Name: 5785-06-8|3-Methoxybenzhydrazide|98%
Brand: Ambeed
SKU: A711278
Price: 5.0 USD
Availability: InStock
Rating: 96 (29 reviews)

1
[ 5368-81-0 ]
[ 5785-06-8 ]

Yield	Reaction Conditions	Operation in experiment
93%	With hydrazine hydrate monohydrate In ethanol for 7h; Reflux;
93%	With hydrazine hydrate monohydrate In ethanol; lithium hydroxide monohydrate at 80℃; for 24h;
90%	With hydrazine hydrate monohydrate In ethanol Reflux;	1.1 Part 1- Synthesis of 3-Methoxybenzohydrazide To a solution of methyl 3-methoxybenzoate (5.0 g, 30.1 mmol, 1.00 equiv) in EtOH (50 mL) was added hydrazine hydrate (80%, 9.4 g, 150 mmol, 5.00 equiv). The reaction was refluxed overnight, then concentrated under vacuum. The residue solidified upon standing at rt. The solid was triturated with hexane (100 mL) and the resulting solid separated and dried to yield 4.5 g (90%) of the desired product as a white solid.

86%	With hydrazine monohydrate In ethanol for 0.266667h; Reflux; Microwave irradiation;
85%	With hydrazine In methanol for 3h; Reflux;
	With hydrazine hydrate monohydrate
	With hydrazine In ethanol for 12h; Heating;
	With hydrazine hydrate monohydrate
	With hydrazine In lithium hydroxide monohydrate at 60℃;
	With hydrazine hydrate monohydrate In ethanol at 70℃; for 3h;
	With hydrazine hydrate monohydrate In methanol Reflux;
	With hydrazine hydrate monohydrate In ethanol Reflux;	General procedure for the synthesis of the hydrazide ligands General procedure: Different substituted carboxylic acids (20 mmol) (A) were stirred with thionyl chloride (100 mmol) in dry methanol (75 ml) or 5-6 h to synthesize corresponding methyl esters (B) (Scheme1). After extraction of esters in chloroform, solvent was evaporated and esters (66 mmol) were refluxed with hydrazine hydrate(330 mmol) in ethanol (75 ml) for 4-5 h. A solid was obtained upon removal of the solvent by rotary evaporation. The resulting solid was washed with hexane to afford hydrazide ligand (C). The spectral and analytical data are given below.
	With hydrazine hydrate monohydrate In methanol
	With hydrazine hydrate monohydrate In methanol for 5h; Reflux;	General procedure: Compounds 6a-t were synthesized from substituted benzoic acid via six steps according to the literature method as described. Various substituted benzoic acids 1a-t were treated with SOCl2 to give compounds 2a-t, which were reacted with CH3OH and EtN3 in CH2Cl2 at 0 to afford compounds 3a-t. Compounds 4a-t were prepared by the reaction of compounds 3a-t, hydrazine hydrate in CH3OH under reflux condition about 5h. Subsequently, compounds 5a-t were obtained by reaction of compounds 4a-t with CS2 and KOH in CH3OH. Compounds 6a-t were obtained by the cyclization reaction of compounds 5a-t in the presence of HCl at 0-5°C.
	With hydrazine hydrate monohydrate In ethanol Reflux;
	With hydrazine hydrate monohydrate
	With hydrazine hydrate monohydrate In methanol at 65 - 67℃; for 9h;
	With hydrazine hydrate monohydrate Cooling with ice; Reflux;	General procedure for synthesis of hydrazides (5a-l)¹ General procedure: Carboxylic acids (10 mmol) were refluxed for 1-2 h in methanol (5 mL) in presence of conc. H2SO4 (catalytic amount) with continuous stirring. The reaction was monitored by TLC till the acids were fully converted to the corresponding esters [Eluent: EtOAc/Hexanes (1:4)]. The reaction mixture was allowed to cool down to room temperature and hydrazine monohydrate 80% (40 mmol, 1.91 mL) was added slowly in an ice bath. The reaction was then warmed to room temperature and refluxed for another 1-2 h and followed by TLC till formation of hydrazide. The reaction mixture was kept at refrigerator till the product precipitated. All hydrazides were isolated in quantitative yields and in a pure form. There melting points were in full agreement with the literature melting points of the same compounds.
	With hydrazine hydrate monohydrate In methanol at 85℃; for 14h;
	With hydrazine hydrate monohydrate In methanol Reflux; Inert atmosphere;	2.1.1. General procedure for the synthesis of hydrazides 2 General procedure: Hydrazine hydrate (5 mL, 40%) was added to a solution of requiredester (5.0 mmol) in methanol (20 mL). The solution was refluxed for12-24 h and monitored by TLC until starting material was completelyconsumed. After that, solvent was evaporated under reduced pressureand a small amount of water (5 mL) was added to precipitate the hydrazide,which was filtered and dried in vacuum to give a shiny white toyellow solid in excellent yields, without further purification.
	With hydrazine hydrate monohydrate In methanol at 0 - 20℃; for 4h;	4.3 General procedure for the synthesis of compounds 3a-3q General procedure: Compound 2a was dissolved in methanol and the mixture was cooled in an ice bath. Hydrazine hydrate (3 eq.) was added dropwise at 0°C. The resulting reaction mixture was stirred at room temperature for 4h. The reaction progress was monitored by TLC (MeOH/DCM=1:20) until it was completed. A crude solid 3a was obtained by filtering and washing with ice methanol, which was used to the next step without further purification. Preparation method of 3b∼3q was same as 3a.
	With hydrazine hydrate monohydrate In ethanol Reflux;	Synthesis of benzohydrazide derivatives (4a-m) General procedure: Method A Methyl benzoate derivatives (2, 1 eq) and 85% hydrazine hydrate (10 eq) were dissolved in ethanol (45 mL). The mixture was refluxed overnight. After cooling, the solvent was removed in vacuo and the residue was separated on the Biotage SNAP Cartridge KP-Sil 100 g eluting with 0-60 % ethyl acetate/petroleum ether to afford compound 4.
	With hydrazine monohydrate In methanol Reflux;
	With hydrazine hydrate monohydrate In ethanol at 90℃;

Reference： [1]Karabanovich, Galina; Zemanová, Júlia; Smutný, Tomáš; Székely, Rita; Šarkan, Michal; Centárová, Ivana; Vocat, Anthony; Pávková, Ivona; Čonka, Patrik; Němeček, Jan; Stolaříková, Jiřina; Vejsová, Marcela; Vávrová, Kateřina; Klimešová, Věra; Hrabálek, Alexandr; Pávek, Petr; Cole, Stewart T.; Mikušová, Katarína; Roh, Jaroslav [Journal of Medicinal Chemistry, 2016, vol. 59, # 6, p. 2362 - 2380]
[2]Barreiro, Eliezer J.; Noël, François G.; Pedreira, Júlia Galvez Bulhões; Silva, Rafaela Ribeiro [Molecules, 2021, vol. 26, # 23]
[3]Current Patent Assignee: LYCERA CORPORATION - WO2016/138335, 2016, A1 Location in patent: Paragraph 00215
[4]Zaheer, Muhammad; Zia-Ur-Rehman, Muhammad; Rahman, Salma; Ahmed, Naveed; Chaudhary, Muhammad Nawaz [Journal of the Chilean Chemical Society, 2012, vol. 57, # 4, p. 1492 - 1496]
[5]Popiołek, Łukasz; Biernasiuk, Anna [Journal of Enzyme Inhibition and Medicinal Chemistry, 2016, vol. 31, p. 62 - 69]
[6]Hutton [Journal of Organic Chemistry, 1955, vol. 20, p. 855,858]
[7]Skoumbourdis, Amanda P.; Huang, Ruili; Southall, Noel; Leister, William; Guo, Vicky; Cho, Ming-Hsuang; Inglese, James; Nirenberg, Marshall; Austin, Christopher P.; Xia, Menghang; Thomas, Craig J. [Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 4, p. 1297 - 1303]
[8]Palmer, James T.; Hirschbein, Bernard L.; Cheung, Harry; McCarter, John; Janc, James W.; Yu, Z. Walter; Wesolowski, Gregg [Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 11, p. 2909 - 2914]
[9]Rando, Daniela G.; Avery, Mitchell A.; Tekwani, Babu L.; Khan, Shabana I.; Ferreira, Elizabeth I. [Bioorganic and Medicinal Chemistry, 2008, vol. 16, # 14, p. 6724 - 6731]
[10]Kümmerle, Arthur E.; Schmitt, Martine; Cardozo, Suzana V. S.; Lugnier, Claire; Villa, Pascal; Lopes, Alexandra B.; Romeiro, Nelilma C.; Justiniano, Hélène; Martins, Marco A.; Fraga, Carlos A. M.; Bourguignon, Jean-Jacques; Barreiro, Eliezer J. [Journal of Medicinal Chemistry, 2012, vol. 55, # 17, p. 7525 - 7545]
[11]Rafiq, Muhammad; Saleem, Muhammad; Hanif, Muhammad; Maqsood, Muhammad Rizwan; Rama, Nasim Hasan; Lee, Ki-Hwan; Seo, Sung-Yum [Bulletin of the Korean Chemical Society, 2012, vol. 33, # 12, p. 3943 - 3949]
[12]Ain, Qurrat Ul; Ashiq, Uzma; Jamal, Rifat Ara; Mahrooof-Tahir, Mohammad [Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2013, vol. 115, p. 683 - 689]
[13]Li, Pei; Yin, Juan; Xu, Weiming; Wu, Jian; He, Ming; Hu, Deyu; Yang, Song; Song, Baoan [Chemical Biology and Drug Design, 2013, vol. 82, # 5, p. 546 - 556]
[14]Li, Liangjing; Ding, Hao; Wang, Baogang; Yu, Shichong; Zou, Yan; Chai, Xiaoyun; Wu, Qiuye [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 1, p. 192 - 194]
[15]Qurrat-Ul-Ain; Rasheed, Saima; Mahroof-Tahir, Mohammad; Ashiq, Uzma; Jamal, Rifat Ara; Khurshid, Sumaira; Mustafa, Sana [Journal of the Chemical Society of Pakistan, 2016, vol. 38, # 5, p. 864 - 881]
[16]Jasiak, Karolina; Kudelko, Agnieszka; Zieliński, Wojciech; Kuźnik, Nikodem [Arkivoc, 2016, vol. 2017, # 2, p. 87 - 106]
[17]Ganesh Kumar; Gautham Shenoy; Kar, Sidhartha Sankar; Shenoy, Vishnu; Bairy, Indira [Pharmaceutical Chemistry Journal, 2018, vol. 51, # 10, p. 907 - 917]
[18]Goher, Shaimaa S.; Griffett, Kristine; Hegazy, Lamees; Elagawany, Mohamed; Arief, Mohamed M.H.; Avdagic, Amer; Banerjee, Subhashis; Burris, Thomas P.; Elgendy, Bahaa [Bioorganic and Medicinal Chemistry Letters, 2019, vol. 29, # 3, p. 449 - 453]
[19]Kahl, Dylan J.; Hutchings, Kim M.; Lisabeth, Erika Mathes; Haak, Andrew J.; Leipprandt, Jeffrey R.; Dexheimer, Thomas; Khanna, Dinesh; Tsou, Pei-Suen; Campbell, Phillip L.; Fox, David A.; Wen, Bo; Sun, Duxin; Bailie, Marc; Neubig, Richard R.; Larsen, Scott D. [Journal of Medicinal Chemistry, 2019, vol. 62, # 9, p. 4350 - 4369]
[20]Chen, Lixia; Gao, Suyu; Li, Hua; Li, Mingxue; Li, Xingzhou; Liu, Yang; Wu, Canrong; Yang, Kaiyin; Zhang, Yujie; Zheng, Mengzhu [Bioorganic Chemistry, 2020, vol. 96]
[21]Zhou, Wenjuan; Xu, Chenhao; Dong, Guanjun; Qiao, Hui; Yang, Jing; Liu, Hongmin; Ding, Lina; Sun, Kai; Zhao, Wen [European Journal of Medicinal Chemistry, 2021, vol. 217]
[22]Lin, Lin; Lin, Guangyao; Zhou, Qingtong; Bathgate, Ross A.D.; Gong, Grace Qun; Yang, Dehua; Liu, Qing; Wang, Ming-Wei [Bioorganic Chemistry, 2021, vol. 110]
[23]Maniak, Halina; Talma, Michał; Giurg, Mirosław [International Journal of Molecular Sciences, 2021, vol. 22, # 22]
[24]Chen, Chong-Hao; Fang, Ze-Yu; Lv, Peng-Cheng; Ni, Lei-Qiang; Sun, Juan; Wu, Yuan-Feng; Zhang, Yi-Heng; Zheng, Qi [Chemistry and biodiversity, 2022]

2
[ 5785-06-8 ]
[ 134-81-6 ]
[ 110249-07-5 ]

Yield	Reaction Conditions	Operation in experiment
87%	Stage #1: benzil With N,N,N’,N’-tetrabromobenzene-1,3-disulfonamide In neat (no solvent) at 100℃; for 0.05h; Stage #2: 3-methoxybenzoic hydrazide With ammonium acetate In neat (no solvent) at 100℃; for 3.58h;
	With ammonium acetate; acetic acid

Reference： [1]Ghorbani-Vaghei, Ramin; Shahriari, Azadeh; Salimi, Zahra; Hajinazari, Somayeh [RSC Advances, 2015, vol. 5, # 5, p. 3665 - 3669]
[2]Laakso et al. [Tetrahedron, 1957, vol. 1, p. 103,109]

3
[ 75-15-0 ]
[ 5785-06-8 ]
Potassium 2-(3-methoxybenzoyl) hydrazine-1-carbodithioate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 3-methoxybenzoic hydrazide With potassium hydroxide In ethanol at 20℃; for 1h; Stage #2: carbon disulfide In ethanol
	With potassium hydroxide In ethanol at 20℃; for 12h;
	With potassium hydroxide In ethanol at 20℃; for 12h;

	With potassium hydroxide In methanol at 0 - 5℃;	Synthesis of 3-Substituted 4-Amino-5-aryl-3H-1,2,4-triazole-3-thiones 5a-j. Potassium hydroxide (0.125 mol) was dissolved in dry methanol (50 mL). To the solution, aryl acid hydrazide 3a-j (0.125 mol) was added and cooled the solution in ice. To this, carbon disulfide (0.125 mol) was added in small portions with constant stirring. The solid product of potassium dithiocarbazate 4a-j was formed, filtered, washed with chilled diethyl ether, dried and was taken in water (20 mL) and hydrazine hydrate (0.250 mol) was added, and followed by refluxed for 10-12 h. The reaction mixture turned to green with evolution of hydrogensulfide and finally it became homogeneous. It was then poured in ice and acidified with 37% hydrochloric acid. The white precipitates was filtered, washed with cold water and recrystallized from aqueous methanol.
	With potassium hydroxide In methanol at 20℃; Reflux;	General procedure: Compounds 6a-t were synthesized from substituted benzoic acid via six steps according to the literature method as described. Various substituted benzoic acids 1a-t were treated with SOCl2 to give compounds 2a-t, which were reacted with CH3OH and EtN3 in CH2Cl2 at 0 to afford compounds 3a-t. Compounds 4a-t were prepared by the reaction of compounds 3a-t, hydrazine hydrate in CH3OH under reflux condition about 5h. Subsequently, compounds 5a-t were obtained by reaction of compounds 4a-t with CS2 and KOH in CH3OH. Compounds 6a-t were obtained by the cyclization reaction of compounds 5a-t in the presence of HCl at 0-5°C.
	With potassium hydroxide In ethanol at 20℃;
12.4 g	With potassium hydroxide In ethanol at 0℃; for 0.25h;	16.2 (2) The compound 3 - methoxy benzoyl hydrazine 8 g and 3 g of potassium hydroxide dissolved in 30 ml ethanol stirring,Add 1.3 mL of carbon disulfide,The above solution was allowed to react at 0 ° C for 15 minutes, a solid appeared,Filtered and dried to give the compound potassium salt 12.4 g;Take 8 g of potassium salt, add 30 mL of water,Then add 1.5 mL of hydrazine hydrate,The solution was reacted at 100 ° C for 5 hours, and after the completion of the reaction,The reaction solution was poured into ice water, adjusted to neutral with 5 mol / L hydrochloric acid,A solid appeared, filtered, and dried to yield 5.1 g of compound VIII in 80% yield.
	With potassium hydroxide In methanol at 0℃;	General procedure: Potassium hydroxide (0.125 mol, 1eq) was dissolved in drymethanol (50 mL). To the solution, substituted acid hydrazides 3(0.125 mol, 1eq) was added and cooled the solution in ice. To this,carbon disulfide (0.125 mol, 1eq) was added with constant stirringfor 1e2 h. The solid product of potassium salt of hydrazinecarbodithioates5 formed, was filtered, washed with chilled diethyl etherand dried. It was directly used for next step without further purification.The potassium salt of hydrazinecarbodithioates 5 wastaken in deionized water (50 mL) and hydrazine hydrate(0.250 mol) was added, followed by reflux overnight. The reactionmixture turned to yellowish green with evolution of hydrogensulfide and finally it became homogeneous. It was then poured incrushed ice and neutralized with hydrochloric acid to afford whiteprecipitates of substituted triazole derivatives 6 which was filtered,washed with cold water and crystallized on methanol.
	With potassium hydroxide In methanol at 25℃;	4.1.1 General synthetic procedure for the key intermediates 7 General procedure: The substituted hydrazides 5 (10mmol) were stirred with potassium hydroxide (15mmol) in absolute methanol. Then CS2 (12mmol) was slowly added and the mixture was stirred at 25°C for 1-6h. After the reaction completed, the solid was precipitated and dried to afford compounds 6. The compounds 6 was refluxed with excess 80% hydrazine hydrate in water under microwave irradiation at 250W, 100°C, for 60min. After completion of the reaction, the mixture was acidified with concentrated HCl and the precipitate solid was filtered, washed with water, dried and recrystallized from aqueous methanol to obtain the intermediates 7.
	With potassium hydroxide In methanol at 0℃;	Synthesis of 4-amino-5-aryl-4H-1,2,4-triazole-3-thiol (6) General procedure: Potassium hydroxide (0.56 g, 10 mmol) was added to a solution ofaryl hydrazide 4 (10 mmol) in methanol (25 mL) at 0 °C with stirring.Carbon disulfide (0.5 mL) was then added slowly and the reactionmixture was stirred and monitored by TLC. After reaction completion,the solid product potassium dithiocarbazinate 5 was filtered, washedwith chilled methanol and dried. Without any purification, potassiumdithiocarbazinate 5 was dissolved in water (20 mL) and hydrazinehydrate (1 mL) was added. The mixture was heated under reflux untilthe reaction was complete, and then diluted with a little cold water andacidified with conc. hydrochloric acid. The white precipitated solid 6was filtered, washed with cold water and recrystallised from aqueous methanol.
	With potassium hydroxide In ethanol at 20 - 25℃; for 3h;	6.c c: Dissolve the hydrazide obtained in b in anhydrous ethanol, add dropwise an anhydrous ethanol solution containing 1.0g KOH after it is completely dissolved, slowly add CS2 until a white solid is produced, the amount of CS2 is 1.5mL. After reacting at 20-25°C for 3 hours, it was filtered off with suction and washed with absolute ethanol several times.

Reference： [1]Sarva, Maria Concetta; Romeo, Giuseppe; Guerrera, Francesco; Siracusa, Mariangela; Salerno, Loredana; Russo, Filippo; Cagnotto, Alfredo; Goegan, Mara; Mennini, Tiziana [Bioorganic and Medicinal Chemistry, 2002, vol. 10, # 2, p. 313 - 323]
[2]Skoumbourdis, Amanda P.; Huang, Ruili; Southall, Noel; Leister, William; Guo, Vicky; Cho, Ming-Hsuang; Inglese, James; Nirenberg, Marshall; Austin, Christopher P.; Xia, Menghang; Thomas, Craig J. [Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 4, p. 1297 - 1303]
[3]Location in patent: scheme or table Baeeri, Maryam; Foroumadi, Alireza; Motamedi, Maryam; Yahya-Meymandi, Azadeh; Firoozpour, Loghman; Ostad, Seyed N.; Shafiee, Abbas; Souzangarzadeh, Saeid; Abdollahi, Mohammad [Chemical Biology and Drug Design, 2011, vol. 78, # 3, p. 438 - 444]
[4]Rafiq, Muhammad; Saleem, Muhammad; Hanif, Muhammad; Maqsood, Muhammad Rizwan; Rama, Nasim Hasan; Lee, Ki-Hwan; Seo, Sung-Yum [Bulletin of the Korean Chemical Society, 2012, vol. 33, # 12, p. 3943 - 3949]
[5]Li, Liangjing; Ding, Hao; Wang, Baogang; Yu, Shichong; Zou, Yan; Chai, Xiaoyun; Wu, Qiuye [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 1, p. 192 - 194]
[6]Karabanovich, Galina; Zemanová, Júlia; Smutný, Tomáš; Székely, Rita; Šarkan, Michal; Centárová, Ivana; Vocat, Anthony; Pávková, Ivona; Čonka, Patrik; Němeček, Jan; Stolaříková, Jiřina; Vejsová, Marcela; Vávrová, Kateřina; Klimešová, Věra; Hrabálek, Alexandr; Pávek, Petr; Cole, Stewart T.; Mikušová, Katarína; Roh, Jaroslav [Journal of Medicinal Chemistry, 2016, vol. 59, # 6, p. 2362 - 2380]
[7]Current Patent Assignee: JIANGSU OCEAN UNIVERSITY - CN106008623, 2016, A Location in patent: Paragraph 0047
[8]Rafiq, Muhammad; Saleem, Muhammad; Jabeen, Farukh; Hanif, Muhammad; Seo, Sung-Yum; Kang, Sung Kwon; Lee, Ki Hwan [Journal of Molecular Structure, 2017, vol. 1138, p. 177 - 191]
[9]Xu, Qile; Sun, Maolin; Bai, Zhaoshi; Wang, Yueting; Wu, Yue; Tian, Haiqiu; Zuo, Daiying; Guan, Qi; Bao, Kai; Wu, Yingliang; Zhang, Weige [European Journal of Medicinal Chemistry, 2017, vol. 139, p. 242 - 249]
[10]Liu, Xiu-Jian; Wang, Lei; Yin, Long; Cheng, Feng-Chang; Sun, Hui-Min; Liu, Wei-Wei; Shia, Da-Hua; Caoa, Zhi-Ling [Journal of Chemical Research, 2017, vol. 41, # 10, p. 571 - 575]
[11]Current Patent Assignee: NORTHWESTERN UNIVERSITY (ILLINOIS) - CN112125860, 2020, A Location in patent: Paragraph 0112; 0117

4
[ 5785-06-8 ]
[ 3697-66-3 ]
1-[<i>N</i>'-(3-methoxy-benzoyl)-hydrazinocarbonyl]-cyclopropanecarboxylic acid ethyl ester [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 4233 - 4236

5
[ 5785-06-8 ]
[ 380151-85-9 ]
(CH₃)4C₂O₂BC₆H₄CHNNHCOC₆H₄OCH₃ [ No CAS ]

Reference： [1]Dalton Transactions,2007,p. 5031 - 5042
[2]Dalton Transactions,2007,p. 5031 - 5042

6
[ 1711-05-3 ]
[ 5785-06-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: Et₃N / CH₂Cl₂ / 2 h 2: 37percent aq. HCl / 0.5 h
	With hydrazine hydrate; triethylamine In acetonitrile for 3h; Reflux;	2.3. Synthesis of aralkanoic acid hydrazides 3 General procedure: Aralkanoic acid chlorides 2 were synthesized by the reaction ofaralkanoic acids 1 (1 mmol) in the presence of 1,2edichloroethane(12 mL) solvent and phosphorous oxychloride (0.4 mL) as chlorinatingagent under reflux for 3 h. Then, the resulting solution wascooled to room temperature, and the solvent was removed underreduced pressure to afford aralkanoic acid chlorides 2, which wasdirectly used in the next step without further purification. Aralkanoicacid chlorides 2 was dissolved in acetonitrile (80 mL), addeddrop wise to a solution containing hydrazine hydrate (1 mmol), TEA(0.5 mL) and acetonitrile (20 mL) and allowed to reflux for 3 h withmonitoring by TLC. After consumption of the starting material, thereaction mixture was cooled to room temperature. Evaporation ofthe solvent under reduced pressure yielded crude substituted aromaticacid hydrazides 3 as a white solid on cooling, which waspurified by column chromatography and crystallized on methanol.
	With hydrazine hydrate In dichloromethane at 20℃;	General procedure: Method B Substituted benzoyl chloride (3, 1 eq) and 85% hydrazine hydrate (2 eq) were dissolved in dichloromethane (25 mL). The mixture was stirred at room temperature overnight. The progress was monitored by TLC and the terminated by addition of water. The mixture was extracted with dichloromethane, washed with water and dried over anhydrous Na2SO4. After filtration, the solvent was removed in vacuo and the residue was separated on the Biotage SNAP Cartridge KP-Sil 100 g eluting with 0-60% ethyl acetate/petroleum ether to afford compound 4.

Multi-step reaction with 2 steps 1: sulfuric acid / 5 h / 60 °C 2: hydrazine hydrate / 12 h / 80 °C

Reference： [1]Omodei-Sale, Amedeo; Consonni, Pietro; Galliani, Giulio [Journal of Medicinal Chemistry, 1983, vol. 26, # 8, p. 1187 - 1192]
[2]Rafiq, Muhammad; Saleem, Muhammad; Jabeen, Farukh; Hanif, Muhammad; Seo, Sung-Yum; Kang, Sung Kwon; Lee, Ki Hwan [Journal of Molecular Structure, 2017, vol. 1138, p. 177 - 191]
[3]Lin, Lin; Lin, Guangyao; Zhou, Qingtong; Bathgate, Ross A.D.; Gong, Grace Qun; Yang, Dehua; Liu, Qing; Wang, Ming-Wei [Bioorganic Chemistry, 2021, vol. 110]
[4]Bai, Hangyu; Jiang, Weiqi; Li, Qi; Li, Tian; Ma, Shichuang; Shi, Baojun; Wu, Wenjun [Journal of Agricultural and Food Chemistry, 2021, vol. 69, # 39, p. 11572 - 11581]

7
[ 532-54-7 ]
[ 5785-06-8 ]
N'-(2-(hydroxyimino)-1-phenylethylidene)-3-methoxybenzohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
32%	With sulfuric acid In methanol for 16h; Heating / reflux;	3 General Procedure X The relevant hydrazide of formula II as described herein (2.4 mmol) was dissolved in MeOH (10 mL) and cooled to 0°C. Two drops of concentrated sulfuric acid were added followed by dropwise addition of the relevant oxime of formula III as described herein (2 mmol) dissolved in MeOH (10 mL). The reaction was heated at reflux for 16 h. The product could be isolated by chromatography or, if a precipitate is formed during the reaction, this could be filtered off, washed with MeOH and recrystallised from MeOH/water. Example 3 '- (2-(Hydroxyimino)-1-phenylethylidene)-3-methoxybenzohydrazide General procedure X was employed to give the title compound as a white crystalline solid in 32% isolated yield. 1H-NMR (300 MHz, DMSO-d6) No. 13. 05 (s, 1H), 12.60 (s, 1H), 8.51 (s, 1H), 7.77-7. 76 (m, 2H), 7.51-7. 41 (m, 6H), 7.23-7. 20 (m, 1H), 3.85 (s, 3H).

Reference： [1]Current Patent Assignee: OREXO AB - WO2005/84656, 2005, A1 Location in patent: Page/Page column 37; 42

8
[ 5785-06-8 ]
[ 149-73-5 ]
[ 5378-30-3 ]

Yield	Reaction Conditions	Operation in experiment
93%	With Al³⁺-K₁₀ montmorillonite clay In neat (no solvent) at 55℃; for 0.25h; Microwave irradiation;	General procedure for 1,3,4-oxadiazole synthesis General procedure: A 5 mL microwave vial was charged with acidhydrazide (100 mg, 1 eq), trimethyl orthoester (2 eq) and Al3+-K10 clay (75 mg). The resulting mixture was kept under microwave irradiation maintaining the temperature at 55 °C for 15 min (Microwave irradiations were performed on CEM-discover model No. 908010). The reaction was monitored by TLC. After completion of the reaction, reaction mixture was diluted with ethyl acetate stirred well, filtered, washed well with ethyl acetate. Filtrate was evaporated under reduced pressure to obtain highly pure product. In some cases, products were purified by column chromatography using 60-120 mesh silica with 20-100 % ethyl acetate in pet ether as eluting solvents. The catalyst recovered by filtration was reused for another 5 more times.

Reference： [1]Suresh, Dhanusu; Kanagaraj, Kuppusamy; Pitchumani, Kasi [Tetrahedron Letters, 2014, vol. 55, # 27, p. 3678 - 3682]
[2]Palmer, James T.; Hirschbein, Bernard L.; Cheung, Harry; McCarter, John; Janc, James W.; Yu, Z. Walter; Wesolowski, Gregg [Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 11, p. 2909 - 2914]

9
[ 5785-06-8 ]
[ 453-71-4 ]
4-(3-nitro-4-fluorophenyl)-1-(3-methoxybenzoyl)semicarbazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	With diphenyl phosphoryl azide; triethylamine In acetonitrile at 120℃;

Reference： [1]Location in patent: experimental part Baumann, Marcus; Baxendale, Ian R.; Ley, Steven V.; Nikbin, Nikzad; Smith, Christopher D.; Tierney, Jason P. [Organic and Biomolecular Chemistry, 2008, vol. 6, # 9, p. 1577 - 1586]

10
[ 10259-22-0 ]
[ 5785-06-8 ]

Yield	Reaction Conditions	Operation in experiment
100%	With hydrazine hydrate; In ethanol; water;Reflux;	EXAMPLE 5; 4-[5-(3-methoxyphenyD- 1 ,3,4-oxadiazol:2-yl]-N-methylaniline; Step 1: To a solution of ethyl 3-methoxy benzoate (1.0 g, 5.55 mmol) in EtOH (11 mL) was added 80% hydrazine in water (1.09 mL, 27.7 mmol), and the resulting solution was heated to reflux overnight. The reaction mixture was then cooled to room temperature and the volatiles were removed in vacuo to afford 3-methoxy-benzoic acid hydrazide (920 mg, 5.55 mmol, 100% yield) which was used without further purification. ES MS (M+H+) = 167.
84%	With hydrazine hydrate; In ethanol; water;Reflux;	General procedure: Hydrazides (30-58) were synthesized by one pot conventionalmethod24 Benzoic acid or its derivative (10 mmol) was dissolvedin ethanol (20 mL). Sulfuric acid (3 N, 2 mL) was added and thereaction contents were refluxed for six hours. The reaction wasmonitored with TLC. After the completion of the reaction, the reactionmixture was neutralized by adding solid NaHCO3, and filteredto remove excess of NaHCO3. In the neutralized reaction mixture which contains ethyl ester, hydrazine monohydrate (1.5 mL,3 mmol) was added and refluxed for 3-6 h to complete the reaction.Ethanol and unreacted hydrazine were removed by distillationupto 1/3 volume. The reaction contents were cooled, filteredand recrystallized from methanol to obtain the desired hydrazidecrystals (see Supporting information).
	With hydrazine hydrate; In ethanol;Reflux;	General procedure: Hydrazide ligands (1-12) were synthesized by reportedmethod [28,29]. Ethylbenzoate (25 mmol) was dissolved inethanol (75 mL), and then hydrazine hydrate (100 mmol)was added and the mixture refluxed for 5 h. The solid obtainedwas washed with hexane to afford the hydrazide.Other ligands were prepared from their respective esters. Theanalytical data of benzohydrazide (1), M.P. 116 C; 2-fluorobenzohydrazide (2), M.P. 74 C; 2-methoxybenzohydrazide(3), M.P. 83 C; 2-aminobenzohydrazide (4), M.P.124 C; 4-phenylsemicarbazide (5), M.P. 125 C; 3-aminobenzohydrazide(6), M.P. 79C; 4-aminobenzohydrazide (7),M.P. 229 C; 3-methoxybenzohydrazide (8), M.P. 94 C; 3-fluorobenzohydrazide (9), M.P. 138 C; 3-iodobenzohydrazide(10), M.P. 141 C; 4-iodobenzohydrazide (11) M.P.170 C and 3-bromobenzohydrazide (12) M.P. 160 C; werereported previously [28,30].

With hydrazine hydrate; In ethanol; for 5h;Reflux;

General procedure: 5mL of hydrazine monohydrate (80%) was added to a solution of intermediate 3 (5mmol) in ethanol (5mL). The reaction mixture was maintained under reflux for 5h. was then concentrated under reduced pressure and the resulting solid was collected by filtration, washed with cold water and dried to give the desired intermediate 4 as a white solid.

Reference： [1]Patent: WO2009/146343,2009,A1 .Location in patent: Page/Page column 56
[2]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 6014 - 6024
[3]European Journal of Medicinal Chemistry,2009,vol. 44,p. 2985 - 2993
[4]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 332 - 335
[5]Medicinal Chemistry Research,2013,vol. 22,p. 5344 - 5348
[6]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 5154 - 5156
[7]Medicinal Chemistry,2015,vol. 11,p. 798 - 806
[8]Journal of Molecular Structure,2017,vol. 1129,p. 50 - 59
[9]Chemical Biology and Drug Design,2017,vol. 90,p. 236 - 243
[10]Bioorganic and Medicinal Chemistry,2017,vol. 25,p. 5652 - 5661
[11]European Journal of Pharmaceutical Sciences,2019,vol. 136
[12]Journal of Molecular Structure,2019,vol. 1197,p. 171 - 182
[13]Bioorganic Chemistry,2020,vol. 94

11
[ 10541-83-0 ]
[ 5785-06-8 ]
[ 1196986-64-7 ]

Yield	Reaction Conditions	Operation in experiment
26%	With 2-chloro-1,3-dimethylimidazolinium chloride; triethylamine In dichloromethane at 20℃;	5.2 Step 2: To a solution of 3-methoxy-benzoic acid hydrazide (100 mg, 0.60 mmol) and 4- methylamino-benzoic acid (91 mg, 0.60 mmol) in CH2Cl2 (1.5 mL) at room temperature was added El3N (0.34 mL, 2.41 mmol) followed by 2-chloro-l,3-dimethylimidazolinium chloride (201 mg, 1.20 mmol) causing a slightly exothermal reaction. The resulting mixture was allowed to stir overnight at room temperature before the volatiles were removed in vacuo and purified by reversed phase HPLC to afford 4-[5-(3-methoxyphenyl)-l,3,4-oxadiazol-2-yl]-N-methylaniline (44 mg, 0.16 mmol 26% yield). ES MS (M+H+) = 282; 1H NMR (499 MHz, DMSO): δ 7.85 (2 H, d, J = 8.61 Hz), 7.66 (1 H9 d, J - 7.69 Hz), 7.58 (1 H, t, J = 1.92 Hz), 7.53 (1 H, t, J = 7.98 Hz)5 7.19 (1 H, dd, J - 8.29, 2.62 Hz), 6.69 (2 H, d, J = 8.61 Hz), 6.55 (1 H, q, J = 5.00 Hz), 3.87 (3 H, s), 2.76 (3 H, d, J - 5.01 Hz); HRMS m/z 282.1227 (C16Hi5N3O2 + H+ requires 282.1237).

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2009/146343, 2009, A1 Location in patent: Page/Page column 56-57

12
[ 5785-06-8 ]
[ 1259052-00-0 ]
[ 1259051-85-8 ]

Yield	Reaction Conditions	Operation in experiment
65.4%	With triethylamine In ethanol at 20 - 60℃; for 72h;	15.7; 16.7 Step 7: Synthesis of 4-[N'-(3-Methoxy-benzoyl)-hydrazino]-7-methyl-2-oxo-1,5-diphenyl-1,2,5,8-tetrahydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid ethyl ester [Show Image] The compound of step 6 (100 mg, 0.237 mmol) was taken in 2 ml EtOH and treated successively with m-anisic hydrazide (99.6 mg, 0.6 mmol) and TEA (Triethylamine) (35 microl, 0.25 mmol) at room temperature and stirred at 60 °C for 72 h. The reaction mixture was partitioned between water (25 ml) and DCM (30 ml). The organic phase was separated and the solvent was evaporated under vacuum at 40 °C. The product was purified with HPLC on a RP-18 column (Sphinx, 21 mm x 250 mm, 5 microm, Macherey-Nagel) with a gradient 30-100% MeCN with 0.02% HCOOH in 22 min and a flow rate of 21 ml/min yielding a light yellow solid (85.5 mg, 0.155 mmol, 65.4%).

Reference： [1]Current Patent Assignee: Helmholtz Association - EP2266985, 2010, A1 Location in patent: Page/Page column 21-22

13
[ 75-15-0 ]
[ 5785-06-8 ]
[ 108413-55-4 ]

Yield	Reaction Conditions	Operation in experiment
87%	With potassium hydroxide In ethanol for 38h; Reflux;
86%	With N,N-dimethyl-formamide for 18h; Sonication; Green chemistry;
64%	In N,N-dimethyl-formamide at 40 - 70℃; Inert atmosphere;	4.10 4.1.2. General procedure for synthesis of 5-substituted 1,3,4-oxadiazole-2-thiols General procedure: To a solution of acid hydrazide in anhydrous 5-15mL of DMF, carbon disulfide (2.5mL/mmol) was added at room temperature and under a nitrogen atmosphere. The reaction mixture was then heated to 40°C for 15min and then to 70°C for 4-8h until the reaction was completed. After completion, the reaction mixture was cooled to room temperature and poured dropwise into ice cold water. The solids formed were separated by filtration, washed with water and dried in vacuo.

	With potassium hydroxide In ethanol
	In ethanol for 5h; Reflux;
	Stage #1: carbon disulfide; 3-methoxybenzoic hydrazide With potassium hydroxide In ethanol Reflux; Stage #2: With hydrogenchloride In ethanol; water
	With potassium hydroxide In ethanol Reflux;
	With potassium hydroxide In ethanol for 20h; Reflux;
	With triethylamine In methanol at 65 - 67℃; for 10h;
	Stage #1: carbon disulfide; 3-methoxybenzoic hydrazide With potassium hydroxide In ethanol Stage #2: With hydrogenchloride In water
	With potassium hydroxide In ethanol; water at 95℃; for 16h; Inert atmosphere;
	Stage #1: 3-methoxybenzoic hydrazide With potassium hydroxide In ethanol for 0.166667h; Inert atmosphere; Stage #2: carbon disulfide In ethanol Reflux; Stage #3: In water at 70 - 80℃;	4.1.2 General synthetic procedure for the key intermediate 5(a-c): General procedure: The intermediate 5(a-c) were synthesized by two step reaction. Firstly, to a 100mL flask was added the intermediate compound 3(a-b) (1mmol) and milled potassium hydroxide (1.1mmol) in ethanol (5mL), stirred for 10min under nitrogen atmosphere. Later, slowly added carbon disulphide (2mmol) to the reaction mixture, solid will observed (if necessary, add ethanol) and heated to reflux for 4-5 h. The reaction progress was detected by using TLC technique. After completion of the reaction, the reaction mass was cooled to room temperature and concentrated under reduced pressure to afford a crude solid 4(a-d). The obtained crude solid was taken as such for further step. (0029) The obtained crude intermediate 4(a-d) was taken in water and heated to reflux at 70-80°C for 7-8 h. After completion of the reaction, the reaction mixture was gradually brought to room temperature followed cooled to 0 to 5°C. Then neutralised with 10% hydrochloric acid solution, the precipitated solid was filtered, and several times washed with cold water. The obtained solid was dried and used as it is for next step.
	With potassium hydroxide In ethanol for 12h; Reflux;

Reference： [1]Karabanovich, Galina; Zemanová, Júlia; Smutný, Tomáš; Székely, Rita; Šarkan, Michal; Centárová, Ivana; Vocat, Anthony; Pávková, Ivona; Čonka, Patrik; Němeček, Jan; Stolaříková, Jiřina; Vejsová, Marcela; Vávrová, Kateřina; Klimešová, Věra; Hrabálek, Alexandr; Pávek, Petr; Cole, Stewart T.; Mikušová, Katarína; Roh, Jaroslav [Journal of Medicinal Chemistry, 2016, vol. 59, # 6, p. 2362 - 2380]
[2]Yarmohammadi, Elahe; Beyzaei, Hamid; Aryan, Reza; Moradi, Ashraf [Molecular Diversity, 2021, vol. 25, # 4, p. 2367 - 2378]
[3]Kummari, Lalith K.; Butler, Mark S.; Furlong, Emily; Blundell, Ross; Nouwens, Amanda; Silva, Alberto B.; Kappler, Ulrike; Fraser, James A.; Kobe, Bostjan; Cooper, Matthew A.; Robertson, Avril A.B. [Bioorganic and Medicinal Chemistry, 2018, vol. 26, # 20, p. 5408 - 5419]
[4]Location in patent: scheme or table Zareefa, Muhammad; Iqbal, Rashid; Zaidi, Javid Hussain; Arfan, Muhammad; Ali, Muhammad; Khan, Khalid M. [Letters in Organic Chemistry, 2010, vol. 7, # 5, p. 411 - 414]
[5]Deora, Girdhar Singh; Karthikeyan, Chandrabose; Moorthy, N. S. Hari Narayana; Rathore, Vandana; Rawat, Arun K.; Tamrakar, Akhilesh K.; Srivastava; Trivedi, Piyush [Medicinal Chemistry Research, 2013, vol. 22, # 11, p. 5344 - 5348]
[6]Li, Pei; Yin, Juan; Xu, Weiming; Wu, Jian; He, Ming; Hu, Deyu; Yang, Song; Song, Baoan [Chemical Biology and Drug Design, 2013, vol. 82, # 5, p. 546 - 556]
[7]Ahmed, Muhammad Naeem; Yasin, Khawaja Ansar; Hameed, Shahid; Ayub, Khurshid; Haq, Ihsan-ul; Tahir, M. Nawaz; Mahmood, Tariq [Journal of Molecular Structure, 2017, vol. 1129, p. 50 - 59]
[8]Wang, Zi-Zhen; Sun, Wen-Xue; Wang, Xue; Zhang, Ya-Han; Qiu, Han-Yue; Qi, Jin-Liang; Pang, Yan-Jun; Lu, Gui-Hua; Wang, Xiao-Ming; Yu, Fu-Gen; Yang, Yong-Hua [Chemical Biology and Drug Design, 2017, vol. 90, # 2, p. 236 - 243]
[9]Ganesh Kumar; Gautham Shenoy; Kar, Sidhartha Sankar; Shenoy, Vishnu; Bairy, Indira [Pharmaceutical Chemistry Journal, 2018, vol. 51, # 10, p. 907 - 917]
[10]Wang, Pei-Yi; Wang, Ming-Wei; Zeng, Dan; Xiang, Meng; Rao, Jia-Rui; Liu, Qing-Qing; Liu, Li-Wei; Wu, Zhi-Bing; Li, Zhong; Song, Bao-An; Yang, Song [Journal of Agricultural and Food Chemistry, 2019, vol. 67, # 13, p. 3535 - 3545]
[11]Kahl, Dylan J.; Hutchings, Kim M.; Lisabeth, Erika Mathes; Haak, Andrew J.; Leipprandt, Jeffrey R.; Dexheimer, Thomas; Khanna, Dinesh; Tsou, Pei-Suen; Campbell, Phillip L.; Fox, David A.; Wen, Bo; Sun, Duxin; Bailie, Marc; Neubig, Richard R.; Larsen, Scott D. [Journal of Medicinal Chemistry, 2019, vol. 62, # 9, p. 4350 - 4369]
[12]Vanjare, Balasaheb D.; Choi, Nam Gyu; Mahajan, Prasad G.; Raza, Hussain; Hassan, Mubashir; Han, Yohan; Yu, Seon-Mi; Kim, Song Ja; Seo, Sung-Yum; Lee, Ki Hwan [Bioorganic and Medicinal Chemistry, 2021, vol. 41]
[13]Cheng, Wanqing; Fan, Jiangping; Guo, Yong; Han, Meiyue; Ma, Nannan; Yan, Xiaoting; Yang, Ruige [Journal of Agricultural and Food Chemistry, 2021, vol. 69, # 51, p. 15544 - 15553]

14
[ 5785-06-8 ]
C₁₂H₆ClN₃O₄ [ No CAS ]
[ 1296210-40-6 ]

Yield	Reaction Conditions	Operation in experiment
	With dmap In dichloromethane at 0 - 20℃; for 36.5h;	4.1.2. General procedure for the synthesis of N'-substituted-2-(5-nitrofuran or 5-nitrothiophen-2-yl)-3H-benzo[d]imidazole-5-carbohydrazide derivatives 5a-i, 6a-i General procedure: A mixture of 3a,b (0.3 mmol), thionyl chloride (1.5 mmol), and benzene 25 mL was gradually heated to boiling, whereupon the acid chloride dissolved. After refluxing for 12 h, excess of thionyl chloride and solvent were removed in vacuo. The acid chloride was not characterized, then to a solution of acid chloride, DMAP (1.5 mmol) in dry CH2Cl2 (10 mL) was slowly added a dry CH2Cl2 (10 mL) solution of carbohydrazide respective (0.4 mmol) (30 min) at 0 °C, and the mixture was stirred for 36 h at rt. The solvent was removed in vacuo and the residue was slowly added water 5% KOH at 0 °C and the mixture stirred for 30 min. The solid was washed with water, methanol and ethyl ether, recrystallized from a mixture of ethanol and water (1:1) to give 5a-i, 6a-i.

Reference： [1]Location in patent: experimental part Camacho, José; Barazarte, Arthur; Gamboa, Neira; Rodrigues, Juan; Rojas, Rosario; Vaisberg, Abraham; Gilman, Robert; Charris, Jaime [Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 6, p. 2023 - 2029]

15
[ 5785-06-8 ]
C₁₂H₆ClN₃O₃S [ No CAS ]
[ 1296210-49-5 ]

Yield	Reaction Conditions	Operation in experiment
	With dmap In dichloromethane at 0 - 20℃; for 36.5h;	4.1.2. General procedure for the synthesis of N'-substituted-2-(5-nitrofuran or 5-nitrothiophen-2-yl)-3H-benzo[d]imidazole-5-carbohydrazide derivatives 5a-i, 6a-i General procedure: A mixture of 3a,b (0.3 mmol), thionyl chloride (1.5 mmol), and benzene 25 mL was gradually heated to boiling, whereupon the acid chloride dissolved. After refluxing for 12 h, excess of thionyl chloride and solvent were removed in vacuo. The acid chloride was not characterized, then to a solution of acid chloride, DMAP (1.5 mmol) in dry CH2Cl2 (10 mL) was slowly added a dry CH2Cl2 (10 mL) solution of carbohydrazide respective (0.4 mmol) (30 min) at 0 °C, and the mixture was stirred for 36 h at rt. The solvent was removed in vacuo and the residue was slowly added water 5% KOH at 0 °C and the mixture stirred for 30 min. The solid was washed with water, methanol and ethyl ether, recrystallized from a mixture of ethanol and water (1:1) to give 5a-i, 6a-i.

Reference： [1]Location in patent: experimental part Camacho, José; Barazarte, Arthur; Gamboa, Neira; Rodrigues, Juan; Rojas, Rosario; Vaisberg, Abraham; Gilman, Robert; Charris, Jaime [Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 6, p. 2023 - 2029]

16
[ 5785-06-8 ]
[ 635-93-8 ]
[ 351366-73-9 ]

Yield	Reaction Conditions	Operation in experiment
83%	In methanol at 20℃; for 0.5h;	Synthesis of H2L1 5-Chlorosalicylaldehyde (1.0 mmol, 0.16 g) and 3-methoxybenzohydrazide (1.0 mmol, 0.17 g)were dissolved in methanol (30 mL) with stirring. The mixture was stirred for about 30 min at room temperature to give colorless solution. The solution was left still in air to slow evaporate of most of the solvent, to give crystalline product of H2L2. The product was isolated by filtration and washed with cold methanol. Yield, 83%; m.p. 181.0-182.5 °C. Analysis: found: C 59.23%,H 4.26%, N 9.07%; calculated for C15H13ClN2O3: C 59.12%, H 4.30%, N 9.19%. IR data (cm-1,KBr): 3447 (w), 3195 (w), 1653 (s), 1611 (m), 1589 (m), 1561 (m), 1494 (s), 1435 (s), 1357(w), 1332 (w), 1301 (w), 1267 (m), 1153 (s), 1114 (m), 1080 (s), 1035 (m), 996 (m), 853 (s),781 (w), 745 (w), 727 (w), 546 (w), 470 (w). 1H NMR (300 MHz, d6-DMSO): 12.41 (s, 1H),11.72 (s, 1H), 8.61 (s, 1H), 7.85 (t, 1H), 7.60 (m, 2H), 7.38 (d, 1H), 7.19 (d, 1H), 6.91 (d, 1H),6.85 (s, 1H), 3.79 (s, 3H). 13C NMR (75 MHz, d6-DMSO): 164.03, 161.54, 158.37, 145.71,134.10, 132.82, 129.88, 128.75, 121.63, 120.70, 119.53, 117.37, 116.86, 112.45, 55.71.
82%	In methanol for 2h; Reflux;

Reference： [1]Zhang, Xiu-Zhen; Li, Li-Xue; Li, Hai-Hua; You, Zhonglu; Zhu, Hai-Liang [Bulletin of the Chemical Society of Ethiopia, 2015, vol. 29, # 3, p. 423 - 430]
[2]Location in patent: experimental part Ngan, Ngui Khiong; Lo, Kong Mun; Wong, Chee Seng Richard [Polyhedron, 2011, vol. 30, # 17, p. 2922 - 2932]

17
[ 5785-06-8 ]
[ 1364195-36-7 ]
[ 1364195-45-8 ]

Yield	Reaction Conditions	Operation in experiment
67%	In butan-1-ol at 130℃; for 24h; Inert atmosphere;	6.2. General procedure for the preparation of triazolo-benzodiazepines 4a-e General procedure: Thiolactam 2 (1.0 equiv) and carboxylic acid hydrazide 3a-e (2.0 equiv) were dissolved in n-butanol and heated to 130 °C in a sealed vial under nitrogen atmosphere for 24 h. The reaction mixture was cooled to room temperature and stirred with an aqueous glucose solution for 2 h. The crude product was extracted several times with dichloromethane. The combined organic layers were washed with water, dried over sodium sulfate, filtered and evaporated. Purification was done by flash column chromatography (dichloromethane/methanol, 9:1), giving the triazolo-benzodiazepines 4a-e in 17-67% yield.

Reference： [1]Location in patent: experimental part Filippakopoulos, Panagis; Picaud, Sarah; Fedorov, Oleg; Keller, Marco; Wrobel, Matthias; Morgenstern, Olaf; Bracher, Franz; Knapp, Stefan [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 6, p. 1878 - 1886]

18
[ 5785-06-8 ]
[ 344567-18-6 ]
[ 1430092-72-0 ]

Yield	Reaction Conditions	Operation in experiment
78%	In methanol for 3h; Reflux;	5.2.1 A general procedure for the synthesis of compounds General procedure: A mixture of the corresponding hydrazide (0.01 mol) and STB (0.0075 mol) in MeOH (50 mL) was refluxed for 3 h. The hot mixture was filtered. Water (50 mL) was added to the filtrate and the filtrate was left at room temperature (48 h) (compounds 1, 9-11, 14 and 18) or the filtrate was concentrated (compounds 3, 5-8, 12, 13, 16, 19, 21). The obtained solid was recrystallized from MeOH/H2O.

Reference： [1]Skrzypek, Alicja; Matysiak, Joanna; Niewiadomy, Andrzej; Bajda, Marek; Szymanski, Pawel [European Journal of Medicinal Chemistry, 2013, vol. 62, p. 311 - 319]

19
[ 5785-06-8 ]
[ 14527-26-5 ]
C₉H₁₂N₄O₂ [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2013,vol. 67,p. 325 - 334

20
(2E,4E)-5-(3,4-methylenedioxyphenyl)penta-2,4-dienal [ No CAS ]
[ 5785-06-8 ]
[ 1458033-80-1 ]

Yield	Reaction Conditions	Operation in experiment
64%	With acetic acid In ethanol Reflux;	Synthesis of piperine-based hydrazone derivatives (6a-p) General procedure: A mixture of 5 (80.8 mg, 0.4 mmol), hydrazides or hydrazines (0.4 mmol), and two drops of HOAc in EtOH (5 mL) was refluxed. When the reaction was complete checked by TLC after 1-3 h, the resulting reaction mixture was cooled to room temperature until no more precipitate was observed. The crude solid was collected by ltration, and washed with cooled ethanol and petroleum ether to afford 6a-p in 33-86%.

Reference： [1]Qu, Huan; Yu, Xiang; Zhi, Xiaoyan; Lv, Min; Xu, Hui [Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 20, p. 5552 - 5557]

21
[ 5785-06-8 ]
palladium dichloride [ No CAS ]
[Pd(3-methoxybenzoic acid hydrazide)₂Cl₂] [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	In acetonitrile for 3h;	General procedure for the synthesis of the palladium(II)-hydrazide complexes General procedure: The complexes 1a-4a were prepared in CH3CN while complexes 5a and 6a were synthesized in H2O. Complexation was carried out at room temperature. A solution of metal salt PdCl2, (1 mmol) in water or CH3CN (30 ml) was added slowly with stirring to a solution (30 ml) of hydrazide (2 mmol). The reaction mixture was stirred for about 3 h, during which time solid complex was separated. The solid complex was filtered and washed with water or acetonitrile to remove the unreacted metal salt and ligand. Physical and analytical data of complexes 1a-6a is given in Table 1.

Reference： [1]Ain, Qurrat Ul; Ashiq, Uzma; Jamal, Rifat Ara; Mahrooof-Tahir, Mohammad [Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2013, vol. 115, p. 683 - 689]

22
[ 5785-06-8 ]
[ 611-73-4 ]
[ 1537255-16-5 ]

Yield	Reaction Conditions	Operation in experiment
94%	In water at 50 - 60℃; for 2h;	4 General procedure A solution of 1 (5.2 mmol) in water (60 mL) was added dropwise(over 1-2 h) under vigorous stirring to a solution of hydrazide2 (5.2 mmol) in water (60 mL) heated to 50-60° C. The mixture was stirred for additional 2 h, and then cooled on an ice bath untilthe complete precipitation of the white solid. After filtration, the solid was successively washed with cold water and cold diethylether (or 2-propanol). The hydrazones have been used in the nextstep without further purification.

Reference： [1]Ţînţaş, Mihaela Liliana; Diac, Andreea Petronela; Soran, Albert; Terec, Anamaria; Grosu, Ion; Bogdan, Elena [Journal of Molecular Structure, 2014, vol. 1058, # 1, p. 106 - 113]

23
[ 5785-06-8 ]
[ 222420-23-7 ]
[ 1567311-63-0 ]

Yield	Reaction Conditions	Operation in experiment
70%	With acetic acid at 50℃; for 0.5h;	(Z)-6-hexyl-7-hydroxy-2-(2-(3-methoxybenzoyl)hydrazono)-2H-chromene-3-carboxamide (Z)-6-hexyl-7-hydroxy-2-(2-(3-methoxybenzoyl)hydrazono)-2H-chromene-3-carboxamide (6). A suspension of hydrazide 5 and 2-iminococumarine 4 (3 g) in acetic acid (10 mL) was heated at 50 °C for 30 minutes. The reaction mixture was cooled to room temperature followed by addition of water. The formed solid was filtered off to provide pure product 6 in 70% yield (4.1 g).
70%	With acetic acid at 50℃; for 0.5h;	(Z)-6-hexyl-7-hydroxy-2-(2-(3-methoxybenzoyl)hydrazono)-2H-chromene-3-carboxamide (6) (Z)-6-hexyl-7-hydroxy-2-(2-(3-methoxybenzoyl)hydrazono)-2H-chromene-3-carboxamide (6) A suspension of hydrazide 5 and 2-iminococumarine 4 (3 g) in acetic acid (10 mL) was heated at 50° C. for 30 minutes. The reaction mixture was cooled to room temperature followed by addition of water. The formed solid was filtered off to provide pure product 6 in 70% yield (4.1 g).

Reference： [1]Current Patent Assignee: UNIVERSITY OF SOUTHERN CALIFORNIA - WO2014/28025, 2014, A1 Location in patent: Page/Page column 28-29
[2]Current Patent Assignee: UNIVERSITY OF SOUTHERN CALIFORNIA - US2014/51709, 2014, A1 Location in patent: Paragraph 0112; 0115

24
[ 5785-06-8 ]
(3aS,4R,5R)-5-(3,4,5-Trimethoxy-phenyl)-3,3a,4,5-tetrahydro-2,7,9-trioxa-1-aza-dicyclopenta[a,g]naphthalene-4-carbaldehyde [ No CAS ]
[ 1610059-67-0 ]

Yield	Reaction Conditions	Operation in experiment
76%	With acetic acid In ethanol Reflux;	General Procedure for Synthesis of Compounds 8a-v General procedure: To a mixture of 7 (82.2 mg, 0.20 mmol) and the corresponding hydrazides or hydrazines (0.22 mmol) in EtOH (5 mL), two drops of AcOH was added. Then the above mixture was refluxed. When the reaction was complete according to TLC analysis, the mixture was concentrated in vacuo, and water (20 mL) was added to the residue, which was extracted with DCM (3 × 40 mL). The combined organic phase was dried over anhydrous Na2SO4, concentrated under reduced pressure, and puried by PTLC to afford 8a-v in 62-98% yields.

Reference： [1]Wang, Yi; Yu, Xiang; Zhi, Xiaoyan; Xiao, Xiao; Yang, Chun; Xu, Hui [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 12, p. 2621 - 2624]

25
[ 1445-45-0 ]
[ 5785-06-8 ]
2-(3-methoxyphenyl)-5-methyl-1,3,4-oxadiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	With Al³⁺-K₁₀ montmorillonite clay In neat (no solvent) at 55℃; for 0.25h; Microwave irradiation;	General procedure for 1,3,4-oxadiazole synthesis General procedure: A 5 mL microwave vial was charged with acidhydrazide (100 mg, 1 eq), trimethyl orthoester (2 eq) and Al3+-K10 clay (75 mg). The resulting mixture was kept under microwave irradiation maintaining the temperature at 55 °C for 15 min (Microwave irradiations were performed on CEM-discover model No. 908010). The reaction was monitored by TLC. After completion of the reaction, reaction mixture was diluted with ethyl acetate stirred well, filtered, washed well with ethyl acetate. Filtrate was evaporated under reduced pressure to obtain highly pure product. In some cases, products were purified by column chromatography using 60-120 mesh silica with 20-100 % ethyl acetate in pet ether as eluting solvents. The catalyst recovered by filtration was reused for another 5 more times.

Reference： [1]Suresh, Dhanusu; Kanagaraj, Kuppusamy; Pitchumani, Kasi [Tetrahedron Letters, 2014, vol. 55, # 27, p. 3678 - 3682]

26
[ 5785-06-8 ]
C₃₉H₆₀O₈ [ No CAS ]
C₄₇H₆₈N₂O₉ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
58%	With phosphotungstic acid In N,N-dimethyl-formamide at 60℃; for 4h;	3.6.1. Brevenal Derivatives General procedure: In a typical reaction, brevenal was dissolved in DMF and the hydrazide (2 eq) was added, followed by addition of a catalytic amount of tungstophosphoric acid. The reaction mixture was heated at 60 °C for 4 h. The solvents were evaporated under vacuum and the residue was taken up in methanol. The mixture was filtered through a 0.2 μm nylon filter and subjected to purification by HPLC. Desired products were positively identified by HRMS mass spectrometry and NMR. Spectroscopic data collected for all compounds can be found in the supplementary data document.

Reference： [1]Goodman, Allan; McCall, Jennifer R.; Jacocks, Henry M.; Thompson, Alysha; Baden, Daniel; Abraham, William M.; Bourdelais, Andrea [Marine Drugs, 2014, vol. 12, # 4, p. 1839 - 1858]

27
[ 5785-06-8 ]
[ 79-11-8 ]
[ 36770-18-0 ]

Yield	Reaction Conditions	Operation in experiment
71.5%	With trichlorophosphate for 6h; Reflux;	2. General experimental procedure for synthesis of compound 7 General procedure: A mixture of aryl acid hydrazide (10mmol), chloroacetic acid (10mmol) and POCl3 (7mL) was heated under reflux for 6h. The excess POCl3 was removed under reduced pressure and the residue was poured onto crushed ice. The resuting precipitate was filtered, washed with saturated sodium bicarbonate solution and then with water, dried and recrystallized from ethanol/water to afford compound 7.

Reference： [1]Zhang, Kai; Wang, Peng; Xuan, Li-Na; Fu, Xiao-Yun; Jing, Fen; Li, Sha; Liu, Yu-Ming; Chen, Bao-Quan [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 22, p. 5154 - 5156]

28
[ 110-82-7 ]
[ 5785-06-8 ]
[ 1390625-62-3 ]

Yield	Reaction Conditions	Operation in experiment
58%	With tert.-butylhydroperoxide; copper diacetate; tetra-(n-butyl)ammonium iodide at 140℃; for 36h; Inert atmosphere;	General procedure: A mixture of 1 (0.2 mmol), cycloalkane (2 mL), Cu(OAc)2(10 mol%), TBAI (20 mol%), and TBHP (3 equiv) was stirred at 140 °C under N2 atmosphere for 36 h. The reaction mixture was washed with H2O and the aqueous phase was extracted with EtOAc (3×). The combined organic layer was washed with brine, dried over Na2SO4, and evaporated underreduced pressure. The crude product was purified by silicagel column chromatography to give the corresponding product.

Reference： [1]Liu, Guifeng; Jin, Can; Wu, Guomin [Synlett, 2014, vol. 25, # 20, p. 2908 - 2912]

29
[ 10025-98-6 ]
[ 5785-06-8 ]
[Pd(3-methoxybenzoic acid hydrazide)₂Cl₂] [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
99%	In methanol; water for 1h;	Complex IV or [Pd(3-MH)₂Cl₂] This complex was first synthesized by Ain et al using a different method [20]. In this work, this complex was synthesized as follows: to a solution of K2PdCl4 0.0816g (0.25mmol) in water (5mL), 5.0mL of a methanolic solution of 3-methoxybenzoic hydrazide (0.5mmol) was added dropwise. The mixture was stirred for 1h and the solid formed was separated by filtration, washed with water, methanol and dried under reduced pressure. Yield: 99%. Color: Yellow. Molar weight (gmol-1): 509.32. Anal. Calcd. for [Pd(C8H10N2O2)2Cl2]: C, 37.73; H, 3.97; N, 11.00%; Found: C, 37.25; H, 3.95; N, 10.73%. IR spectra in KBr, ν(cm-1): 3306, 3241, 3203, 3129, 3070, 3032, 3004, 2944, 2837, 1704, 1652, 1621, 1586, 1506, 1488, 1423, 1384, 1322, 1286, 1265, 1246, 1235, 1171, 1131, 1032, 942, 881, 816, 742, 681, 637, 609. ΛM=5.14μs/cm.

Reference： [1]Sousa; Corbi; Formiga; Lancellotti, Marcelo; Marzano; Pereira-Maia; Von Poelhsitz; Guerra [Journal of Molecular Structure, 2015, vol. 1097, p. 15 - 22]

30
[ 5785-06-8 ]
[ 100-06-1 ]
[ 5378-30-3 ]

Yield	Reaction Conditions	Operation in experiment
84%	Stage #1: 1-(4-methoxyphenyl)ethanone With iodine; dimethyl sulfoxide In water at 110℃; for 1h; Sealed tube; Stage #2: 3-methoxybenzoic hydrazide With potassium carbonate In water; dimethyl sulfoxide at 110℃; for 15h; Sealed tube;

Reference： [1]Gao, Qinghe; Liu, Shan; Wu, Xia; Zhang, Jingjing; Wu, Anxin [Organic Letters, 2015, vol. 17, # 12, p. 2960 - 2963]

31
[ 5785-06-8 ]
[ 219861-08-2 ]
(S)-3-{1-(4-fluorophenyl)-5-[5-(3-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-1,3-dihydroisobenzofuran-1-yl}-N,N-dimethylpropan-1-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With potassium carbonate In butan-1-ol at 150℃;	27 Synthesis of escitalopram triazoles General procedure: The triazoles of escitalopram (60-88) were synthesized byfollowing a reported method for triazole formation.25 A mixtureof a benzohydrazide (33 mmol), escitalopram (59-oxalate,10 mmol) and K2CO3 (0.5 mmol) in n-butanol (2 mL) was heatedat 150 C for 5-6 h. The reaction was monitored with TLC. Afterthe completion of the reaction, the solvent was removed underreduced pressure. Finally, the triazole derivatives of escitalopram(60-88) were purified with column chromatography using solventsystem CH3OH/CH3Cl = 60:40 and finally with preparative thinlayer chromatography.

Reference： [1]Mehr-Un-Nisa; Munawar, Munawar A.; Chattha, Fauzia A.; Kousar, Samina; Munir, Jawaria; Ismail, Tayaba; Ashraf, Muhammad; Khan, Misbahul A. [Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 17, p. 6014 - 6024]

32
[ 5785-06-8 ]
[ 50868-68-3 ]
2-[(E)-2-(5-bromothiophen-2-yl)ethenyl]-5-(3-methoxyphenyl)-1,3,4-oxadiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
18%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In ethyl acetate at 160℃; Sealed tube; Inert atmosphere; Microwave irradiation;	23 General procedure for two steps synthesis of 1,3,4-oxadiazole derivatives 8-17 (Method A) and general procedure for one-step synthesis of 1,3,4-oxadiazole derivatives 8-28 (Method B) General procedure: Method B; To a stirred solution of acrylic acid (200mg, 1 eq) and substituted hydrazide (1 eq) in dry ethyl acetate (5-10mL) were added dropwise T3P (3 eq, 50% solution in EtOAc) and triethylamine (5 eq). The reaction vessel was sealed under argon atmosphere and the mixture was heated under microwave conditions at 160°C for 20min to 30min. The completion of reaction was confirmed by TLC. The mixture was cooled to room temperature. The organic layer was washed twice with 1N HCl, once with H2O and once with brine. The organic layer was dried under Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel flash chromatography (cyclohexan/EtOAc or DCM/Methanol) to afford the desired 1,3,4-oxadiazole derivative.; 4.1.2.23 2-[(E)-2-(5-bromothiophen-2-yl)ethenyl]-5-(3-methoxyphenyl)-1,3,4-oxadiazole 28 1H RMN (DMSO-d6, 250 MHz): δ = 7.96 (d, J = 16.2 Hz, 1H), 7.73 (d, J = 8.0 Hz, 1H), 7.64 (d, J = 1.8 Hz, 1H), 7.59 (d, J = 7.9 Hz, 1H), 7.49 (d, J = 4.0 Hz, 1H), 7.38 (d, J = 3.9 Hz, 1H), 7.28 (dd, J = 8.2 Hz and J = 2.6 Hz, 1H), 7.12 (d, J = 16.2 Hz, 1H), 3.93 (s, 3H); 13C NMR (DMSO-d6, 101 MHz): δ = 164.21, 163.72, 160.25, 141.94, 132.46, 131.86, 131.65, 131.29, 124.98, 119.48, 118.52, 115.34, 112.08, 109.51, 56.04; LC/MS (ESI): 362.80 [M+H]+ and isotopic peak: 364.80; purity = 98%; HRMS (TOF, ESI+) cald for C15H12N2O2SBr (M + H)+ 362.9803, found 362.9807; brown solid. Yield = 18%.

Reference： [1]Benmansour, Fatiha; Eydoux, Cécilia; Querat, Gilles; De Lamballerie, Xavier; Canard, Bruno; Alvarez, Karine; Guillemot, Jean-Claude; Barral, Karine [European Journal of Medicinal Chemistry, 2016, vol. 109, p. 146 - 156]

33
[ 100-42-5 ]
[ 5785-06-8 ]
[ 5378-30-3 ]

Yield	Reaction Conditions	Operation in experiment
74%	Stage #1: styrene With iodine; oxygen In dimethyl sulfoxide at 120℃; for 6h; Stage #2: 3-methoxybenzoic hydrazide With oxygen; potassium carbonate In dimethyl sulfoxide at 120℃; for 2h;

Reference： [1]Fan, Yuxing; He, Yongqin; Liu, Xingxing; Hu, Ting; Ma, Haojie; Yang, Xiaodong; Luo, Xinliang; Huang, Guosheng [Journal of Organic Chemistry, 2016, vol. 81, # 15, p. 6820 - 6825]

34
[ 5785-06-8 ]
[ 1225376-13-5 ]
N-(1H-indazol-5-yl)-5-(3-methoxyphenyl)-1,3,4-thiadiazol-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	Stage #1: 3-methoxybenzoic hydrazide; tert-butyl 5-isothiocyanato-1H-indazole-1-carboxylate In dichloromethane at 20℃; for 4h; Stage #2: With sulfuric acid In dichloromethane at 20℃; for 1h;	1.2 Part 2- Synthesis of N-(1H-Indazol-5-yl)-5-(3-methoxyphenyl)-1,3,4-thiadiazol-2-amine 2,2,2-trifluoroacetic acid solvate [00216] To a 50-mL round bottom flask was added a solution of 3-methoxybenzohydrazide (166 mg, 1.00 mmol, 1.00 equiv) in dichloromethane (DCM) (5 mL). tert-Butyl 5- isothiocyanato-1H-indazole-1-carboxylate (275 mg, 1.00 mmol, 1.00 equiv) was added to the reaction mixture. The reaction mixture was stirred at rt for 4 h, until all the starting material was consumed. Concentrated sulfuric acid (0.3 mL, excess) was added to the reaction mixture, and the reaction mixture was stirred at rt for 1 h. An aqueous solution of Na2CO3 (10%, 20 mL) was added to the reaction mixture dropwise. A beige solid precipitated out of solution and was collected by filtration to yield 286 mg (88%) of the desired product as a beige solid. A part of this material (25 mg) was further purified by preparative HPLC to yield 7.4 mg of N-(1H- indazol-5-yl)-5-(3-methoxyphenyl)-1,3,4-thiadiazol-2-amine 2,2,2-trifluoroacetic acid solvate as a white solid. (ES-ESI, m/z): 323.95 [M+H]+; 1H NMR (400 MHz, DMSO-d6 + CD3OD) ^ 8.25-8.33 (m, 1H), 8.08-8.14 (m, 1H), 7.43-7.66 (m, 5H), 8.08-8.14 (m, 1H), 3.90-3.95 (m, 3H).

Reference： [1]Current Patent Assignee: LYCERA CORPORATION - WO2016/138335, 2016, A1 Location in patent: Paragraph 00216

35
[ 5785-06-8 ]
[ 54881-49-1 ]
N-[(2-chloro-3-methoxyphenyl)methylidene]-3-methoxybenzhydrazide [ No CAS ]

Reference： [1]Journal of Enzyme Inhibition and Medicinal Chemistry,2016,vol. 31,p. 62 - 69

36
[ 4903-09-7 ]
[ 5785-06-8 ]
N-[(3-chloro-4-methoxyphenyl)methylidene]-3-methoxybenzhydrazide [ No CAS ]

Reference： [1]Journal of Enzyme Inhibition and Medicinal Chemistry,2016,vol. 31,p. 62 - 69

37
[ 118-48-9 ]
[ 5785-06-8 ]
[ 104-88-1 ]
N-(2-(4-chlorophenyl)-1,2-dihydro-4-oxoquinazolin-3(4H)-yl)-3-methoxybenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	Stage #1: isatoic anhydride; 3-methoxybenzoic hydrazide In ethanol; water Reflux; Green chemistry; Stage #2: 4-chlorobenzaldehyde With N,N,N’,N’-tetrabromobenzene-1,3-disulfonamide In ethanol; water for 1h; Reflux; Green chemistry;	Typical procedure for the preparation of N-(2-(4-chlorophenyl)-1,2-dihydro-4-oxoquinazolin-3(4H)-yl)-3-methoxybenzamide (Table 2, entry 7): In a round flask, a mixture of isatoic anhydride (0.163 g, 1 mmol) and 3-methoxy benzhydrazide (0.16 g, 1 mmol) in 5 mL EtOH/H2O (4:1) were heated and refluxed. Then, TBBDA (0.05 g, 0.10 mmol) or PBBS (0.1 g) and 4-chlorobenzaldehyde (0.14 g,1 mmol) was added to the mixture and stirred for an appropriate time (Table 2,entry 7). After completion of the reaction, when bright blue spot appeared on thin layer chromatography (TLC) [solvent ratio: acetone/n-hexane (8:20)], the solid was filtered and washed with ethanol (2 9 3 mL) and ether. The crude product was recrystallized in hot ethanol (to obtain sulfonamide, the solid was filtered; then, solvent was evaporated and CH2Cl2 (5 mL) was added, the precipitated sulfonamide was recovered by filtration. Furthermore, sulfonamide can be reused for preparation of TBBDA), the pure product (0.38 g, 95 %) was obtained as a cream powder. Mp:199-200 °C; IR (KBr): t (cm-1) 3417, 3199, 1660, 1651, 1580, 1284, 804;1H NMR(400 MHz, DMSO-d6): dH (ppm) 3.75 (s, OCH3, 3H), 4.65 (s, CH, 1H), 6.38 (s, NH,1H), 6.69-7.95 (m, CH aromatic, 12H), 8.9 (s, NH, 1H).13C NMR (100 MHz,DMSO-d6): dc (ppm) 55.29, 74.35, 111.78, 114.66, 114.74, 118.96, 119.29, 119.84,129.05, 129.14, 129.20, 129.34, 129.48, 131.49, 132.55, 134.63, 135.74, 135.85,146.43, 159.46, 164.52, 166.35. MS: m/z 408 (M+, 4 %), 257 (98), 242 (72), 214(13), 180 (84), 151 (18).

Reference： [1]Ghorbani-Vaghei, Ramin; Shahriari, Azadeh; Maghbooli, Yaser; Mahmoudi, Jafar [Research on Chemical Intermediates, 2017, vol. 43, # 2, p. 983 - 993]

38
[ 98-01-1 ]
[ 5785-06-8 ]
2-(2-furyl)-5-(3-methoxyphenyl)-1,3,4-oxadiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	With hydrogenchloride In ethanol for 2h; Reflux;	General procedure for the one-pot synthesis of 2,5-disubstituted 1,3,4-oxadiazoles 4a-s. General procedure: To a stirred solutionof acid hydrazide 1a-i (2.50 mmol) and aldehyde 2a-h (2.50 mmol) in dry toluene (30 mL) were added p-TsOH(0.01 g, 0.05 mmol) and DDQ (0.57 g, 2.50 mmol). The mixture was stirred at reflux until the starting materialwas completely consumed (monitored by TLC, 3 h) and then cooled down to room temperature. Afterfiltration and evaporation of solvent from the filtrate, the resulting residue was purified by silica gel columnchromatography (benzene/EtOAc, 3:1 v/v), affording the pure 1,3,4-oxadiazole derivative 4a-s.
	Multi-step reaction with 2 steps 1: hydrogenchloride / ethanol / 2 h / Reflux 2: 2,3-dicyano-5,6-dichloro-p-benzoquinone / toluene / Reflux

Reference： [1]Jasiak, Karolina; Kudelko, Agnieszka; Zieliński, Wojciech; Kuźnik, Nikodem [Arkivoc, 2016, vol. 2017, # 2, p. 87 - 106]
[2]Jasiak, Karolina; Kudelko, Agnieszka; Zieliński, Wojciech; Kuźnik, Nikodem [Arkivoc, 2016, vol. 2017, # 2, p. 87 - 106]

39
[ 98-01-1 ]
[ 5785-06-8 ]
N'-(2-furylmethylene)-3-methoxybenzhydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With hydrogenchloride In ethanol for 2h; Reflux;	General procedure for the synthesis of N-acylhydrazones 3a-s. General procedure: N-acylhydrazones 3a-s were prepared by HCl catalyzed condensation of acid hydrazides 1a-i with the selected aromatic and aliphatic aldehydes 2a-h in ethanol according to the procedure described in the literature.82 The resulting precipitate was isolated by filtration, washed with EtOH and then recrystallized from EtOH to afford the pure N-acylhydrazone 3a-s.

Reference： [1]Jasiak, Karolina; Kudelko, Agnieszka; Zieliński, Wojciech; Kuźnik, Nikodem [Arkivoc, 2016, vol. 2017, # 2, p. 87 - 106]

40
[ 98-03-3 ]
[ 5785-06-8 ]
3-methoxy-N’-(thiophen-2-yl-methylene)benzohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	With hydrogenchloride In ethanol for 2h; Reflux;	General procedure for the synthesis of N-acylhydrazones 3a-s. General procedure: N-acylhydrazones 3a-s were prepared by HCl catalyzed condensation of acid hydrazides 1a-i with the selected aromatic and aliphatic aldehydes 2a-h in ethanol according to the procedure described in the literature.82 The resulting precipitate was isolated by filtration, washed with EtOH and then recrystallized from EtOH to afford the pure N-acylhydrazone 3a-s.
85%	With hydrogenchloride In ethanol at 20℃;	3.1. Synthesis of N-Acylhydrazones (3-8, 13, and 14) General procedure: The corresponding hydrazide (11a, 11b, 18 or 19) [29,30,37,39] was solubilized inEtOH solution with 1% v/v HCl (0.2-0.3 M). The aldehsyde was added, and the reactionstirred at room temperature. After ca. 30 min to 1 h, a precipitate was formed. The reactionwas monitoressd via TLC (20-70% EtOAc/n-hex) until completion. The work up was madeby evaporating the solvent on a rotary evaporator, the addition of water, and filtrationunder vacuum on a Büchner funnel.

Reference： [1]Jasiak, Karolina; Kudelko, Agnieszka; Zieliński, Wojciech; Kuźnik, Nikodem [Arkivoc, 2016, vol. 2017, # 2, p. 87 - 106]
[2]Barreiro, Eliezer J.; Noël, François G.; Pedreira, Júlia Galvez Bulhões; Silva, Rafaela Ribeiro [Molecules, 2021, vol. 26, # 23]

41
[ 98-03-3 ]
[ 5785-06-8 ]
2-(3-methoxyphenyl)-5-(2-thienyl)-1,3,4-oxadiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	With hydrogenchloride In ethanol for 2h; Reflux;	General procedure for the one-pot synthesis of 2,5-disubstituted 1,3,4-oxadiazoles 4a-s. General procedure: To a stirred solutionof acid hydrazide 1a-i (2.50 mmol) and aldehyde 2a-h (2.50 mmol) in dry toluene (30 mL) were added p-TsOH(0.01 g, 0.05 mmol) and DDQ (0.57 g, 2.50 mmol). The mixture was stirred at reflux until the starting materialwas completely consumed (monitored by TLC, 3 h) and then cooled down to room temperature. Afterfiltration and evaporation of solvent from the filtrate, the resulting residue was purified by silica gel columnchromatography (benzene/EtOAc, 3:1 v/v), affording the pure 1,3,4-oxadiazole derivative 4a-s.

Reference： [1]Jasiak, Karolina; Kudelko, Agnieszka; Zieliński, Wojciech; Kuźnik, Nikodem [Arkivoc, 2016, vol. 2017, # 2, p. 87 - 106]

42
[ 5785-06-8 ]
[ 642-31-9 ]
C₂₃H₁₈N₂O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	With hydrogenchloride In ethanol for 2h; Reflux;	General procedure for the synthesis of N-acylhydrazones 3a-s. General procedure: N-acylhydrazones 3a-s were prepared by HCl catalyzed condensation of acid hydrazides 1a-i with the selected aromatic and aliphatic aldehydes 2a-h in ethanol according to the procedure described in the literature.82 The resulting precipitate was isolated by filtration, washed with EtOH and then recrystallized from EtOH to afford the pure N-acylhydrazone 3a-s.

Reference： [1]Jasiak, Karolina; Kudelko, Agnieszka; Zieliński, Wojciech; Kuźnik, Nikodem [Arkivoc, 2016, vol. 2017, # 2, p. 87 - 106]

43
[ 5785-06-8 ]
[ 642-31-9 ]
2-(9-anthryl)-5-(3-methoxyphenyl)-1,3,4-oxadiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With hydrogenchloride In ethanol for 2h; Reflux;	General procedure for the one-pot synthesis of 2,5-disubstituted 1,3,4-oxadiazoles 4a-s. General procedure: To a stirred solutionof acid hydrazide 1a-i (2.50 mmol) and aldehyde 2a-h (2.50 mmol) in dry toluene (30 mL) were added p-TsOH(0.01 g, 0.05 mmol) and DDQ (0.57 g, 2.50 mmol). The mixture was stirred at reflux until the starting materialwas completely consumed (monitored by TLC, 3 h) and then cooled down to room temperature. Afterfiltration and evaporation of solvent from the filtrate, the resulting residue was purified by silica gel columnchromatography (benzene/EtOAc, 3:1 v/v), affording the pure 1,3,4-oxadiazole derivative 4a-s.
	Multi-step reaction with 2 steps 1: hydrogenchloride / ethanol / 2 h / Reflux 2: 2,3-dicyano-5,6-dichloro-p-benzoquinone / toluene / Reflux

Reference： [1]Jasiak, Karolina; Kudelko, Agnieszka; Zieliński, Wojciech; Kuźnik, Nikodem [Arkivoc, 2016, vol. 2017, # 2, p. 87 - 106]
[2]Jasiak, Karolina; Kudelko, Agnieszka; Zieliński, Wojciech; Kuźnik, Nikodem [Arkivoc, 2016, vol. 2017, # 2, p. 87 - 106]

44
[ 906457-43-0 ]
[ 5785-06-8 ]
(E)-N′-((E)-2-((E)-4-methoxystyryl)-4,6-dimethoxybenzylidene)-3-methoxybenzohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%	With acetic acid In ethanol at 85℃; for 7h;
72%	With acetic acid In ethanol at 85℃; for 7h;	22 Example 22 (E) -N '- ((E) -2 - ((E) -4-methoxystyryl) Dimethoxybenzylidene) -3-methoxybenzoate Manufacture of hydrazides (E) -2- (4-methoxystyryl) -4,6-dimethoxybenzaldehyde (Compound 37; 90 mg, 0.3 mmol) And m-aniso hydrazide (compound 36; 48 mg, 0.3 mmol) were dissolved in ethanol (10 mL). To the reaction mixture was added glacial acetic acid in a catalytic amount, and the reaction mixture was refluxed at 85 DEG C for 7 hours. Next, after cooling to room temperature, the resulting precipitate was filtered and recrystallized from methanol to obtain the target compound (Yield: 72%; m.p: 160-164 degree C)

Reference： [1]Koh, Dongsoo; Jung, Yearam; Ahn, Seunghyun; Mok, Kenneth Hun; Shin, Soon Young; Lim, Yoongho [Magnetic Resonance in Chemistry, 2017, vol. 55, # 9, p. 864 - 876]
[2]Current Patent Assignee: KONKUK UNIVERSITY - KR2018/130974, 2018, A Location in patent: Paragraph 0157-0158

45
[ 73-68-7 ]
[ 5785-06-8 ]
N’-((4-amino-2-methylpyrimidin-5-yl)methylene)-3-methoxybenzohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%	With acetic acid In ethanol for 3h;	23 5.5 General procedure for preparation of target compounds A, B, and C General procedure: Appropriate substituted benzoyl hydrazine 4 (1 equiv) was added to a solution of intermediate 2 (1mmol) in ethanol (10mL). The reaction mixture was stirred for 3h at reflux under the condition of the presence of acetic acid as catalyzer, then poured into cold water and the resulting solid was collected by filtrated, washed with EtOH (10mL), and dried in the atmospheric pressure to give the desired title compounds A, B, and C.

Reference： [1]He, Haifeng; Xia, Hongying; Xia, Qin; Ren, Yanliang; He, Hongwu [Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 20, p. 5652 - 5661]

46
[ 91-02-1 ]
[ 5785-06-8 ]
2-benzoylpyridine-3-methoxybenzhydrazone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	In methanol for 4h; Reflux;	1 2.2.1 Synthesis of 2-benzoylpyridine-3-methoxybenzhydrazone (HL) HL was synthesized by refluxing 0.183 g (1 mmol) of 2-benzoylpyridine in MeOH with 0.166 g (1 mmol) of 3-methoxybenzhydrazide in methanol for 4 h. After one week, yellow crystals separated from the mother liquor on cooling and these were washed with methanol, recrystallized from DMF and dried over P4O10 in vacuo. For HL: Yield: 77% (0.254 g). Color: Yellow. Anal. Calc. for C20H17N3O2 (M.W.: 331.36 g mol-1) C, 55.95; H, 3.76; N, 9.79%. Found: C, 55.98; H, 3.73; N, 9.75%.

Reference： [1]Fousiamol; Sithambaresan; Smolenski, Victoria A.; Jasinski, Jerry P.; Kurup, M.R. Prathapachandra [Polyhedron, 2018, vol. 141, p. 60 - 68]

47
[ 103854-64-4 ]
[ 5785-06-8 ]
C₁₉H₁₇N₃O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol; at 80℃; for 3h;	General procedure: 8-Methoxyquinoline-2-carbaldehyde (25, 0.534 mmol) was refluxedwith various substituted acylhydrazines (0.587 mmol, 1.1 eq) in ethanol(5-10 mL) to get acyl hydrazides of 8-hydroxyquinoline. After completionof reaction, quinoline acyl hydrazides were found as precipitateson cooling to -15 C. Precipitates were washed with coldethanol and dried under vacuum. These acyl hydrazides were used directlyfor one pot synthesis of 2,5-disubstituted-1,3,4-oxadiazole usingiodine/K2CO3 catalysed oxidative cyclization. To the acyl hydrazides(1.0 eq) in DMSO (5-10 mL), K2CO3 (3.0 eq) and iodine (1.2 eq) wereadded in sequence and refluxed at 110 C. After the completion, thereaction mixture was cooled and saturated solution of sodium thiosulfatewas added. The precipitates were collected and dried under highvacuum to get the respective compounds (33-50).

Reference： [1]Bioorganic Chemistry,2018,vol. 80,p. 591 - 601

48
[ 35272-15-2 ]
[ 5785-06-8 ]
N′-(3-methoxybenzoyl)-2-methylthiazole-4-carbohydrazide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2018,vol. 61,p. 5881 - 5899

49
[ 5785-06-8 ]
[ 148-53-8 ]
2-hydroxy-3-methoxybenzaldehyde 3-methoxybenzohydrazone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	In methanol for 3h; Reflux;	2.2.1. Synthesis of the aroylhydrazone ligand: 2-hydroxy-3-methoxybenzaldehyde-3-methoxy-benzohydrazone, (H2L) 2-Hydroxy-3-methoxybenzaldehyde, 0.152 g (1.0mmol) in 20 mlmethanol was added to a methanolic solution of 0.166 g (1.0mmol) of 3-methoxybenzhydrazide. The solution mixture was refluxed with vigorousstirring for 3 h resulting in a light yellow colored solution. Thesolution was then allowed to stand at room temperature. After 4 days alight yellow crystalline compound was obtained which was filtered,washed with methanol and dried in air (Scheme 1). Yield: 0.18 g, 63%;1H NMR (DMSO-d6, δ ppm): 3.8 (3H, OeCH3), 3.8 (3H, OeCH3), 6.8-7.5(7H, aromatic), 8.6 (1H, HC=N), 10.9 (eOH), 12.0 (1H, NeNH).
63%	In methanol for 3h; Reflux;	2-Hydroxy-3-methoxybenzaldehyde-3-methoxybenzhydrazone (H2L3OMe): 2-Hydroxy-3-methoxybenzaldehyde, 0.152 g(1.0 mmol) was dissolved in 20 ml methanol. The solution wasthen added to a methanolic solution of 0.166 g (1.0 mmol) of3-methoxybenzhydrazide. The reaction mixture was refluxed for3 h resulting in a light yellow colored solution. A precipitate wasformed when the solution was allowed to cool at room temperatureovernight. The yellow precipitate obtained was filtered,washed with methanol and dried in air (Scheme 2). Yield: 0.18 g, 63%. Anal. Cal. for C16H16N2O4 (300.31 g mol-1); C,63.99; H, 5.37; N, 9.33. Found: C, 63.92; H, 5.29; N, 9.35. IR (KBr) νmax, cm-1: ν(O-H) 3580(m), ν(N-H) 3184(m), ν(C=O) 1645(s).1H NMR (400 MHz, DMSO-d6, Me4Si, ppm) δ: 3.806 (s, 3H, methoxy),3.824 (s, 3H, methoxy), 6.851-7.520 (m, 7H, aromatic), 8.645 (s, 1H, H=CN), 10.993 (s, 1H, OH group), 12.081 (s, 1H, NHgroup). UV-Vis (DMF) λmax, nm (ε, L mol-1 cm-1): 302 (15600).

Reference： [1]Asha; Kurup, M.R. Prathapachandra [Inorganica Chimica Acta, 2018, vol. 483, p. 44 - 52]
[2]Asha; Kurup [Polyhedron, 2019, vol. 169, p. 151 - 161]

50
[ 5785-06-8 ]
benzene-1,3,5-triyl triformate [ No CAS ]
[ 5378-30-3 ]

Yield	Reaction Conditions	Operation in experiment
45%	With trifluoroacetic acid In toluene at 130℃; for 12h;	1,3,4-Oxadiazoles 2; General Procedure General procedure: A 25 mL pressure tube was charged with arylhydrazide 1 (0.5 mmol), TFBen (53 mg, 0.25 mmol, white solid, mp 57.2-58.5 °C), TFA (38 μL, 1.0 equiv), and toluene (4 mL). The tube was then heated by stirring the contents at 130 °C for 12 h. Afterwards, the mixture was cooled to r.t., quenched with sat. aq NaHCO3 (3 mL), and extracted with EtOAc (3 4 mL). The combined organic layers were dried (anhyd Na2SO4), filtered, and concentrated under reduced pressure. The pure product 2 was obtained after purification by column chromatography (EtOAc/ pentane 1:3).

Reference： [1]Yin, Zhiping; Power, Dennis J.; Wang, Zechao; Stewart, Scott G.; Wu, Xiao-Feng [Synthesis, 2018, vol. 50, # 16, p. 3238 - 3242]

51
[ 5785-06-8 ]
1-(3-methylbut-2-en-1-yl)indoline-2,3-dione [ No CAS ]
3-methoxy-N'-(1-(3-methylbut-2-en-1-yl)-2-oxoindolin-3-ylidene)benzohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
59.8%	With acetic acid In ethanol at 20℃; for 2h;	General method of synthesis of N'-(1-(3-methylbut-2-en-1-yl)-2-oxoindolin-3-ylidene) hydrazine derivatives (S1-S20) General procedure: To intermediate B (0.5 mmol, 109.5 mg) in ethanol (5 mL), substituted benzoyl hydrazine or phenylhydrazine (0.5 mmol) was added. Then 200 μL glacial acetic acid was dripped in. After 2 h, the mixture was filtered and dried. The target compounds S1-S20 was then obtained through silica column (PE:EA = 4:1 v/v). In some cases, ultrasonic vibration can contribute to precipitation. No cis-trans isomerism was found during reaction and NMR data indicated all this series were trans configuration.

Reference： [1]Yang, Yu-Shun; Su, Mi-Mi; Zhang, Xu-Ping; Liu, Qi-Xing; He, Zhen-Xiang; Xu, Chen; Zhu, Hai-Liang [Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 19, p. 3182 - 3186]

52
[ 550363-85-4 ]
[ 5785-06-8 ]
2-fluoro-5-[[(3-methoxyphenyl)formamido]imino}methyl]benzoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	With acetic acid In ethanol at 20℃;

Reference： [1]Ekström, Alexander G.; Wang, Jue Theresa; Bella, Juraj; Campopiano, Dominic J. [Organic and Biomolecular Chemistry, 2018, vol. 16, # 43, p. 8144 - 8149]

53
[ 5785-06-8 ]
[ 100-47-0 ]
3-(3-methoxyphenyl)-5-phenyl-1H-1,2,4-triazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
36%	With potassium carbonate In butan-1-ol at 150℃;	General procedure for synthesis of 3, 5-disubstituted-1H-1, 2, 4-triazoles (6a-l)² General procedure: Hydrazides 5a-l (15 mmol, 1 equiv.) were dissolved in n-butanol (least amount) and nitriles 4a-b (45 mmol, 3 equiv.) was added to the reaction mixture. Potassium carbonate anhydrous (15 mmol, 1 equiv.) was then added and the reaction was heated to 150 C in an oil bath for 4-5 h. The reaction was monitored by TLC (EtOAc/Hexanes 1:1) till no more conversion of starting materials was observed. The reaction mixture was poured into water (50 mL) and the product was extracted with EtOAc (3 x 40 mL). The organic layer was washed with HCl (2N) (3x), brine (1x) and dried over sodium sulphate anhydrous. The solvent was evaporated, and the crude products were purified using column chromatography (EtOAc/Hexanes 1:1).

Reference： [1]Goher, Shaimaa S.; Griffett, Kristine; Hegazy, Lamees; Elagawany, Mohamed; Arief, Mohamed M.H.; Avdagic, Amer; Banerjee, Subhashis; Burris, Thomas P.; Elgendy, Bahaa [Bioorganic and Medicinal Chemistry Letters, 2019, vol. 29, # 3, p. 449 - 453]

54
[ 678556-45-1 ]
[ 5785-06-8 ]
(E)-3-methoxy-N'-(1-(4-methylbenzyl)-3-oxoindolin-2-ylidene)benzohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%	With (4,4'-di-tert-butyl-2,2'-dipyridyl)-bis-(2-phenylpyridine(-1H))-iridium(III) hexafluorophosphate; oxygen; tetra-(n-butyl)ammonium iodide In acetonitrile at 20℃; for 24h; Irradiation; regioselective reaction;

Reference： [1]Shukla, Gaurav; Alam, Tipu; Srivastava, Hemant Kumar; Kumar, Ritush; Patel, Bhisma K. [Organic Letters, 2019, vol. 21, # 10, p. 3543 - 3547]

55
[ 673-22-3 ]
[ 5785-06-8 ]
[ 677313-81-4 ]

Yield	Reaction Conditions	Operation in experiment
67%	In methanol for 3h; Reflux;	2-Hydroxy-3-methoxybenzaldehyde-3-methoxybenzhydrazone (H2L3OMe): General procedure: 2-Hydroxy-3-methoxybenzaldehyde, 0.152 g(1.0 mmol) was dissolved in 20 ml methanol. The solution wasthen added to a methanolic solution of 0.166 g (1.0 mmol) of3-methoxybenzhydrazide. The reaction mixture was refluxed for3 h resulting in a light yellow colored solution. A precipitate wasformed when the solution was allowed to cool at room temperatureovernight. The yellow precipitate obtained was filtered,washed with methanol and dried in air (Scheme 2).

Reference： [1]Asha; Kurup [Polyhedron, 2019, vol. 169, p. 151 - 161]

56
[ 672-13-9 ]
[ 5785-06-8 ]
2-hydroxy-5-methoxybenzaldehyde-3-methoxybenzohydrazone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57%	In methanol for 3h; Reflux;	2-Hydroxy-3-methoxybenzaldehyde-3-methoxybenzhydrazone (H2L3OMe): General procedure: 2-Hydroxy-3-methoxybenzaldehyde, 0.152 g(1.0 mmol) was dissolved in 20 ml methanol. The solution wasthen added to a methanolic solution of 0.166 g (1.0 mmol) of3-methoxybenzhydrazide. The reaction mixture was refluxed for3 h resulting in a light yellow colored solution. A precipitate wasformed when the solution was allowed to cool at room temperatureovernight. The yellow precipitate obtained was filtered,washed with methanol and dried in air (Scheme 2).

Reference： [1]Asha; Kurup [Polyhedron, 2019, vol. 169, p. 151 - 161]

57
[ 5785-06-8 ]
[ 17356-08-0 ]
[ 289710-96-9 ]

Yield	Reaction Conditions	Operation in experiment
90%	With potassium carbonate; dimethyl sulfate In water at 50℃; for 20h; Green chemistry;	General procedure for the preparation of 1,2,4-triazol-5(3)-amines 4a-j General procedure: A suspension of thiourea (1) (0.076 g, 1 mmol), hydrazides 3a-j (1 mmol), dimethyl sulfate (2) (0.063 g, 0.5 mmol) and potassium carbonate (0.069 g, 0.5 mmol) in 4 mL water was heated at 50 °C for 15-20 h. The reaction progress was checked with TLC. The mixture was cooled in an ice bath in order to increase in total precipitation. The solid was fltered of, washed with cold water and ethanol, and dried in an oven at 60 °C without need for further purifcation.

Reference： [1]Beyzaei, Hamid; Khosravi, Zahra; Aryan, Reza; Ghasemi, Behzad [Journal of the Iranian Chemical Society, 2019, vol. 16, # 12, p. 2565 - 2573]

58
[ 118-48-9 ]
[ 5785-06-8 ]
[ 90-02-8 ]
N-(2-(2-hydroxyphenyl)-4-oxo-1,2-dihydroquinazolin-3(4H)-yl)-3-methoxybenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%	Stage #1: isatoic anhydride; 3-methoxybenzoic hydrazide With toluene-4-sulfonic acid In ethanol; water Sonication; Stage #2: salicylaldehyde In ethanol; water Sonication;	2.1.3. General procedure for synthesis of quinazolinone benzamides 4a-4h General procedure: The 50 mL round bottom flask was equipped with an equimolaramount of isatoic anhydride (1 mmol) and m-Anisic hydrazide(1 mmol) in 10 mL of water: ethanol (6:4 v/v) mixed solvent and p-TSA (10 mol %). The resultant reaction mixturewas sonicated till thecompletion of reaction. Then, respective aldehyde (1 mmol) was sequentially added to the same reaction mixture. The reactionmixture was further sonicated, and the progress of reaction wasmonitored by thin layer chromatography (TLC) for specific reactiontime. After completion of reaction, the product was isolated bysimple filtration method and washed with ethanol. Scheme 1 illustratesthe synthetic route for quinazolinone benzamides 4a-4h.The structures of final products 4a-4h shown in Fig. 2. Table 1represents substituents on designed molecule, time required forcompletion of each reaction to form 4a-4h and obtained product yield.

Reference： [1]Mahajan, Prasad G.; Dige, Nilam C.; Vanjare, Balasaheb D.; Raza, Hussain; Hassan, Mubashir; Seo, Sung-Yum; Kim, Chong- Hyeak; Lee, Ki Hwan [Journal of Molecular Structure, 2019, vol. 1198]

59
[ 118-48-9 ]
[ 5785-06-8 ]
[ 100-52-7 ]
3-methoxy-N-(4-oxo-2-phenyl-1,2-dihydroquinazolin-3(4H)-yl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	Stage #1: isatoic anhydride; 3-methoxybenzoic hydrazide With toluene-4-sulfonic acid In ethanol; water Sonication; Stage #2: benzaldehyde In ethanol; water Sonication;	2.1.3. General procedure for synthesis of quinazolinone benzamides 4a-4h General procedure: The 50 mL round bottom flask was equipped with an equimolaramount of isatoic anhydride (1 mmol) and m-Anisic hydrazide(1 mmol) in 10 mL of water: ethanol (6:4 v/v) mixed solvent and p-TSA (10 mol %). The resultant reaction mixturewas sonicated till thecompletion of reaction. Then, respective aldehyde (1 mmol) was sequentially added to the same reaction mixture. The reactionmixture was further sonicated, and the progress of reaction wasmonitored by thin layer chromatography (TLC) for specific reactiontime. After completion of reaction, the product was isolated bysimple filtration method and washed with ethanol. Scheme 1 illustratesthe synthetic route for quinazolinone benzamides 4a-4h.The structures of final products 4a-4h shown in Fig. 2. Table 1represents substituents on designed molecule, time required forcompletion of each reaction to form 4a-4h and obtained product yield.

Reference： [1]Mahajan, Prasad G.; Dige, Nilam C.; Vanjare, Balasaheb D.; Raza, Hussain; Hassan, Mubashir; Seo, Sung-Yum; Kim, Chong- Hyeak; Lee, Ki Hwan [Journal of Molecular Structure, 2019, vol. 1198]

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	5785-06-8	MDL No. :	MFCD00007601
Formula :	C₈H₁₀N₂O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	VMZSDAQEWPNOIB-UHFFFAOYSA-N
M.W :	166.18 g/mol	Pubchem ID :	79848
Synonyms :

Num. heavy atoms :	12
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.12
Num. rotatable bonds :	3
Num. H-bond acceptors :	3.0
Num. H-bond donors :	2.0
Molar Refractivity :	43.83
TPSA :	64.35 Å²

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-7.03 cm/s

Log Po/w (iLOGP) :	1.54
Log Po/w (XLOGP3) :	0.4
Log Po/w (WLOGP) :	0.3
Log Po/w (MLOGP) :	0.88
Log Po/w (SILICOS-IT) :	0.19
Consensus Log Po/w :	0.66

[ CAS No. 5785-06-8 ]

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[ 5785-06-8 ] Synthesis Path-Downstream 1~59

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

Log S (ESOL) :	-1.29
Solubility :	8.44 mg/ml ; 0.0508 mol/l
Class :	Very soluble
Log S (Ali) :	-1.32
Solubility :	8.0 mg/ml ; 0.0481 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-2.16
Solubility :	1.15 mg/ml ; 0.00695 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	2.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.26

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P301+P312-P302+P352-P304+P340-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

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[ CAS No. 5785-06-8 ]

Quality Control of [ 5785-06-8 ]

Related Doc. of [ 5785-06-8 ]

Product Details of [ 5785-06-8 ]

Calculated chemistry of [ 5785-06-8 ]

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[ 5785-06-8 ] Synthesis Path-Downstream 1~59

Related Functional Groups of [ 5785-06-8 ]

Aryls

Ethers

Amides

Hydrazides

Amines

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Precautionary Statements-General

Prevention

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Related Functional Groups of
[ 5785-06-8 ]