylamine In methanol; dichloromethane at 20℃; for 4h; Inert atmosphere;	4.1.1.2. Synthesis of derivatives 7a-7g and 8a-8f General procedure: Vanillylamine(1.1 mmol) and triethylamine (1 mmol) were diluted in 40 mL ofdichloromethane:methanol (DCM:MeOH - 8:2) in a 100 mL doubleneck round bottom flask coupled with an addition funnel of 50 mL.Isocyanate (1 mmol) or isothiocyanate (1 mmol) was dissolved in DCM(5 mL) and added dropwise to the solution of vanillylamine. Themixture was kept under stirring in nitrogen atmosphere for 4 h. Then,the solvent was evaporated under reduced pressure and the product waspurified by recrystallization.

Reference： [1]Pereira, Gustavo José Vasco; Tavares, Maurício Temotheo; Azevedo, Ricardo Alexandre; Martins, Barbara Behr; Cunha, Micael Rodrigues; Bhardwaj, Rajesh; Cury, Yara; Zambelli, Vanessa Olzon; Barbosa, Euzébio Guimarães; Hediger, Matthias A.; Parise-Filho, Roberto [Bioorganic and Medicinal Chemistry, 2019, vol. 27, # 13, p. 2893 - 2904]

65
[ 1196-92-5 ]
[ 622-58-2 ]
1-(4-hydroxy-3-methoxybenzyl)-3-(p-tolyl)urea [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	With triethylamine In methanol; dichloromethane at 20℃; for 4h; Inert atmosphere;	4.1.1.2. Synthesis of derivatives 7a-7g and 8a-8f General procedure: Vanillylamine(1.1 mmol) and triethylamine (1 mmol) were diluted in 40 mL ofdichloromethane:methanol (DCM:MeOH - 8:2) in a 100 mL doubleneck round bottom flask coupled with an addition funnel of 50 mL.Isocyanate (1 mmol) or isothiocyanate (1 mmol) was dissolved in DCM(5 mL) and added dropwise to the solution of vanillylamine. Themixture was kept under stirring in nitrogen atmosphere for 4 h. Then,the solvent was evaporated under reduced pressure and the product waspurified by recrystallization.

Reference： [1]Pereira, Gustavo José Vasco; Tavares, Maurício Temotheo; Azevedo, Ricardo Alexandre; Martins, Barbara Behr; Cunha, Micael Rodrigues; Bhardwaj, Rajesh; Cury, Yara; Zambelli, Vanessa Olzon; Barbosa, Euzébio Guimarães; Hediger, Matthias A.; Parise-Filho, Roberto [Bioorganic and Medicinal Chemistry, 2019, vol. 27, # 13, p. 2893 - 2904]

66
[ 1196-92-5 ]
[ 111-36-4 ]
1-butyl-3-(4-hydroxy-3-methoxybenzyl)urea [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
20%	With triethylamine In methanol; dichloromethane at 20℃; for 4h; Inert atmosphere;	4.1.1.2. Synthesis of derivatives 7a-7g and 8a-8f General procedure: Vanillylamine(1.1 mmol) and triethylamine (1 mmol) were diluted in 40 mL ofdichloromethane:methanol (DCM:MeOH - 8:2) in a 100 mL doubleneck round bottom flask coupled with an addition funnel of 50 mL.Isocyanate (1 mmol) or isothiocyanate (1 mmol) was dissolved in DCM(5 mL) and added dropwise to the solution of vanillylamine. Themixture was kept under stirring in nitrogen atmosphere for 4 h. Then,the solvent was evaporated under reduced pressure and the product waspurified by recrystallization.

Reference： [1]Pereira, Gustavo José Vasco; Tavares, Maurício Temotheo; Azevedo, Ricardo Alexandre; Martins, Barbara Behr; Cunha, Micael Rodrigues; Bhardwaj, Rajesh; Cury, Yara; Zambelli, Vanessa Olzon; Barbosa, Euzébio Guimarães; Hediger, Matthias A.; Parise-Filho, Roberto [Bioorganic and Medicinal Chemistry, 2019, vol. 27, # 13, p. 2893 - 2904]

67
[ 1196-92-5 ]
[ 2525-62-4 ]
1-hexyl-3-(4-hydroxy-3-methoxybenzyl)urea [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
42%	With triethylamine In methanol; dichloromethane at 20℃; for 4h; Inert atmosphere;	4.1.1.2. Synthesis of derivatives 7a-7g and 8a-8f General procedure: Vanillylamine(1.1 mmol) and triethylamine (1 mmol) were diluted in 40 mL ofdichloromethane:methanol (DCM:MeOH - 8:2) in a 100 mL doubleneck round bottom flask coupled with an addition funnel of 50 mL.Isocyanate (1 mmol) or isothiocyanate (1 mmol) was dissolved in DCM(5 mL) and added dropwise to the solution of vanillylamine. Themixture was kept under stirring in nitrogen atmosphere for 4 h. Then,the solvent was evaporated under reduced pressure and the product waspurified by recrystallization.

Reference： [1]Pereira, Gustavo José Vasco; Tavares, Maurício Temotheo; Azevedo, Ricardo Alexandre; Martins, Barbara Behr; Cunha, Micael Rodrigues; Bhardwaj, Rajesh; Cury, Yara; Zambelli, Vanessa Olzon; Barbosa, Euzébio Guimarães; Hediger, Matthias A.; Parise-Filho, Roberto [Bioorganic and Medicinal Chemistry, 2019, vol. 27, # 13, p. 2893 - 2904]

68
[ 1196-92-5 ]
[ 2131-61-5 ]
1-(4-hydroxy-3-methoxybenzyl)-3-(4-nitrophenyl)thiourea [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
39%	With triethylamine In methanol; dichloromethane at 20℃; for 4h; Inert atmosphere;	4.1.1.2. Synthesis of derivatives 7a-7g and 8a-8f General procedure: Vanillylamine(1.1 mmol) and triethylamine (1 mmol) were diluted in 40 mL ofdichloromethane:methanol (DCM:MeOH - 8:2) in a 100 mL doubleneck round bottom flask coupled with an addition funnel of 50 mL.Isocyanate (1 mmol) or isothiocyanate (1 mmol) was dissolved in DCM(5 mL) and added dropwise to the solution of vanillylamine. Themixture was kept under stirring in nitrogen atmosphere for 4 h. Then,the solvent was evaporated under reduced pressure and the product waspurified by recrystallization.

Reference： [1]Pereira, Gustavo José Vasco; Tavares, Maurício Temotheo; Azevedo, Ricardo Alexandre; Martins, Barbara Behr; Cunha, Micael Rodrigues; Bhardwaj, Rajesh; Cury, Yara; Zambelli, Vanessa Olzon; Barbosa, Euzébio Guimarães; Hediger, Matthias A.; Parise-Filho, Roberto [Bioorganic and Medicinal Chemistry, 2019, vol. 27, # 13, p. 2893 - 2904]

69
[ 1196-92-5 ]
[ 2131-55-7 ]
1-(4-chlorophenyl)-3-(4-hydroxy-3-methoxybenzyl)thiourea [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
51%	With triethylamine In methanol; dichloromethane at 20℃; for 4h; Inert atmosphere;	4.1.1.2. Synthesis of derivatives 7a-7g and 8a-8f General procedure: Vanillylamine(1.1 mmol) and triethylamine (1 mmol) were diluted in 40 mL ofdichloromethane:methanol (DCM:MeOH - 8:2) in a 100 mL doubleneck round bottom flask coupled with an addition funnel of 50 mL.Isocyanate (1 mmol) or isothiocyanate (1 mmol) was dissolved in DCM(5 mL) and added dropwise to the solution of vanillylamine. Themixture was kept under stirring in nitrogen atmosphere for 4 h. Then,the solvent was evaporated under reduced pressure and the product waspurified by recrystallization.

Reference： [1]Pereira, Gustavo José Vasco; Tavares, Maurício Temotheo; Azevedo, Ricardo Alexandre; Martins, Barbara Behr; Cunha, Micael Rodrigues; Bhardwaj, Rajesh; Cury, Yara; Zambelli, Vanessa Olzon; Barbosa, Euzébio Guimarães; Hediger, Matthias A.; Parise-Filho, Roberto [Bioorganic and Medicinal Chemistry, 2019, vol. 27, # 13, p. 2893 - 2904]

70
[ 1196-92-5 ]
[ 2284-20-0 ]
1-(4-hydroxy-3-methoxybenzyl)-3-(4-methoxyphenyl)thiourea [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56%	With triethylamine In methanol; dichloromethane at 20℃; for 4h; Inert atmosphere;	4.1.1.2. Synthesis of derivatives 7a-7g and 8a-8f General procedure: Vanillylamine(1.1 mmol) and triethylamine (1 mmol) were diluted in 40 mL ofdichloromethane:methanol (DCM:MeOH - 8:2) in a 100 mL doubleneck round bottom flask coupled with an addition funnel of 50 mL.Isocyanate (1 mmol) or isothiocyanate (1 mmol) was dissolved in DCM(5 mL) and added dropwise to the solution of vanillylamine. Themixture was kept under stirring in nitrogen atmosphere for 4 h. Then,the solvent was evaporated under reduced pressure and the product waspurified by recrystallization.

Reference： [1]Pereira, Gustavo José Vasco; Tavares, Maurício Temotheo; Azevedo, Ricardo Alexandre; Martins, Barbara Behr; Cunha, Micael Rodrigues; Bhardwaj, Rajesh; Cury, Yara; Zambelli, Vanessa Olzon; Barbosa, Euzébio Guimarães; Hediger, Matthias A.; Parise-Filho, Roberto [Bioorganic and Medicinal Chemistry, 2019, vol. 27, # 13, p. 2893 - 2904]

71
[ 1196-92-5 ]
[ 622-59-3 ]
1-(4-hydroxy-3-methoxybenzyl)-3-(p-tolyl)thiourea [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
48%	With triethylamine In methanol; dichloromethane at 20℃; for 4h; Inert atmosphere;	4.1.1.2. Synthesis of derivatives 7a-7g and 8a-8f General procedure: Vanillylamine(1.1 mmol) and triethylamine (1 mmol) were diluted in 40 mL ofdichloromethane:methanol (DCM:MeOH - 8:2) in a 100 mL doubleneck round bottom flask coupled with an addition funnel of 50 mL.Isocyanate (1 mmol) or isothiocyanate (1 mmol) was dissolved in DCM(5 mL) and added dropwise to the solution of vanillylamine. Themixture was kept under stirring in nitrogen atmosphere for 4 h. Then,the solvent was evaporated under reduced pressure and the product waspurified by recrystallization.

Reference： [1]Pereira, Gustavo José Vasco; Tavares, Maurício Temotheo; Azevedo, Ricardo Alexandre; Martins, Barbara Behr; Cunha, Micael Rodrigues; Bhardwaj, Rajesh; Cury, Yara; Zambelli, Vanessa Olzon; Barbosa, Euzébio Guimarães; Hediger, Matthias A.; Parise-Filho, Roberto [Bioorganic and Medicinal Chemistry, 2019, vol. 27, # 13, p. 2893 - 2904]

72
[ 1196-92-5 ]
[ 592-82-5 ]
N-(4-hydroxy-3-methoxybenzyl)-N'-hexylthiourea [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
22%	With triethylamine In methanol; dichloromethane at 20℃; for 4h; Inert atmosphere;	4.1.1.2. Synthesis of derivatives 7a-7g and 8a-8f General procedure: Vanillylamine(1.1 mmol) and triethylamine (1 mmol) were diluted in 40 mL ofdichloromethane:methanol (DCM:MeOH - 8:2) in a 100 mL doubleneck round bottom flask coupled with an addition funnel of 50 mL.Isocyanate (1 mmol) or isothiocyanate (1 mmol) was dissolved in DCM(5 mL) and added dropwise to the solution of vanillylamine. Themixture was kept under stirring in nitrogen atmosphere for 4 h. Then,the solvent was evaporated under reduced pressure and the product waspurified by recrystallization.

Reference： [1]Pereira, Gustavo José Vasco; Tavares, Maurício Temotheo; Azevedo, Ricardo Alexandre; Martins, Barbara Behr; Cunha, Micael Rodrigues; Bhardwaj, Rajesh; Cury, Yara; Zambelli, Vanessa Olzon; Barbosa, Euzébio Guimarães; Hediger, Matthias A.; Parise-Filho, Roberto [Bioorganic and Medicinal Chemistry, 2019, vol. 27, # 13, p. 2893 - 2904]

73
[ 1196-92-5 ]
C₁₉H₁₆F₃NO₂ [ No CAS ]
N-(4-hydroxy-3-methoxybenzyl)-2,3-dimethyl-1-(3-(trifluoromethyl)benzyl)-1H-indole-5-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: C₁₉H₁₆F₃NO₂ With N-ethyl-N,N-diisopropylamine; HATU In dichloromethane for 0.0833333h; Stage #2: Vanillylamin In dichloromethane at 20℃; for 0.5h;	General procedure: Aminoacid coupling General procedure: To a mixtureof the acid (1eq) in DCM was added DIEA (10 equivalents) and HATU (1equivalents). The mixture was stirred for 5 min, and then the appropriate amine(1 equivalents) was added. The reaction mixture was stirred at room temperaturefor 30 min. The completion of the reaction was monitored by TLC. The solventwas removed in vacuo to obtain the crude which was purified by flash chromatographyto provide product.

Reference： [1]Eeda, Venkateswararao; Wu, Dan; Lim, Hui-Ying; Wang, Weidong [Bioorganic and Medicinal Chemistry Letters, 2019, vol. 29, # 22]

74
[ 1196-92-5 ]
1-((2'-carboxy-[1,1'-biphenyl]-4-yl)methyl)-2,3-dimethyl-1H-indole-5-carboxylic acid [ No CAS ]
4'-((5-((4-hydroxy-3-methoxybenzyl)carbamoyl)-2,3-dimethyl-1H-indol-1-yl)methyl)-[1,1'-biphenyl]-2-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 1-((2'-carboxy-[1,1'-biphenyl]-4-yl)methyl)-2,3-dimethyl-1H-indole-5-carboxylic acid With N-ethyl-N,N-diisopropylamine; HATU In dichloromethane for 0.0833333h; Stage #2: Vanillylamin In dichloromethane at 20℃; for 0.5h;	General procedure: Aminoacid coupling General procedure: To a mixtureof the acid (1eq) in DCM was added DIEA (10 equivalents) and HATU (1equivalents). The mixture was stirred for 5 min, and then the appropriate amine(1 equivalents) was added. The reaction mixture was stirred at room temperaturefor 30 min. The completion of the reaction was monitored by TLC. The solventwas removed in vacuo to obtain the crude which was purified by flash chromatographyto provide product.

Reference： [1]Eeda, Venkateswararao; Wu, Dan; Lim, Hui-Ying; Wang, Weidong [Bioorganic and Medicinal Chemistry Letters, 2019, vol. 29, # 22]

75
[ 1196-92-5 ]
[ 5963-14-4 ]
[ 19408-84-5 ]

Yield	Reaction Conditions	Operation in experiment
88%	With triethyl borate In toluene for 4h; Dean-Stark; Reflux; Green chemistry;	5-6 Example 5 This embodiment provides a method for preparing dihydrocapsaicin, which specifically includes the following steps:1) A 100ml three-necked bottle with water separator (connected to the condenser tube), magnetic stirrer and thermometer;Add 1.50g vanillylamine, 1.96g 8-methylnonanoic acid, 1.46g triethyl borate and 30ml toluene in sequence;2) Stir and heat to reflux water separation reaction for 4 hours; change the water separation device to a distillation device, and distill the solvent and triethyl borate at atmospheric pressure;3) The residue was dissolved in 40ml ethyl acetate, washed successively with 20ml dilute hydrochloric acid and 20ml water, dried over Na2SO4 and the solvent was removed under reduced pressure. The residue was added with 20ml n-hexane, stirred at room temperature for 3h, filtered and dried to obtain 2.7g white solid.Yield: 88%; HPLC purity 99.5%.
83%	In ethanol at 50℃;	2.1-2.3 Vanillin is reductively amination to obtain 20g vanillin-catalyst-water solid mixture (containing vanillin 8.5g), mixed with 2g industrial alcohol and 9.8g 8-methylnonanoic acid, and heated to 50°C under stirring,All vanillin solids are dissolved, and a clear liquid containing catalyst solids is obtained.2) The catalyst is removed by magnetic filtration, and the remaining mother liquor is cooled to below 5°C for crystallization.3) Filter, wash the solid with cold water, and dry to obtain 15g vanillyl amine 8-methylnonanoate solid,The yield was 83%.
82%	With SiO₂-H₃BO₃ In toluene for 6h; Reflux;	7; 8 Example 8 This embodiment provides a method for preparing dihydrocapsaicin by using SiO2-H3BO3 catalyst repeatedly.Specifically, the following steps are included1) Add 5.00 g of vanillin free base,5.62g 8-methyl decanoic acid,Example 7 recovered SiO2-H3BO3 catalyst and 100 ml of toluene,Add 0.05 g of the catalyst prepared in the above Example 4The rest of the reaction steps were the same as in Example 7.Yield of dihydrocapsaicin product: 82%HPLC purity of dihydrocapsaicin product: 99.0%

With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In octane at 90℃; for 15h; Inert atmosphere;

1; 3; 6; 8-9 Mix 8-methylnonanoic acid, vanillylamine, DMAP, EDC and n-octane,Stir the temperature to 90°C in a nitrogen atmosphere, keep it warm for 15 hours, and cool to room temperature.Wash with deionized water, extract with chloroform, dry the extract and spin dry.The obtained dihydrocapsaicin is measured by high-purity liquid chromatography (HPLC),Its purity is 98%.

Reference： [1]Current Patent Assignee: SUINING JINGAN TECH - CN113024398, 2021, A Location in patent: Paragraph 0037; 0127-0140
[2]Current Patent Assignee: SUINING JINGAN TECH - CN112608247, 2021, A Location in patent: Paragraph 0124-0128
[3]Current Patent Assignee: Liu Xiaozhen - CN110305031, 2019, A Location in patent: Paragraph 0153-0167
[4]Current Patent Assignee: CHINESE ACADEMY OF SCIENCES; USTC (in: CAS) - CN111187161, 2020, A Location in patent: Paragraph 0084; 0088-0092; 0101; 0104-0106; 0119; 0122-0124

76
[ 1196-92-5 ]
[ 741265-23-6 ]
2-((5-chloro-2-methylphenyl)amino)-N-(4-hydroxy-3-methoxybenzyl)-6-(trifluoromethyl)nicotinamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	Stage #1: 2-(5-chloro-2-methyl-phenylamino)-6-trifluoromethyl-nicotinic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In acetonitrile at 20℃; for 0.5h; Stage #2: Vanillylamin In acetonitrile at 20℃; for 24h;	4.1.2. General Procedure for the Synthesis of Amides (25-52) General procedure: A mixture of acid 10 (0.33 g, 1 mmol), EDCI (1.92 g, 1.1 mmol), and HOBt (0.13 g, 1 mmol) in dry MeCN (10 mL) was stirred at room temperature for 30 min and then treated with the appropriate amine (1 mmol). The mixture was stirred at room temperature for an additional 24 h. Then the solution was evaporated to dryness in vacuo. The residue was dissolved in ethyl acetate (20 mL) and washed sequentially with brine (2 x 5 mL), 10% aqueous sodium carbonate (2 x 5 mL), 10% aqueous citric acid(2 x 5 mL), and water (2 x 5 mL). The organic layer was dried over anhydrous magnesium sulfate. Concentration of the dried extracts yielded a solid residue which was washed with ethyl ether, filteredoff, and dried to give the amide derivatives in analytically pure form without additional purificationby crystallization if not elsewhere indicated.

Reference： [1]Cheng, Yung-Chi; Corona, Angela; Del Vecchio, Claudia; Esposito, Francesca; Onnis, Valentina; Tramontano, Enzo [Molecules, 2020, vol. 25, # 6]

77
1-acetyl-9H-β-carboline-3-carboxylic acid [ No CAS ]
[ 1196-92-5 ]
C₂₂H₁₉N₃O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
>99 %Chromat.	With ATP In aq. phosphate buffer at 37℃; for 16h; Enzymatic reaction;

Reference： [1]Fairlamb, Ian J. S.; Grogan, Gideon; Lloyd, Richard C.; Petchey, Mark R.; Rowlinson, Benjamin [ACS Catalysis, 2020, vol. 10, # 8, p. 4659 - 4663]

78
[ 1196-92-5 ]
[ 473257-46-4 ]
5-chloro-3-((3,5-dimethylphenyl)sulfonyl)-N-(4-hydroxy-3-methoxybenzyl)-1H-indole-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66%	With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; triethylamine In N,N-dimethyl-formamide at 25℃; for 12h;	5.1.12 5-Chloro-3-((3,5-dimethylphenyl)sulfonyl)-N-(4-hydroxy-3-methoxybenzyl)-1H-indole-2-carboxamide (22) General procedure: A mixture of 30 [19] (100mg, 0.27mmol), 2-(aminomethyl)phenol (100mg, 0.82mmol), triethylamine (55mg, 0.11mL, 0.54mmol), and benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (143mg, 0.27mmol) in anhydrous N,N-dimethylformamide (5mL) was stirred at 25°C for 12h, diluted with water and extracted with ethyl acetate. The organic layer was washed with brine, dried and filtered. Removal of the solvent gave a residue that was purified by column chromatography (silica gel, ethyl acetate:n-hexane=1:2 as eluent) to furnish 12 (35mg, 28%), mp 252°C (from ethanol).

Reference： [1]Nalli, Marianna; Armijos Rivera, Jorge I.; Masci, Domiziana; Coluccia, Antonio; Badia, Roger; Riveira-Muñoz, Eva; Brambilla, Alessandro; Cinquina, Elisabetta; Turriziani, Ombretta; Falasca, Francesca; Catalano, Myriam; Limatola, Cristina; Esté, José A.; Maga, Giovanni; Silvestri, Romano; Crespan, Emmanuele; La Regina, Giuseppe [European Journal of Medicinal Chemistry, 2020, vol. 208]

79
[ 1196-92-5 ]
[ 622-78-6 ]
1-benzyl-3-(4-hydroxy-3-methoxybenzyl)-thiourea [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In dichloromethane at 0℃; for 3h; Inert atmosphere;	General preparation of ureas/ thioureas derivatives (4-15) General procedure: Isothiocyanate/ isocyanate derivatives (1mmol) were added dropwise to a solution of appropriate substituted amine (1 mmol)/ Phenylhydrazine derivatives (1.2mmol) in dichloromethane (20 ml) with stirring under nitrogen. Triethylamine was added (0.1ml) and the reaction mixture was stirred at 0°C for 3h. The solution mixture was evaporated under vacuum, and the residue was purified by column chromatography on silica gel 97:3 (dichloromethane / methanol) to give 4-15. 1-Benzyl-3-(4-hydroxy-3-methoxy-benzyl)-thiourea (4) : White solid, Yields; m.p. 80-82. 1H NMR (CDCl3) d ppm; 3.84 (s, 3H, OCH3), 4.53 (s, 2H, CH2), 4.64 (s, 2H, CH2), 5.60 (s, 1H, NH D2O exch.), 6.20 (s, 1H, NH D2O exch.), 6.74(d, 1H, J =7.3Hz, C-5`H), 6.77 (d, 1H, J =7.5Hz, C-6`H), 6.79 (s, 1H, C-2H), 7.29 (d, 2H, J =7.7Hz C-2H, C-6H), 7.34 (t, 1H, J =7.5 Hz, C-4H), 7.38 (d, 2H, C-3H, J =7.7Hz, C-5H), 9.97 (s, 1H, OH). 13C NMR (CDCl3)d ppm;48.92 (2xCH2), 55.92 (OCH3), 110.29 (C-2), 114.33 (C -5`), 120.66 (C-6), 123.75(C-4), 125.76 (C-2, C-6), 128.87 (C-3, C-5), 129.08 (C-1`), 136.90 (C-1), 145.42 (C-3), 146.88 (C-4), 182.64 (C=S). MS m/z calculated 302.39, found 303 [M+1]. Analysis calc. for C16H18 N2O2S. C, 63.55; H, 6.00; N, 9.26; Found: C, 63.35; H, 6.19; N; 9.54

Reference： [1]Elseginy, Samia A.; Hamdy, Rania; Menon, Varsha; Almehdi, Ahmed M.; El-Awady, Raafat; Soliman, Sameh S.M. [Bioorganic and Medicinal Chemistry Letters, 2020, vol. 30, # 24]

80
[ 1196-92-5 ]
[ 107624-53-3 ]
N-(4-hydroxy-3-methoxybenzyl)-1-methyl-9H-carbazole-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In N,N-dimethyl-formamide at 20℃;	4.6 General synthetic procedure for the target compounds 8a-l General procedure: The typical process for the synthesis of target carbazole amides 8a-l is shown as following: To a solution of multi-substituted carbazole-2-carboxylic acid 5a-b (1mmol) in DMF (5mL), HOBt (1.5mmol), EDCI (1.5mmol), Et3N (2mmol) and appropriate substituted amine (1.2mmol) was added, and then the mixture were stirred at room temperature overnight. After the completion of reaction, the water was added to the mixture, and which was extracted with ethyl acetate, and the organic layer was washed with water and brine, and dried with anhydrous Na2SO4. The solvent was removed to give crude target compounds, and which were purified by silica gel column-chromatography (ethyl acetate/petroleum ether) or recrystallization to give pure compounds. All the compounds were characterized by ESI-MS, 1H NMR, 13C NMR and HRMS spectroscopic data, and their physico-chemical properties and spectra data are as follows:
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In N,N-dimethyl-formamide at 20℃;

Reference： [1]Huang, Wenbo; Gao, Zilin; Zhang, Zhigang; Fang, Wei; Wang, Zuoqian; Wan, Zhongyi; Shi, Liqiao; Wang, Kaimei; Ke, Shaoyong [Bioorganic Chemistry, 2021, vol. 113]
[2]Feng, Hui; Huang, Wenbo; Ke, Shaoyong; Li, Feng; Liu, Sisi; Lu, Xu; Wei, Dengguo; Yang, Wanneng; Ye, Junli; Zhang, Xianpeng [Journal of Agricultural and Food Chemistry, 2021, vol. 69, # 26, p. 7458 - 7466]

81
[ 1196-92-5 ]
1,9-dimethyl-9H-carbazole-2-carboxylic acid [ No CAS ]
N-(4-hydroxy-3-methoxybenzyl)-1,9-dimethyl-9H-carbazole-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In N,N-dimethyl-formamide at 20℃;	4.6 General synthetic procedure for the target compounds 8a-l General procedure: The typical process for the synthesis of target carbazole amides 8a-l is shown as following: To a solution of multi-substituted carbazole-2-carboxylic acid 5a-b (1mmol) in DMF (5mL), HOBt (1.5mmol), EDCI (1.5mmol), Et3N (2mmol) and appropriate substituted amine (1.2mmol) was added, and then the mixture were stirred at room temperature overnight. After the completion of reaction, the water was added to the mixture, and which was extracted with ethyl acetate, and the organic layer was washed with water and brine, and dried with anhydrous Na2SO4. The solvent was removed to give crude target compounds, and which were purified by silica gel column-chromatography (ethyl acetate/petroleum ether) or recrystallization to give pure compounds. All the compounds were characterized by ESI-MS, 1H NMR, 13C NMR and HRMS spectroscopic data, and their physico-chemical properties and spectra data are as follows:

Reference： [1]Huang, Wenbo; Gao, Zilin; Zhang, Zhigang; Fang, Wei; Wang, Zuoqian; Wan, Zhongyi; Shi, Liqiao; Wang, Kaimei; Ke, Shaoyong [Bioorganic Chemistry, 2021, vol. 113]

82
[ 1196-92-5 ]
[ 123-38-6 ]
[ 27246-51-1 ]

Yield	Reaction Conditions	Operation in experiment
96%	With indium(III) chloride; oxygen; ferric nitrate at 30℃; for 0.5h; Schlenk technique;	12 Example 12: N-vanillylpropionamide Add 0.12g iron nitrate (0.5mmol), 0.11g indium trichloride (0.5mmol) and 50mL trifluoromethylbenzene into the schlenk reaction tube, and stir for 30 minutes; add 0.87g propionaldehyde (15mmol) and 1.53g vanillylamine (10mmol), plug in a pure oxygen bag, ventilate 3 times, put the reaction tube in a 30°C constant temperature oil bath, and stir to react.The reaction was detected by TLC until the reaction was complete. The reaction solution was filtered through a sand core funnel filled with silica gel, washed with ethyl acetate, and the organic phases were combined and concentrated to obtain a crude product. The crude product was subjected to silica gel column chromatography (ethyl acetate: petroleum Ether = 15:1) purification to obtain the corresponding N-vanillylpropionamide 2g, yield 96%;

Reference： [1]Current Patent Assignee: SUZHOU HUADAO BIOLOGICAL PHARMACY - CN112939800, 2021, A Location in patent: Paragraph 0083-0086

83
[ 1196-92-5 ]
[ 64-17-5 ]
[ 53527-04-1 ]

Yield	Reaction Conditions	Operation in experiment
96%	With indium(III) chloride; oxygen; ferric nitrate at 30℃; for 0.5h; Schlenk technique;	1 Example 1: Synthesis of N-acetate vanillylamide Add 0.24g iron nitrate (1mmol), 0.22g indium trichloride (1mmol) and 50mL trifluoromethylbenzene into the schlenk reaction tube, and stir for 30 minutes; add 0.69g ethanol (15mmol) and 1.53g vanillylamine(10mmol) , plug in the pure oxygen bag, pump and ventilate 3 times, put the reaction tube in a 30°C constant temperature oil bath, and stir the reaction.TLC detects the reaction until the reaction is complete. The reaction solution is filtered through a sand core funnel filled with silica gel, washed with ethyl acetate, and the organic phases are combined and concentrated to obtain a crude product. The crude product is subjected to silica gel column chromatography (the eluent is acetic acid). Ethyl: Petroleum ether = 15:1) purify to obtain the corresponding N-acetic acid vanillamide 1.87g, the yield is 96%;

Reference： [1]Current Patent Assignee: SUZHOU HUADAO BIOLOGICAL PHARMACY - CN112939800, 2021, A Location in patent: Paragraph 0049-0052

84
1-(1H-indol-3-ylcarbonyl)-9H-pyrido[3,4-b]indole-3-carboxylic acid [ No CAS ]
[ 1196-92-5 ]
N-(4-hydroxy-3-methoxybenzyl)-1-(1H-indole-3-carbonyl)-9H-pyrido[3,4-b]indole-3-carboxamid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In N,N-dimethyl-formamide at 20℃;
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In N,N-dimethyl-formamide at 20℃;	3.3. General synthesis of carboline derivatives General procedure: All the carboline derivatives were efficiently prepared using a similarmethod reported in our previous research, and their basic physicochemicalproperties and spectra data were consistent with the literature(Xu et al., 2019)

Reference： [1]Zhou, Shiyang; Huang, Gangliang; Chen, Guangying [Bioorganic and Medicinal Chemistry Letters, 2021, vol. 41]
[2]Huang, Daye; Zhang, Zhigang; Li, Yanyan; Liu, Fang; Huang, Wenbo; Min, Yong; Wang, Kaimei; Yang, Jingzhong; Cao, Chunxia; Gong, Yan; Ke, Shaoyong [Phytochemistry Letters, 2022, vol. 48, p. 100 - 105]

85
[ 793695-77-9 ]
[ 1196-92-5 ]
ethyl (3aR,3bS,4aS,5R,5aS)-5-(6-((4-hydroxy-3-methoxybenzyl)amino)-2-iodo-9H-purin-9-yl)-2,2-dimethyltetrahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxole-3b(3aH)-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	With N-ethyl-N,N-diisopropylamine In isopropyl alcohol at 20℃;	4.1.2.27. Ethyl (3aR,3bS,4aS,5R,5aS)-5-(2-iodo-6-(phenethylamino)-9H-purin-9-yl)-2,2-dimethyltetrahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxole-3b(3aH)-carboxylate (41) General procedure: 2-Phenylethylamine (88 mL, 0.14 mmol) and DIPEA (0.25 mL,0.7 mmol) were added to a solution of compound 40 (71 mg,0.14 mmol) in isopropanol (2 mL) and the mixture stirred at roomtemperature overnight. Solventwas evaporated under vacuum, andthe residue was purified on flash silica gel column chromatography(hexane:ethyl acetate 2:1) to give the compound 41 (80 mg, 96%)as colorless foamy solid.

Reference： [1]Auchampach, John A.; Bitant, Amelia; Campbell, Ryan G.; Gao, Zhan-Guo; Gavrilova, Oksana; Jacobson, Kenneth A.; Liu, Naili; Pottie, Eline; Rao, Harsha; Salmaso, Veronica; Stove, Christophe P.; Tosh, Dilip K. [European Journal of Medicinal Chemistry, 2022, vol. 228]

86
[ 1196-92-5 ]
ethyl 3-formyl-1-(4-methoxybenzyl)-6-methyl-1H-indole-2-carboxylate [ No CAS ]
ethyl 3-(((4-hydroxy-3-methoxybenzyl)amino)methyl)-1-(4-methoxybenzyl)-6-methyl-1H-indole-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol at 20℃;	1.4 General synthetic procedures of step 4 General procedure: Taking the synthesis of C10e as an example. To a solution of anhydrous ethanol (10 mL)were added C10d (1 mmol), substituted anilines (1.5 mmol) and Na(AcO)3BH (3 mmol). Thesesubstituted anilines included (3-methoxyphenyl) methanamine (for C10d),4-(aminomethyl)-2-methoxyphenol, 3-(aminomethyl)phenol and SM-C. The mixture was stirredfor 24-48 h at room temperature, which was monitored by TLC. When the reaction wasaccomplished, enough 5% NaHCO3 was added into the mixture to change it into alkalinecondition. Then 10 mL dichloromethane was added and the suspension was stratified, while theorganic layer was reserved and the aqueous phase was extracted by 10mL dichloromethane fortwice. The organic phase was collected and separately washed by 5% NaHCO3 and saturated NaClfor once. Then the organic phase would be dried over anhydrous sodium sulfate and filtered. Thesolvent was removed in vacuo and the residue was purified by silica gel column chromatography(petroleum ether : ethyl acetate = 2 : 1), affording the purified C10e as white crystals (C14e isyellow), yield 69.3%.
	In ethanol at 20℃;	1.4 General synthetic procedures of step 4 General procedure: Taking the synthesis of C10e as an example. To a solution of anhydrous ethanol (10 mL)were added C10d (1 mmol), substituted anilines (1.5 mmol) and Na(AcO)3BH (3 mmol). Thesesubstituted anilines included (3-methoxyphenyl) methanamine (for C10d),4-(aminomethyl)-2-methoxyphenol, 3-(aminomethyl)phenol and SM-C. The mixture was stirredfor 24-48 h at room temperature, which was monitored by TLC. When the reaction wasaccomplished, enough 5% NaHCO3 was added into the mixture to change it into alkalinecondition. Then 10 mL dichloromethane was added and the suspension was stratified, while theorganic layer was reserved and the aqueous phase was extracted by 10mL dichloromethane fortwice. The organic phase was collected and separately washed by 5% NaHCO3 and saturated NaClfor once. Then the organic phase would be dried over anhydrous sodium sulfate and filtered. Thesolvent was removed in vacuo and the residue was purified by silica gel column chromatography(petroleum ether : ethyl acetate = 2 : 1), affording the purified C10e as white crystals (C14e isyellow), yield 69.3%.

Reference： [1]Chen, Dawei; Chen, Linbo; Fan, Tingting; Gao, Zhenxiong; Jiang, Yuyang; Li, Yuan; Liu, Zijian; Qiu, Zixuan; Wai Wong, Vincent Kam; Wu, Weibin; Yang, Mengchu; Zhang, Cunlong; Zhou, Yaoyao [European Journal of Medicinal Chemistry, 2022, vol. 238]
[2]Chen, Dawei; Chen, Linbo; Fan, Tingting; Gao, Zhenxiong; Jiang, Yuyang; Li, Yuan; Liu, Zijian; Qiu, Zixuan; Wai Wong, Vincent Kam; Wu, Weibin; Yang, Mengchu; Zhang, Cunlong; Zhou, Yaoyao [European Journal of Medicinal Chemistry, 2022, vol. 238]

87
[ 1196-92-5 ]
ethyl 3-formyl-1-(4-methoxybenzyl)-1H-indole-2-carboxylate [ No CAS ]
ethyl 3-(((4-hydroxy-3-methoxybenzyl)amino)methyl)-1-(4-methoxybenzyl)-1H-indole-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol at 20℃;	1.4 General synthetic procedures of step 4 General procedure: Taking the synthesis of C10e as an example. To a solution of anhydrous ethanol (10 mL)were added C10d (1 mmol), substituted anilines (1.5 mmol) and Na(AcO)3BH (3 mmol). Thesesubstituted anilines included (3-methoxyphenyl) methanamine (for C10d),4-(aminomethyl)-2-methoxyphenol, 3-(aminomethyl)phenol and SM-C. The mixture was stirredfor 24-48 h at room temperature, which was monitored by TLC. When the reaction wasaccomplished, enough 5% NaHCO3 was added into the mixture to change it into alkalinecondition. Then 10 mL dichloromethane was added and the suspension was stratified, while theorganic layer was reserved and the aqueous phase was extracted by 10mL dichloromethane fortwice. The organic phase was collected and separately washed by 5% NaHCO3 and saturated NaClfor once. Then the organic phase would be dried over anhydrous sodium sulfate and filtered. Thesolvent was removed in vacuo and the residue was purified by silica gel column chromatography(petroleum ether : ethyl acetate = 2 : 1), affording the purified C10e as white crystals (C14e isyellow), yield 69.3%.
	In ethanol at 20℃;	1.4 General synthetic procedures of step 4 General procedure: Taking the synthesis of C10e as an example. To a solution of anhydrous ethanol (10 mL)were added C10d (1 mmol), substituted anilines (1.5 mmol) and Na(AcO)3BH (3 mmol). Thesesubstituted anilines included (3-methoxyphenyl) methanamine (for C10d),4-(aminomethyl)-2-methoxyphenol, 3-(aminomethyl)phenol and SM-C. The mixture was stirredfor 24-48 h at room temperature, which was monitored by TLC. When the reaction wasaccomplished, enough 5% NaHCO3 was added into the mixture to change it into alkalinecondition. Then 10 mL dichloromethane was added and the suspension was stratified, while theorganic layer was reserved and the aqueous phase was extracted by 10mL dichloromethane fortwice. The organic phase was collected and separately washed by 5% NaHCO3 and saturated NaClfor once. Then the organic phase would be dried over anhydrous sodium sulfate and filtered. Thesolvent was removed in vacuo and the residue was purified by silica gel column chromatography(petroleum ether : ethyl acetate = 2 : 1), affording the purified C10e as white crystals (C14e isyellow), yield 69.3%.

Reference： [1]Chen, Dawei; Chen, Linbo; Fan, Tingting; Gao, Zhenxiong; Jiang, Yuyang; Li, Yuan; Liu, Zijian; Qiu, Zixuan; Wai Wong, Vincent Kam; Wu, Weibin; Yang, Mengchu; Zhang, Cunlong; Zhou, Yaoyao [European Journal of Medicinal Chemistry, 2022, vol. 238]
[2]Chen, Dawei; Chen, Linbo; Fan, Tingting; Gao, Zhenxiong; Jiang, Yuyang; Li, Yuan; Liu, Zijian; Qiu, Zixuan; Wai Wong, Vincent Kam; Wu, Weibin; Yang, Mengchu; Zhang, Cunlong; Zhou, Yaoyao [European Journal of Medicinal Chemistry, 2022, vol. 238]

88
[ 1196-92-5 ]
ethyl 3-formyl-6-isopropyl-1-(4-methoxybenzyl)-1H-indole-2-carboxylate [ No CAS ]
ethyl 3-(((4-hydroxy-3-methoxybenzyl)amino)methyl)-6-isopropyl-1-(4-methoxybenzyl)-1H-indole-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol at 20℃;	1.4 General synthetic procedures of step 4 General procedure: Taking the synthesis of C10e as an example. To a solution of anhydrous ethanol (10 mL)were added C10d (1 mmol), substituted anilines (1.5 mmol) and Na(AcO)3BH (3 mmol). Thesesubstituted anilines included (3-methoxyphenyl) methanamine (for C10d),4-(aminomethyl)-2-methoxyphenol, 3-(aminomethyl)phenol and SM-C. The mixture was stirredfor 24-48 h at room temperature, which was monitored by TLC. When the reaction wasaccomplished, enough 5% NaHCO3 was added into the mixture to change it into alkalinecondition. Then 10 mL dichloromethane was added and the suspension was stratified, while theorganic layer was reserved and the aqueous phase was extracted by 10mL dichloromethane fortwice. The organic phase was collected and separately washed by 5% NaHCO3 and saturated NaClfor once. Then the organic phase would be dried over anhydrous sodium sulfate and filtered. Thesolvent was removed in vacuo and the residue was purified by silica gel column chromatography(petroleum ether : ethyl acetate = 2 : 1), affording the purified C10e as white crystals (C14e isyellow), yield 69.3%.
	In ethanol at 20℃;	1.4 General synthetic procedures of step 4 General procedure: Taking the synthesis of C10e as an example. To a solution of anhydrous ethanol (10 mL)were added C10d (1 mmol), substituted anilines (1.5 mmol) and Na(AcO)3BH (3 mmol). Thesesubstituted anilines included (3-methoxyphenyl) methanamine (for C10d),4-(aminomethyl)-2-methoxyphenol, 3-(aminomethyl)phenol and SM-C. The mixture was stirredfor 24-48 h at room temperature, which was monitored by TLC. When the reaction wasaccomplished, enough 5% NaHCO3 was added into the mixture to change it into alkalinecondition. Then 10 mL dichloromethane was added and the suspension was stratified, while theorganic layer was reserved and the aqueous phase was extracted by 10mL dichloromethane fortwice. The organic phase was collected and separately washed by 5% NaHCO3 and saturated NaClfor once. Then the organic phase would be dried over anhydrous sodium sulfate and filtered. Thesolvent was removed in vacuo and the residue was purified by silica gel column chromatography(petroleum ether : ethyl acetate = 2 : 1), affording the purified C10e as white crystals (C14e isyellow), yield 69.3%.

Reference： [1]Chen, Dawei; Chen, Linbo; Fan, Tingting; Gao, Zhenxiong; Jiang, Yuyang; Li, Yuan; Liu, Zijian; Qiu, Zixuan; Wai Wong, Vincent Kam; Wu, Weibin; Yang, Mengchu; Zhang, Cunlong; Zhou, Yaoyao [European Journal of Medicinal Chemistry, 2022, vol. 238]
[2]Chen, Dawei; Chen, Linbo; Fan, Tingting; Gao, Zhenxiong; Jiang, Yuyang; Li, Yuan; Liu, Zijian; Qiu, Zixuan; Wai Wong, Vincent Kam; Wu, Weibin; Yang, Mengchu; Zhang, Cunlong; Zhou, Yaoyao [European Journal of Medicinal Chemistry, 2022, vol. 238]

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+

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CAS No. :	1196-92-5	MDL No. :	MFCD00044577
Formula :	C₈H₁₁NO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	WRPWWVNUCXQDQV-UHFFFAOYSA-N
M.W :	153.18	Pubchem ID :	70966
Synonyms :		Chemical Name :	4-(Aminomethyl)-2-methoxyphenol

Num. heavy atoms :	11
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.25
Num. rotatable bonds :	2
Num. H-bond acceptors :	3.0
Num. H-bond donors :	2.0
Molar Refractivity :	42.63
TPSA :	55.48 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) :	-7.43 cm/s

[ CAS No. 1196-92-5 ] {[proInfo.proName]}

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Physicochemical Properties

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Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 1196-92-5 ]

Application In Synthesis of [ 1196-92-5 ]

[ 1196-92-5 ] Synthesis Path-Upstream 1~4

[ 1196-92-5 ] Synthesis Path-Downstream 1~88

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Log Po/w (iLOGP) :	1.52
Log Po/w (XLOGP3) :	-0.27
Log Po/w (WLOGP) :	0.71
Log Po/w (MLOGP) :	0.6
Log Po/w (SILICOS-IT) :	0.95
Consensus Log Po/w :	0.7

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Log S (ESOL) :	-0.89
Solubility :	19.7 mg/ml ; 0.128 mol/l
Class :	Very soluble
Log S (Ali) :	-0.44
Solubility :	56.1 mg/ml ; 0.366 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-1.98
Solubility :	1.61 mg/ml ; 0.0105 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.06

Signal Word:	Danger	Class:	8
Precautionary Statements:	P264-P270-P271-P280-P303+P361+P353-P304+P340-P305+P351+P338-P310-P330-P331-P363-P403+P233-P501	UN#:	3259
Hazard Statements:	H302-H314	Packing Group:	Ⅲ
GHS Pictogram:

Yield	Reaction Conditions	Operation in experiment
87.4%	With boric acid In toluene at 130℃; for 8 h;	In a three-neck 500 mL flask, 30.0 g (0.196 mol) of vanillin was added.31.0 g (0.196 mol) of n-decanoic acid and 300 mL of toluene were added.Boric acid 0.6g (9.8mmol), a three-neck flask fitted with a thermometer,A mouth water separator + reflux condenser (the water separator is loaded into the reaction flask,Then install the reflux condenser above the water separator.)Another mouth is closed, stirring is started, and the temperature is raised to 130°C for 8 hours.After the reaction is completed, it is cooled to room temperature.Add 50mL of water twice to wash (extract boric acid),After drying over anhydrous sodium sulfate,Recovery of toluene under reduced pressure at 60 °C using a rotary evaporatorTo the distillation of toluene is 2/3 of the original volume, stop decompression recovery,The remaining liquid is transferred to the cryogenic reactor,Stir and crystallize at -20°C for 3h, filter,The resulting crystals are washed with toluene.Drained to give 50.3 g of a white powdery solid with a yield of 87.4percent.HPLC purity 99.1percent.White powder solids analysis:
74%	With Candida antarctica lipase B In toluene at 80℃; for 36 h; Inert atmosphere; Molecular sieve; Enzymatic reaction	A microwave-vial containing a solution of 1 (0.2 mmol, 1.0 equiv.), ammonium formiate (37.8 mg, 0.6 mmol, 3.0 equiv.) and Pd°-catalyst(Pd°-AmP-MFC, 13.4 mg, 0.01 mmol, 8 wtpercent, 5 molpercent) or(Pd°-CPG, 569A, 74.0 mg, 0.013 mmol, 6.6 molpercent) in toluene (1 mL) under ISfc conditions was stirred at 80^°C for the time shown in Table 3. Afterwards, molecular sieves 4A, acid 4 (0.2 mmol, 1.0 equiv.) and lipase (120 mg/mmol) were added to reaction mixture and stirred at 80^°C for 36h. The crude reaction mixture was filtrated through Celite using CHCb(10 mL) as eluent and evaporated. The crude material was purified by silica gel flash column chromatography to afford the corresponding amide 3 as indicated in Table 3. The lipase is preferably Novozyme-435 immobilized on a macroporous anionic resin.
52%	With lipase In tert-Amyl alcohol at 45℃; for 48 h; Molecular sieve; Enzymatic reaction	The dried crude reaction mixture from the previous step (containing vanillylamine 94 mg, 0.62 mmol, 1.00 equiv.) was dissolved in 2-methyl-2-butanol (31 mL, 20 mM). To the reaction was added Ms 4A (2 g), compound 5b (98.7 mg, 0.62 mmol, 1.00 equiv.) and lipase (1.9 g, 20 mg/niL). The reaction was stirred at 45°C for 48 h. Afterwards the reaction was cooled to room temperature and filtered. The solvent was removed under reduced pressure and the crude material was purified by chromatography to afford nonivamide (7b) (isolated yield 52 percent) as light yellow oil.

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Code	Phrase
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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