Name: 574-17-4|1-Acetylindoline-2,3-dione|98%
Brand: Ambeed
SKU: A349426
Price: 26.0 USD
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1
[ 574-17-4 ]
[ 64-17-5 ]
[ 84859-27-8 ]
[ 108897-91-2 ]

Reference： [1]Journal of the Chemical Society,1959,p. 2825,2827

2
[ 574-17-4 ]
[ 84859-27-8 ]
[ 108897-91-2 ]

Reference： [1]Journal of the Chemical Society,1959,p. 2825,2827

3
[ 574-17-4 ]
[ 15733-89-8 ]

Reference： [1]Synthetic Communications,2005,vol. 35,p. 2243 - 2250
[2]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,2008,vol. 47,p. 117 - 128
[3]Archiv der Pharmazie,1899,vol. 237,p. 687
[4]Helvetica Chimica Acta,1957,vol. 40,p. 499
[5]Journal of the Chemical Society,1926,p. 2908
[6]Journal of the Chemical Society,1926,p. 2908

4
[ 574-17-4 ]
[ 32375-61-4 ]

Yield	Reaction Conditions	Operation in experiment
90%	With acetic acid In water at 30℃; for 48h;
	With sodium hydroxide at 90℃;
	With sodium carbonate

	With sodium acetate
	With sodium hydroxide Faellen der Loesung mit verd. Schwefelsaeure;

Reference： [1]Abuzeid, Mahmoud A.; Aly, Moustafa F.; Dardeer, Hemat M.; Elboray, Elghareeb E. [Egyptian Journal of Chemistry, 2022, vol. 65, # 1, p. 341 - 351]
[2]Aeschlimann [Journal of the Chemical Society, 1926, p. 2908]
[3]Aeschlimann [Journal of the Chemical Society, 1926, p. 2908]
[4]Aeschlimann [Journal of the Chemical Society, 1926, p. 2908]
[5]Suida [Chemische Berichte, 1878, vol. 11, p. 586] Camps [Archiv der Pharmazie, 1899, vol. 237, p. 687]

5
[ 91-56-5 ]
[ 108-24-7 ]
[ 574-17-4 ]

Yield	Reaction Conditions	Operation in experiment
95%	at 80℃; for 0.166667h; Reflux;	3.2. Synthesis of 1-Acetyl-1H-indole-2,3-dione (N-acetylisatin) (1) Microwave method (B): A multimode reactor (Anton Paar GmbH Synthos 3000, 1,400 W maximummagnetron) was used. The initial step was conducted with a 2-Teflon vessels rotor (MF 100). Isatin(5 mmol) was suspended in acetic anhydride (10 mL) and the reaction was processed by heating thevessels for 5 min. at 80 °C and holding it at the same temperature for 5 min (under 0.2/s bar pressure,400 W). Cooling was accomplished by a fan (for 5 min) and the desired product was obtained as ayellow needle in excellent yield without further recrystallization. The spectral data were in accordancewith the data reported in the literature [30].
95%	With sulfuric acid for 0.0833333h; Reflux;	1 Example 1-Synthesis of 1-Acetylindoline-2,3-Dione (Compound 1) N-acetylindoline-2,3-dione can be obtained from N-acetylation of isatin with acetic anhydride, under reflux for 4 hours, providing this compound 1 in 83% yield. An optimized alternative method consists in reacting isatin with five equivalents of acetic anhydride and two drops of concentrated sulfuric acid for 5 minutes to produce the compound 1 in 95% yield. This Compound 1 was characterized by mass spectrometry coupled to gas chromatography (GC-MS), presenting a fragmentation profile compatible with its chemical structure. The melting point was consistent with the one disclosed in the literature. (0034) In a bitubulated flask coupled to a reflux condenser, 1 g of indoline-2,3-dione, five equivalents of acetic anhydride and two drops of sulfuric acid were added. The reaction medium was kept at reflux with magnetic stirring for 5 minutes. The flask was then cooled to room temperature and taken to the freezer (-20° C.) for 12 hours. The obtained solid was washed with water and allowed to air dry. The product was recrystallized from ethyl acetate:hexane (1:1) with active charcoal. The obtained solid was filtered and washed with ice-cold hexane. (0035) Obtained mass: 1.22 g Yield: 95%. (0036) CG-EM: m/z 189 (11%), m/z 146 (100%), m/z 147 (22%), m/z 90 (34%), m/z 43 (45%) (0037) Measured melting point: 141-143° C./Literature: 141° C.
93%	at 160 - 170℃; for 0.5h;

92%	With pyridine at 125℃; Microwave irradiation;
91%	With sodium acetate at 102℃; for 0.05h;
90%	for 6h; Reflux;
89%	With sulfuric acid for 0.0833333h; Reflux;	Isatin 3a (2.0 g, 1 equiv) was dissolved in 20 mL of acetic anhydride and the reaction mixture was refluxed for ~5 min. The solution obtained was cooled in refrigeration for ~ 12 h and the crude solid product 3e formed was separated by vacuum filtration by washing with copious amount of water to remove the acid impurities. The bright reddish green product 3e formed was dried and used in the next step without any purification. [00209] Yield = 89%. 1H NMR (500 MHz, CDCl3, δ ppm) 8.43 (d, J = 8.3 Hz, 1H), 7.79 (ddd, J = 7.6, 1.4, 0.5 Hz, 1H), 7.74 (ddd, J = 8.3, 7.6, 1.5 Hz, 1H), 7.36 (td, J = 7.5, 0.8 Hz, 1H), 2.75 (s, 3H). 13C NMR (125 MHz, CDCl3, δ ppm) 180.2, 169.7, 158.0, 148.6, 139.0, 126.2, 125.3, 119.2, 118.3, 26.5. FIG.9A shows the 1H NMR spectrum of 3e, and FIG.9B shows the 13C NMR spectrum of 3e
87.3%	With perchloric acid for 2h;
85%	for 4h; Reflux;
82%	for 4h; Heating;
82%	Reflux;	General procedure for the synthesis of 12 (a-e) General procedure: To a 100-mL flask equipped with a reflux condenser wereadded 5-substituted isatin (7a-e) (1 mol) and 20 moles ofpreviously distilled acetic anhydride. The reaction mixturewas kept under magnetic stirring at reflux for 2-4 h until thereaction was complete. The completion of the reaction wasmonitored by TLC. The reaction mixture was cooled in thefreezer for 2 h, and after this time, the precipitate was filteredunder vacuum, washed with hexane and dried at roomtemperature. The solids were recrystallized with hexane andethyl acetate (1:1). The derivatives were characterized byGC-MS, and melting points were compared with the literature(Boechat et al. 2008; James et al. 1989).
82%	for 4h; Reflux;	4.1.1. General procedure for preparing 1-acetylindoline-2,3-dione (27a-d) General procedure: The 1-acetylindoline-2,3-diones (27a-d) were prepared according tothe methodology described in the literature.27 A total of 13 mmol of theproper indoline-2,3-dione (26a-d) and 15 equivalents of freshly distilledacetic anhydride were added to a round-bottom flask connected to areflux condenser. The reaction medium was heated to reflux withmagnetic stirring for 4 h. Then, the flask was cooled to room temperatureand taken to the freezer (-20 C) for 12 h. The formed solid wasfiltered and washed with water and hexane and allowed to air dry. Theproduct was recrystallized in ethyl acetate: hexane (1:1) with activatedcharcoal. The solid formed was filtered and washed with cold hexane.
82%	With sulfuric acid In water at 140℃; for 0.0833333h; Inert atmosphere; Sealed tube;
79%	With phosphorus pentaoxide; perchloric acid In benzene at 50℃;
72%	for 4h; Heating;
70%	for 0.0833333h; microwave irradiation;
62%	at 90 - 100℃; Inert atmosphere;
61%	for 3h; Inert atmosphere; Reflux;
55%	With pyridine
	Darstellung;
	for 2h; Heating;
	for 4h; Heating;
	Reflux;
	With dmap Reflux;
	Reflux;
	at 120℃; for 4h;	Indandione (10.0 g, 0.07 mmol) was placed in around-bottom flask containing 25 mL acetic anhydride and the resulting solution was stirred magnetically under oil-bath for 4 hr at 120°C. After cooling to ambient temperature, the solid was precipitated and washed three times with ether (m.p. 132-35°C). Anal.Calcd for C10H7O3N: C, 63.29; H, 3.56; N, 7.11.Found: C, 63.49; H, 3.70; O, 25.40; N, 7.41%.
	at 100℃; for 4h;	General procedure for the synthesis of N-acetylisatin⁵ A solution of isatins I (2.0 mmol, 1.0 equiv) and Ac2O (5 mL) was heated to 100 °C for 4hs. The reaction was monitored by TLC until I was fully consumed. Volatiles were removed in vacuum to afford the crude product which was purified by column chromatography on silica gel (petroleum ether/ethyl acetate combination) to give N-acetylisatin.
	at 140℃; for 5h;	Procedure for the preparation of 1k-o General procedure: Isatin-derivative S0 (10 mmol) was dissolved in Ac2O (50 mL) at 140 °C for 5 h.After the reaction was completed, the reaction was cooled, the precipitated solid wasfiltered off, washed with petroleum and recrystallized from CH2Cl2 to give purerproduct S3.
	at 20 - 150℃; for 28h;
	With sulfuric acid for 0.0833333h; Reflux;	4.1.1.2. Improved method for N-acetylation of isatins General procedure: To a flask wasadded 13 mmol of the corresponding isatin, 5 equivalents of aceticanhydride and two drops of sulfuric acid. The reaction mediumwasmaintained at reflux for 5 min. The flask was then cooled to roomtemperature and kept at 20 °C for 12 h. The formed solid was washed with water, having sufficient purity to be used in the nextstep.4.1.1.2.1. 1-acetylindoline-2,3-dione (19a). Yield: 95%. Yellowsolid, mp: 141-143 °C (Lit.: 141 C) [45]. MS (EI): m/z 189 (11%), m/z146 (100%), m/z 147 (22%), m/z 90 (34%), m/z 43 (45%)
	for 4h; Reflux;
	With dmap

Reference： [1]El-Faham, Ayman; Al Marhoon, Zainab; Abdel-Megeed, Ahmed; Albericio, Fernando [Molecules, 2013, vol. 18, # 12, p. 14747 - 14759]
[2]Current Patent Assignee: OSWALDO CRUZ FOUNDATION - US2017/369445, 2017, A1 Location in patent: Paragraph 0033-0037
[3]Nayyar, Amit; Jain, Rahul [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2008, vol. 47, # 1, p. 117 - 128]
[4]Location in patent: scheme or table Hossain, Mamun M.; Islam, Rabiul M.; Saha, Sukanta K.; Islam, Mohammad K. [Tetrahedron Letters, 2010, vol. 51, # 8, p. 1155 - 1157]
[5]Somogyi [Bulletin of the Chemical Society of Japan, 2001, vol. 74, # 5, p. 873 - 881]
[6]Boraei, Ahmed T. A.; El Tamany, El Sayed H.; Ali, Ibrahim A. I.; Gebriel, Sara M. [Journal of Heterocyclic Chemistry, 2017, vol. 54, # 5, p. 2881 - 2888]
[7]Current Patent Assignee: UNIVERSITY SYSTEM OF OHIO - WO2021/236489, 2021, A1 Location in patent: Paragraph 00206-00209
[8]Tomchin, A. B.; Fradkina, S. P.; Krylova, I. M.; Khromenkova, Z. A. [Journal of Organic Chemistry USSR (English Translation), 1986, vol. 22, # 11, p. 2163 - 2172][Zhurnal Organicheskoi Khimii, 1986, vol. 22, # 11, p. 2409 - 2420]
[9]Almutairi, Maha S.; Muthu; Prasana, Johanan C.; Chandralekha; Al-Ghamdi, Alwah R.; Attia, Mohamed I. [Open Chemistry, 2017, vol. 15, # 1, p. 225 - 237]
[10]Boechat, Nubia; Kover, Warner B.; Bastos, Monica M.; Romeiro, Nelilma C.; Silva, Alessa S. C.; Santos, Fernanda C.; Valverde, Alessandra L.; Azevedo, Maria L. G.; Wollinger, Wagner; Souza, Thiago M. L.; De Souza, Silmara Lucia Oliveira; De Frugulhetti, Izabel Christina P. P. [Medicinal Chemistry Research, 2007, vol. 15, # 9, p. 492 - 510]
[11]Azevedo, Liviane D.; Bastos, Mônica M.; Vasconcelos, Flávia C.; Hoelz, Lucas V. B.; Junior, Floriano P. S.; Dantas, Rafael F.; de Almeida, Ana C. M.; de Oliveira, Andressa Paula; Gomes, Larissa C.; Maia, Raquel C.; Boechat, Nubia [Medicinal Chemistry Research, 2017, vol. 26, # 11, p. 2929 - 2941]
[12]Boechat, Nubia; Carvalho, Rita C.C.; Ferreira, Maria de Lourdes G.; Coutinho, Julia Penna; Sa, Paula M.; Seito, Leonardo N.; Rosas, Elaine C.; Krettli, Antoniana U.; Bastos, Monica M.; Pinheiro, Luiz C.S. [Bioorganic and Medicinal Chemistry, 2020, vol. 28, # 24]
[13]Prusty, Namrata; Kinthada, Lakshmana K.; Meena, Rohit; Chebolu, Rajesh; Ravikumar, Ponneri Chandrababu [Organic and Biomolecular Chemistry, 2021, vol. 19, # 4, p. 891 - 905]
[14]Tomchin, A.B. [Journal of Organic Chemistry USSR (English Translation), 1981, vol. 17, p. 504 - 510][Zhurnal Organicheskoi Khimii, 1981, vol. 17, # 3, p. 589 - 595]
[15]Padhy; Sahu; Panda; Kar; Misro [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2004, vol. 43, # 5, p. 971 - 975]
[16]El Ashry, El Sayed H.; Ramadan, El Sayed; Hamid, Hamida Abdel; Hagar, Mohamed [Synthetic Communications, 2005, vol. 35, # 17, p. 2243 - 2250]
[17]Banerjee, Prabal; Pandey, Ashok Kumar [RSC Advances, 2014, vol. 4, # 63, p. 33236 - 33244]
[18]Location in patent: body text Allous, Iyad; Comesse, Sebastien; Sanselme, Morgane; Daich, Adam [European Journal of Organic Chemistry, 2011, # 27, p. 5303 - 5310]
[19]Chen, Gang; Hao, Xiaojiang; Wang, Ye; Mu, Shuzhen [Letters in drug design and discovery, 2015, vol. 12, # 10, p. 813 - 818]
[20]Beckmann; Bark [Journal fur praktische Chemie (Leipzig 1954), 1922, vol. <2> 105, p. 328,335] Jacobs; Winstein; Linden [Organic Syntheses, 1948, vol. 28, p. 70]
[21]Suida [Chemische Berichte, 1878, vol. 11, p. 586] Camps [Archiv der Pharmazie, 1899, vol. 237, p. 687]
[22]Karali; Capan; Ergenc; Guersoy [Scientia Pharmaceutica, 1997, vol. 65, # 4, p. 277 - 287] Mashaly; Seleem; El-Behairy; Habib [Polish Journal of Chemistry, 2004, vol. 78, # 11-12, p. 2055 - 2074]
[23]Suida [Chemische Berichte, 1878, vol. 11, p. 586] Camps [Archiv der Pharmazie, 1899, vol. 237, p. 687]
[24]Cheah, Wai Ching; Black, David StC; Goh, Wai Kean; Kumar, Naresh [Tetrahedron Letters, 2008, vol. 49, # 18, p. 2965 - 2968]
[25]Location in patent: body text Ghazzali, Mohamed; El-Faham, Ayman; Abdel-Megeed, Ahmed; Al-Farhan, Khalid [Journal of Molecular Structure, 2012, vol. 1013, p. 163 - 167]
[26]Yang, Wen; Du, Da-Ming [Chemical Communications, 2013, vol. 49, # 78, p. 8842 - 8844]
[27]Jeankumar, Variam U.; Alokam, Reshma; Sridevi, Jonnalagadda P.; Suryadevara, Priyanka; Matikonda, Siddharth S.; Peddi, Santosh; Sahithi, Seedarala; Alvala, Mallika; Yogeeswari, Perumal; Sriram, Dharmarajan [Chemical Biology and Drug Design, 2014, vol. 83, # 4, p. 498 - 506]
[28]Liu, Qing; Wang, Weiwei; Huang, Yan; Zhang, Qi; Hua, Mingqing; Cao, Bennan [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2014, vol. 53, # 8, p. 1110 - 1114]
[29]Liang, Jin-Yan; Wang, Hui; Yang, Yan-Li; Shen, Shou-Jie; Chen, Jian-Xin [Tetrahedron Letters, 2017, vol. 58, # 27, p. 2636 - 2639]
[30]Du, Yonglei; Li, Jian; Chen, Kerong; Wu, Chenglin; Zhou, Yu; Liu, Hong [Beilstein Journal of Organic Chemistry, 2017, vol. 13, p. 1342 - 1349]
[31]Aldilla, Vina R.; Nizalapur, Shashidhar; Martin, Adam; Marjo, Chris E.; Rich, Anne; Yee, Eugene; Suwannakot, Panthipa; Black, David Stc.; Thordarson, Pall; Kumar, Naresh [New Journal of Chemistry, 2017, vol. 41, # 22, p. 13462 - 13471]
[32]Castelo-Branco, Frederico Silva; de Lima, Evanoel Crizanto; Domingos, Jorge Luiz de Oliveira; Pinto, Angelo C.; Lourenço, Maria Cristina S.; Gomes, Karen Machado; Costa-Lima, Mariana Marques; Araujo-Lima, Carlos Fernando; Aiub, Claudia Alessandra Fortes; Felzenszwalb, Israel; Costa, Thadeu Estevam M.M.; Penido, Carmen; Henriques, Maria G.; Boechat, Nubia [European Journal of Medicinal Chemistry, 2018, vol. 146, p. 529 - 540]
[33]Crizanto de Lima, Evanoel; Castelo-Branco, Frederico S.; Maquiaveli, Claudia C.; Farias, André B.; Rennó, Magdalena N.; Boechat; Silva, Edson R. [Bioorganic and Medicinal Chemistry, 2019, vol. 27, # 17, p. 3853 - 3859]
[34]Hu, Wen-Bo; Song, Xixi; Wang, Min-Can [Organic and Biomolecular Chemistry, 2021, vol. 19, # 9, p. 2055 - 2062]

6
[ 120-72-9 ]
[ 574-17-4 ]
[ 75833-81-7 ]

Yield	Reaction Conditions	Operation in experiment
93%	With 1-methyl-3-(4-sulfobutyl)-1H-imidazol-3-ium hydrogensulfate In water at 20℃; for 0.916667h;
90%	at 205℃;

Reference： [1]Location in patent: experimental part Karimi, Narges; Oskooi, Hooesin; Heravi, Majid; Saeedi, Mina; Zakeri, Masoumeh; Tavakoli, Niloofar [Chinese Journal of Chemistry, 2011, vol. 29, # 2, p. 321 - 323]
[2]Bergman, Jan; Eklund, Nils [Tetrahedron, 1980, vol. 36, p. 1445 - 1450]

7
[ 13754-19-3 ]
[ 574-17-4 ]
[ 93065-32-8 ]

Reference： [1]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,1984,vol. 23,p. 114 - 116

8
[ 15108-18-6 ]
[ 574-17-4 ]
1-Acetyl-3-[(1H-benzoimidazol-2-yl)-hydrazono]-1,3-dihydro-indol-2-one [ No CAS ]

Reference： [1]Revue Roumaine de Chimie,1993,vol. 38,p. 1457 - 1460

9
[ 91-56-5 ]
[ 75-36-5 ]
[ 574-17-4 ]

Yield	Reaction Conditions	Operation in experiment
88%	With potassium carbonate In N,N-dimethyl-formamide for 2h; Ambient temperature;
67%	With C₂₁H₁₇N₃O2Cl^(1-)2C₁₈H₁₅P*Ni⁽²⁺⁾; sodium carbonate In dimethyl sulfoxide at 100℃;	3.2. General Procedure for the N-Acylation of heterocycleswith acetyl chloride General procedure: The N-acylation of heterocycles reactions was carried outby the reported procedure [32]. In two necked round bottomflask, complex (0.05mmol), acetyl chloride (0.5mmol), heterocycles(1mmol), Na2CO3 (1mmol) and 3 ml DMSO wererefluxed at 1000 C in a preheated oil bath for 0.5-1 h. Thereaction is monitored with TLC. After the completion of thereaction, 10ml H2O was added and extracted with ethyl acetate(3×20ml). The combined organic phase was washedwith water and brine dried over anhydrous Na2SO4 and concentratedin vacuo. The residue was purified by flash columnchromatography on silica gel (ethyl acetate/petroleum ether2:1) to afford the target product.
50%	With triethylamine In N,N-dimethyl acetamide at 0℃; for 1h; Sealed tube; Inert atmosphere;

With sodium ethanolate 1.) ethanol, room temp.,1 h; 2.) benzene, reflux, 1 h; Yield given. Multistep reaction;

Reference： [1]Radul, O. M.; Zhungietu, G. I.; Rekhter, M. A.; Bukhanyuk, S. M. [Chemistry of Heterocyclic Compounds, 1983, vol. 19, # 3, p. 286 - 288][Khimiya Geterotsiklicheskikh Soedinenii, 1983, # 3, p. 353 - 355]
[2]Hegade, Sujit; Gaikwad, Gautam; Jadhav, Yuvraj; Chavan, Sanjay; Mulik, Ganpatrao [Letters in Organic Chemistry, 2021, vol. 18, # 8, p. 611 - 616]
[3]Xiong, Li; Deng, Rong; Liu, Tingting; Luo, Zhongfeng; Wang, Zijia; Zhu, Xiao-Feng; Wang, Hui; Zeng, Zhuo [Advanced Synthesis and Catalysis, 2019, vol. 361, # 23, p. 5383 - 5391]
[4]Tomchin, A. B.; Fradkina, S. P.; Krylova, I. M.; Khromenkova, Z. A. [Journal of Organic Chemistry USSR (English Translation), 1986, vol. 22, # 11, p. 2163 - 2172][Zhurnal Organicheskoi Khimii, 1986, vol. 22, # 11, p. 2409 - 2420]
[5]Black, David StC.; Condie, Glenn C.; Craig, Donald C.; McConnell, Darryl B. [Molecular Crystals and Liquid Crystals, 2005, vol. 440, p. 141 - 146]

10
[ 13754-19-3 ]
[ 574-17-4 ]
[ 93065-32-8 ]
[ 174320-65-1 ]

Reference： [1]Recueil des Travaux Chimiques des Pays-Bas,1996,vol. 115,p. 31 - 36

11
[ 20662-84-4 ]
[ 574-17-4 ]
C₁₆H₁₆N₂O₄ [ No CAS ]
C₁₆H₁₆N₂O₄ [ No CAS ]

Reference： [1]Organic Letters,2004,vol. 6,p. 4893 - 4895
[2]Journal of Organic Chemistry,2010,vol. 75,p. 7757 - 7768

12
[ 20662-89-9 ]
[ 574-17-4 ]
C₂₉H₂₁N₃O₇ [ No CAS ]

Reference： [1]Organic Letters,2004,vol. 6,p. 4893 - 4895
[2]Journal of Organic Chemistry,2010,vol. 75,p. 7757 - 7768

13
[ 574-17-4 ]
[ 74-86-2 ]
(Z)-1-acetyl-3-buta-1,3-dienyl-3-hydroxy-1,3-dihydro-indol-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	With di[(η-1,2,5,6)-1,5-cyclooctadiene] rhodium hexafluoroantimonate; hydrogen; 2,2'-bis(diphenylphosphino)biphenyl In 1,2-dichloro-ethane at 45℃; for 72h;

Reference： [1]Kong, Jong Rock; Krische, Michael J. [Journal of the American Chemical Society, 2006, vol. 128, # 50, p. 16040 - 16041]

14
[ 574-17-4 ]
[ 504-02-9 ]
[ 109-77-3 ]
1'-acetyl-2-amino-2',5-dioxo-1',2',5,6,7,8-hexahydrospiro[chromene-4,3'-indole]-3-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	With <i>L</i>-proline In ethanol at 20℃; for 0.1h;
88%	With gold(III) chloride trihydrate In decaethylene glycol at 70℃; for 0.5h;
87%	With sodium bromide In ethanol at 20℃; for 0.533333h; Electrolysis;

87%	With tetrabutyl ammonium fluoride In water for 1h; Heating;
85%	With hexamethylenetetramine In water at 60℃; for 0.583333h;

Reference： [1]Location in patent: experimental part Raghuvanshi, Dushyant Singh; Singh, Krishna Nand [Journal of Heterocyclic Chemistry, 2010, vol. 47, # 6, p. 1323 - 1327]
[2]Location in patent: experimental part Kidwai, Mazaahir; Jahan, Anwar; Mishra, Neeraj Kumar [Applied Catalysis A: General, 2012, vol. 425-426, p. 35 - 43]
[3]Elinson, Michail N.; Ilovaisky, Alexey I.; Dorofeev, Alexander S.; Merkulova, Valentina M.; Stepanov, Nikita O.; Miloserdov, Fedor M.; Ogibin, Yuri N.; Nikishin, Gennady I. [Tetrahedron, 2007, vol. 63, # 42, p. 10543 - 10548]
[4]Gao, Shijay; Tsai, Cheng Hsuan; Tseng, Chi; Yao, Ching-Fa [Tetrahedron, 2008, vol. 64, # 38, p. 9143 - 9149]
[5]Wang, Guo-Dong; Zhang, Xiao-Nan; Zhang, Zhan-Hui [Journal of Heterocyclic Chemistry, 2013, vol. 50, # 1, p. 61 - 65]

15
[ 574-17-4 ]
[ 126-81-8 ]
[ 109-77-3 ]
1'-acetyl-2-amino-1',2',5,6,7,8-hexahydro-7,7-dimethyl-2',5-dioxospiro[4H-1-benzopyran-4,3'-[3H]indole]-3-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
99%	With sodium acetate In neat (no solvent) at 25℃; for 0.333333h; Green chemistry;	General procedure General procedure: Isatin 1 (3 mmol), 0.198 g malononitrile (3 mmol),0.420 g dimedone (3 mmol), and 0.025 g sodium acetate(0.3 mmol) were grinded with the pestle in mortar atambient temperature for 15 min. The resulting mixture wasair dried. Crude solid was then put on filter, rinsed withwater (2 9 2 cm3), and dried with water pump.
97%	With sodium bromide In ethanol at 20℃; for 0.533333h; Electrolysis;
92%	With <i>L</i>-proline In ethanol at 20℃; for 0.116667h;

91%	With gold(III) chloride trihydrate In decaethylene glycol at 70℃; for 0.5h;
90%	With tetrabutyl ammonium fluoride In water for 1h; Heating;
88%	In PEG-400 at 50℃; for 0.833333h;
83%	With hexamethylenetetramine In water at 60℃; for 0.416667h;

Reference： [1]Elinson, Michail N.; Ryzhkov, Fedor V.; Zaimovskaya, Tatiana A.; Egorov, Mikhail P. [Monatshefte fur Chemie, 2016, vol. 147, # 4, p. 755 - 760]
[2]Elinson, Michail N.; Ilovaisky, Alexey I.; Dorofeev, Alexander S.; Merkulova, Valentina M.; Stepanov, Nikita O.; Miloserdov, Fedor M.; Ogibin, Yuri N.; Nikishin, Gennady I. [Tetrahedron, 2007, vol. 63, # 42, p. 10543 - 10548]
[3]Location in patent: experimental part Raghuvanshi, Dushyant Singh; Singh, Krishna Nand [Journal of Heterocyclic Chemistry, 2010, vol. 47, # 6, p. 1323 - 1327]
[4]Location in patent: experimental part Kidwai, Mazaahir; Jahan, Anwar; Mishra, Neeraj Kumar [Applied Catalysis A: General, 2012, vol. 425-426, p. 35 - 43]
[5]Gao, Shijay; Tsai, Cheng Hsuan; Tseng, Chi; Yao, Ching-Fa [Tetrahedron, 2008, vol. 64, # 38, p. 9143 - 9149]
[6]Location in patent: experimental part Meshram, Harshadas Mitaram; Kumar, Dachepally Aravind; Prasad, Busam Ramalinga Vara; Goud, Palakuri Ramesh [Helvetica Chimica Acta, 2010, vol. 93, # 4, p. 648 - 653]
[7]Wang, Guo-Dong; Zhang, Xiao-Nan; Zhang, Zhan-Hui [Journal of Heterocyclic Chemistry, 2013, vol. 50, # 1, p. 61 - 65]

16
[ 574-17-4 ]
[ 161528-88-7 ]
[ 1021906-82-0 ]

Yield	Reaction Conditions	Operation in experiment
65%	With sodium hydrogencarbonate In dichloromethane at 0 - 20℃; for 24h;
40%	With sodium hydrogencarbonate In dichloromethane; water at 5 - 20℃; for 24h;	4.1.1. Methyl 2-(2-(2-acetamidophenyl)-2-oxoacetamido)acetate (2a) General procedure: To a stirred solution of the N-acetylisatin (0.50 g, 2.6 mmol) in dichloromethane (10 mL) was added a mixture of glycine methyl ester hydrochloride (1.10 g, 8.9 mmol) and saturated sodium hydrogen carbonate solution (3 mL) in water (7 mL) at 5 °C. The reaction mixture was warmed to room temperature and stirred for 24 h. The organic layer was diluted with dichloromethane (20 mL) and extracted with aqueous hydrochloric acid (0.5 M, 15 mL) and water (20 mL). The organic extract was dried over anhydrous Na2SO4, filtered and concentrated under vacuum. The crude product was purified by gravity column chromatography over silica with dichloromethane to give the title compound 2a as an off-white solid (0.45 g, 62%).

Reference： [1]Cheah, Wai Ching; Black, David StC; Goh, Wai Kean; Kumar, Naresh [Tetrahedron Letters, 2008, vol. 49, # 18, p. 2965 - 2968]
[2]Location in patent: experimental part Cheah, Wai Ching; Wood, Kasey; Black, David Stc; Kumar, Naresh [Tetrahedron, 2011, vol. 67, # 39, p. 7603 - 7610]

17
[ 574-17-4 ]
[ 1021907-07-2 ]
[ 1021906-83-1 ]

Yield	Reaction Conditions	Operation in experiment
55%	With sodium hydrogencarbonate In dichloromethane at 0 - 20℃; for 24h;
36%	With sodium hydrogencarbonate In dichloromethane; water at 5 - 20℃; for 24h;	4.1.1. Methyl 2-(2-(2-acetamidophenyl)-2-oxoacetamido)acetate (2a) General procedure: To a stirred solution of the N-acetylisatin (0.50 g, 2.6 mmol) in dichloromethane (10 mL) was added a mixture of glycine methyl ester hydrochloride (1.10 g, 8.9 mmol) and saturated sodium hydrogen carbonate solution (3 mL) in water (7 mL) at 5 °C. The reaction mixture was warmed to room temperature and stirred for 24 h. The organic layer was diluted with dichloromethane (20 mL) and extracted with aqueous hydrochloric acid (0.5 M, 15 mL) and water (20 mL). The organic extract was dried over anhydrous Na2SO4, filtered and concentrated under vacuum. The crude product was purified by gravity column chromatography over silica with dichloromethane to give the title compound 2a as an off-white solid (0.45 g, 62%).

Reference： [1]Cheah, Wai Ching; Black, David StC; Goh, Wai Kean; Kumar, Naresh [Tetrahedron Letters, 2008, vol. 49, # 18, p. 2965 - 2968]
[2]Location in patent: experimental part Cheah, Wai Ching; Wood, Kasey; Black, David Stc; Kumar, Naresh [Tetrahedron, 2011, vol. 67, # 39, p. 7603 - 7610]

18
[ 574-17-4 ]
[ 1021906-64-8 ]
[ 1021906-90-0 ]

Yield	Reaction Conditions	Operation in experiment
42%	With sodium hydrogencarbonate In dichloromethane; water at 5 - 20℃; for 24h;	4.1.1. Methyl 2-(2-(2-acetamidophenyl)-2-oxoacetamido)acetate (2a) General procedure: To a stirred solution of the N-acetylisatin (0.50 g, 2.6 mmol) in dichloromethane (10 mL) was added a mixture of glycine methyl ester hydrochloride (1.10 g, 8.9 mmol) and saturated sodium hydrogen carbonate solution (3 mL) in water (7 mL) at 5 °C. The reaction mixture was warmed to room temperature and stirred for 24 h. The organic layer was diluted with dichloromethane (20 mL) and extracted with aqueous hydrochloric acid (0.5 M, 15 mL) and water (20 mL). The organic extract was dried over anhydrous Na2SO4, filtered and concentrated under vacuum. The crude product was purified by gravity column chromatography over silica with dichloromethane to give the title compound 2a as an off-white solid (0.45 g, 62%).
30%	With sodium hydrogencarbonate In dichloromethane at 0 - 20℃; for 24h;

Reference： [1]Location in patent: experimental part Cheah, Wai Ching; Wood, Kasey; Black, David Stc; Kumar, Naresh [Tetrahedron, 2011, vol. 67, # 39, p. 7603 - 7610]
[2]Cheah, Wai Ching; Black, David StC; Goh, Wai Kean; Kumar, Naresh [Tetrahedron Letters, 2008, vol. 49, # 18, p. 2965 - 2968]

19
[ 574-17-4 ]
[ 5680-79-5 ]
[ 1021906-66-0 ]

Yield	Reaction Conditions	Operation in experiment
97%	With sodium hydrogencarbonate In dichloromethane at 0 - 20℃; for 24h;
62%	With sodium hydrogencarbonate In dichloromethane; water at 5 - 20℃; for 24h;	4.1.1. Methyl 2-(2-(2-acetamidophenyl)-2-oxoacetamido)acetate (2a) To a stirred solution of the N-acetylisatin (0.50 g, 2.6 mmol) in dichloromethane (10 mL) was added a mixture of glycine methyl ester hydrochloride (1.10 g, 8.9 mmol) and saturated sodium hydrogen carbonate solution (3 mL) in water (7 mL) at 5 °C. The reaction mixture was warmed to room temperature and stirred for 24 h. The organic layer was diluted with dichloromethane (20 mL) and extracted with aqueous hydrochloric acid (0.5 M, 15 mL) and water (20 mL). The organic extract was dried over anhydrous Na2SO4, filtered and concentrated under vacuum. The crude product was purified by gravity column chromatography over silica with dichloromethane to give the title compound 2a as an off-white solid (0.45 g, 62%). Mp 142-145 °C; Rf 0.29 (EtOAc/CH2Cl2, v/v 2:8). Found: C, 56.27; H, 5.16; N, 10.10%. C13H14N2O5 requires: C, 56.11; H, 5.07; N, 10.07%. 1H NMR (300 MHz; CDCl3): δ 10.9 (1H, br s, NHCO), 8.66 (1H, dd, J 1.1, 8.6 Hz, H7), 8.36 (1H, dd, J 1.1, 8.1 Hz, H4), 7.60 (1H, dt, J 1.5, 8.0 Hz, H6), 7.36 (1H, br s, CONH), 7.12 (1H,dt, J 1.5, 7.7 Hz, H5), 4.19 (2H, d, J 5.6 Hz, CONHCH2CO), 3.81 (3H, s, COOCH3), 2.22 (3H, s, COCH3). 13C NMR (75 MHz; CDCl3) δ 190.9, 169.2, 169.1, 162.8, 142.1, 136.6, 134.3, 122.5, 120.6, 118.4, 52.5, 41.1, 25.3. IR (KBr): νmax 3319, 3264, 3077, 2958, 1748, 1673, 1655, 1605, 1582, 1564, 1530, 1451, 1417, 1371, 1333, 1297, 1211, 1166, 1094, 1033, 1004, 979, 966, 941, 764, 708, 681, 598, 524, 490 cm-1. UV (MeOH): λmax 339 ( 3040 cm-1 M-1), 267 (7350), 234 (20,076), 205 (10,940). HRMS (ESI) m/z 301.0800 (M+Na)+, C13H14N2O5Na requires: 301.0795.

Reference： [1]Cheah, Wai Ching; Black, David StC; Goh, Wai Kean; Kumar, Naresh [Tetrahedron Letters, 2008, vol. 49, # 18, p. 2965 - 2968]
[2]Location in patent: experimental part Cheah, Wai Ching; Wood, Kasey; Black, David Stc; Kumar, Naresh [Tetrahedron, 2011, vol. 67, # 39, p. 7603 - 7610]

20
[ 574-17-4 ]
[ 6306-52-1 ]
[ 1021906-67-1 ]

Yield	Reaction Conditions	Operation in experiment
97%	With sodium hydrogencarbonate In dichloromethane at 0 - 20℃; for 24h;
97%	With sodium hydrogencarbonate In dichloromethane; water at 5 - 20℃; for 24h;	4.1.1. Methyl 2-(2-(2-acetamidophenyl)-2-oxoacetamido)acetate (2a) General procedure: To a stirred solution of the N-acetylisatin (0.50 g, 2.6 mmol) in dichloromethane (10 mL) was added a mixture of glycine methyl ester hydrochloride (1.10 g, 8.9 mmol) and saturated sodium hydrogen carbonate solution (3 mL) in water (7 mL) at 5 °C. The reaction mixture was warmed to room temperature and stirred for 24 h. The organic layer was diluted with dichloromethane (20 mL) and extracted with aqueous hydrochloric acid (0.5 M, 15 mL) and water (20 mL). The organic extract was dried over anhydrous Na2SO4, filtered and concentrated under vacuum. The crude product was purified by gravity column chromatography over silica with dichloromethane to give the title compound 2a as an off-white solid (0.45 g, 62%).

Reference： [1]Cheah, Wai Ching; Black, David StC; Goh, Wai Kean; Kumar, Naresh [Tetrahedron Letters, 2008, vol. 49, # 18, p. 2965 - 2968]
[2]Location in patent: experimental part Cheah, Wai Ching; Wood, Kasey; Black, David Stc; Kumar, Naresh [Tetrahedron, 2011, vol. 67, # 39, p. 7603 - 7610]

21
[ 574-17-4 ]
[ 7524-50-7 ]
[ 1021906-68-2 ]

Yield	Reaction Conditions	Operation in experiment
98%	With sodium hydrogencarbonate In dichloromethane at 0 - 20℃; for 24h;
98%	With sodium hydrogencarbonate In dichloromethane; water at 5 - 20℃; for 24h;	4.1.1. Methyl 2-(2-(2-acetamidophenyl)-2-oxoacetamido)acetate (2a) General procedure: To a stirred solution of the N-acetylisatin (0.50 g, 2.6 mmol) in dichloromethane (10 mL) was added a mixture of glycine methyl ester hydrochloride (1.10 g, 8.9 mmol) and saturated sodium hydrogen carbonate solution (3 mL) in water (7 mL) at 5 °C. The reaction mixture was warmed to room temperature and stirred for 24 h. The organic layer was diluted with dichloromethane (20 mL) and extracted with aqueous hydrochloric acid (0.5 M, 15 mL) and water (20 mL). The organic extract was dried over anhydrous Na2SO4, filtered and concentrated under vacuum. The crude product was purified by gravity column chromatography over silica with dichloromethane to give the title compound 2a as an off-white solid (0.45 g, 62%).
58%	With sodium hydrogencarbonate In dichloromethane at 20℃; for 16h;

Reference： [1]Cheah, Wai Ching; Black, David StC; Goh, Wai Kean; Kumar, Naresh [Tetrahedron Letters, 2008, vol. 49, # 18, p. 2965 - 2968]
[2]Location in patent: experimental part Cheah, Wai Ching; Wood, Kasey; Black, David Stc; Kumar, Naresh [Tetrahedron, 2011, vol. 67, # 39, p. 7603 - 7610]
[3]Aldilla, Vina R.; Nizalapur, Shashidhar; Martin, Adam; Marjo, Chris E.; Rich, Anne; Yee, Eugene; Suwannakot, Panthipa; Black, David Stc.; Thordarson, Pall; Kumar, Naresh [New Journal of Chemistry, 2017, vol. 41, # 22, p. 13462 - 13471]

22
[ 574-17-4 ]
[ 13033-84-6 ]
[ 1021906-69-3 ]

Yield	Reaction Conditions	Operation in experiment
98%	With sodium hydrogencarbonate In dichloromethane at 0 - 20℃; for 24h;
98%	With sodium hydrogencarbonate In dichloromethane; water at 5 - 20℃; for 24h;	4.1.1. Methyl 2-(2-(2-acetamidophenyl)-2-oxoacetamido)acetate (2a) General procedure: To a stirred solution of the N-acetylisatin (0.50 g, 2.6 mmol) in dichloromethane (10 mL) was added a mixture of glycine methyl ester hydrochloride (1.10 g, 8.9 mmol) and saturated sodium hydrogen carbonate solution (3 mL) in water (7 mL) at 5 °C. The reaction mixture was warmed to room temperature and stirred for 24 h. The organic layer was diluted with dichloromethane (20 mL) and extracted with aqueous hydrochloric acid (0.5 M, 15 mL) and water (20 mL). The organic extract was dried over anhydrous Na2SO4, filtered and concentrated under vacuum. The crude product was purified by gravity column chromatography over silica with dichloromethane to give the title compound 2a as an off-white solid (0.45 g, 62%).

Reference： [1]Cheah, Wai Ching; Black, David StC; Goh, Wai Kean; Kumar, Naresh [Tetrahedron Letters, 2008, vol. 49, # 18, p. 2965 - 2968]
[2]Location in patent: experimental part Cheah, Wai Ching; Wood, Kasey; Black, David Stc; Kumar, Naresh [Tetrahedron, 2011, vol. 67, # 39, p. 7603 - 7610]

23
[ 574-17-4 ]
[ 2491-18-1 ]
[ 1021906-70-6 ]

Yield	Reaction Conditions	Operation in experiment
85%	With sodium hydrogencarbonate In dichloromethane at 0 - 20℃; for 24h;
85%	With sodium hydrogencarbonate In dichloromethane; water at 5 - 20℃; for 24h;	4.1.1. Methyl 2-(2-(2-acetamidophenyl)-2-oxoacetamido)acetate (2a) General procedure: To a stirred solution of the N-acetylisatin (0.50 g, 2.6 mmol) in dichloromethane (10 mL) was added a mixture of glycine methyl ester hydrochloride (1.10 g, 8.9 mmol) and saturated sodium hydrogen carbonate solution (3 mL) in water (7 mL) at 5 °C. The reaction mixture was warmed to room temperature and stirred for 24 h. The organic layer was diluted with dichloromethane (20 mL) and extracted with aqueous hydrochloric acid (0.5 M, 15 mL) and water (20 mL). The organic extract was dried over anhydrous Na2SO4, filtered and concentrated under vacuum. The crude product was purified by gravity column chromatography over silica with dichloromethane to give the title compound 2a as an off-white solid (0.45 g, 62%).

Reference： [1]Cheah, Wai Ching; Black, David StC; Goh, Wai Kean; Kumar, Naresh [Tetrahedron Letters, 2008, vol. 49, # 18, p. 2965 - 2968]
[2]Location in patent: experimental part Cheah, Wai Ching; Wood, Kasey; Black, David Stc; Kumar, Naresh [Tetrahedron, 2011, vol. 67, # 39, p. 7603 - 7610]

24
[ 574-17-4 ]
[ 10342-47-9 ]
[ 1021906-81-9 ]

Yield	Reaction Conditions	Operation in experiment
65%	With sodium hydrogencarbonate In dichloromethane at 0 - 20℃; for 24h;
40%	With sodium hydrogencarbonate In dichloromethane; water at 5 - 20℃; for 24h;	4.1.1. Methyl 2-(2-(2-acetamidophenyl)-2-oxoacetamido)acetate (2a) General procedure: To a stirred solution of the N-acetylisatin (0.50 g, 2.6 mmol) in dichloromethane (10 mL) was added a mixture of glycine methyl ester hydrochloride (1.10 g, 8.9 mmol) and saturated sodium hydrogen carbonate solution (3 mL) in water (7 mL) at 5 °C. The reaction mixture was warmed to room temperature and stirred for 24 h. The organic layer was diluted with dichloromethane (20 mL) and extracted with aqueous hydrochloric acid (0.5 M, 15 mL) and water (20 mL). The organic extract was dried over anhydrous Na2SO4, filtered and concentrated under vacuum. The crude product was purified by gravity column chromatography over silica with dichloromethane to give the title compound 2a as an off-white solid (0.45 g, 62%).

Reference： [1]Cheah, Wai Ching; Black, David StC; Goh, Wai Kean; Kumar, Naresh [Tetrahedron Letters, 2008, vol. 49, # 18, p. 2965 - 2968]
[2]Location in patent: experimental part Cheah, Wai Ching; Wood, Kasey; Black, David Stc; Kumar, Naresh [Tetrahedron, 2011, vol. 67, # 39, p. 7603 - 7610]

25
[ 60-27-5 ]
[ 574-17-4 ]
C₁₄H₁₄N₄O₄ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 4468 - 4471

26
[ 574-17-4 ]
[ 126-81-8 ]
2-(1-acetyl-3-hydroxy-2-oxo-2,3-dihydro-1H-indol-3-yl)-5,5-dimethylcyclohexane-1,3-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	With sodium bromide In ethanol at 20℃; for 0.0333333h; Electrochemical reaction;

Reference： [1]Location in patent: experimental part Elinson, Michail N.; Merkulova, Valentina M.; Ilovaisky, Alexey I.; Chizhov, Alexander O.; Belyakov, Pavel A.; Barba, Fructuoso; Batanero, Belen [Electrochimica Acta, 2010, vol. 55, # 6, p. 2129 - 2133]

27
[ 574-17-4 ]
[ 21905-78-2 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrazine hydrate; potassium hydroxide In ethylene glycol at 100℃; for 1h;	4.2. General procedure for the synthesis of indolin-2-ones from isatins General procedure: A mixture of substituted isatin (12.3 mmol), hydrazine hydrate (368 mmol), potassium hydroxide (245 mmol), and ethylene glycol (242 mmol) were heated at 100 °C for 1 h. The reaction mixture was cooled on ice bath and acidified using concd HCl (drop wise addition) along with vigorous stirring. The precipitated product was vacuum filtered and washed with hexanes to give substituted indolin-2-ones in 90-95% yield.

Reference： [1]Location in patent: experimental part Jha, Mukund; Chou, Ting-Yi; Blunt, Brian [Tetrahedron, 2011, vol. 67, # 5, p. 982 - 989]

28
[ 574-17-4 ]
[ 1333311-07-1 ]
[ 1333311-12-8 ]

Yield	Reaction Conditions	Operation in experiment
44%	With sodium hydrogencarbonate In dichloromethane; water at 5 - 20℃; for 24h;	4.1.1. Methyl 2-(2-(2-acetamidophenyl)-2-oxoacetamido)acetate (2a) General procedure: To a stirred solution of the N-acetylisatin (0.50 g, 2.6 mmol) in dichloromethane (10 mL) was added a mixture of glycine methyl ester hydrochloride (1.10 g, 8.9 mmol) and saturated sodium hydrogen carbonate solution (3 mL) in water (7 mL) at 5 °C. The reaction mixture was warmed to room temperature and stirred for 24 h. The organic layer was diluted with dichloromethane (20 mL) and extracted with aqueous hydrochloric acid (0.5 M, 15 mL) and water (20 mL). The organic extract was dried over anhydrous Na2SO4, filtered and concentrated under vacuum. The crude product was purified by gravity column chromatography over silica with dichloromethane to give the title compound 2a as an off-white solid (0.45 g, 62%).

Reference： [1]Location in patent: experimental part Cheah, Wai Ching; Wood, Kasey; Black, David Stc; Kumar, Naresh [Tetrahedron, 2011, vol. 67, # 39, p. 7603 - 7610]

29
[ 574-17-4 ]
[ 13515-93-0 ]
[ 1333311-10-6 ]

Yield	Reaction Conditions	Operation in experiment
52%	With sodium hydrogencarbonate In dichloromethane; water at 5 - 20℃; for 24h;	4.1.1. Methyl 2-(2-(2-acetamidophenyl)-2-oxoacetamido)acetate (2a) General procedure: To a stirred solution of the N-acetylisatin (0.50 g, 2.6 mmol) in dichloromethane (10 mL) was added a mixture of glycine methyl ester hydrochloride (1.10 g, 8.9 mmol) and saturated sodium hydrogen carbonate solution (3 mL) in water (7 mL) at 5 °C. The reaction mixture was warmed to room temperature and stirred for 24 h. The organic layer was diluted with dichloromethane (20 mL) and extracted with aqueous hydrochloric acid (0.5 M, 15 mL) and water (20 mL). The organic extract was dried over anhydrous Na2SO4, filtered and concentrated under vacuum. The crude product was purified by gravity column chromatography over silica with dichloromethane to give the title compound 2a as an off-white solid (0.45 g, 62%).

Reference： [1]Location in patent: experimental part Cheah, Wai Ching; Wood, Kasey; Black, David Stc; Kumar, Naresh [Tetrahedron, 2011, vol. 67, # 39, p. 7603 - 7610]

30
[ 574-17-4 ]
[ 32213-95-9 ]
[ 1333311-11-7 ]

Yield	Reaction Conditions	Operation in experiment
81%	With potassium carbonate In acetonitrile at 20℃;	General Method for the synthesis of 4a-f General procedure: L-Amino acid ester (12 mmol) and K2CO3 (1.66 g, 12 mmol) were added to the solution of N-acetylisatin 1 (1.89 g, 10 mmol) in CH3CN (50 mL) with intensive stirring. This mixture was stirred at room temperature overnight. The reaction mixture was then filtered and washed with 10 mL of acetonitrile. The solvent was removed under vacuum to dryness, and the crude product was recrystallized from dichloromethane-hexane to afford the pure product.
54%	With sodium hydrogencarbonate In dichloromethane; water at 5 - 20℃; for 24h;	4.1.1. Methyl 2-(2-(2-acetamidophenyl)-2-oxoacetamido)acetate (2a) General procedure: To a stirred solution of the N-acetylisatin (0.50 g, 2.6 mmol) in dichloromethane (10 mL) was added a mixture of glycine methyl ester hydrochloride (1.10 g, 8.9 mmol) and saturated sodium hydrogen carbonate solution (3 mL) in water (7 mL) at 5 °C. The reaction mixture was warmed to room temperature and stirred for 24 h. The organic layer was diluted with dichloromethane (20 mL) and extracted with aqueous hydrochloric acid (0.5 M, 15 mL) and water (20 mL). The organic extract was dried over anhydrous Na2SO4, filtered and concentrated under vacuum. The crude product was purified by gravity column chromatography over silica with dichloromethane to give the title compound 2a as an off-white solid (0.45 g, 62%).

Reference： [1]El-Faham, Ayman; Al Marhoon, Zainab; Abdel-Megeed, Ahmed; Khattab, Sherine N.; Bekhit, Adnan A.; Albericio, Fernando [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 1, p. 70 - 74]
[2]Location in patent: experimental part Cheah, Wai Ching; Wood, Kasey; Black, David Stc; Kumar, Naresh [Tetrahedron, 2011, vol. 67, # 39, p. 7603 - 7610]

31
[ 574-17-4 ]
[ 1099-45-2 ]
[ 291532-31-5 ]

Yield	Reaction Conditions	Operation in experiment
	In toluene Reflux;
	In dichloromethane at 0℃; for 8h;	4.2 Representative procedure for the synthesis of 3-ylideneoxindoles 1a General procedure: To a stirred solution of ethyl 2-(triphenylphosphoranylidene)acetate (3.83 g, 11.0 mmol) in CH2Cl2 (30.0 mL) was added isatin (1.47 g, 10.0 mmol) at 0 °C. After stirring for 8 h at 0 °C, the mixture was concentrated by rotary evaporation. The residue was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate=3:1-10:1) to afford the compound 1a as a red solid (1.78 g, 82 %).
	In tetrahydrofuran at 0℃;

Reference： [1]Cao, Yiming; Jiang, Xianxing; Liu, Luping; Shen, Fangfang; Zhang, Futing; Wang, Rui [Angewandte Chemie - International Edition, 2011, vol. 50, # 39, p. 9124 - 9127]
[2]Zhao, Jia; Guan, Shuicheng; Zhou, Xiaojian; Han, Wenyong; Cui, Baodong; Chen, Yongzheng [Tetrahedron, 2016, vol. 72, # 22, p. 3098 - 3104]
[3]Liu, Yi-Yin; Duan, Shu-Wen; Zhang, Rui; Liu, Yun-Hang; Chen, Jia-Rong; Xiao, Wen-Jing [Organic and Biomolecular Chemistry, 2016, vol. 14, # 23, p. 5224 - 5228]

32
[ 574-17-4 ]
[ 608-07-1 ]
[ 1340563-64-5 ]

Yield	Reaction Conditions	Operation in experiment
87%	With (R)-3,3'-bis(9-anthracenyl)-1,1'-binaphthyl-2,2'-diyl hydrogenphosphate In dichloromethane at 25℃; Inert atmosphere;	General Procedures for Chiral-Acid Catalyzed Spirocyclization of Tryptamines with Isatins, Method A. General procedure: A solution of isatin (0.035 mmol, 1.2 equiv), tryptamine (0.03 mmol, 1.0 equiv) and (R)-3,3'-bis(9-anthracenyl)-1,1'-binaphthyl-2,2'-diyl hydrogenphosphate (0.006 mmol, 0.2 equiv) was prepared in dry CH2Cl2 (0.06 M) at 25 °C in an oven-dried and Ar-purged 4 mL vial fitted with a magnetic stir bar. The reaction was stirred until it was complete as judged by TLC (80% EtOAc/hexanes). The reaction was then concentrated and loaded onto a flash silica gel column (gradient of EtOAc/hexanes ending in 80% EtOAc/hexanes) to afford the spiroindolone product.

Reference： [1]Badillo, Joseph J.; Silva-García, Abel; Shupe, Benjamin H.; Fettinger, James C.; Franz, Annaliese K. [Tetrahedron Letters, 2011, vol. 52, # 43, p. 5550 - 5553]

33
[ 574-17-4 ]
[ 106-49-0 ]
[ 1370040-05-3 ]

Yield	Reaction Conditions	Operation in experiment
97%	In ethanol at 100℃; for 0.166667h; Microwave irradiation;	2.1.2. Method B (microwave irradiation) General procedure: Employing a multimode reactor (Synthos 3000, Aton Paar GmbH, 1400 W maximum magnetron), the initial step was conducted with 4-Teflon vessels rotor (MF 100). N-acetylisatin (10 mmol) and aniline derivatives (10 mmol) in ethanol (10 mL) were mixed and the reactions were processed by heating the vessels for 5 min. at 100 °C and hold at the same temperature for 5 min (0.2/s bar pressure, 800 W). Cooling was accomplished by a fan (5 min) and the desired product with enhanced yield was filtered and recrystallized from ethanol.

Reference： [1]Location in patent: experimental part Ghazzali, Mohamed; El-Faham, Ayman; Abdel-Megeed, Ahmed; Al-Farhan, Khalid [Journal of Molecular Structure, 2012, vol. 1013, p. 163 - 167]

34
[ 574-17-4 ]
[ 24313-88-0 ]
[ 440117-61-3 ]

Yield	Reaction Conditions	Operation in experiment
92%	In ethanol at 100℃; for 0.166667h; Microwave irradiation;	2.1.2. Method B (microwave irradiation) General procedure: Employing a multimode reactor (Synthos 3000, Aton Paar GmbH, 1400 W maximum magnetron), the initial step was conducted with 4-Teflon vessels rotor (MF 100). N-acetylisatin (10 mmol) and aniline derivatives (10 mmol) in ethanol (10 mL) were mixed and the reactions were processed by heating the vessels for 5 min. at 100 °C and hold at the same temperature for 5 min (0.2/s bar pressure, 800 W). Cooling was accomplished by a fan (5 min) and the desired product with enhanced yield was filtered and recrystallized from ethanol.

Reference： [1]Location in patent: experimental part Ghazzali, Mohamed; El-Faham, Ayman; Abdel-Megeed, Ahmed; Al-Farhan, Khalid [Journal of Molecular Structure, 2012, vol. 1013, p. 163 - 167]

35
[ 574-17-4 ]
[ 106-40-1 ]
[ 440117-49-7 ]

Yield	Reaction Conditions	Operation in experiment
95%	In ethanol at 100℃; for 0.166667h; Microwave irradiation;	2.1.2. Method B (microwave irradiation) General procedure: Employing a multimode reactor (Synthos 3000, Aton Paar GmbH, 1400 W maximum magnetron), the initial step was conducted with 4-Teflon vessels rotor (MF 100). N-acetylisatin (10 mmol) and aniline derivatives (10 mmol) in ethanol (10 mL) were mixed and the reactions were processed by heating the vessels for 5 min. at 100 °C and hold at the same temperature for 5 min (0.2/s bar pressure, 800 W). Cooling was accomplished by a fan (5 min) and the desired product with enhanced yield was filtered and recrystallized from ethanol.

Reference： [1]Location in patent: experimental part Ghazzali, Mohamed; El-Faham, Ayman; Abdel-Megeed, Ahmed; Al-Farhan, Khalid [Journal of Molecular Structure, 2012, vol. 1013, p. 163 - 167]

36
[ 3859-41-4 ]
[ 574-17-4 ]
[ 109-77-3 ]
[ 1374210-50-0 ]

Yield	Reaction Conditions	Operation in experiment
83%	With gold(III) chloride trihydrate In decaethylene glycol at 70℃; for 0.5h;

Reference： [1]Location in patent: experimental part Kidwai, Mazaahir; Jahan, Anwar; Mishra, Neeraj Kumar [Applied Catalysis A: General, 2012, vol. 425-426, p. 35 - 43]

37
[ 574-17-4 ]
[ 107-97-1 ]
[ 130-15-4 ]
[ 1376662-39-3 ]

Yield	Reaction Conditions	Operation in experiment
96%	With air In ethanol for 1.5h; Reflux;	5.1.1. Experimental procedure for the synthesis of spirooxindole derivatives (12a-n) General procedure: A mixture of substituted isatin 8a-n (1 mmol), sarcosine 9 (1 mmol) and 1,4-naphthoquinone 10 (1 mmol) was refluxed in ethanol (5 ml). Completion of the reaction was evidenced by TLC analysis. After completion of the reaction, the reaction mixture was poured into ice-water, the resulting solid was filtered off and purified by column chromatography using ethyl acetate: petroleum ether (3:7) as an eluent to afford pure spirooxindoles (12a-n).

Reference： [1]Location in patent: experimental part Bhaskar, Gangaru; Arun, Yuvaraj; Balachandran, Chandrasekar; Saikumar, Chandrasekara; Perumal, Paramasivan T. [European Journal of Medicinal Chemistry, 2012, vol. 51, p. 79 - 91]

38
[ 38521-46-9 ]
[ 574-17-4 ]
[ 106-49-0 ]
[ 1385027-14-4 ]

Yield	Reaction Conditions	Operation in experiment
88%	With ZSM-5-([MIM]⁺BF₄^-) In water at 95℃; for 0.116667h; Sonication; Green chemistry;
80%	With ZSM-5 zeolyte-supported 1-methylimidazolium tetrafluoroborate In water at 95℃; for 0.25h; Sonication;

Reference： [1]Arya, Kapil; Tomar, Pooja; Singh, Jyoti [RSC Advances, 2014, vol. 4, # 6, p. 3060 - 3064]
[2]Location in patent: experimental part Arya, Kapil; Rawat, Diwan Singh; Sasai, Hiroaki [Green Chemistry, 2012, vol. 14, # 7, p. 1956 - 1963]

39
[ 38521-46-9 ]
[ 574-17-4 ]
[ 104-94-9 ]
[ 1385027-12-2 ]

Yield	Reaction Conditions	Operation in experiment
89%	With ZSM-5 zeolyte-supported 1-methylimidazolium tetrafluoroborate In water at 95℃; for 0.216667h; Sonication;
87%	With ZSM-5-([MIM]⁺BF₄^-) In water at 95℃; for 0.166667h; Sonication; Green chemistry;

Reference： [1]Location in patent: experimental part Arya, Kapil; Rawat, Diwan Singh; Sasai, Hiroaki [Green Chemistry, 2012, vol. 14, # 7, p. 1956 - 1963]
[2]Arya, Kapil; Tomar, Pooja; Singh, Jyoti [RSC Advances, 2014, vol. 4, # 6, p. 3060 - 3064]

40
[ 574-17-4 ]
[ 68014-21-1 ]
[ 1373942-85-8 ]

Yield	Reaction Conditions	Operation in experiment
83%	In 1,4-dioxane Inert atmosphere; Reflux;
	In 1,4-dioxane for 6h; Reflux;

Reference： [1]Yan, Wenjin; Wang, Dong; Feng, Jingchao; Li, Peng; Zhao, Depeng; Wang, Rui [Organic Letters, 2012, vol. 14, # 10, p. 2512 - 2515]
[2]Feng, Jingchao; Yan, Wenjin; Wang, Dong; Li, Peng; Sun, Quantao; Wang, Rui [Chemical Communications, 2012, vol. 48, # 64, p. 8003 - 8005]

41
[ 14678-02-5 ]
[ 67-52-7 ]
[ 574-17-4 ]
[ 1397289-46-1 ]

Yield	Reaction Conditions	Operation in experiment
68%	With toluene-4-sulfonic acid In water at 70℃; for 24h;	4.4. General procedure for the synthesis of spiro[indoline-isoxazolo[4',3':5,6]pyrido[2,3-d]pyrimidine]triones (6) General procedure: A solution of isatin (1 mmol), barbituric acid (1 mmol), 3-amino-5-methyl isoxazole (1 mmol), and p-TsOH (0.2 mmol) in water (10 mL) was stirred for 24 h at 70 °C in oil bath. After completion of the reaction, which was followed by TLC (n-hexane/EtOAc), the warm reaction mixture was filtered. The residue was washed with water and then recrystallized from ethanol to give the pure product.

Reference： [1]Location in patent: experimental part Rahmati, Abbas; Khalesi, Zahra [Tetrahedron, 2012, vol. 68, # 40, p. 8472 - 8479]

42
[ 14678-02-5 ]
[ 769-42-6 ]
[ 574-17-4 ]
[ 1397289-53-0 ]

Yield	Reaction Conditions	Operation in experiment
57%	With toluene-4-sulfonic acid In water at 70℃; for 24h;	4.4. General procedure for the synthesis of spiro[indoline-isoxazolo[4',3':5,6]pyrido[2,3-d]pyrimidine]triones (6) General procedure: A solution of isatin (1 mmol), barbituric acid (1 mmol), 3-amino-5-methyl isoxazole (1 mmol), and p-TsOH (0.2 mmol) in water (10 mL) was stirred for 24 h at 70 °C in oil bath. After completion of the reaction, which was followed by TLC (n-hexane/EtOAc), the warm reaction mixture was filtered. The residue was washed with water and then recrystallized from ethanol to give the pure product.

Reference： [1]Location in patent: experimental part Rahmati, Abbas; Khalesi, Zahra [Tetrahedron, 2012, vol. 68, # 40, p. 8472 - 8479]

43
[ 574-17-4 ]
[ 614-20-0 ]
[ 141939-07-3 ]

Yield	Reaction Conditions	Operation in experiment
95%	In ethyl acetate at 20℃; for 1h; Molecular sieve; Sealed tube;	General procedure: To a mixture of isatin 4a (14.7 mg, 0.1 mmol) and β-ketoacid 2a (19.7 mg, 0.12 mmol) inethyl acetate (1.0 mL) at room temperature was added 4 Å molecular sieve (5 mg). The flaskwas sealed, and the reaction mixture was stirred 1 hr. The mixture was filtered and thefiltrate was then concentrated. The residue was purified directly by column chromatographyon silica gel using hexane/ethyl acetate (5:1 to 2:1) as an eluent to afford 5a as a white solid(24.8 mg, 93% yield).

Reference： [1]Zhong, Fangrui; Jiang, Chunhui; Yao, Weijun; Xu, Li-Wen; Lu, Yixin [Tetrahedron Letters, 2013, vol. 54, # 32, p. 4333 - 4336]

44
[ 574-17-4 ]
[ 1439-36-7 ]
C₁₃H₁₁NO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In toluene at 90℃;
	In dichloromethane at 20℃; for 8h;	Procedure for the preparation of 1a-j General procedure: To a stirred solution of S0 (10 mmol) in CH2Cl2 (180 mL) was added slowlytriphenylphosphoranylidene-2-propanon (11 mmol, 1.1 equiv) in CH2Cl2 (20 mL) atroom temperature, and the resulting mixture was stirred at the same temperature for 8hours. Then the mixture was concentrated under reduced pressure, and the crudeproduct was purified by column chromatography on silica gel to afford the desiredproduct S1 (yield, 90%).

Reference： [1]Yang, Wen; Du, Da-Ming [Chemical Communications, 2013, vol. 49, # 78, p. 8842 - 8844]
[2]Du, Yonglei; Li, Jian; Chen, Kerong; Wu, Chenglin; Zhou, Yu; Liu, Hong [Beilstein Journal of Organic Chemistry, 2017, vol. 13, p. 1342 - 1349]

45
[ 574-17-4 ]
[ 97-02-9 ]
[ 1558013-10-7 ]

Yield	Reaction Conditions	Operation in experiment
56%	With triethylamine In dichloromethane at 20℃; for 24h; Inert atmosphere;	Synthesis of 2-(2-acetamidophenyl)-N-(2,4-dinitrophenyl)-2-oxoacetamide 5 This compound was prepared by the same method as compound 4 from N-acetylisatin (5.29 mmol, 1.01 g), 2,4-dinitroaniline (5.29 mmol, 0.97 g) and triethylamine (2.5 mL) as an off-white solid (1.11 g, 56%). M.p. 174 °C; UV(MeOH): λmax 228 (ε 50,086 cm-1 M-1), 261 (29,350), 330 (26,650); IR (KBr): νmax 3448, 3336, 3226, 3110, 2770, 2497, 1957, 1739, 1632, 1581, 1520, 1453, 1388, 1324, 1262, 1168, 1127, 1061, 982, 925, 834, 743 cm-1, 1H NMR (300 MHz, acetone-d6): δ 2.20 (s, 3H, COCH3), 7.23-7.28 (m, 2H, Ar-H), 7.67-7.74 (m, 1H, ArH), 7.82 (dd, J = 8.0, 1.6 Hz, 1H, ArH), 7.94 (s, 1H, COCONH), 8.22 (dd, J = 9.3, 2.7 Hz, 1H, ArH), 8.61(dd, J = 8.5, 0.9 Hz, 1H, ArH), 8.92 (d, J = 2.7 Hz, 1H, ArH), 10.87 (s, 1H, NHCO); 13C NMR (75 MHz, acetone-d6): δ 24.10 (COCH3), 117.84, 119.37, 120.19, 141.79, 149.5 (5 * ArC), 119.45, 120.27, 122.60, 123.14, 129.24, 133.20, 136.25 (7 * ArCH), 164.16, 168.78, 190.93 (3 * C=O); MS (TOF-ESI) m/z calculated for C16H13N4O7 (M + H)+ 373.07. Found 373.08; Anal. Calcd. for C16H12N4O7. H2O: C = 49.24; H = 3.62; N = 14.35. Found: C, 49.57; H, 3.49; N, 14.26%.

Reference： [1]Suryanti, Venty; Bhadbhade, Mohan; Chawla, Har Mohindra; Howe, Ethan; Thordarson, Pall; Black, David Stc; Kumar, Naresh [Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2014, vol. 121, p. 662 - 669]

46
[ 574-17-4 ]
[ 100-01-6 ]
[ 1558013-09-4 ]

Yield	Reaction Conditions	Operation in experiment
63%	With triethylamine In dichloromethane at 20℃; for 24h; Inert atmosphere;	Synthesis of 2-(2-acetamidophenyl)-N-(4-nitrophenyl)-2-oxoacetamide 4 A mixture of N-acetylisatin (5.29 mmol, 1.02 g), 4-nitroaniline (5.29 mmol, 0.73 g) and triethylamine (2.5 mL) in dry dichloromethane (50 mL) was stirred at room temperature for 24 h under nitrogen. The resulting precipitate was collected and washed with hydrochloric acid (0.5 M, 75 mL) and subsequently with dichloromethane (75 mL). The title compound was obtained as an off-white solid (1.09 g, 63%). M.p. 232 °C; UV(MeOH): λmax 230 (ε 28,050 cm-1 M-1), 321 (22,050); IR (KBr): νmax 3244, 3213, 3051, 3018, 1702, 1671, 1654, 1591, 1542, 1508, 1453, 1410, 1374, 1335, 1296, 1243, 1165, 1041, 997, 853, 763 cm-1; 1H NMR (300 MHz, acetone-d6): δ 2.13 (s, 3H, COCH3), 7.24-7.28 (m, 1H, ArH), 7.64-7.69 (m, 1H, ArH), 7.97 (dd, J = 8.0, 1.6 Hz, 1H, ArH), 8.13 (d, J = 9.3 Hz, 2H, ArH), 8.18 (dd, J = 8.4, 1.0 Hz, 1H, ArH), 8.32 (d, J = 9.3 Hz, 2H, ArH), 10.42 (s, 1H, COCONH), 10.48 (s, 1H, NHCO), 13C NMR (75 MHz, acetone-d6): δ 23.6 (COCH3), 119.4, 120.71, 120.4, 123.0, 124.8, 132.7, 135.0 (7 * ArCH), 119.9, 124.3, 125.3, 143.9 (4 * ArC), 162.0, 168.8, 189.9 (3 * C=O); HRMS (ESI) m/z calculated for C16H14N3O5 (M + H)+ 328.0855. Found 328.0922; Anal. Calcd. for C16H13N3O5: C, 58.72; H, 4.00; N, 12.84. Found: C, 58.98; H, 3.95; N, 13.00%.

Reference： [1]Suryanti, Venty; Bhadbhade, Mohan; Chawla, Har Mohindra; Howe, Ethan; Thordarson, Pall; Black, David Stc; Kumar, Naresh [Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2014, vol. 121, p. 662 - 669]

47
[ 606-23-5 ]
[ 574-17-4 ]
[ 134-32-7 ]
1'-acetylspiro[benzo[h]indeno[1,2-b]quinoline-7,3'-indoline]-2',8(13H)-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	With acetic acid at 80℃; for 24h;
68%	With acetic acid at 80℃; for 24h;	General procedure for the synthesisof 8H-spiro[benzo[h]quinoline-7,3-indolines] 4a-n General procedure: A solution of an isatin (3) (1 mmol), a C-H acidderivative (2) (1 mmol), and naphthalen-1-amine (1)(1 mmol) was heated at 80 C in acetic acid (5 mL)for 24 h. After completion of the reaction as indicatedby TLC (MeOH/AcOEt, 1:4), the residue wasfiltered and washed successively with gl. acetic acid andCHCl3 (3 × 10 ml). The crude product thus obtainedwas crystallized from MeOH or EtOH and dried atroom temperature. The final product was obtained as a powder.

Reference： [1]Rahmati, Abbas; Eskandari-Vashareh, Miranda [Journal of Chemical Sciences, 2014, vol. 126, # 1, p. 169 - 176]
[2]Rahmati, Abbas; Eskandari-Vashareh, Miranda [Journal of Chemical Sciences, 2014, vol. 126, # 1, p. 169 - 176]

48
[ 574-17-4 ]
[ 1616063-62-7 ]
[ 1616063-77-4 ]

Yield	Reaction Conditions	Operation in experiment
77%	In ethanol for 10h; Reflux;	4.1.17 4-(3-(1-Acetyl-2-oxoindolin-3-ylideneamino)-5-(4-bromophenyl)-4-imino-3,4-dihydropyrrolo[2,3-d]pyrimidin-7-yl)benzenesulfonamide (23) A mixture of 8 (4.59 g, 0.01 mol) and N-acetylisatin (1.75 g, 0.01 mol) in absolute ethanol (30 mL) was refluxed for 10 h. After cooling the product was filtered off and recrystallized from dioxane to give 23. (0036) Yield% 77, mp 340.3 °C; IR (KBr, cm-1): 3298, 3210 (NH, NH2), 1691, 1683 (2C=O), 1585 (C=N), 1338, 1161 (SO2). 1H NMR (DMSO-d6) δ 2.1 [s, 3H, COCH3], 6.6 [s, 1H, CH pyrrole], 7.2-8.6 [m, 14H, Ar-H+SO2NH2], 9.4 [s, 1H, CH pyrimidine], 10.5 [s, 1H, NH, D2O-exchangeable]. 13C NMR (DMSO-d6) δ 18.5, 110.1, 117.3, 118.1, 120.1, 120.8, 122.9 (2), 123.2, 124.5, 124.8, 127.0 (2), 130.1, 130.7 (2), 131.6, 131.9 (2), 132.3, 138.2, 141.5, 143.1, 144.0, 160.0, 164.3, 167.8, 173.8. Anal. Calcd for C28H20BrN7O4S (630.47): C, 53.34; H, 3.20; N, 15.55. Found: C, 53.10; H, 3.57; N, 15.21.

Reference： [1]Ghorab, Mostafa M.; Alsaid, Mansour S.; Ceruso, Mariangela; Nissan, Yassin M.; Supuran, Claudiu T. [Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 14, p. 3684 - 3695]

49
[ 574-17-4 ]
[ 150-13-0 ]
[ 702669-44-1 ]

Yield	Reaction Conditions	Operation in experiment
86%	In methanol at 80℃; for 0.0666667h; Sealed tube;	3.3. Synthesis of 4-(2-(2-Acetamidophenyl)-2-oxoacetamido)benzoic Acid (3) Microwave method (B): A multimode reactor (Synthos 3000 Aton Paar, GmbH, 1400 W maximummagnetron) was used. The initial step was conducted with 2-Teflon vessels rotor (MF 100) that allowsthe reaction to be processed under the same conditions. N-acetylisatin and 4-aminobenzoic acid weremixed in methanol as a solvent in the presence or absence of glacial acetic acid (2-3 drops).The individual vessels were placed in the corresponding rotor, and finally the rotor was closed with aprotective hood. The vessels were heated for 2 min. at 80 °C and held at the same temperature foranother 2 min (~2 bar pressure, 400 W). Cooling was accomplished by a fan (5 min). The final productwas washed with cold methanol, and then dried under vacuum to afford the product in a pure state asobserved from spectral analysis.
86%	With acetic acid In methanol for 1h; Reflux;	Synthesis of 4-(2-(2-acetamidophenyl)-2-oxoacetamido)benzoic acid 5 N-acetylisatin and 4-aminobenzoic acid were refluxed in methanol as a solvent in the presence of glacial acetic acid (2-3 drops) for 1 h. After cooling, the solid product was filtered, washed with cold methanol, and then dried under vacuum to afford the product in a pure form.

Reference： [1]El-Faham, Ayman; Al Marhoon, Zainab; Abdel-Megeed, Ahmed; Albericio, Fernando [Molecules, 2013, vol. 18, # 12, p. 14747 - 14759]
[2]El-Faham, Ayman; Al Marhoon, Zainab; Abdel-Megeed, Ahmed; Khattab, Sherine N.; Bekhit, Adnan A.; Albericio, Fernando [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 1, p. 70 - 74]

50
[ 574-17-4 ]
[ 1361200-95-4 ]
(E)-methyl 2-((E)-(1-acetyl-2-oxoindolin-3-ylidene)methyl)-3-phenylacrylate [ No CAS ]
(E)-methyl 2-((Z)-(1-acetyl-2-oxoindolin-3-ylidene)methyl)-3-phenylacrylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate In acetonitrile at 20℃; for 3h;	Typical Procedure for the Synthesis of 3a. General procedure: A mixture of MBH bromide 1a-Z (306 mg, 1.2 mmol) and PPh3 (315 mg, 1.2 mmol) in CH3CN (3.0 mL) was stirred at room temperature for 4 h. The corresponding phosphonium salt, monitored by TLC, was formed quantitatively. To the reaction mixture, isatin (2a, 147 mg, 1.0 mmol) and K2CO3 (276 mg, 2.0 mmol) were added, and the reaction mixture was stirred at room temperature for 3 h. After the usual aqueous extractive work-up and column chromatographic purification process (hexanes/EtOAc, 2:1), compounds 3a-EE (156 mg, 51%) and 3a-ZE (125 mg, 41%) were obtained as yellow solids. Other compounds were synthesized similarly.

Reference： [1]Moon, Hye Ran; Kim, Ko Hoon; Lee, Junseong; Kim, Jae Nyoung [Bulletin of the Korean Chemical Society, 2015, vol. 36, # 1, p. 219 - 225]

51
[ 574-17-4 ]
[ 99-61-6 ]
C₁₇H₁₂N₄O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With zirconium(IV) oxide; ammonium acetate In neat (no solvent) at 110℃; for 0.5h;

Reference： [1]Bajpai, Shivam; Singh, Sundaram; Srivastava, Vandana [RSC Advances, 2015, vol. 5, # 36, p. 28163 - 28170]

52
[ 574-17-4 ]
[ 23239-88-5 ]
ethyl 4-(2-(2-acetamidophenyl)-2-oxoacetamido)benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	With potassium carbonate In acetonitrile at 20℃;	General Method for the synthesis of 4a-f General procedure: L-Amino acid ester (12 mmol) and K2CO3 (1.66 g, 12 mmol) were added to the solution of N-acetylisatin 1 (1.89 g, 10 mmol) in CH3CN (50 mL) with intensive stirring. This mixture was stirred at room temperature overnight. The reaction mixture was then filtered and washed with 10 mL of acetonitrile. The solvent was removed under vacuum to dryness, and the crude product was recrystallized from dichloromethane-hexane to afford the pure product.

Reference： [1]El-Faham, Ayman; Al Marhoon, Zainab; Abdel-Megeed, Ahmed; Khattab, Sherine N.; Bekhit, Adnan A.; Albericio, Fernando [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 1, p. 70 - 74]

53
[ 574-17-4 ]
[ 7517-19-3 ]
methyl 2-(2-(2-acetamidophenyl)-2-oxoacetamido)-4-methylpentanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	With potassium carbonate In acetonitrile at 20℃;	General Method for the synthesis of 4a-f General procedure: L-Amino acid ester (12 mmol) and K2CO3 (1.66 g, 12 mmol) were added to the solution of N-acetylisatin 1 (1.89 g, 10 mmol) in CH3CN (50 mL) with intensive stirring. This mixture was stirred at room temperature overnight. The reaction mixture was then filtered and washed with 10 mL of acetonitrile. The solvent was removed under vacuum to dryness, and the crude product was recrystallized from dichloromethane-hexane to afford the pure product.

Reference： [1]El-Faham, Ayman; Al Marhoon, Zainab; Abdel-Megeed, Ahmed; Khattab, Sherine N.; Bekhit, Adnan A.; Albericio, Fernando [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 1, p. 70 - 74]

54
[ 574-17-4 ]
[ 3196-73-4 ]
methyl 3-(2-(2-acetamidophenyl)-2-oxoacetamido)propanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	With potassium carbonate In acetonitrile at 20℃;	General Method for the synthesis of 4a-f General procedure: L-Amino acid ester (12 mmol) and K2CO3 (1.66 g, 12 mmol) were added to the solution of N-acetylisatin 1 (1.89 g, 10 mmol) in CH3CN (50 mL) with intensive stirring. This mixture was stirred at room temperature overnight. The reaction mixture was then filtered and washed with 10 mL of acetonitrile. The solvent was removed under vacuum to dryness, and the crude product was recrystallized from dichloromethane-hexane to afford the pure product.

Reference： [1]El-Faham, Ayman; Al Marhoon, Zainab; Abdel-Megeed, Ahmed; Khattab, Sherine N.; Bekhit, Adnan A.; Albericio, Fernando [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 1, p. 70 - 74]

55
[ 574-17-4 ]
[ 13031-60-2 ]
methyl 4-(2-(2-acetamidophenyl)-2-oxoacetamido)butanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With potassium carbonate In acetonitrile at 20℃;	General Method for the synthesis of 4a-f General procedure: L-Amino acid ester (12 mmol) and K2CO3 (1.66 g, 12 mmol) were added to the solution of N-acetylisatin 1 (1.89 g, 10 mmol) in CH3CN (50 mL) with intensive stirring. This mixture was stirred at room temperature overnight. The reaction mixture was then filtered and washed with 10 mL of acetonitrile. The solvent was removed under vacuum to dryness, and the crude product was recrystallized from dichloromethane-hexane to afford the pure product.

Reference： [1]El-Faham, Ayman; Al Marhoon, Zainab; Abdel-Megeed, Ahmed; Khattab, Sherine N.; Bekhit, Adnan A.; Albericio, Fernando [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 1, p. 70 - 74]

56
[ 574-17-4 ]
[ 1926-80-3 ]
methyl 6-(2-(2-acetamidophenyl)-2-oxoacetamido)hexanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	With potassium carbonate; In acetonitrile; at 20℃;	General procedure: L-Amino acid ester (12 mmol) and K2CO3 (1.66 g, 12 mmol) were added to the solution of N-acetylisatin 1 (1.89 g, 10 mmol) in CH3CN (50 mL) with intensive stirring. This mixture was stirred at room temperature overnight. The reaction mixture was then filtered and washed with 10 mL of acetonitrile. The solvent was removed under vacuum to dryness, and the crude product was recrystallized from dichloromethane-hexane to afford the pure product.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 70 - 74

57
[ 574-17-4 ]
[ 27271-28-9 ]
ethyl-(E)-4-((E)-1-acetyl-2-oxoindolin-3-ylidene)-3-ethoxybut-2-enoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	In toluene at 85℃; for 2.5h; Inert atmosphere;	Generalprocedure for the synthesis of 1. General procedure: To an oven-dried round bottom flask was added N-acetyl isatin xx and yilde xx dissolved in 10 mL toluene, the reaction mixture was stirred at 85 °C, After completion of the reaction (the reaction was monitored by TLC plate), the residue was purified by a flash column chromatography (ethyl acetate/ petroleum ether = 1:5, Rf= 0.5) to yield 1 as a colorless solid.

Reference： [1]Liu, Yufen; Du, Yanlong; Yu, Aimin; Qin, Dabin; Meng, Xiangtai [Tetrahedron, 2015, vol. 71, # 40, p. 7706 - 7716]

58
[ 574-17-4 ]
C₂₅H₂₅O₃P [ No CAS ]
ethyl (E)-4-((E)-1-acetyl-2-oxoindolin-3-ylidene)-3-methoxybut-2-enoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	In toluene at 85℃; for 2h; Inert atmosphere;	Generalprocedure for the synthesis of 1. General procedure: To an oven-dried round bottom flask was added N-acetyl isatin xx and yilde xx dissolved in 10 mL toluene, the reaction mixture was stirred at 85 °C, After completion of the reaction (the reaction was monitored by TLC plate), the residue was purified by a flash column chromatography (ethyl acetate/ petroleum ether = 1:5, Rf= 0.5) to yield 1 as a colorless solid.

Reference： [1]Liu, Yufen; Du, Yanlong; Yu, Aimin; Qin, Dabin; Meng, Xiangtai [Tetrahedron, 2015, vol. 71, # 40, p. 7706 - 7716]

59
[ 574-17-4 ]
[ 22632-36-6 ]
N-(2-(2-oxo-2-(2-(2-propylpentanoyl)hydrazinyl)acetyl)phenyl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	With acetic acid In ethanol Reflux;	General Method for Preparation of N′-(2-Oxoindolin-3-ylidene)-2-propylpentane HydrazideDerivatives 4a-h General procedure: A solution of valproic hydrazide 2 (316 mg, 2 mmol) in ethanol (20 mL) was added to a solution ofsubstituted isatin 3a-h (1 mmol) in ethanol (20 mL), and glacial acetic acid (2 drops); the reaction mixturewas refluxed for 3-4 h. The product was separated out on cooling, filtered, and recrystallized from ethanolor ethylacetate to afford N′-(2-oxoindolin-3-ylidene)-2-propylpentanehydrazide derivatives 4a-h.

Reference： [1]El-Faham, Ayman; Farooq, Muhammad; Khattab, Sherine N.; Abutaha, Nael; Wadaan, Mohammad A.; Ghabbour, Hazem A.; Fun, Hoong-Kun [Molecules, 2015, vol. 20, # 8, p. 14638 - 14655]

60
[ 67-56-1 ]
[ 574-17-4 ]
[ 2719-08-6 ]

Yield	Reaction Conditions	Operation in experiment
68%	With [bis(acetoxy)iodo]benzene at 20℃; for 48h;	General experimental procedure for the synthesis of alkyl 2-acetamidobenzoate from Nacetylisatin: General procedure: To the stirred solution of N-acetyl isatin (1 mmol) in an appropriate alcohol (5mL), (diacetoxyiodo)benzene (2 mmol) was added. The reaction mixture was stirred for 48 hat room temperature. The progress of the reaction was monitored by TLC. After completionof reaction, the solvent was evaporated on rotatory vacuum evaporator and the crude productwas purified by column chromatography using petroleum ether and ethyl acetate to afford 4agin moderate yields.

Reference： [1]Kalbandhe, Amit H.; Kavale, Ashish C.; Thorat, Prerana B.; Karade, Nandkishor N. [Synlett, 2016, vol. 27, # 5, p. 763 - 768]

61
[ 574-17-4 ]
[ 64-17-5 ]
[ 20628-20-0 ]

Yield	Reaction Conditions	Operation in experiment
62%	With [bis(acetoxy)iodo]benzene at 20℃; for 48h;	General experimental procedure for the synthesis of alkyl 2-acetamidobenzoate from Nacetylisatin: General procedure: To the stirred solution of N-acetyl isatin (1 mmol) in an appropriate alcohol (5mL), (diacetoxyiodo)benzene (2 mmol) was added. The reaction mixture was stirred for 48 hat room temperature. The progress of the reaction was monitored by TLC. After completionof reaction, the solvent was evaporated on rotatory vacuum evaporator and the crude productwas purified by column chromatography using petroleum ether and ethyl acetate to afford 4agin moderate yields.

Reference： [1]Kalbandhe, Amit H.; Kavale, Ashish C.; Thorat, Prerana B.; Karade, Nandkishor N. [Synlett, 2016, vol. 27, # 5, p. 763 - 768]

62
[ 574-17-4 ]
[ 79-19-6 ]
C₁₁H₁₀N₄O₂S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	With 1,1'-sulfinyldipyridinium bis (hydrogen sulfate) In ethanol at 20℃; for 1h; Green chemistry;	The general procedure for the synthesis of 1,2,4-triazole-3-thiones [4] General procedure: A mixture of ketone (1 mmol), thiosemicarbazide (1 mmol), and 10 mol% of [(Py)2SO][HSO4]2 in ethanol (5 mL) was stirred at room temperature for the time specified in Table 2 till completion of reaction, monitored by TLC. After completion of reaction, the mixture was cooled and filtered to furnish the desired product in good yields.

Reference： [1]Patil, Pradeep B.; Patil, Jayavant D.; Korade, Suyog N.; Kshirsagar, Siddheshwar D.; Govindwar, Sanjay P.; Pore, Dattaprasad M. [Research on Chemical Intermediates, 2016, vol. 42, # 5, p. 4171 - 4180]

63
[ 574-17-4 ]
[ 3749-51-7 ]
[ 109-77-3 ]
C₁₉H₁₄N₄O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	With pyridine; for 1h;Reflux; Green chemistry;	General procedure: Isatin 1 (3 mmol), malononitrile (3 mmol), <strong>[3749-51-7]4-hydroxy-6-methylpyridin-2(1H)-one</strong> 2 (3 mmol) were refluxed for 60 minin ethanol (5 ml) with sodium acetate (10 molpercent) or in pyridine (without any catalyst). After the reaction was finished, the solid was filtered,washed with ice ethanol and dried to isolate pure products 3. For their characteristics, see Online Supplementary Materials.

Reference： [1]Mendeleev Communications,2016,vol. 26,p. 399 - 401

64
[ 59-48-3 ]
[ 574-17-4 ]
[ 476-34-6 ]

Yield	Reaction Conditions	Operation in experiment
69%	With zirconium(IV) chloride In ethanol Reflux;	General procedure for the synthesis of isoindigo derivatives 3 General procedure: A mixture of isatins (1, 1.0 mmol), indolin-2-ones (2, 1.0 mmol) and ZrCl4 (23 mg, 0.1 mmol) was heated in anhydrous ethanol (5 mL) under reflux. After the disappearance of the reactants (8-12 h, monitored by TLC), the mixture was slowly cooled to room temperature. The red solids precipitated and were collected by filtration, then washed by a small amount of anhydrous ethanol to deliver pure compounds 3.

Reference： [1]Liu, Meilin; Qiu, Shaozhong; Ye, Yu; Yin, Guodong [Tetrahedron Letters, 2016, vol. 57, # 52, p. 5856 - 5858]

65
[ 574-17-4 ]
[ 479486-96-9 ]
C₁₆H₂₂N₂O₄Si [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	In benzene at 60℃; for 0.1h; Molecular sieve; Inert atmosphere;	General procedure for the reaction of carbamoylsilane with isatin derivatives General procedure: A 5 mL of two-necked flask with 25 mg of freshly activated 4Å molecular sieves and micro stirbar was flame heated under vacuum and refilled with Nitrogen. Isatin derivative (0.10 mmol, in 0.5 mL of benzene, 0.5 M) was charged to the cooled round bottom under argon, followed by addition of carbamoylsilane (0.15 mmol) in 0.1 mL of benzene. The sealed reaction mixture was stirred at 60 °C until no isatin derivatives could be detected by TLC. Volatiles were removed in vacuum to afford the crude product which was purified by column chromatography on silica gel (petroleum ether/ethyl acetate combination) to give compound 3.6

Reference： [1]Liang, Jin-Yan; Wang, Hui; Yang, Yan-Li; Shen, Shou-Jie; Chen, Jian-Xin [Tetrahedron Letters, 2017, vol. 58, # 27, p. 2636 - 2639]

66
[ 574-17-4 ]
[ 63-74-1 ]
[ 947253-66-9 ]

Yield	Reaction Conditions	Operation in experiment
65%	With acetic acid In ethanol for 4h;	General procedure: 4-Aminobenzenesulfanilamide (0.002 M, 0.34g) in ethanol (10 mL) was added to astirred solution of 1-(furan-2-yl)ethanone (0.002 M,0.22 g) in ethanol (10 mL) followed by 2-3 drops of acetic acid. The reaction mixture was stirred for 4 h with continuous monitoring by TLC. The mixture was left overnight at room temperature. Precipitate formedwas filtered off, washed with cold ethanol, then withether, dried, and recrystallized from a mixture ofethanol:dichloromethane (1 : 1). Ligands L2 and L3 were synthesized according to the same method.

Reference： [1]Rani; Sumrra; Chohan [Russian Journal of General Chemistry, 2017, vol. 87, # 8, p. 1834 - 1842][Zh. Obshch. Khim.]

67
[ 50-00-0 ]
[ 574-17-4 ]
[ 17356-08-0 ]
[ 135-19-3 ]
C₂₂H₁₇N₃O₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	With toluene-4-sulfonic acid In ethanol at 20℃;	4 14.2. General procedure for synthesis of 2-naphthalenol-indolin-2-one-thiocarbamides (5a-l) General procedure: In the reaction, β-naphthol (0.01 mol), thiourea (0.01 mol),formaldehyde (0.01 mol) and different substituted isatin (0.01 mol)were stirred in ethanol in the presence of p-toluenesulfonic acid (p-TSA) (0.001 mol) at room temperature for 8 h. All the reactions were monitored by thin-layer chromatography (TLC) and the solid precipitated out were confirmed by Gas Chromatography MS(GCMS). After the reaction was complete, the mixture wasconcentrated and purified by flash column chromatography onsilica gel (petroleum ether/EtOAc as the eluent 10:1 v/v) to furnish the corresponding product 5a-l.

Reference： [1]Manikandan; Moharil, Pearl; Sathishkumar; Muñoz-Garay; Sivakumar [European Journal of Medicinal Chemistry, 2017, vol. 141, p. 417 - 426]

68
[ 574-17-4 ]
1-acetyl-3,3-difluoroindolin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	With diethylamino-sulfur trifluoride In dichloromethane at 20℃; for 16h; Sealed tube; Inert atmosphere;	4.1.2. General procedure for preparing 1-acetyl-3,3-difluoroindolin-2-ones(28a-d) General procedure: The 1-acetyl-3,3-difluoroindolin-2-ones (28a-d) were prepared accordingto methodology described in the literature.27 The corresponding1-acetyl-indoline-2,3-dione (27a-d) (6 mmol) was added to a roundbottomflask and then sealed with a septum. The atmosphere of thesystem was replaced by argon, and 37 equivalents of freshly distilledanhydrous dichloromethane were added. The mixture was stirred for 5min. Then, 2 equivalents of diethylaminosulfur trifluoride (DAST) wereadded through a syringe. The reaction medium was stirred for 16 h atroom temperature under argon atmosphere. After this period, the reactionmixture was poured into crushed ice. The organic phase wasseparated, washed 2 times with distilled water, dried with anhydrous Na2SO4 and concentrated under a vacuum. The product was purified byvacuum sublimation and stored in amber vials in an argon atmosphere.
91%	With diethylamino-sulfur trifluoride In dichloromethane at 20℃; for 4h;	General procedure for the synthesis of 13 (a-e) General procedure: To a 250-mL flask were added 1 mol of (12a-e) and50 mL of fresh distilled dichloromethane (CH2Cl2). Next, 4moles of DAST were added, and the reaction mixture wasmaintained under magnetic stirring at room temperature for4 h. The completion of the reaction was monitored byTLC, and the mixture was poured onto ice. The organiclayer was washed with distilled water (3 × 30 mL), and thedichloromethane solution was dried with anhydrous sodiumsulfate, dried and filtered. The solvent was evaporated in arotavapor, and the product was vacuum dried. Derivativeswere characterized by GC-MS and melting points arecompared with the literature (Cheah et al. 2008).
65%	With diethylamino-sulfur trifluoride In dichloromethane at 20℃; for 16h; Inert atmosphere;	4.1.2.1. General procedure General procedure: The corresponding 1-acetyl-indoline-2,3-dione (6 mmol) and a magnet were added to a round-bottomflask and then sealed with a septum. The atmosphere of the systemwas replaced by argon, and 37 equivalents of freshly distilledanhydrous dichloromethane were added. The mixture was stirredfor 5 min. Then, 2 equivalents of diethylaminosulfur trifluoride(DAST) were added through a syringe. The reaction medium wasstirred for 16 h at room temperature under argon atmosphere. Afterthis period, the reaction mixture was poured into crushed ice. Theorganic phase was separated, washed 2 times with distilled water,dried with anhydrous Na2SO4 and concentrated under vacuum. Theproduct was purified by vacuum sublimation and stored in ambervials in an argon atmosphere.4.1.2.1.1. 1-acetyl-3,3-difluoroindolin-2-one (20a). Yield: 65%.Off-white solid, mp: 110e113 C (Lit.: 109-111 °C) [22]. MS (EI): m/z211 (13%), m/z 169 (100%), m/z 141 (66%), m/z 114 (12%), m/z 43(61%).

With diethylamino-sulfur trifluoride In dichloromethane at 20℃; for 16h; chemoselective reaction;

Reference： [1]Boechat, Nubia; Carvalho, Rita C.C.; Ferreira, Maria de Lourdes G.; Coutinho, Julia Penna; Sa, Paula M.; Seito, Leonardo N.; Rosas, Elaine C.; Krettli, Antoniana U.; Bastos, Monica M.; Pinheiro, Luiz C.S. [Bioorganic and Medicinal Chemistry, 2020, vol. 28, # 24]
[2]Azevedo, Liviane D.; Bastos, Mônica M.; Vasconcelos, Flávia C.; Hoelz, Lucas V. B.; Junior, Floriano P. S.; Dantas, Rafael F.; de Almeida, Ana C. M.; de Oliveira, Andressa Paula; Gomes, Larissa C.; Maia, Raquel C.; Boechat, Nubia [Medicinal Chemistry Research, 2017, vol. 26, # 11, p. 2929 - 2941]
[3]Castelo-Branco, Frederico Silva; de Lima, Evanoel Crizanto; Domingos, Jorge Luiz de Oliveira; Pinto, Angelo C.; Lourenço, Maria Cristina S.; Gomes, Karen Machado; Costa-Lima, Mariana Marques; Araujo-Lima, Carlos Fernando; Aiub, Claudia Alessandra Fortes; Felzenszwalb, Israel; Costa, Thadeu Estevam M.M.; Penido, Carmen; Henriques, Maria G.; Boechat, Nubia [European Journal of Medicinal Chemistry, 2018, vol. 146, p. 529 - 540]
[4]Crizanto de Lima, Evanoel; Castelo-Branco, Frederico S.; Maquiaveli, Claudia C.; Farias, André B.; Rennó, Magdalena N.; Boechat; Silva, Edson R. [Bioorganic and Medicinal Chemistry, 2019, vol. 27, # 17, p. 3853 - 3859]

69
[ 60-27-5 ]
[ 574-17-4 ]
1-acetyl-3-hydroxy-3-(2-imino-3-methyl-5-oxoimidazolidin-4-yl)indolin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	With chloroauric acid; In water; for 0.5h;Reflux;	General procedure: Water (15 mL) was added to a mixture of 1.0 mmol of isatin derivative, 1.2 mmol of <strong>[60-27-5]creatinine</strong> (for 2p, 2.3 mmol of <strong>[60-27-5]creatinine</strong>) and 1 mol% of HAuCl4 and the resulting suspension was heated to reflux for 30 min. The clear reaction mixture was cooled to 15-20 C. The precipitated aldol product was filtered and washed with copious amount of water and then with methanol and ethyl acetate (EtOAc). The obtained product was thoroughly dried under vacuum to afford the pure product 2a-2p.

Reference： [1]Cuihua Xuebao/Chinese Journal of Catalysis,2017,vol. 38,p. 775 - 783

70
[ 574-17-4 ]
[ 38017-65-1 ]
(2-(2-acetamidophenyl)-2-oxoacetyl)-L-phenylalanyl-L-phenylalanine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: triethylamine / acetonitrile / 20 °C / Inert atmosphere 2: sodium hydroxide / methanol / 16 h / 20 °C

Reference： [1]Aldilla, Vina R.; Nizalapur, Shashidhar; Martin, Adam; Marjo, Chris E.; Rich, Anne; Yee, Eugene; Suwannakot, Panthipa; Black, David Stc.; Thordarson, Pall; Kumar, Naresh [New Journal of Chemistry, 2017, vol. 41, # 22, p. 13462 - 13471]

71
[ 574-17-4 ]
[ 38017-65-1 ]
methyl (2-(2-acetamidophenyl)-2-oxoacetyl)-L-phenylalanyl-L-phenylalaninate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With triethylamine In acetonitrile at 20℃; Inert atmosphere;

Reference： [1]Aldilla, Vina R.; Nizalapur, Shashidhar; Martin, Adam; Marjo, Chris E.; Rich, Anne; Yee, Eugene; Suwannakot, Panthipa; Black, David Stc.; Thordarson, Pall; Kumar, Naresh [New Journal of Chemistry, 2017, vol. 41, # 22, p. 13462 - 13471]

72
[ 54-85-3 ]
[ 574-17-4 ]
N-(2-(2-(2-isonicotinoylhydrazinyl)-2-oxoacetyl)phenyl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	In water; acetonitrile at 20℃; for 16h;	2 Example 2-Synthesis of N-(2-(2-(2-Isonicotinoylhydrazine)-2-Oxoacetyl)Phenyl) Acetamide (Compound 2) This derivative, Compound 2, was synthesized by reacting Compound 1 with isoniazid in acetonitrile and water for 16 hours at room temperature, yielding 68% (Scheme 2). (0039) 500 mg of 1-acetylindoline-2,3-dione (2.6 mmol), 15 ml of acetonitrile, 10 ml of distilled water and 397 mg (1.1 equivalents) of Isoniazid were added to a flask. The reaction medium was kept under stirring at room temperature for 16 hours. The resulting suspension was vacuum filtered and the solid washed 3 times with 10 mL of ice-cold acetonitrile and then with distilled water until there was no further presence of residual isoniazid (detectable by ultraviolet light in thin layer chromatography). The product was air dried and stored in an amber flask under argon atmosphere. (0040) Compound 2 was characterized by mass spectrometry (ESi-MS (-)), 1H and 13C nuclear magnetic resonance, infrared spectroscopy and elemental analysis, having provided experimental data compatible with its chemical structure. (0041) The overall yield of Compound 2 was 56%, in two steps, which makes this synthesis quite interesting and viable from the industrial point of view and also from the medicinal chemistry. (0042) Obtained mass: 585 mg/Yield: 68%. (0043) ESI-MS(-): m/z 325 (0044) 1H NMR (DMSO D6, 400 MHz, δ): 2.17 (s, 3H), 7.32 (t, J=7.7 Hz, 1H), 7.70 (t, J=7.7 Hz, 1H), 7.83 (d, J=5.2 Hz, 2H), 7.96 (d, J=7.7 Hz, 1H), 8.09 (d, J=7.7 Hz, 1H), 8.81 (d, J=5.2 Hz, 2H), 10.70 (s, 111), 11.01 (s, 2H) ppm. (0045) 13C NMR (DMSO D6, 100 MHz, δ): 24.42 (s), 121.16 (s), 121.39 (s), 121.93 (s), 123.37 (s), 132.62 (s), 135.29 (s), 139.08 (s), 139.50 (s), 150.58 (s), 163.50 (s), 164.07 (s), 169.20 (s), 191.53 (s) ppm. (0046) Elemental analysis (CHN): (0047) >Experimental: (% C) 58.93, (% H) 4.29, (% N) 17.09 (0048) >Theoretical: (% C) 58.89 (% H) 4.32, (% N) 17.17 (0049) Measured melting point: 197-199° C.
68%	In water; acetonitrile at 20℃; for 16h;	4.1.8. Synthesis of the final derivatives 14-17 General procedure: To a flaskwas added 0.002 mol of the corresponding 1-acylisatin(6a-d), the ACN: water (1.5: 1) solvent system (0.1 M) and 1:1equivalent of isoniazid. The reaction medium was stirred at roomtemperature for 16 h. The resulting suspension was cooled to 4 °Cand vacuum filtered. The solid was washed 3 times with 2-5mL ofice-cold distilled water and 5-10 mL of ice-cold ACN. The productwas vacuum dried. 4.1.8.1. N-(2-(2-(2-isonicotinoylhydrazinyl)-2-oxoacetyl)phenyl)acetamide (14). Yield: 68%. White solid, mp: 197-199 °C. IR nmax(cm-1) 3166, 1705, 1690, 1665. 1643. 1H NMR (DMSO-d6, 400 MHz)δ ppm d 10.99 (s, 2H), 10.69 (s, 1H), 8.84-8.77 (m, 1H), 8.11 (dd, J 1.1, 8.4 Hz, 1H), 7.97 (dd, J 1.6, 8.0 Hz, 1H), 7.86-7.79 (m, 1H), 7,70(td, J 1.6, 7.4, 8.4 Hz, 1H), 7.31 (td, J 1.1, 7.4, 8.0 Hz, 1H), 2.17 (s,1H). 13C NMR (DMSO-d6, 100 MHz) δ ppm 191.40, 169.04, 163.92,163.37, 150.44, 139.38, 138.93, 135.15, 132.49, 123.21, 121.76, 121.25,121.01, 24.30. HRESI-MS(): calcd. for C16H15N4O4: m/z 327.1088,found: m/z 327.1094. HPLC-UV: 99.2% (R.T. 9.61 min, l 225 nm). 192.69, 165.79, 164.09, 163.81, 150.53, 139.41, 138.90, 136.13, 133.52,124.01, 121.32, 120.86, 120.69, 43.37. HRESI-MS(+): calcd. forC16H14ClN4O4 m/z 361.0698, found: m/z 361.0682. HPLC-UV: 100%(R.T. 8,22 min, l 225 nm).

Reference： [1]Current Patent Assignee: OSWALDO CRUZ FOUNDATION - US2017/369445, 2017, A1 Location in patent: Paragraph 0038-0049
[2]Castelo-Branco, Frederico Silva; de Lima, Evanoel Crizanto; Domingos, Jorge Luiz de Oliveira; Pinto, Angelo C.; Lourenço, Maria Cristina S.; Gomes, Karen Machado; Costa-Lima, Mariana Marques; Araujo-Lima, Carlos Fernando; Aiub, Claudia Alessandra Fortes; Felzenszwalb, Israel; Costa, Thadeu Estevam M.M.; Penido, Carmen; Henriques, Maria G.; Boechat, Nubia [European Journal of Medicinal Chemistry, 2018, vol. 146, p. 529 - 540]

73
[ 574-17-4 ]
[ 186828-50-2 ]
1-acetyl-3-(benzo[d]oxazol-2-yldifluoromethyl)-3-hydroxyindolin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	With tetrakis(acetonitrile)copper(I)tetrafluoroborate; toluene-4-sulfonic acid In tetrahydrofuran at 20℃; for 16h; Inert atmosphere;	20 Example 20: Under a nitrogen atmosphere, Cu(MeCN)4BF4 (2.5 mmol) was sequentially added to a 10 ml reaction tube containing a magnet.1-acetylindole-2,3-dione (2.5 mmol), bromodifluoromethyl-1,3-benzoxazole (2.5 mmol),p-Toluenesulfonic acid (0.5 mmol), 3.0 ml of dry THF was added, and the mixture was reacted at room temperature for 16 hours.After the reaction was stopped, the solid in the reaction mixture was filtered through a short silica gel column, and the filtrate was extracted with saturated brine and ethyl acetate.The organic layer was taken and dried over anhydrous sodium sulfate. Filter and concentrate. The crude product was separated and purified by column chromatography to give the desired product 3l, yield 82%.

Reference： [1]Current Patent Assignee: SHANGHAI UNIVERSITY - CN108467391, 2018, A Location in patent: Paragraph 0037

74
[ 70254-44-3 ]
[ 574-17-4 ]
[ 109-77-3 ]
1-acetyl-2'-amino-2,5'-dioxo-5',6'-dihydrospiro[indoline-3,4'-pyrano[3,2-c]quinoline]-3'-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With sodium acetate In ethanol at 20℃; for 0.25h; Milling; Green chemistry;	General procedure. General procedure: Isatin 1 (3 mmol), malononitrile (0.2 g, 3 mmol,), bicyclic CH-acid 2 (3 mmol) and sodium acetate (0.025 g, 0.3 mmol) in 'solvent-free' manner or with additive ('on-solvent' manner) were grinded with a pestle and mortar at ambient temperature for 15 minutes. After the reaction was finished, the mixture was air-dried. Then the crude solid was put on filter, rinsed with water (2 mL) and EtOH (2 mL), and then dried with a water pump to isolate the spiro-oxindole 3.

Reference： [1]Elinson, Michail N.; Vereshchagin, Anatoly N.; Ryzhkov, Fedor V.; Anisina, Yuliya E. [Arkivoc, 2018, vol. 2018, # 4, p. 276 - 285]

75
[ 1076-38-6 ]
[ 574-17-4 ]
[ 109-77-3 ]
[ 126115-67-1 ]

Yield	Reaction Conditions	Operation in experiment
96%	With sodium acetate In ethanol at 20℃; for 0.25h; Milling; Green chemistry;	General procedure. General procedure: Isatin 1 (3 mmol), malononitrile (0.2 g, 3 mmol,), bicyclic CH-acid 2 (3 mmol) and sodium acetate (0.025 g, 0.3 mmol) in 'solvent-free' manner or with additive ('on-solvent' manner) were grinded with a pestle and mortar at ambient temperature for 15 minutes. After the reaction was finished, the mixture was air-dried. Then the crude solid was put on filter, rinsed with water (2 mL) and EtOH (2 mL), and then dried with a water pump to isolate the spiro-oxindole 3.

Reference： [1]Elinson, Michail N.; Vereshchagin, Anatoly N.; Ryzhkov, Fedor V.; Anisina, Yuliya E. [Arkivoc, 2018, vol. 2018, # 4, p. 276 - 285]

76
[ 574-17-4 ]
[ 927-74-2 ]
(S*)-1-acetyl-3-hydroxy-3-((R*)-3-oxotetrahydrofuran-2-yl)indolin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%	With 5-bromo-2-methyl-pyridine-N-oxide; [BrettPhosAu]NTf₂; trifluoroacetic acid In 1,2-dichloro-ethane at 20℃; for 6h; Inert atmosphere; Darkness; diastereoselective reaction;

Reference： [1]Cai, Ju; Wang, Xin; Qian, Yu; Qiu, Lihua; Hu, Wenhao; Xu, Xinfang [Organic Letters, 2019, vol. 21, # 2, p. 369 - 372]

77
[ 574-17-4 ]
N-(2-hydrazinyl-2-oxoethyl)-1H-indole-2-carboxamide [ No CAS ]
N-[2-(2-[2-(acetylamino)phenyl](oxo)acetyl}hydrazinyl)-2-oxoethyl]-1H-indole-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61%	In acetonitrile for 2h; Reflux;	3.2.1. General Procedure for the Synthesis of the Target Compounds 5a-h General procedure: The appropriate N-acetylisatin 4a-d (1 mmol) was added to a suspension containing the properacid hydrazide 3a,b (1 mmol) in acetonitrile (15 mL). The reaction mixture was heated to reflux fortwo hours, cooled to room temperature, and filtered. The collected solid was dried and re-crystallizedfrom ethanol to give the title compounds 5a-h.

Reference： [1]Almutairi, Maha S.; Zakaria, Azza S.; Al-Wabli, Reem I.; Hubert Joe; Abdelhameed, Ali S.; Attia, Mohamed I. [Molecules, 2018, vol. 23, # 5]

78
[ 574-17-4 ]
[ 5055-39-0 ]
N-(2-[2-(1H-indol-2-yl-carbonyl)hydrazinyl](oxo)acetyl}phenyl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
58%	In acetonitrile for 2h; Reflux;	3.2.1. General Procedure for the Synthesis of the Target Compounds 5a-h General procedure: The appropriate N-acetylisatin 4a-d (1 mmol) was added to a suspension containing the properacid hydrazide 3a,b (1 mmol) in acetonitrile (15 mL). The reaction mixture was heated to reflux fortwo hours, cooled to room temperature, and filtered. The collected solid was dried and re-crystallizedfrom ethanol to give the title compounds 5a-h.N-(2-[2-(1H-Indol-2-ylcarbonyl)hydrazinyl](oxo)acetyl}phenyl)acetamide (5a): Yellow powder;m.p. 249-250 °C (yield 58%); 1H-NMR (DMSO-d6): δ(ppm) 2.20 (s, 3H, CH3), 7.09 (t, J = 7.5 Hz, 1H,Ar-H), 7.24 (t, J = 7.5 Hz, 1H, Ar-H), 7.27 (d, J = 1.5 Hz, 1H, CH-3-indole), 7.31 (t, J = 7.5 Hz, 1H, Ar-H),7.47 (d, J = 8.5 Hz, 1H, Ar-H), 7.68 (d, J = 8.0 Hz, 1H, Ar-H), 7.73 (dd, J = 1.5, 8.5 Hz, 1H, Ar-H), 8.11(dd, J = 1.0, 8.0 Hz, 1H, Ar-H), 8.21 (d, J = 8.0 Hz, 1H, Ar-H), 10.71 (s, 1H, NH), 10.75 (s, 1H, NH), 10.90(s, 1H, NH), 11.85 (s, 1H, NH-indole); 13C-NMR (DMSO-d6): δ(ppm) 24.9 (CH3), 104.2, 112.9, 120.5,121.5, 121.9, 122.3, 123.6, 124.4, 127.4, 129.5, 133.5, 135.9, 137.3, 140.3 (Ar-CH and Ar-C), 158.3, 164.5,169.6, 192.7 (4 C=O); MS m/z (ESI): 363 [M - H]-; HR-MS (MALDI) calcd for C19H16N4O4: 363.1093,found: 363.1028 (M - H).

Reference： [1]Almutairi, Maha S.; Zakaria, Azza S.; Al-Wabli, Reem I.; Hubert Joe; Abdelhameed, Ali S.; Attia, Mohamed I. [Molecules, 2018, vol. 23, # 5]

79
[ 574-17-4 ]
[ 20948-65-6 ]
N-{2-[{2-[(5-methoxy-1H-indol-2-yl)carbonyl]hydrazinyl}(oxo)acetyl]phenyl}acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
52%	In acetonitrile for 2h; Reflux;	3.2.1. General Procedure for the Synthesis of the Target Compounds 5a-h General procedure: The appropriate N-acetylisatin 4a-d (1 mmol) was added to a suspension containing the properacid hydrazide 3a,b (1 mmol) in acetonitrile (15 mL). The reaction mixture was heated to reflux fortwo hours, cooled to room temperature, and filtered. The collected solid was dried and re-crystallizedfrom ethanol to give the title compounds 5a-h.

Reference： [1]Almutairi, Maha S.; Zakaria, Azza S.; Al-Wabli, Reem I.; Hubert Joe; Abdelhameed, Ali S.; Attia, Mohamed I. [Molecules, 2018, vol. 23, # 5]

80
[ 574-17-4 ]
[ 6346-09-4 ]
2-(2-acetamidophenyl)-N-(4,4-diethoxybutyl)-2-oxoacetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%	In dichloromethane at 20℃; for 6h;	General procedure for the synthesis of compounds 4-6. General procedure: An equimolar amount of 4,4-diethoxybutan- 1-amine was added dropwise to a solution of 0.5 g of 1-acetylisatin 1-3 in 10 mL of anhydrous methylene chloride on stirring at 20°C. The mixture was stirred for 6 h and evaporated under reduced pressure (15 mm), the residue was treated with diethyl ether, and the white solid was filtered off and dried under reduced pressure (15 mm). 2-(2-Acetamidophenyl)-N-(4,4-diethoxybutyl)-2- oxoacetamide (4). Yield 97%, mp 86°C. IR spectrum, ν, cm-1: 3348, 3285, 3072, 2974, 2931, 2876, 1674, 1655, 1605, 1580, 1524, 1484, 1450, 1372, 1294, 1220, 1155, 1060. 1H NMR spectrum (CDCl3), δ, ppm (J, Hz): 1.11 t (6H, CH3, 3J = 7.0), 1.52-1.57 m (4H, CH2), 2.08 s (3H, COCH3), 3.20-3.23 m (2H, NCH2), 3.41-3.46 m (2H, OCH2), 3.54-3.59 m (2H, OCH2), 4.48 t (1H, CH, 3J = 5.0), 7.23 d.d (1H, 5-H, 3J = 7.5, 7.5), 7.60-7.65 m (2H, 4-H, 6-H), 7.92 d (1H, 3-H, 3J = 8.2), 8.69 t (1H, 3J = 5.4, NHCH2), 10.59 s (1H, AcNH). 13C NMR spectrum (DMSO-d6), δC, ppm: 191.93 (C=O), 168.70 (C=O), 163.71 (C=O), 138.71, 134.09 (CH), 131.65 (CH), 123.41, 123.25 (CH), 121.29 (CH), 101.89 (CH), 60.54 (CH2), 38.32 (CH2), 30.68 (CH2), 24.11 (COCH3), 24.01 (OCH2), 23.99 (OCH2), 15.25 (OCH2CH3), 15.23 (OCH2CH3). Mass spectrum (MALDI): m/z 351 [M + H]+. Found, %: C 61.58; H 7.36; N 7.90. C18H26N2O5. Calculated, %: C 61.70; H 7.48 N 7.99.

Reference： [1]Bogdanov; Gazizov; Smolobochkin; Mironov [Russian Journal of Organic Chemistry, 2019, vol. 55, # 1, p. 121 - 123][Zh. Org. Khim., 2019, vol. 55, # 1, p. 157 - 159,3]

81
[ 574-17-4 ]
[ 22979-35-7 ]
[ 53123-88-9 ]
C₇₀H₉₄N₂O₁₈ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%		Weigh rapamycin (0.05mmol), isatin 3q (0.10mmol) and rhodium octanoate dimer(0.0005mmo),They were placed in a reaction flask, 2.0 mL of dry dichloromethane was added, and after stirring at room temperature for 5 minutes,Phenyldiazo 2a (0.10 mmol) was weighed and dissolved in dry dichloromethane (1.0 mL), and slowly added dropwise to the reaction system (about 1 hour), and stirring was continued for half an hour.The solvent was removed by rotary distillation to give a crude product. The rapamycin analog I-q was obtained by column chromatography (eluent: petroleum ether: ethyl acetate = 1:10 to 1:4).The yield was 89%.

Reference： [1]Patent: CN109776571,2019,A .Location in patent: Paragraph 0089-0092

82
[ 574-17-4 ]
[ 123-46-6 ]
N,N,N-trimethyl-2-oxo-2-[2-(2-oxo-1,2-dihydro-3H-indol-3-ylidene)hydrazinyl]ethane-1-aminiumchloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With trifluoroacetic acid In ethanol at 78℃; for 2h;	N,N,N-Trimethyl-2-oxo-2-[2-(2-oxo-1,2-dihydro-3H-indol-3-ylidene)hydrazinyl]ethane-1-aminiumchloride (9) General procedure: Three drops of trifluoroacetic acid wereadded to a mixture of 1-(aminomethyl)isatin derivative 1-4 or 1-acylisatin 6-8 (5 mmol) and Girard’s reagentT 5 (5 mmol) in 7 mL of absolute ethanol. The reaction mixture was refluxed for 2 h. After spontaneous cooling of the solution to room temperature, the precipitated compound 9 was filtered off, washed with absolute diethyl ether, and dried in vacuum (12 mmHg). Yield 93%, yellow powder, mp 183°C (mp 185°C [25-27]). All physico-chemical characteristics (MALDI spectra, IR and NMR) completely coincided with those described earlier.

Reference： [1]Bogdanov, A. V.; Kulik, N. V.; Mironov, V. F.; Sapunova, A. S.; Voloshina, A. D. [Russian Journal of General Chemistry, 2020, vol. 90, # 9, p. 1591 - 1600][Zh. Obshch. Khim., 2020, vol. 90, # 9, p. 1326 - 1336]

83
[ 574-17-4 ]
[ 7597-14-0 ]
2-(2-acetamidophenyl)-N-(3-((7-chloroquinolin-4-yl)amino)propyl)-2-oxoacetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
40%	In acetonitrile at 25℃;	4.1.4. General procedure for preparing 2-(2-acetamidophenyl)-N-(3-((7-chloroquinolin-4-yl)amino)alkyl)-2-oxoacetamides (1-10) and 2-(2-acetamidophenyl)-N-(3-((7-chloroquinolin-4-yl)amino)alkyl)-2,2-difluoroacetamides (11-13) General procedure: A total of 1.0 mmol of the corresponding 1-acetylindoline-2,3-diones(27a-d) or 1-acetyl-3,3-difluoroindolin-2-ones (28a-d) and 50 mL ofCH3CN were added to a round-bottom flask coupled to a condenser. Themixture was stirred at 25 C for 5-10 min. Then, 1 equivalent of properaminoquinoline (22-24) or primaquine was added. The reaction waskept under stirring at 25 C for 2-3 h. At the end of this period, theformed precipitate was vacuum filtered and washed with cold CH3CN.The residual crude product was purified via silica gel column chromatographyusing a gradient mixture of CHCl3/MeOH. Compounds 1-13were obtained as white solids with 60-3% yield.27Primaquine was obtained from the treatment of primaquinediphosphate with NaOH (10% solution aq.) for 2 h. The obtained brownoil was extracted from the medium with CH2Cl2 (30 mL) washed withwater (3 × 10 mL), dried (magnesium sulfate anhydrous), concentratedunder vacuum and stored under argon atmosphere with protection fromlight.

Reference： [1]Boechat, Nubia; Carvalho, Rita C.C.; Ferreira, Maria de Lourdes G.; Coutinho, Julia Penna; Sa, Paula M.; Seito, Leonardo N.; Rosas, Elaine C.; Krettli, Antoniana U.; Bastos, Monica M.; Pinheiro, Luiz C.S. [Bioorganic and Medicinal Chemistry, 2020, vol. 28, # 24]

84
[ 574-17-4 ]
[ 53186-45-1 ]
2-(2-acetamidophenyl)-N-(4-((7-chloroquinolin-4-yl)amino)butyl)-2-oxoacetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%	In acetonitrile at 25℃;	4.1.4. General procedure for preparing 2-(2-acetamidophenyl)-N-(3-((7-chloroquinolin-4-yl)amino)alkyl)-2-oxoacetamides (1-10) and 2-(2-acetamidophenyl)-N-(3-((7-chloroquinolin-4-yl)amino)alkyl)-2,2-difluoroacetamides (11-13) General procedure: A total of 1.0 mmol of the corresponding 1-acetylindoline-2,3-diones(27a-d) or 1-acetyl-3,3-difluoroindolin-2-ones (28a-d) and 50 mL ofCH3CN were added to a round-bottom flask coupled to a condenser. Themixture was stirred at 25 C for 5-10 min. Then, 1 equivalent of properaminoquinoline (22-24) or primaquine was added. The reaction waskept under stirring at 25 C for 2-3 h. At the end of this period, theformed precipitate was vacuum filtered and washed with cold CH3CN.The residual crude product was purified via silica gel column chromatographyusing a gradient mixture of CHCl3/MeOH. Compounds 1-13were obtained as white solids with 60-3% yield.27Primaquine was obtained from the treatment of primaquinediphosphate with NaOH (10% solution aq.) for 2 h. The obtained brownoil was extracted from the medium with CH2Cl2 (30 mL) washed withwater (3 × 10 mL), dried (magnesium sulfate anhydrous), concentratedunder vacuum and stored under argon atmosphere with protection fromlight.

Reference： [1]Boechat, Nubia; Carvalho, Rita C.C.; Ferreira, Maria de Lourdes G.; Coutinho, Julia Penna; Sa, Paula M.; Seito, Leonardo N.; Rosas, Elaine C.; Krettli, Antoniana U.; Bastos, Monica M.; Pinheiro, Luiz C.S. [Bioorganic and Medicinal Chemistry, 2020, vol. 28, # 24]

85
[ 574-17-4 ]
[ 90-34-6 ]
2-(2-acetamidophenyl)-N-(4-((6-methoxyquinolin-8-yl)amino)pentyl)-2-oxoacetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
43%	In acetonitrile at 25℃;	4.1.4. General procedure for preparing 2-(2-acetamidophenyl)-N-(3-((7-chloroquinolin-4-yl)amino)alkyl)-2-oxoacetamides (1-10) and 2-(2-acetamidophenyl)-N-(3-((7-chloroquinolin-4-yl)amino)alkyl)-2,2-difluoroacetamides (11-13) General procedure: A total of 1.0 mmol of the corresponding 1-acetylindoline-2,3-diones(27a-d) or 1-acetyl-3,3-difluoroindolin-2-ones (28a-d) and 50 mL ofCH3CN were added to a round-bottom flask coupled to a condenser. Themixture was stirred at 25 C for 5-10 min. Then, 1 equivalent of properaminoquinoline (22-24) or primaquine was added. The reaction waskept under stirring at 25 C for 2-3 h. At the end of this period, theformed precipitate was vacuum filtered and washed with cold CH3CN.The residual crude product was purified via silica gel column chromatographyusing a gradient mixture of CHCl3/MeOH. Compounds 1-13were obtained as white solids with 60-3% yield.27Primaquine was obtained from the treatment of primaquinediphosphate with NaOH (10% solution aq.) for 2 h. The obtained brownoil was extracted from the medium with CH2Cl2 (30 mL) washed withwater (3 × 10 mL), dried (magnesium sulfate anhydrous), concentratedunder vacuum and stored under argon atmosphere with protection fromlight.

Reference： [1]Boechat, Nubia; Carvalho, Rita C.C.; Ferreira, Maria de Lourdes G.; Coutinho, Julia Penna; Sa, Paula M.; Seito, Leonardo N.; Rosas, Elaine C.; Krettli, Antoniana U.; Bastos, Monica M.; Pinheiro, Luiz C.S. [Bioorganic and Medicinal Chemistry, 2020, vol. 28, # 24]

86
[ 574-17-4 ]
[ 5407-57-8 ]
2-(2-acetamidophenyl)-N-(2-((7-chloroquinolin-4-yl)amino)ethyl)-2-oxoacetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
36%	In acetonitrile at 25℃;	4.1.4. General procedure for preparing 2-(2-acetamidophenyl)-N-(3-((7-chloroquinolin-4-yl)amino)alkyl)-2-oxoacetamides (1-10) and 2-(2-acetamidophenyl)-N-(3-((7-chloroquinolin-4-yl)amino)alkyl)-2,2-difluoroacetamides (11-13) General procedure: A total of 1.0 mmol of the corresponding 1-acetylindoline-2,3-diones(27a-d) or 1-acetyl-3,3-difluoroindolin-2-ones (28a-d) and 50 mL ofCH3CN were added to a round-bottom flask coupled to a condenser. Themixture was stirred at 25 C for 5-10 min. Then, 1 equivalent of properaminoquinoline (22-24) or primaquine was added. The reaction waskept under stirring at 25 C for 2-3 h. At the end of this period, theformed precipitate was vacuum filtered and washed with cold CH3CN.The residual crude product was purified via silica gel column chromatographyusing a gradient mixture of CHCl3/MeOH. Compounds 1-13were obtained as white solids with 60-3% yield.27Primaquine was obtained from the treatment of primaquinediphosphate with NaOH (10% solution aq.) for 2 h. The obtained brownoil was extracted from the medium with CH2Cl2 (30 mL) washed withwater (3 × 10 mL), dried (magnesium sulfate anhydrous), concentratedunder vacuum and stored under argon atmosphere with protection fromlight.

Reference： [1]Boechat, Nubia; Carvalho, Rita C.C.; Ferreira, Maria de Lourdes G.; Coutinho, Julia Penna; Sa, Paula M.; Seito, Leonardo N.; Rosas, Elaine C.; Krettli, Antoniana U.; Bastos, Monica M.; Pinheiro, Luiz C.S. [Bioorganic and Medicinal Chemistry, 2020, vol. 28, # 24]

87
[ 574-17-4 ]
2-((1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene)hydrazono)thiazolidin-4-one [ No CAS ]
5‑(1‑methyl‑2‑oxoindolin‑3‑ylidene)‑2‑((1,7,7‑trimethylbicyclo[2.2.1]heptan‑2‑ylidene)hydrazono)thiazolidin‑4‑one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%	With sodium acetate; acetic acid Reflux;	5-(2-oxoindolin-3-ylidene)-2-((1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene)hydrazono)thiazolidin-4-one(6a) General procedure: To a solution of compound 2 (2.65 g, 0.01 mol) in 20 mlglacial acetic acid, isatin (1.47 g, 0.01 mol) and sodiumacetate (1.23 g, 0.015 mol) were added. The solution wasrefluxed till completion of the reaction monitored by TLC(chloroform/methanol, 5:1). After cooling, the solid formedwas filtered, washed with water several times and recrystallizedfrom ethanol as yellowish red powder.

Reference： [1]Abo-Bakr, Ahmed M.; Hassan, Entesar A.; Mahdy, Al-Hassan S.; Zayed, Salem E. [Journal of the Iranian Chemical Society, 2021, vol. 18, # 10, p. 2757 - 2769]

88
[ 574-17-4 ]
[ 325798-54-7 ]
1-acetyl-3-[4'-(4"-fluorobenzyloxy)benzohydrazono]isatin [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	With acetic acid In ethanol for 2h; Reflux;	3-[4'-(4"-Fluorobenzyloxy)-benzohydrazono]isatin, 3 General procedure: A mixture of 4-(4'-fluorobenzyloxy)-benzohydrazide 2 (0.01 mol) and isatin (0.01 mol) in ethanol (70 mL) containing 2-3 drops of glacial acetic acid was refluxed for 2 h and left overnight at room temperature. The separated solid was filtered and washed with methanol.

Reference： [1]Rastogi, Nisheeth [Indian Journal of Heterocyclic Chemistry, 2019, vol. 29, # 1, p. 73 - 77]

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	574-17-4	MDL No. :	MFCD00158542
Formula :	C₁₀H₇NO₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	LPGDEHBASRKTDG-UHFFFAOYSA-N
M.W :	189.17	Pubchem ID :	11321
Synonyms :

Num. heavy atoms :	14
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.1
Num. rotatable bonds :	1
Num. H-bond acceptors :	3.0
Num. H-bond donors :	0.0
Molar Refractivity :	52.06
TPSA :	54.45 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) :	-7.2 cm/s

Log Po/w (iLOGP) :	1.28
Log Po/w (XLOGP3) :	0.36
Log Po/w (WLOGP) :	0.38
Log Po/w (MLOGP) :	0.67
Log Po/w (SILICOS-IT) :	1.26
Consensus Log Po/w :	0.79

[ CAS No. 574-17-4 ] {[proInfo.proName]}

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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) :	-1.49
Solubility :	6.11 mg/ml ; 0.0323 mol/l
Class :	Very soluble
Log S (Ali) :	-1.07
Solubility :	16.2 mg/ml ; 0.0855 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-2.4
Solubility :	0.753 mg/ml ; 0.00398 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.65

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	Packing Group:	N/A
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[ CAS No. 574-17-4 ] {[proInfo.proName]}

Quality Control of [ 574-17-4 ]

Related Doc. of [ 574-17-4 ]

Product Details of [ 574-17-4 ]

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[ 574-17-4 ] Synthesis Path-Upstream 1~1

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