Name: 16133-49-6|5-Methoxy-2-nitrophenylamine|97%
Brand: Ambeed
SKU: A137083
Price: 6.0 USD
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1
[ 20628-18-6 ]
[ 16133-49-6 ]

Yield	Reaction Conditions	Operation in experiment
100%	Stage #1: 1-acetamido-5-methoxy-2nitrobenzene With hydrogenchloride In water Heating / reflux; Stage #2: With sodium hydroxide; sodium hydrogencarbonate In water	5-Methoxy-2-nitrophenylamine (Intermediate A59) N-(3-methoxy-2-nitrophenyl)acetamide (Intermediate A58, 3.62 g, 0.0173 mol) was added to 6 N HCl (20 mL) heated to reflux and then cooled. The reaction mixture was filtered and the filtrate was basified with 1 N NaOH and saturated sodium bicarbonate then extracted with ethyl acetate. The solid was partitioned between ethyl acetate and saturated sodium bicarbonate. The two ethyl acetate layers were combined and washed twice with water. The ethyl acetate layer was concentrated under reduced pressure and dried to give 2.92 g (100%) of the title compound.
85%	With hydrogenchloride for 5h; Heating;
	With sulfuric acid

	With hydrogenchloride
	With hydrogenchloride Heating;

Reference： [1]Current Patent Assignee: ALEVIUM PHARMACEUTICALS - US2005/38076, 2005, A1 Location in patent: Page/Page column 26
[2]Zhang; Zhang, Zhoupeng; Tillekeratne; Hudson; Hudson, Richard A. [Synthesis, 1996, # 3, p. 377 - 382]
[3]Reverdin; Widmer [Chemische Berichte, 1913, vol. 46, p. 4074]
[4]Reverdin; Widmer [Chemische Berichte, 1913, vol. 46, p. 4074]
[5]Acheson,R.M. et al. [Journal of the Chemical Society. Perkin transactions I, 1978, p. 1117 - 1125]

2
[ 28987-59-9 ]
[ 16133-49-6 ]

Reference： [1]Journal of the Chemical Society,1929,p. 2778
[2]Heterocyclic Communications,2019,vol. 25,p. 8 - 14

3
[ 16133-49-6 ]
[ 76372-29-7 ]
[ 98447-11-1 ]

Yield	Reaction Conditions	Operation in experiment
7.5%	With iodine; copper; potassium carbonate In neat (no solvent) at 120℃; for 24h; pression flask;

Reference： [1]Gansser; Migambanou; Viel; et al. [Farmaco, Edizione Scientifica, 1985, vol. 40, # 7, p. 459 - 476]

4
[ 16133-49-6 ]
[ 104503-84-6 ]

Yield	Reaction Conditions	Operation in experiment
75%	Stage #1: 5-methoxy-2-nitroaniline With hydrogenchloride; sodium nitrite In water at 0 - 20℃; for 1h; Stage #2: With sodium azide In water at 20℃; for 3h;	1 To a stirred mixture of 5-methoxy-2-nitroaniline (5g, 29.7 mmol) in HCI (cone. 39 mL) at 0°C was added drop wise a solution of NaN02 (2.05 g, 29.7 mmol) in H20 (19 mL). The internal temperature was kept below 10°C. After addition, the mixture was stirred at room temperature for 1 h. The diazonium salt was collected by filtration, and was used in the next step. To the diazonium salt in a crystallization dish under fast stirring at room temperature was added drop wise a solution of NaN3 (1.93 g, 29.6 mmol) in H20 (7 mL). After gas evolution stopped (3 h), it was filtered. The collected solid was re-crystallized from MeOH to give 4.342 g (yield 75% for 2 steps) of the product 13 as a yellow solid. To a mixture of the phenylazide 13 (1.94 g, 10 mmol) and diethyl 1,3- acetone-diacrboxylate (2.20 mL, 12 mmol) in EtOH (40 mL) at room temperature was added Et3N (1.67 mL, 12 mmol). After the mixture was stirred at room temperature for 60 h, the initial suspension turned into a clear yellow solution. The solution was concentrated under vacuum and the residue was purified by chromatography {RediSep 24 g silica-gel column, 10% to 40% EtOAc in hexanes) to give 2.905 g of triazole 14 as a yellow solid. MS: [M+l] = 379.
	With sodium azide; sulfuric acid; sodium acetate; acetic acid; sodium nitrite 1.) from 5 to 10 deg C, 60 min; Yield given. Multistep reaction;
2.905 g	Stage #1: 5-methoxy-2-nitroaniline With hydrogenchloride; sodium nitrite In water at 0 - 20℃; for 1h; Stage #2: With sodium azide In water at 20℃; for 3h;	1 To a stirred mixture of 5-methoxy-2-nitroaniline (5g, 29.7 mmol) in HC1 (cone.39 mL) at 0°C was added drop wise a solution of NaNO2 (2.05 g, 29.7 mmol) in H20 (19 mL). The internal temperature was kept below 10°C. After addition, the mixture was stirred at room temperature for 1 h. The diazonium salt was collected by filtration, and was used in the next step. To the diazonium salt in a crystallization dish under faststirring at room temperature was added drop wise a solution of NaN3 (1.93 g, 29.6 mmol) in H20 (7 mL). After gas evolution stopped (3 h), it was filtered. The collected solid was re-crystallized from MeOH to give 4.342 g (yield 75% for 2 steps) of the product 13 as a yellow solid. To a mixture of the phenylazide 13 (1.94 g, 10 mmol) and diethyl 1,3-acetone-diacrboxylate (2.20 mL, 12 mmol) in EtOH (40 mL) at room temperature was added Et3N (1.67 mL, 12 mmol). After the mixture was stirred at room temperature for 60 h, the initial suspension turned into a clear yellow solution. The solution was concentrated under vacuum and the residue was purified by chromatography (Red/Sep 24g silica-gel column, 10% to 40% EtOAc in hexanes) to give 2.905 g of triazole 14 as a yellow solid. MS: [M+1] = 379.

4.342 g	Stage #1: 5-methoxy-2-nitroaniline With hydrogenchloride; sodium nitrite In water at 0 - 20℃; for 1h; Stage #2: With sodium azide In water at 20℃; for 3h;	1 Synthesis of Compound 1 To a stirred mixture of 5-methoxy-2-nitroaniline (5 g, 29.7 mmol) in HC1 (conc. 39 mE) at 00 C. was added drop wise a solution of NaNO2 (2.05 g, 29.7 mmol) in H20 (19 mE). The internal temperature was kept below 100 C. After addition, the mixture was stirred at room temperature for 1 h. The diazonium salt was collected by filtration, and was used in the next step. To the diazonium salt in a crystallization dish under fast stirring at room temperature was added drop wise a solution of NaN3 (1.93 g, 29.6 mmol) in H20 (7 mE). After gas evolution stopped (3 h), it was filtered. The collected solid was re-crystallized from MeOH to give 4.342 g (yield 75% for 2 steps) of the product 13 as a yellow solid. To a mixture of the phenylazide 13 (1.94 g, 10 mmol) and diethyl 1,3-acetone-diacrboxylate (2.20 mE, 12 mmol) in EtOH (40 mE) at room temperature was added Et3N (1.67 mE, 12 mmol). Afier the mixture was stirred at room temperature for 60 h, the initial suspension turned into a clear yellow solution. The solution was concentrated under vacuum and the residue was purified by chromatography (RediSep 24 g silica-gel column, 10% to 40% EtOAc in hexanes) to give 2.905 g of triazole 14 as a yellow solid.
	Stage #1: 5-methoxy-2-nitroaniline With toluene-4-sulfonic acid; sodium nitrite In water at 20℃; for 0.0833333h; Stage #2: With sodium azide In water at 20℃; for 0.0833333h;
4.342 g	Stage #1: 5-methoxy-2-nitroaniline With hydrogenchloride; sodium nitrite In water at 0 - 20℃; for 1h; Stage #2: With sodium azide In water at 20℃; for 3h;	1 To a stirred mixture of 5-methoxy-2-nitroaniline (5g, 29.7 mmol) in HC1 (cone. 39 mL) at 0°C was added drop wise a solution of NaN02 (2.05 g, 29.7 mmol) in H20 (19 mL). The internal temperature was kept below l0°C. After addition, the mixture was stirred at room temperature for 1 h. The diazonium salt was collected by filtration, and was used in the next step. To the diazonium salt in a crystallization dish under fast stirring at room temperature was added drop wise a solution of NaN3 (1.93 g, 29.6 mmol) in H20 (7 mL). After gas evolution stopped (3 h), it was filtered. The collected solid was re-crystallized from MeOH to give 4.342 g (yield 75% for 2 steps) of the product 13 as a yellow solid. To a mixture of the phenylazide 13 (1.94 g, 10 mmol) and diethyl 1,3- acetone-diacrboxylate (2.20 mL, 12 mmol) in EtOH (40 mL) at room temperature was added Et3N (1.67 mL, 12 mmol). After the mixture was stirred at room temperature for 60 h, the initial suspension turned into a clear yellow solution. The solution was concentrated under vacuum and the residue was purified by chromatography ( RediSep 24 g silica-gel column, 10% to 40% EtOAc in hexanes) to give 2.905 g of triazole 14 as a yellow solid. MS: [M+l] = 379.

Reference： [1]Current Patent Assignee: AGENEBIO; HAGER BIOSCIENCES - WO2015/95783, 2015, A1 Location in patent: Paragraph 0240
[2]Dyall, Leonard K. [Australian Journal of Chemistry, 1986, vol. 39, # 1, p. 89 - 101]
[3]Current Patent Assignee: AGENEBIO; HAGER BIOSCIENCES - WO2016/205739, 2016, A1 Location in patent: Paragraph 0260
[4]Current Patent Assignee: AGENEBIO; HAGER BIOSCIENCES - US2018/170941, 2018, A1 Location in patent: Paragraph 1146; 1147
[5]Rayam, Parsharamulu; Polkam, Naveen; Kummari, Bhaskar; Banothu, Venkanna; Gandamalla, Durgaiah; Yellu, Narsimha Reddy; Anireddy, Jaya Shree [Journal of Heterocyclic Chemistry, 2019, vol. 56, # 1, p. 296 - 305]
[6]Current Patent Assignee: AGENEBIO - WO2019/246300, 2019, A1 Location in patent: Paragraph 0309

5
[ 16133-49-6 ]
[ 102-51-2 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogen In ethanol for 2h;
	With hydrogen In methanol at 20℃; for 2h;
	With palladium on activated charcoal; hydrogen In methanol

	With 5%-palladium/activated carbon; hydrogen In methanol at 20 - 30℃; for 0.5h; Autoclave;	1.8 [Synthesis of (A) Dye] [Example 1] 15.2 parts of 2-methyl-6-nitroaniline was dissolved in 300 parts of methanol. The obtained solution was transferred into an autoclave, 2.0 parts of 5% Pd / carbon was added, reacted at 20 ° C. to 30 ° C. under a hydrogen pressure of 0.2 MPa-0.5 MPa until absorption of hydrogen ceased, The reaction was further continued at the same temperature for 30 minutes. The catalyst (5% Pd / carbon) was separated by filtration to obtain a solution (filtrate) containing the compound represented by the following formula (24).
	With hydrazine hydrate In methanol Reflux;	In a 250 ml single-mouth flask, add 0.1 mol 5-methoxy-o-nitroaniline, 40 ml methanol, 75 ml hydrazine hydrate (85%), 0.25-0.45 Raney Ni (wet weight). Heat to reflux. for the disappearance of the TCL tracking to the raw materials, the reaction after cooling to room temperature, filtering to remove the Raney Ni, reduced pressure distillation to remove the solvent to obtain the light brown crystal, to get the formula 1 compound of formula 1 o-phenylenediamine. In a 250 ml single-mouth flask, add the 0.1 mol o-phenylenediamine. Use 100 ml ethanol to dissolve. Then slowly add dropwise MBF. During the add dropwise process, yellow solid appears. According to the substituent R1 changes, different reaction time, the reaction time at room temperature for 30-120 min, after the reaction is complete, filtering to remove the solvent, washing three times with ethanol, to obtain the formula 2 compound 7-methoxy-2-hydroxy-3-phenylquinoxaline. The compound 2 was added in 40 mL POCl3 as the solvent. Under the condition of heating and refluxing, chlorinated. for the disappearance of the TLC tracking to the raw materials, after the reaction cooled to the room temperature, slowly poured into the 500g ice water, immediately separate out a large amount of yellow solid, filtering, washing and drying, to obtain the compound of formula 3. In 250 ml three-mouthed flasks, add compound 3 and use 60 ml ethanol as solvent. Slowly add dropwise 18g (0.3 mol) 85% hydrazine hydrate. After adding dropwise, heat to reflux. React for 4-5h. After the reaction cooled to room temperature, poured into the 300g the ice water, immediately separate out a large amount of white solid, after filtering, washing and drying, the obtained crude product, through re-crystallization is shown as formula 4 represented compound 4. In a 50 ml round bottom flask was added 0.377g (0.002 mol) of the hydrazine, add 15 ml ethanol as solvent. Under stirring conditions, slowly add dropwise 0.002 mol substituted aldehyde compound, the raw material is quickly dissolved, then solid is precipitated out. Stir at room temperature overnight. board monitoring, the raw material after the reaction is complete, filtering, petroleum ether and ethanol mixed solution for washing three times, be red yellow solid powder, that formula (I) shown in benzene and pyrazine structure of the hydrazone compound.
	With 5%-palladium/activated carbon; hydrogen In methanol at 30℃; for 0.5h;	1.8 15.2 parts of 2-methyl-6-nitroaniline was dissolved in 300 parts of methanol.The obtained solution was transferred into an autoclave, 2.0 parts of 5% Pd / carbon was added,After reacting at 20 ° C. to 30 ° C. under a hydrogen pressure of 0.2 MPa - 0.5 MPa until hydrogen absorption disappeared, the reaction was further continued at the same temperature for 30 minutes.The catalyst (5% Pd / carbon) was separated by filtration to obtain a solution (filtrate) containing the compound represented by the following formula (22).
	With hydrazine hydrate In methanol Reflux;	1 General procedure: In a 250 mL single-necked flask, 0.1 mol of 7-methoxy o-nitroaniline, 40 mL of methanol,75 mL hydrazine hydrate (85%), 0.25 to 0.45 Raney Ni (wet weight), heated to reflux,TCL tracking to the disappearance of raw materials, the reaction after the end of cooling to room temperature, filter to remove Raney Ni,The solvent was removed by distillation under reduced pressure to give a pale brown crystal, i.e., the compound 1 o-phenylenediamine was obtained as shown in Formula 1.In a 250 mL single-necked flask, 0.1 mol of o-phenylenediamine was added, dissolved in 100 mL of ethanol,And then slowly dropping MBF, in the drop process has a yellow solid appears, according to the change of the substituent R1,Reaction time is different at room temperature reaction time period of 30-120min, the reaction is complete,The solvent was removed by filtration, washed three times with ethanol,To give the compound 7-methoxy-2-hydroxy-3-phenylquinoxaline as shown in Formula 2.In the compound 2 by adding 40mLPOCl3 as a solvent, heating under reflux conditions for chlorination,With TLC traced to the disappearance of raw materials, the reaction after the end of cooling to room temperature, slowly into the 500g ice water,A large amount of a yellow solid was immediately precipitated, and the mixture was filtered and washed and dried to obtain Compound 3 as shown in Formula 3.In a 250 mL three-necked flask, compound 3 was added and treated with 60 mL of ethanol as solvent,18 g (0.3 mol) of 85% hydrazine hydrate was slowly added dropwise, and the temperature was raised to reflux after completion of the dropwise addition,The reaction was carried out for 4-5 hours. After completion of the reaction, the mixture was cooled to room temperature, poured into 300 g of ice water, and a large amount of white solid was precipitated by filtration, washed and dried to obtain a crude product which was recrystallized to give compound 4 as shown in Formula 4.To a 50 mL round bottom flask was added 0.377 g (0.002 mol) of hydrazine, 15 mL of ethanol was added as a solvent,Stir under the conditions of slowly dropping 0.002mol substitution aldehydes compounds, the rapid dissolving of raw materials,Followed by solid precipitation, stirring at room temperature overnight, point board monitoring, raw material reaction is complete, the filter,Washed with a mixture of petroleum ether and ethanol three times to give a redish yellow solid powder,I.e., a hydrazone compound containing a methoxybenzopyrazine structure as shown in formula (I).
	With palladium 10% on activated carbon; hydrogen In methanol at 20℃; for 6h;
24 g	With palladium 10% on activated carbon; hydrogen In methanol	1.1 Synthesis of 4-methoxypheny-1,2-dilamine 32 g of 5-methoxy-2-nitroaniline was added to 350 ml of methanol, 3.2 g of 10% palladium carbon was added, hydrogen was bubbled in, stirred overnight, filtered, the filtrate was collected, and concentrated to give 24 g of 4-methoxy-1 2-diphenylamine.
	With hydrogenchloride; tin(ll) chloride In water at 0 - 20℃; for 1h;
90 %Spectr.	With iron; ammonium chloride In methanol at 80℃; for 24h; Schlenk technique; Inert atmosphere;

Reference： [1]Abasolo; Gaozza; Fernandez [Journal of Heterocyclic Chemistry, 1987, vol. 24, # 6, p. 1771 - 1775]
[2]Saha, Biswajit; Sharma, Sunil; Kundu, Bijoy [Synthetic Communications, 2007, vol. 37, # 19, p. 3455 - 3470]
[3]Jarag; Jagtap; Borse; Shukla; Shankarling [Journal of Heterocyclic Chemistry, 2012, vol. 49, # 5, p. 1196 - 1201]
[4]Current Patent Assignee: NIPPON KAYAKU CO LTD - JP2016/175996, 2016, A Location in patent: Paragraph 0147-0148
[5]Current Patent Assignee: ZHEJIANG UNIVERSITY OF TECHNOLOGY - CN106234372, 2016, A Location in patent: Paragraph 0027
[6]Current Patent Assignee: NIPPON KAYAKU CO LTD - JP2016/172816, 2016, A Location in patent: Paragraph 0112-0113
[7]Current Patent Assignee: ZHEJIANG UNIVERSITY OF TECHNOLOGY - CN106220575, 2016, A Location in patent: Paragraph 0025; 0026
[8]Mao, Ruifeng; Shao, Jingwei; Zhu, Kongkai; Zhang, Yuanyuan; Ding, Hong; Zhang, Chenhua; Shi, Zhe; Jiang, Hualiang; Sun, Dequn; Duan, Wenhu; Luo, Cheng [Journal of Medicinal Chemistry, 2017, vol. 60, # 14, p. 6289 - 6304]
[9]Current Patent Assignee: HUNAN HUATENG PHARMACEUTICAL CO LTD - CN107778252, 2018, A Location in patent: Paragraph 0020-0022
[10]Gao, Wen-Cong; Li, Xun; Ma, Xin; Pang, Pan-Pan; Peng, Li-Chun; Yang, Liang; Zheng, Chang-Bo [Bioorganic and Medicinal Chemistry Letters, 2021, vol. 36]
[11]An, Jie; Lai, Zemin; Li, Hengzhao; Peng, Mengqi; Sun, Yanhao; Yan, Zihan; Yang, Ruoyan; Zhang, Yuntong [Green Chemistry, 2022, vol. 24, # 2, p. 748 - 753]

6
[ 16133-49-6 ]
[ 98447-30-4 ]

Reference： [1]Justus Liebigs Annalen der Chemie,1971,vol. 744,p. 129 - 141

7
[ 100-17-4 ]
[ 16133-49-6 ]
[ 100-01-6 ]

Yield	Reaction Conditions	Operation in experiment
1: 44% 2: 29%	With 2,4,6-trichlorosulfenamide; potassium <i>tert</i>-butylate In N,N-dimethyl-formamide at 20℃; for 0.333333h;

Reference： [1]Makosza, Mieczyslaw; Bialecki, Maciej [Journal of Organic Chemistry, 1998, vol. 63, # 15, p. 4878 - 4888]

8
[ 100-17-4 ]
[ 16133-49-6 ]

Yield	Reaction Conditions	Operation in experiment
69%	With O-Methylhydroxylamin; potassium <i>tert</i>-butylate In N,N-dimethyl-formamide at 20℃;

Reference： [1]Seko, Shinzo; Miyake, Kunihito; Kavvamura, Norio [Journal of the Chemical Society. Perkin transactions I, 1999, # 11, p. 1437 - 1444]

9
[ 185428-55-1 ]
[ 16133-49-6 ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 169 - 182

10
[ 16133-49-6 ]
[ 214279-40-0 ]

Reference： [1]Tetrahedron,2009,vol. 65,p. 1281 - 1286
[2]Tetrahedron,2003,vol. 59,p. 5507 - 5514
[3]Organic Letters,2009,vol. 11,p. 4036 - 4039
[4]Organic Letters,2010,vol. 12,p. 1696 - 1699
[5]Angewandte Chemie - International Edition,2014,vol. 53,p. 5170 - 5174

11
[ 696-59-3 ]
[ 16133-49-6 ]
[ 687638-10-4 ]

Yield	Reaction Conditions	Operation in experiment
78%	With acetic acid for 1h; Heating;
	With acetic acid
	With acetic acid Microwave irradiation; Heating;

	With acetic acid Microwave irradiation; Heating;
	With acetic acid at 120℃; for 2h; Inert atmosphere;
	With acetic acid at 120℃; for 2h; Inert atmosphere;	(a) General procedure for the synthesis of 1a-1u^[1] General procedure: Compound 1a was purchased from commercial sources and used as received. Substituted 2-(1H-pyrrol-1-yl)anilines 1b-1u were prepared in the following method. A mixture of substituted S1 (5 mmol) and S2 (5 mmol) in acetic acid (25 mL) wasrefluxed for 2 h with vigorous stirring. After cooling, the reaction mixture was poured into water (100 mL) and extracted with ethyl acetate three times (3×20 mL). The combined organic layers were dried with anhydrous Na2SO4 and the solvent was removed in vacuo to afford S3. Then, the residue S3 was added to iron powder (20 mmol)and NH4Cl (2 mmol) in water (20 mL) and refluxed for 4 h. After cooling, the reaction mixture was poured into water (100 mL) and extracted with ethyl acetate three times (3×20 mL). The combined organic layers were dried with anhydrous Na2SO4 and the solvent was removed in vacuo to afford a residue. The residue was purified by column chromatography on silica gel using petroleum ether/EtOAc as eluent to provide the desired product 1b-1u.
	With acetic acid Reflux;
	In acetic acid at 120℃; for 2h;

Reference： [1]Guillon, Jean; Grellier, Philippe; Labaied, Mehdi; Sonnet, Pascal; Léger, Jean-Michel; Déprez-Poulain, Rébecca; Forfar-Bares, Isabelle; Dallemagne, Patrick; Lemaître, Nicolas; Péhourcq, Fabienne; Rochette, Jacques; Sergheraert, Christian; Jarry, Christian [Journal of Medicinal Chemistry, 2004, vol. 47, # 8, p. 1997 - 2009]
[2]Guillon, Jean; Forfar, Isabelle; Mamani-Matsuda, Maria; Desplat, Vanessa; Saliege, Marion; Thiolat, Denis; Massip, Stephane; Tabourier, Anais; Leger, Jean-Michel; Dufaure, Benoit; Haumont, Gilbert; Jarry, Christian; Mossalayi, Djavad [Bioorganic and Medicinal Chemistry, 2007, vol. 15, # 1, p. 194 - 210]
[3]Ronga, Luisa; Del Favero, Marco; Cohen, Anita; Soum, Claire; Le Pape, Patrice; Savrimoutou, Solène; Pinaud, Noël; Mullié, Catherine; Daulouede, Sylvie; Vincendeau, Philippe; Farvacques, Natacha; Agnamey, Patrice; Pagniez, Fabrice; Hutter, Sébastien; Azas, Nadine; Sonnet, Pascal; Guillon, Jean [European Journal of Medicinal Chemistry, 2014, vol. 81, p. 378 - 393]
[4]Guillon, Jean; Cohen, Anita; Gueddouda, Nassima Meriem; Das, Rabindra Nath; Moreau, Stéphane; Ronga, Luisa; Savrimoutou, Solène; Basmaciyan, Louise; Monnier, Alix; Monget, Myriam; Rubio, Sandra; Garnerin, Timothée; Azas, Nadine; Mergny, Jean-Louis; Mullié, Catherine; Sonnet, Pascal [Journal of Enzyme Inhibition and Medicinal Chemistry, 2017, vol. 32, # 1, p. 547 - 563]
[5]An, Zhenyu; Zhao, Lianbiao; Wu, Mingzhong; Ni, Jixiang; Qi, Zhenjie; Yu, Guiqin; Yan, Rulong [Chemical Communications, 2017, vol. 53, # 84, p. 11572 - 11575]
[6]Cui, Xin-Feng; Hu, Fang-Peng; Huang, Guo-Sheng; Zhan, Zhen-Zhen; Zhou, Xiao-Qiang [Synlett, 2020, vol. 31, # 12, p. 1205 - 1210]
[7]Li, Shichen; Feng, Lei; Ma, Chen [New Journal of Chemistry, 2021, vol. 45, # 21, p. 9320 - 9323]
[8]Hu, Fang-Peng; Zhang, Xue-Guo; Wang, Meng; Wang, He-Song; Huang, Guo-Sheng [Chemical Communications, 2021, vol. 57, # 90, p. 11980 - 11983]

12
[ 536-90-3 ]
[ 16292-88-9 ]
[ 16133-49-6 ]
[ 16554-47-5 ]

Reference： [1]Helvetica Chimica Acta,2004,vol. 87,p. 215 - 226

13
[ 536-90-3 ]
[ 16292-88-9 ]
[ 16133-49-6 ]

Reference： [1]Tetrahedron Letters,2006,vol. 47,p. 6879 - 6881

14
[ 16133-49-6 ]
[ 687638-12-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: AcOH 2: BiCl₃; NaBH₄ / ethanol
	Multi-step reaction with 2 steps 1: 78 percent / AcOH / 1 h / Heating 2: 47 percent / BiCl₃; NaBH₄ / ethanol / 2 h / 20 °C
	Multi-step reaction with 2 steps 1: acetic acid / Microwave irradiation; Heating 2: copper(II) sulfate; sodium tetrahydroborate / ethanol / 20 °C

	Multi-step reaction with 2 steps 1: acetic acid / Microwave irradiation; Heating 2: copper(II) sulfate; sodium tetrahydroborate / ethanol / 20 °C
	Multi-step reaction with 2 steps 1: acetic acid / 2 h / 120 °C / Inert atmosphere 2: iron; ammonium chloride / water / 4 h / Reflux; Inert atmosphere
	Multi-step reaction with 2 steps 1: acetic acid / 2 h / 120 °C / Inert atmosphere 2: iron; ammonium chloride / water / 4 h / Reflux; Inert atmosphere
	Multi-step reaction with 2 steps 1: acetic acid / Reflux 2: iron; ammonium chloride / water / Reflux
	Multi-step reaction with 2 steps 1: acetic acid / 2 h / 120 °C 2: ammonium chloride; iron / water / 4 h / Reflux

Reference： [1]Guillon, Jean; Forfar, Isabelle; Mamani-Matsuda, Maria; Desplat, Vanessa; Saliege, Marion; Thiolat, Denis; Massip, Stephane; Tabourier, Anais; Leger, Jean-Michel; Dufaure, Benoit; Haumont, Gilbert; Jarry, Christian; Mossalayi, Djavad [Bioorganic and Medicinal Chemistry, 2007, vol. 15, # 1, p. 194 - 210]
[2]Guillon, Jean; Grellier, Philippe; Labaied, Mehdi; Sonnet, Pascal; Léger, Jean-Michel; Déprez-Poulain, Rébecca; Forfar-Bares, Isabelle; Dallemagne, Patrick; Lemaître, Nicolas; Péhourcq, Fabienne; Rochette, Jacques; Sergheraert, Christian; Jarry, Christian [Journal of Medicinal Chemistry, 2004, vol. 47, # 8, p. 1997 - 2009]
[3]Ronga, Luisa; Del Favero, Marco; Cohen, Anita; Soum, Claire; Le Pape, Patrice; Savrimoutou, Solène; Pinaud, Noël; Mullié, Catherine; Daulouede, Sylvie; Vincendeau, Philippe; Farvacques, Natacha; Agnamey, Patrice; Pagniez, Fabrice; Hutter, Sébastien; Azas, Nadine; Sonnet, Pascal; Guillon, Jean [European Journal of Medicinal Chemistry, 2014, vol. 81, p. 378 - 393]
[4]Guillon, Jean; Cohen, Anita; Gueddouda, Nassima Meriem; Das, Rabindra Nath; Moreau, Stéphane; Ronga, Luisa; Savrimoutou, Solène; Basmaciyan, Louise; Monnier, Alix; Monget, Myriam; Rubio, Sandra; Garnerin, Timothée; Azas, Nadine; Mergny, Jean-Louis; Mullié, Catherine; Sonnet, Pascal [Journal of Enzyme Inhibition and Medicinal Chemistry, 2017, vol. 32, # 1, p. 547 - 563]
[5]An, Zhenyu; Zhao, Lianbiao; Wu, Mingzhong; Ni, Jixiang; Qi, Zhenjie; Yu, Guiqin; Yan, Rulong [Chemical Communications, 2017, vol. 53, # 84, p. 11572 - 11575]
[6]Cui, Xin-Feng; Hu, Fang-Peng; Huang, Guo-Sheng; Zhan, Zhen-Zhen; Zhou, Xiao-Qiang [Synlett, 2020, vol. 31, # 12, p. 1205 - 1210]
[7]Li, Shichen; Feng, Lei; Ma, Chen [New Journal of Chemistry, 2021, vol. 45, # 21, p. 9320 - 9323]
[8]Hu, Fang-Peng; Zhang, Xue-Guo; Wang, Meng; Wang, He-Song; Huang, Guo-Sheng [Chemical Communications, 2021, vol. 57, # 90, p. 11980 - 11983]

15
[ 16133-49-6 ]
[ 420137-33-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: Et₃N / CH₂Cl₂ / 0 - 20 °C 2: toluene / 10 h / 20 °C 3: H₂ / Pd/C / methanol / 20 °C 4: 0.17 h / 240 °C 5: aq. HBr / 48 h / Heating

Reference： [1]Borza, Istvan; Kolok, Sandor; Gere, Aniko; Nagy, Jozsef; Fodor, Laszlo; Galgoczy, Kornel; Fetter, Jozsef; Bertha, Ferenc; Agai, Bela; Horvath, Csilla; Farkas, Sandor; Domany, Gyoergy [Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 17, p. 4638 - 4640]

16
[ 16133-49-6 ]
[ 420137-32-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: Et₃N / CH₂Cl₂ / 0 - 20 °C 2: toluene / 10 h / 20 °C 3: H₂ / Pd/C / methanol / 20 °C 4: 0.17 h / 240 °C

Reference： [1]Borza, Istvan; Kolok, Sandor; Gere, Aniko; Nagy, Jozsef; Fodor, Laszlo; Galgoczy, Kornel; Fetter, Jozsef; Bertha, Ferenc; Agai, Bela; Horvath, Csilla; Farkas, Sandor; Domany, Gyoergy [Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 17, p. 4638 - 4640]

17
[ 16133-49-6 ]
N-(2-amino-5-methoxy-phenyl)-N'-butyl-oxalamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: Et₃N / CH₂Cl₂ / 0 - 20 °C 2: toluene / 10 h / 20 °C 3: H₂ / Pd/C / methanol / 20 °C

Reference： [1]Borza, Istvan; Kolok, Sandor; Gere, Aniko; Nagy, Jozsef; Fodor, Laszlo; Galgoczy, Kornel; Fetter, Jozsef; Bertha, Ferenc; Agai, Bela; Horvath, Csilla; Farkas, Sandor; Domany, Gyoergy [Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 17, p. 4638 - 4640]

18
[ 16133-49-6 ]
(4-benzylpiperidin-1-yl)-(6-hydroxy-1H-benzimidazol-2-yl)-methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: Et₃N / CH₂Cl₂ / 0 - 20 °C 2: toluene / 10 h / 20 °C 3: H₂ / Pd/C / methanol / 20 °C 4: 0.17 h / 240 °C 5: aq. HBr / 48 h / Heating 6: HBTU; Et₃N / dimethylformamide

Reference： [1]Borza, Istvan; Kolok, Sandor; Gere, Aniko; Nagy, Jozsef; Fodor, Laszlo; Galgoczy, Kornel; Fetter, Jozsef; Bertha, Ferenc; Agai, Bela; Horvath, Csilla; Farkas, Sandor; Domany, Gyoergy [Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 17, p. 4638 - 4640]

19
[ 16133-49-6 ]
[4-(4-chloro-phenoxy)-piperidin-1-yl]-(6-hydroxy-1H-benzimidazol-2-yl)-methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: Et₃N / CH₂Cl₂ / 0 - 20 °C 2: toluene / 10 h / 20 °C 3: H₂ / Pd/C / methanol / 20 °C 4: 0.17 h / 240 °C 5: aq. HBr / 48 h / Heating 6: HBTU; Et₃N / dimethylformamide

Reference： [1]Borza, Istvan; Kolok, Sandor; Gere, Aniko; Nagy, Jozsef; Fodor, Laszlo; Galgoczy, Kornel; Fetter, Jozsef; Bertha, Ferenc; Agai, Bela; Horvath, Csilla; Farkas, Sandor; Domany, Gyoergy [Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 17, p. 4638 - 4640]

20
[ 16133-49-6 ]
(6-hydroxy-1H-benzimidazol-2-yl)-(4-p-tolyloxy-piperidin-1-yl)-methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: Et₃N / CH₂Cl₂ / 0 - 20 °C 2: toluene / 10 h / 20 °C 3: H₂ / Pd/C / methanol / 20 °C 4: 0.17 h / 240 °C 5: aq. HBr / 48 h / Heating 6: HBTU; Et₃N / dimethylformamide

Reference： [1]Borza, Istvan; Kolok, Sandor; Gere, Aniko; Nagy, Jozsef; Fodor, Laszlo; Galgoczy, Kornel; Fetter, Jozsef; Bertha, Ferenc; Agai, Bela; Horvath, Csilla; Farkas, Sandor; Domany, Gyoergy [Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 17, p. 4638 - 4640]

21
[ 16133-49-6 ]
[4-(4-fluoro-phenoxy)-piperidin-1-yl]-(6-hydroxy-1H-benzimidazol-2-yl)-methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: Et₃N / CH₂Cl₂ / 0 - 20 °C 2: toluene / 10 h / 20 °C 3: H₂ / Pd/C / methanol / 20 °C 4: 0.17 h / 240 °C 5: aq. HBr / 48 h / Heating 6: HBTU; Et₃N / dimethylformamide

Reference： [1]Borza, Istvan; Kolok, Sandor; Gere, Aniko; Nagy, Jozsef; Fodor, Laszlo; Galgoczy, Kornel; Fetter, Jozsef; Bertha, Ferenc; Agai, Bela; Horvath, Csilla; Farkas, Sandor; Domany, Gyoergy [Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 17, p. 4638 - 4640]

22
[ 16133-49-6 ]
(6-Hydroxy-1H-benzoimidazol-2-yl)-[4-(4-methyl-benzyl)-piperidine-1-yl]-methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: Et₃N / CH₂Cl₂ / 0 - 20 °C 2: toluene / 10 h / 20 °C 3: H₂ / Pd/C / methanol / 20 °C 4: 0.17 h / 240 °C 5: aq. HBr / 48 h / Heating 6: HBTU; Et₃N / dimethylformamide

Reference： [1]Borza, Istvan; Kolok, Sandor; Gere, Aniko; Nagy, Jozsef; Fodor, Laszlo; Galgoczy, Kornel; Fetter, Jozsef; Bertha, Ferenc; Agai, Bela; Horvath, Csilla; Farkas, Sandor; Domany, Gyoergy [Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 17, p. 4638 - 4640]

23
[ 16133-49-6 ]
(6-hydroxy-1H-benzimidazol-2-yl)-[4-(3-methyl-benzyl)-piperidin-1-yl]-methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: Et₃N / CH₂Cl₂ / 0 - 20 °C 2: toluene / 10 h / 20 °C 3: H₂ / Pd/C / methanol / 20 °C 4: 0.17 h / 240 °C 5: aq. HBr / 48 h / Heating 6: HBTU; Et₃N / dimethylformamide

Reference： [1]Borza, Istvan; Kolok, Sandor; Gere, Aniko; Nagy, Jozsef; Fodor, Laszlo; Galgoczy, Kornel; Fetter, Jozsef; Bertha, Ferenc; Agai, Bela; Horvath, Csilla; Farkas, Sandor; Domany, Gyoergy [Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 17, p. 4638 - 4640]

24
[ 16133-49-6 ]
(6-hydroxy-1H-benzoimidazol-2-yl)-[4-(2-methyl-benzyl)-piperidin-1-yl]-methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: Et₃N / CH₂Cl₂ / 0 - 20 °C 2: toluene / 10 h / 20 °C 3: H₂ / Pd/C / methanol / 20 °C 4: 0.17 h / 240 °C 5: aq. HBr / 48 h / Heating 6: HBTU; Et₃N / dimethylformamide

Reference： [1]Borza, Istvan; Kolok, Sandor; Gere, Aniko; Nagy, Jozsef; Fodor, Laszlo; Galgoczy, Kornel; Fetter, Jozsef; Bertha, Ferenc; Agai, Bela; Horvath, Csilla; Farkas, Sandor; Domany, Gyoergy [Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 17, p. 4638 - 4640]

25
[ 16133-49-6 ]
[4-(3-fluoro-benzyl)-piperidin-1-yl]-(6-hydroxy-1H-benzoimidazol-2-yl)-methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: Et₃N / CH₂Cl₂ / 0 - 20 °C 2: toluene / 10 h / 20 °C 3: H₂ / Pd/C / methanol / 20 °C 4: 0.17 h / 240 °C 5: aq. HBr / 48 h / Heating 6: HBTU; Et₃N / dimethylformamide

Reference： [1]Borza, Istvan; Kolok, Sandor; Gere, Aniko; Nagy, Jozsef; Fodor, Laszlo; Galgoczy, Kornel; Fetter, Jozsef; Bertha, Ferenc; Agai, Bela; Horvath, Csilla; Farkas, Sandor; Domany, Gyoergy [Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 17, p. 4638 - 4640]

26
[ 16133-49-6 ]
[4-(4-fluoro-benzyl)-piperidin-1-yl]-(6-hydroxy-1H-benzimidazol-2-yl)-methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: Et₃N / CH₂Cl₂ / 0 - 20 °C 2: toluene / 10 h / 20 °C 3: H₂ / Pd/C / methanol / 20 °C 4: 0.17 h / 240 °C 5: aq. HBr / 48 h / Heating 6: HBTU; Et₃N / dimethylformamide

Reference： [1]Borza, Istvan; Kolok, Sandor; Gere, Aniko; Nagy, Jozsef; Fodor, Laszlo; Galgoczy, Kornel; Fetter, Jozsef; Bertha, Ferenc; Agai, Bela; Horvath, Csilla; Farkas, Sandor; Domany, Gyoergy [Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 17, p. 4638 - 4640]

27
[ 16133-49-6 ]
(6-hydroxy-1H-benzimidazol-2-yl)-[4-(3-methoxy-benzyl)-piperidin-1-yl]-methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: Et₃N / CH₂Cl₂ / 0 - 20 °C 2: toluene / 10 h / 20 °C 3: H₂ / Pd/C / methanol / 20 °C 4: 0.17 h / 240 °C 5: aq. HBr / 48 h / Heating 6: HBTU; Et₃N / dimethylformamide

Reference： [1]Borza, Istvan; Kolok, Sandor; Gere, Aniko; Nagy, Jozsef; Fodor, Laszlo; Galgoczy, Kornel; Fetter, Jozsef; Bertha, Ferenc; Agai, Bela; Horvath, Csilla; Farkas, Sandor; Domany, Gyoergy [Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 17, p. 4638 - 4640]

28
[ 16133-49-6 ]
[ 687638-13-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 78 percent / AcOH / 1 h / Heating 2: 47 percent / BiCl₃; NaBH₄ / ethanol / 2 h / 20 °C 3: 53 percent / toluene / 4 h / Heating
	Multi-step reaction with 3 steps 1: acetic acid / Microwave irradiation; Heating 2: copper(II) sulfate; sodium tetrahydroborate / ethanol / 20 °C 3: toluene / Heating
	Multi-step reaction with 3 steps 1: acetic acid / Microwave irradiation; Heating 2: copper(II) sulfate; sodium tetrahydroborate / ethanol / 20 °C 3: toluene / Heating

Reference： [1]Guillon, Jean; Grellier, Philippe; Labaied, Mehdi; Sonnet, Pascal; Léger, Jean-Michel; Déprez-Poulain, Rébecca; Forfar-Bares, Isabelle; Dallemagne, Patrick; Lemaître, Nicolas; Péhourcq, Fabienne; Rochette, Jacques; Sergheraert, Christian; Jarry, Christian [Journal of Medicinal Chemistry, 2004, vol. 47, # 8, p. 1997 - 2009]
[2]Ronga, Luisa; Del Favero, Marco; Cohen, Anita; Soum, Claire; Le Pape, Patrice; Savrimoutou, Solène; Pinaud, Noël; Mullié, Catherine; Daulouede, Sylvie; Vincendeau, Philippe; Farvacques, Natacha; Agnamey, Patrice; Pagniez, Fabrice; Hutter, Sébastien; Azas, Nadine; Sonnet, Pascal; Guillon, Jean [European Journal of Medicinal Chemistry, 2014, vol. 81, p. 378 - 393]
[3]Guillon, Jean; Cohen, Anita; Gueddouda, Nassima Meriem; Das, Rabindra Nath; Moreau, Stéphane; Ronga, Luisa; Savrimoutou, Solène; Basmaciyan, Louise; Monnier, Alix; Monget, Myriam; Rubio, Sandra; Garnerin, Timothée; Azas, Nadine; Mergny, Jean-Louis; Mullié, Catherine; Sonnet, Pascal [Journal of Enzyme Inhibition and Medicinal Chemistry, 2017, vol. 32, # 1, p. 547 - 563]

29
[ 16133-49-6 ]
[ 687638-14-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: 78 percent / AcOH / 1 h / Heating 2: 47 percent / BiCl₃; NaBH₄ / ethanol / 2 h / 20 °C 3: 53 percent / toluene / 4 h / Heating 4: 83 percent / POCl₃ / 4 h / Heating
	Multi-step reaction with 4 steps 1: acetic acid / Microwave irradiation; Heating 2: copper(II) sulfate; sodium tetrahydroborate / ethanol / 20 °C 3: toluene / Heating 4: trichlorophosphate / Heating
	Multi-step reaction with 4 steps 1: acetic acid / Microwave irradiation; Heating 2: copper(II) sulfate; sodium tetrahydroborate / ethanol / 20 °C 3: toluene / Heating 4: trichlorophosphate / Heating

Reference： [1]Guillon, Jean; Grellier, Philippe; Labaied, Mehdi; Sonnet, Pascal; Léger, Jean-Michel; Déprez-Poulain, Rébecca; Forfar-Bares, Isabelle; Dallemagne, Patrick; Lemaître, Nicolas; Péhourcq, Fabienne; Rochette, Jacques; Sergheraert, Christian; Jarry, Christian [Journal of Medicinal Chemistry, 2004, vol. 47, # 8, p. 1997 - 2009]
[2]Ronga, Luisa; Del Favero, Marco; Cohen, Anita; Soum, Claire; Le Pape, Patrice; Savrimoutou, Solène; Pinaud, Noël; Mullié, Catherine; Daulouede, Sylvie; Vincendeau, Philippe; Farvacques, Natacha; Agnamey, Patrice; Pagniez, Fabrice; Hutter, Sébastien; Azas, Nadine; Sonnet, Pascal; Guillon, Jean [European Journal of Medicinal Chemistry, 2014, vol. 81, p. 378 - 393]
[3]Guillon, Jean; Cohen, Anita; Gueddouda, Nassima Meriem; Das, Rabindra Nath; Moreau, Stéphane; Ronga, Luisa; Savrimoutou, Solène; Basmaciyan, Louise; Monnier, Alix; Monget, Myriam; Rubio, Sandra; Garnerin, Timothée; Azas, Nadine; Mergny, Jean-Louis; Mullié, Catherine; Sonnet, Pascal [Journal of Enzyme Inhibition and Medicinal Chemistry, 2017, vol. 32, # 1, p. 547 - 563]

30
[ 1882-69-5 ]
[ 16133-49-6 ]

Yield	Reaction Conditions	Operation in experiment
98%	Stage #1: 5-methoxy-2-nitro-benzoic acid With diphenylphosphoranyl azide; triethylamine In <i>tert</i>-butyl alcohol for 16h; Heating / reflux; Stage #2: With hydrogenchloride In methanol; water at 20℃; for 96h; Stage #3: With potassium hydrogencarbonate In water for 0.5h;	19 A mixture of 5-methoxy-2-nitrobenzoic acid (10) (10 g, 50 7 mmol) diphenylphosphorylazide (DPPA) (11.5 mL, 53.3 mmol) and Et3N (7.4 mL, 53.3 mmol) in t-BuOH (200 mL) was heated at reflux temperature for 16 h. The solution was cooled to 20 °C and the solvent evaporated. The residue was dissolved in DCM (300 mL) and washed with water (2 × 100 mL), saturated aqueous KHCO3 (100 mL), brine (50 mL), dried, and the solvent evaporated. The residue was suspended in MeOH (250 mL), cHCl (50 mL) added, and the mixture stirred at 20 °C for 96 h. The solvent was evaporated and the residue suspended in saturated aqueous KHCO3 (400 mL) and stirred for 30 min. The suspension was filtered, the solid washed with water (20 mL) and dried at 80 °C under reduced pressure. The solid was chromatographed, eluting with a gradient (20-30%) of EtOAc/pet. ether, to give 1q (8.26 g, 98%); as a yellow solid, mp 128-130 °C [lit. (Seko et. al., J. Chem. Soc. Perkin Trans. 11999, 1437) mp 130-132 °C], 1H NMR δ 8.07 (d, J = 9.5 Hz, 1 H, H-3), 6.28 (dd, J = 9.5, 2.6 Hz, 1 H, H-4), 6.21 (br s, 2 H, NH2), 6.15 (d, J = 2.6 Hz, 1 H, H-6), 3.83 (s, 3 H, OCH3); 13C NMR δ 165.4, 147.1, 128.5, 126.9, 106.7, 99.4, 55.7.
	Multi-step reaction with 2 steps 1: DPPA; Et₃N / 16 h / Heating 2: 98 percent / aq. HCl / methanol / 96 h / 20 °C

Reference： [1]Current Patent Assignee: THE UNIVERSITY OF AUCKLAND - EP1468688, 2004, A2 Location in patent: Page/Page column 24; 47
[2]Hay, Michael P.; Gamage, Swarna A.; Kovacs, Mary S.; Pruijn, Frederik B.; Anderson, Robert F.; Patterson, Adam V.; Wilson, William R.; Brown, J. Martin; Denny, William A. [Journal of Medicinal Chemistry, 2003, vol. 46, # 1, p. 169 - 182]

31
[ 16133-49-6 ]
[ 492469-55-3 ]

Yield	Reaction Conditions	Operation in experiment
63%		19 6-Methoxy-1,2,4-benzotriazin-3-amine 1-oxide (3q). 6-Methoxy-1,2,4-benzotriazin-3-amine 1-oxide (3q). Method A using 5-methoxy-2-nitroaniline (1q) gave 3q (63%) as a yellow powder, mp (CHCl3) 265-270° C.; 1H NMR [(CD3)2SO] δ 8.04 (d, J=9.5 Hz, 1H, H-8), 7.24 (br s, 2H, NH2), 6.95 (dd, J=9.5, 2.6 Hz, 1H, H-7), 6.86 (d, J=2.6 Hz, 1H, H-5), 3.91 (s, 3H, OCH3); 13C NMR [(CD3)2SO] δ 164.7, 160.7, 151.3, 125.0, 121.5, 117.0, 103.8, 56.0; MS (EI+) m/z 192 (M+, 100%), 176 (5); HRMS (EI) calc. for C8H8N4O2 (M+) m/z 192.0647, found 192.0653; Anal. calc. for C8H8N4O2: C, 50.0; H, 4.2; N, 29.2; found C, 50.0; H, 4.0; N, 29.0%.
	Multi-step reaction with 2 steps 1: HCl / 100 °C 2: aq. NaOH / 1 h / 100 °C

Reference： [1]Current Patent Assignee: THE UNIVERSITY OF AUCKLAND - US2004/192686, 2004, A1
[2]Hay, Michael P.; Gamage, Swarna A.; Kovacs, Mary S.; Pruijn, Frederik B.; Anderson, Robert F.; Patterson, Adam V.; Wilson, William R.; Brown, J. Martin; Denny, William A. [Journal of Medicinal Chemistry, 2003, vol. 46, # 1, p. 169 - 182]

32
[ 536-90-3 ]
[ 16133-49-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 91 percent / 2 M HCl, NaOAc / H₂O / 0.33 h 2: 63 percent / HNO₃, AcOH / acetic anhydride / 6 h / 25 - 40 °C 3: 85 percent / conc. HCl / 5 h / Heating
	With hydrogenchloride; nitric acid; acetic anhydride In acetic acid	8 EXAMPLE 8 STR52 EXAMPLE 8 STR52 A solution of 3-methoxyaniline (2.21 g) in acetic acid (3 ml) and acetic anhydride (10 ml) was stirred at room temperature for 1 hour. The solution was cooled to 5° C. and 60% nitric acid (1 ml) was added dropwise with stirring. When the cooling bath was removed, whereupon the solution temperature rose to 60° C. The solution was allowed to cool down to room temperature, poured into ice-water (100 ml) and neutralized with sodium hydroxide. The separated crystals were collected by suction and washed with water. To the crystals was added 4N hydrochloric acid (45 ml) and the mixture was refluxed for 2 hours. The reaction mixture was alkalized with sodium hydroxide and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure and the residue was purified by silica gel chromatography (eluent: chloroform) to give 0.67 g of 5-methoxy-2-nitroaniline. Mass spectrum (m/z): 168 (M+). NMR (CDCl3) δ: 3.90 (3H, s), 4.32 (2H, br s), 6.12-6.28 (2H, m), 7.94 (1H, d, J=10 Hz).
	Multi-step reaction with 2 steps 1.1: tetrahydrofuran / 0.5 h / 0 - 20 °C 2.1: acetic acid; nitric acid; sulfuric acid / 3.5 h / 0 - 20 °C 2.2: 3 h / Reflux

Reference： [1]Zhang; Zhang, Zhoupeng; Tillekeratne; Hudson; Hudson, Richard A. [Synthesis, 1996, # 3, p. 377 - 382]
[2]Current Patent Assignee: ASTELLAS PHARMA INC. - US5162318, 1992, A
[3]Awasthi, Bhuwan Prasad; Chaudhary, Chhabi Lal; Chaudhary, Prakash; Guragain, Diwakar; Jeong, Byeong-Seon; Kim, Jung-Ae; Lim, Dongchul; Park, Hee Dong [Journal of Enzyme Inhibition and Medicinal Chemistry, 2022, vol. 37, # 1, p. 844 - 856]

33
[ 588-16-9 ]
[ 16133-49-6 ]

Yield	Reaction Conditions	Operation in experiment
13%	Stage #1: m-methoxyacetanilide With sulfuric acid; nitric acid; acetic acid at 0 - 20℃; for 3.5h; Stage #2: With hydrogenchloride In water monomer for 3h; Reflux;
	Multi-step reaction with 2 steps 1: 63 percent / HNO₃, AcOH / acetic anhydride / 6 h / 25 - 40 °C 2: 85 percent / conc. HCl / 5 h / Heating
	Multi-step reaction with 2 steps 1: nitric acid / 65 °C 2: diluted hydrochloric acid

	Multi-step reaction with 2 steps 1: glacial acetic acid; nitric acid / 65 °C 2: diluted hydrochloric acid
	Multi-step reaction with 2 steps 1: HNO₃, Ac₂O 2: aq. HCl / Heating

Reference： [1]Awasthi, Bhuwan Prasad; Chaudhary, Chhabi Lal; Chaudhary, Prakash; Guragain, Diwakar; Jeong, Byeong-Seon; Kim, Jung-Ae; Lim, Dongchul; Park, Hee Dong [Journal of Enzyme Inhibition and Medicinal Chemistry, 2022, vol. 37, # 1, p. 844 - 856]
[2]Zhang; Zhang, Zhoupeng; Tillekeratne; Hudson; Hudson, Richard A. [Synthesis, 1996, # 3, p. 377 - 382]
[3]Reverdin; Widmer [Chemische Berichte, 1913, vol. 46, p. 4074]
[4]Reverdin; Widmer [Chemische Berichte, 1913, vol. 46, p. 4074]
[5]Acheson,R.M. et al. [Journal of the Chemical Society. Perkin transactions I, 1978, p. 1117 - 1125]

34
[ 16133-49-6 ]
[ 7791-49-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 1.) AcOH, conc. H₂SO₄, NaNO₂, 2.) NaN₃, aq. AcONa / 1.) from 5 to 10 deg C, 60 min 2: 98.1 percent Spectr. / decahydronaphthalene / 87.7 °C / ΔE(excit.), ΔS(excit.)
	With sodium hypochlorite; potassium hydroxide In ethanol; water at 0℃; Sealed tube; Inert atmosphere;

Reference： [1]Dyall, Leonard K. [Australian Journal of Chemistry, 1986, vol. 39, # 1, p. 89 - 101]
[2]Sheng, Jinyu; He, Ru; Xue, Jie; Wu, Chao; Qiao, Juan; Chen, Chao [Organic Letters, 2018, vol. 20, # 15, p. 4458 - 4461]

35
[ 1635-61-6 ]
[ 124-41-4 ]
[ 16133-49-6 ]

Yield	Reaction Conditions	Operation in experiment
99%	In methanol at 80℃; for 4h;
85%	In methanol at 20℃; for 28h; Inert atmosphere;
	In methanol for 18h; Heating / reflux;	1.1 1.1 Preparation of 5-methoxy-2-nitroaniline 10 g of 5-chloro-2-nitroaniline are dissolved in 100 ml of methanol, and 32.3 g of sodium methoxide are added. The reaction mixture is heated at the boil under reflux for 18 hours. After cooling, the mixture is evaporated to dryness, 500 ml of water are added, and the crude product is isolated by filtration. Drying gives 9.15 g of 5-methoxy-2-nitroaniline.

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP1191019, 2002, A1 Location in patent: Page 58
[2]Location in patent: experimental part Sheibani, Esmaeil; Waernmark, Kenneth [Organic and Biomolecular Chemistry, 2012, vol. 10, # 10, p. 2059 - 2067]
[3]Current Patent Assignee: MERCK KGAA - US2008/306042, 2008, A1 Location in patent: Page/Page column 37

36
[ 24424-99-5 ]
[ 16133-49-6 ]
[ 314271-23-3 ]

Yield	Reaction Conditions	Operation in experiment
100%	With dmap In ethyl acetate at 25℃; for 3h;
101%	With 2-(Dimethylamino)pyridine In ethyl acetate	1 N-(5-Methoxy-2-nitrophenyl)-N-t-butoxycarbonylcarbamic Acid t-butyl Ester (Exemplification Compound Number 1-2) Example 1 N-(5-Methoxy-2-nitrophenyl)-N-t-butoxycarbonylcarbamic Acid t-butyl Ester (Exemplification Compound Number 1-2) To a solution of 5-methoxy-2-nitroaniline (4.8 g) in ethyl acetate (70 ml) were added dimethylaminopyridine (177 mg) and di-t-butyl dicarbonate (13.9 g) and the mixture was stirred at 25° C. for 3 hours. At the end of this time the reaction mixture was cooled to room temperature and concentrated in vacuo to give the title compound (10.6 g, yield 101%). IR spectrum (KBr, v cm-1): 2980, 1801, 1738, 1601, 1292, 1149, 843. 1H-NMR spectrum (CDCl3, 400 MHz, δ ppm): 1.38(18H, s), 3.87(3H, s), 6.75(1H, d, J=2.7 Hz), 6.91(1H, dd, J=9.2, 2.7 Hz), 8.12(1H, d, J=9.2 Hz).

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP1191019, 2002, A1 Location in patent: Page 54
[2]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - US2003/8907, 2003, A1

37
[ 24424-99-5 ]
[ 16133-49-6 ]
[ 185428-55-1 ]

Yield	Reaction Conditions	Operation in experiment
	With trifluoroacetic acid; In dichloromethane;	Example A12 (5-Methoxy-2-nitro-phenyl)-carbamic acid tert-butyl ester The title compound was prepared via the di-Boc-compound from 5-methoxy-2-nitro-phenylamine [CAS-No. 16133-49-6] (7.73 g, 46 mmol) and Boc2O (20.60 g, 94.3 mmol), followed by treatment with 2 eq. TFA in CH2Cl2 according to the general procedure A (method c). Obtained as a yellow solid (12.234 g). MS (EI) 268.2 (M+); mp 109-112 C.
	With pyridine; dmap; sodium chloride; In tetrahydrofuran;	Preparation 6 N-t-Butoxycarbonyl-5-methoxy-2-nitroaniline 25 g of di-t-butyl dicarbonate, 15 ml of pyridine and 0.6 g of 4-dimethylaminopyridine were added at room temperature to a solution of 16 g of 5-methoxy-2-nitroaniline (prepared as described in Preparation 5) in 500 ml of dehydrated tetrahydrofuran, and the resulting mixture was stirred for 2 hours. At the end of this time, the reaction mixture was freed from the solvent by distillation under reduced pressure, and the resulting residue was diluted with water. The resulting aqueous mixture was extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate, after which the solvent was removed by distillation under reduced pressure. The resulting residue was purified by column chromatography through silica gel using a 1:10 by volume mixture of ethyl acetate and hexane as the eluent, to give 12.5 g of the title compound, melting at 112-114 C.
	With pyridine; dmap; sodium chloride; In tetrahydrofuran;	PREPARATION 6 N-t-Butoxycarbonyl-5-methoxy-2-nitroaniline 25 g of di-t-butyl dicarbonate, 15 ml of pyridine and 0.6 g of 4-dimethylaminopyridine were added at room temperature to a solution of 16 g of 5-methoxy-2-nitroaniline (prepared as described in Preparation 5) in 500 ml of dehydrated tetrahydrofuran, and the resulting mixture was stirred for 2 hours. At the end of this time, the reaction mixture was freed from the solvent by distillation under reduced pressure, and the resulting residue was diluted with water. The resulting aqueous mixture was extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulphate, after which the solvent was removed by distillation under reduced pressure. The resulting residue was purified by column chromatography through silica gel using a 1: 10 by volume mixture of ethyl acetate and hexane as the eluent, to give 12.5 g of the title compound, melting at 112 - 114C.

Reference： [1]Patent: EP1172356,2002,A1 .Location in patent: Page 8
[2]Patent: EP1191019,2002,A1 .Location in patent: Page 56
[3]Patent: US2003/166639,2003,A1
[4]Patent: US5886014,1999,A
[5]Patent: EP745600,1996,A1

38
[ 67-56-1 ]
[ 1635-61-6 ]
[ 16133-49-6 ]

Yield	Reaction Conditions	Operation in experiment
69%	With sodium at 120℃; for 4h; In sealed tube;	162 To freshly prepared sodium methoxide using sodium (900 mg, 39 mmol) and anhydrous methanol (20 mL) was added 3-chloro-6-nitroaniline (2.55 g, 15 mmol). The reaction mixture was heated in a sealed tube at 120° C. for 4 hours. The solvent was removed under reduced pressure and the crude solid was dissolved in water (50 mL) and extracted with ethyl acetate (3×50 mL). The combined ethyl acetate layer was dried over sodium sulfate. The sodium sulfate was removed by filtration and the solvent was removed. The crude was dried to yield a yellow solid (1.75 g, 69%).

Reference： [1]Current Patent Assignee: SANOFI - US2005/245524, 2005, A1 Location in patent: Page/Page column 90

39
[ 16133-49-6 ]
[ 173312-36-2 ]

Yield	Reaction Conditions	Operation in experiment
89%	With N-Bromosuccinimide In acetonitrile Inert atmosphere; Reflux;	B1.1 Step 1: Synthesis of 4-bromo-5-methoxy-2-nitroaniline. NBS (11.6 g, 65 mmol) was added to a solution of 5-methoxy-2-nitroaniline (10 g, 59.5 mmol) in acetonitrile (100 mL) under N2 protection. The reaction mixture was stirred and refluxed overnight. After cooling to room temperature, the mixture was quenched with water,and concentrated to give the crude product. The crude peoduct was washed with water to give 14 g of 4-bromo-5-methoxy-2-nitroaniline (89% yield) as a brown solid. LCMS: m/z 247.1 [M+H]+; tR = 1.69 min.
89%	With N-Bromosuccinimide In acetonitrile at 25℃; for 3h; Inert atmosphere;	1 Step 1 - 4-Bromo-5-methoxy-2-nitro-aniline To a solution of 5-methoxy-2-nitro-aniline (11.0 g, 65.4 mmol, CAS 16133-49-6) in ACN (150 mL) was added NBS (12.8 g, 71.9 mmol) at 25 °C. The mixture was stirred at 25 °C for 3 hours. On completion, the mixture was quenched with sat. aq. Na2SO3 (300 mL) and H2O (500 mL) at 25 °C. A solid was precipitated out from the solution, and the solid was washed with H2O (200 mL) and filtered. The filter cake was dissolved in EA (500 mL), dried over by Na2SO4, filtered and the filtrate was concentrated in vacuo to give the title compound (16.0 g, 89% yield) as a yellow solid.
85%	With N-Bromosuccinimide In acetonitrile at 15 - 30℃; for 3h; Inert atmosphere;	60.1 first step4-bromo-5-methoxy-2-nitroaniline The compound 5-methoxy-2-nitroaniline 60a (2.0 g, 11.9 mmol) was mixed with acetonitrile (30.0 mL).N-bromosuccinimide (2.3 g, 13.1 mmol) was added at room temperature.The reaction was stirred at room temperature for 3 hours.The reaction was quenched with saturated sodium sulfite (60 mL).Dilute with water (100 mL) until a large amount of solid precipitated. filter,The filter cake was dissolved in ethyl acetate (100 mL), dried over anhydrous sodium sulfate and filtered and evaporated to give the title product 4-bromo-5-methoxy-2-nitroaniline 60b (2.5 g,10.1 mmol, yellow solid), yield 85%.

82%	Stage #1: 5-methoxy-2-nitroaniline With N-Bromosuccinimide In acetonitrile at 0℃; Stage #2: With trifluoroacetic acid In acetonitrile at 0 - 20℃; for 24h;
82%	With N-Bromosuccinimide; trifluoroacetic acid at 0 - 20℃; for 4h;	25.1 Step 1: 5-Methoxy-2-nitroaniline (7.2 g, 43 mmol) and NBS (7.5 g, 43 mmol) were dissolved in acetonitrile (70 mL) and cooled to 0 °C. Then TFA (3.2 mL, 43 mmol) was added dropwise into the mixture. The ice-bath was removed and the reaction was stirred for 4 h at room temperature. Water (100 mL) was added and the pH was adjusted to 8 by adding 2.5 M NaOH. The formed precipitate was recrystallized from methanol to give 4-bromo-5-methoxy-2-nitroaniline as a yellow solid (9.65 g, 82%). MS m/z 247, 249 [M+H]+
72%	With N-Bromosuccinimide In acetic acid for 3h; Heating / reflux;	162 A mixture of 3-methoxy-6-nitroaniline (940 mg, 5.6 mmol) and NBS (1.1 g, 6.2 mmol) in glacial acetic acid (25 mL) was heated to reflux under argon for 3 h. The reaction mixture was brought to room temperature and the mixture was diluted with water (100 mL). The yellow precipitate was collected by filtration, washed with water to yield a yellow solid (1 g, 72%).
72%	With N-Bromosuccinimide; trifluoroacetic acid In acetonitrile at 0 - 20℃; for 16.5h;	3.a a. 4-bromo-5-methoxy-2-nitroaniline To a stirred solution of 5-methoxy-2-nitroaniline (100 g, 595 mmol) in acetonitrile (2.5 L) was added NBS (106g, 595 mmol) portion wise at room temperature. The mixture was cooled to 0 °C and added TFA (46 mL, 595 mmol)drop wise for 30 minutes and allowed to stir at room temperature for 16 h. The reaction mixture was diluted with water(1 L) and adjusted the pH to ∼ 8 with IN NaOH. The resulting precipitate was filtered, washed with water (500 mL) anddried under vacuum affording a yellow solid. (105 g, 72%). M/z 247 (M+H)+.
72%	With N-Bromosuccinimide; trifluoroacetic acid In acetonitrile at 0 - 20℃; for 16.5h;	8.a; 52.a a. 4-bromo-5 -methoxy-2-nitroaniline To a stirred solution of 5-methoxy-2-nitroaniline (100 g, 595 mmol) in acetonitrile (2.5 L) was added NBS (106 g, 595 mmol) portion wise at room temperature. The mixture was cooled to 0 °C and added TFA (46 mL, 595 mmol) drop wise for 30 minutes and allowed to stir at room temperature for 16 h. The reaction mixture was diluted with water (1 L) and adjusted the pH to ~ 8 with IN NaOH. The resulting precipitate was fdtered, washed with water (500 mL) and dried under vacuum affording a yellow solid. (105 g, 72%). M/z 247 (M+H)+.
48%	With N-Bromosuccinimide In dichloromethane at 20℃; for 12h; Inert atmosphere;	27.A 4-bromo-5-methoxy-2-nitroaniline To a solution of 5-methoxy-2-nitroaniline (1.99 g, 11.83 mmol) in dry CH2CI2 (60 mL) at room temperature under nitrogen was added NBS (2.74 g, 15.39 mmol). The reaction mixture was stirred at room temperature for 12 h. The reaction mixture was concentrated under reduced pressure and purified by silica gel chromatography (0-100% EtOAc in hexanes). Obtained 4-bromo-5-methoxy-2-nitroaniline (1.4 g, 5.67 mmol, 48 % yield) as yellow solid. 1H NMR (400MHz, CHLOROFORM-d) δ 8.35 (s, 1H), 6.29 (br. s., 2H), 6.19 (s, 1H), 3.92 (s, 3H), LC/MS (ESI) m/e 247.1, 249.1 Br pattern [(M+H)+, calcd for C7H8BrN203 247.0].

Reference： [1]Current Patent Assignee: SKYHAWK THERAPEUTICS INC - WO2020/163541, 2020, A1 Location in patent: Paragraph 0620; 0717
[2]Current Patent Assignee: KYMERA THERAPEUTICS INC - WO2020/264499, 2020, A1 Location in patent: Paragraph 00920; 002817-002819
[3]Current Patent Assignee: NANJING INNOCARE PHARMA TECH; SYNERCARE PHARMA TECH - CN109020957, 2018, A Location in patent: Paragraph 0253
[4]Location in patent: experimental part Sheibani, Esmaeil; Waernmark, Kenneth [Organic and Biomolecular Chemistry, 2012, vol. 10, # 10, p. 2059 - 2067]
[5]Current Patent Assignee: PTC THERAPEUTICS INC - WO2020/5873, 2020, A1 Location in patent: Page/Page column 170
[6]Current Patent Assignee: SANOFI - US2005/245524, 2005, A1 Location in patent: Page/Page column 90
[7]Current Patent Assignee: ANTABIO SAS - EP3628666, 2020, A1 Location in patent: Paragraph 0115-0117
[8]Current Patent Assignee: ANTABIO SAS - WO2021/191240, 2021, A1 Location in patent: Page/Page column 92-93; 139-140
[9]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2016/22312, 2016, A1 Location in patent: Page/Page column 63

40
[ 1635-61-6 ]
[ 16133-49-6 ]

Yield	Reaction Conditions	Operation in experiment
99%	With sodium methylate In <i>N</i>-methyl-acetamide; methanol	R.1 5-Methoxy-2-nitroaniline Reference Example 1 5-Methoxy-2-nitroaniline To a solution of 5-chloro-2-nitroaniline (5.0 g) in dimethylformamide (25 ml) was added 24% sodium methoxide in methanol (11 ml) and the mixture was heated at 80° C. for 4 hours. At the end of this time, the reaction mixture was cooled to room temperature and partitioned between ethyl acetate and water. The extract was washed with 20% aqueous sodium chloride solution and insoluble material was filtered off. The filtrate was concentrated in vacuo to give the desired compound (4.8 g, yield 99%). IR spectrum (KBr, ν cm-1): 3477, 3362, 1626, 1412, 1245, 1108, 830. 1H-NMR spectrum (CDCl3, 400 MHz, δ ppm): 3.82(3H, s), 6.15(1H, d, J=2.7 Hz), 6.21(2H, br.s), 6.28(1H, dd, J=9.5, 2.7 Hz), 8.06(1H, d, J=9.5 Hz).
	With sodium chloride; sodium methylate In 1,4-dioxane	5 5-Methoxy-2-nitroaniline Preparation 5 5-Methoxy-2-nitroaniline 70 ml of a 28% w/v methanolic solution of sodium methoxide were added at room temperature to a solution of 25 g of 5-chloro-2-nitroaniline in 500 ml of 1,4-dioxane, and the resulting mixture was heated under reflux for 4 hours, after which the solvent was removed by distillation under reduced pressure. The resulting residue was diluted with water, and the resulting aqueous mixture was extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate, after which the solvent was removed by distillation under reduced pressure. The resulting residue was purified by column chromatography through silica gel using a gradient elution method, with mixtures of ethyl acetate and hexane in ratios ranging from 1:4 to 1:2 by volume as the eluent, to give 16.3 g of the title compound, melting at 124°-128° C.
	With sodium chloride; sodium methylate In 1,4-dioxane	2.a 2(a) 2(a) 5-Methoxy-2-nitroaniline 70 ml of a 28% w/v methanolic solution of sodium methoxide were added at room temperature to a solution of 25 g. of 5-chloro-2-nitroaniline in 500 ml of 1,4-dioxane, and the resulting mixture was heated under reflux for 4 hours, after which the solvent was removed by distillation under reduced pressure. The resulting residue was diluted with water, and the resulting aqueous mixture was extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate, after which the solvent was removed by distillation under reduced pressure. The resulting residue was purified by column chromatography through silica gel using a gradient elution method, with mixtures of ethyl acetate and hexane in ratios ranging from 1:4 to 1:2 by volume as the eluent, to give 16.3 g of the title compound, melting at 124°-128° C.

With sodium chloride; sodium methylate In 1,4-dioxane

5 5-Methoxy-2-nitroaniline PREPARATION 5 5-Methoxy-2-nitroaniline 70 ml of a 28% w/v methanolic solution of sodium methoxide were added at room temperature to a solution of 25 g of 5-chloro-2-nitroaniline in 500 ml of 1,4-dioxane, and the resulting mixture was heated under reflux for 4 hours, after which the solvent was removed by distillation under reduced pressure. The resulting residue was diluted with water, and the resulting aqueous mixture was extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulphate, after which the solvent was removed by distillation under reduced pressure. The resulting residue was purified by column chromatography through silica gel using a gradient elution method, with mixtures of ethyl acetate and hexane in ratios ranging from 1: 4 to 1: 2 by volume as the eluent, to give 16.3 g of the title compound, melting at 124 - 128°C.

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - US2003/8907, 2003, A1
[2]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - US5886014, 1999, A
[3]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - US5798375, 1998, A
[4]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP745600, 1996, A1

41
[ 438249-85-5 ]
[ 16133-49-6 ]
[ 438249-18-4 ]

Yield	Reaction Conditions	Operation in experiment
58%		182 4-(5-Methoxy-2-nitroanilino)-2-(2-pyrazinyl)-6-trifluoromethylpyrimidine EXAMPLE 182 4-(5-Methoxy-2-nitroanilino)-2-(2-pyrazinyl)-6-trifluoromethylpyrimidine The title compound was prepared from 4-chloro-2-(2-pyrazinyl)-6-trifluoromethylpyrimidine (40 mg, 0.153 mmol) and 5-methoxy-2-nitroaniline (39 mg, 0.230 mmol), similar to Example 180 and was isolated as an off white solid (35 mg, 58%). 1H NMR (CDCl3): 9.69 (d, J=1.5 Hz, 1H), 8.83 (dd, J=1.5, 2.4 Hz, 1H), 8.72 (d, J=2.4 Hz, 1H), 8.08 (d, J=9.6 Hz, 1H), 7.11 (s, 1H), 6.27 (dd, J=2.7, 9.6 Hz, 1H), 6.15 (d, J=2.7 Hz, 1H), 3.83 (s, 3H).

Reference： [1]Current Patent Assignee: IMMUNE PHARMACEUTICALS INC - US2003/69239, 2003, A1

42
[ 24424-99-5 ]
[ 16133-49-6 ]
[ 185428-59-5 ]

Yield	Reaction Conditions	Operation in experiment
	With dimethyl sulfate In tetrahydrofuran; (2S)-N-methyl-1-phenylpropan-2-amine hydrate; toluene	11 Production of N-t-butoxycarbonyl-N-methyl-5-methoxy-2-nitroaniline Example 11 Production of N-t-butoxycarbonyl-N-methyl-5-methoxy-2-nitroaniline 13.10 g of sodium hydride (60% content) was suspended in 175.31 g of tetrahydrofuran and cooled with ice. To the obtained suspension, 227.53 g of a tetrahydrofuran solution containing 25.03 g of 5-methoxy-2-nitroaniline was added, stirred for 10 minutes, allowed to stand at room temperature and stirred for 30 minutes. To the obtained mixture, 35.73 g of di-t-butyl dicarbonate was added at room temperature and stirred for 3 hours. To the reaction mixture, 249.76 g of toluene and 28.74 g of dimethyl sulfate were added at room temperature and stirred for 2 hours. The reaction mixture was added to ice water and extracted with toluene to separate an organic layer and then the organic layer was analyzed by high performance liquid chromatography to find the yield of the desired product was 94%.

Reference： [1]Current Patent Assignee: Sumitomo Chemical (w/o Dongwoo Fine-Chem); SUMITOMO CHEMICAL COMPANY LIMITED - US2002/16506, 2002, A1

43
sodium sulfide [ No CAS ]
aqueous sodium nitrite [ No CAS ]
[ 16133-49-6 ]
[ 104-15-4 ]
hydrochloride salt [ No CAS ]
[ 38088-01-6 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; sodium carbonate; dimethyl amine In ethanol; hexane; water; ethyl acetate; benzene	13 EXAMPLE 13 A suspension of 2-nitro-5-methoxyaniline (3.7 g) in water (25 ml) was heated at 80° C. with 36% hydrochloric acid (7.7 ml) for 30 minutes. It was then treated dropwise with aqueous sodium nitrite solution (1.8 g in 5 ml H2 O) at 0° C. After 1 hour, the mixture was filtered and the filtrate added at 23° C. to a solution of dimethylamine (35% aqueous solution, 3.9 ml) and sodium carbonate (8.2 g) in water (340 ml). After 12 hours at 23° C. a solid was collected by filtration and dissolved in benzene (100 ml). The solution was heated under reflux and treated with p-toluene sulphonic acid (4.0 g) and heated under reflux for 4 hours in a Dean-Stark water separator. The reaction mixture stood for 48 hours and was then partitioned between cold 10% aqueous sodium hydroxide solution and dichloromethane. Evaporation of the organic layer left an oil which was purified on silica column using ethylacetate:hexane as eluant to furnish 5-methoxy-2-nitrobiphenyl which was dissolved in ethanol (30 ml) and heated under reflux with sodium sulphide (5.3 g) for 8 hours. Purification of the product on a silica column gave 2-amino-5-methoxybiphenyl which was converted into its hydro-chloride salt (m.p. 167° C.).

Reference： [1]Current Patent Assignee: WALGREENS BOOTS ALLIANCE, INC., - US5302720, 1994, A

44
ethylacetate-hexane [ No CAS ]
[ 588-16-9 ]
[ 16133-49-6 ]

Yield	Reaction Conditions	Operation in experiment
	With silver nitrate; trifluoroacetic anhydride In ethanol; dichloromethane; chloroform	13 EXAMPLE 13 EXAMPLE 13 A cold (5° C.) slurry of N-acetyl-m-anisidine (1.65 g) and silver nitrate (1.69 g) in trichloromethane (10 ml) was treated dropwise with trifluoroacetic anhydride (5 ml). After stirring at 5° C. for 6 hours and at 23° C. for 12 hours, the reaction mixture was poured onto ice/water. Extraction of the sticky residue in dichloromethane gave a solid which was purified on a silica column using ethylacetate-hexane as eluant to furnish N-acetyl-2-nitro-5-methoxyaniline as golden yellow needles (m.p. 129° C.). N-deacetylation was effected by refluxing ethanolic sodium hydroxide (0.3 g) in (10 ml) ethanol to give 2-nitro-5-methoxyaniline (m.p. 115° C.).

Reference： [1]Current Patent Assignee: WALGREENS BOOTS ALLIANCE, INC., - US5302720, 1994, A

45
[ 16133-49-6 ]
[ 126-98-7 ]
[ 942928-56-5 ]

Yield	Reaction Conditions	Operation in experiment
	In tetrahydrofuran; methanol for 20h; Heating / reflux;	1.2 1.2 Preparation of (R,S)-3-(5-methoxy-2-nitrophenylamino)-2-methylpropionic acid 9.15 g of 5-methoxy-2-nitroaniline are dissolved in 60 ml of THF, and 6.5 ml of 2-methacrylonitrile and 1.35 ml of a 40% solution of benzyltrimethylammonium hydroxide in methanol are added. The reaction mixture is heated at the boil for about 20 hours and, after cooling, evaporated to give an oily residue. The crude product is dissolved in 400 ml of methanol and 150 ml of water, and 150 ml of 32% sodium hydroxide solution are added. The mixture is heated at the boil for 3 hours, cooled, evaporated and worked up, giving 8.9 g of (R,S)-3-(5-methoxy-2-nitrophenylamino)-2-methylpropionic acid as crude product.

Reference： [1]Current Patent Assignee: MERCK KGAA - US2008/306042, 2008, A1 Location in patent: Page/Page column 37

46
[ 24424-99-5 ]
[ 16133-49-6 ]
[ 77-78-1 ]
[ 185428-59-5 ]

Yield	Reaction Conditions	Operation in experiment
94%	Stage #1: 5-methoxy-2-nitroaniline With sodium hydride In tetrahydrofuran at 0 - 20℃; for 0.666667h; Stage #2: di-<i>tert</i>-butyl dicarbonate In tetrahydrofuran at 20℃; for 3h; Stage #3: dimethyl sulfate In tetrahydrofuran at 20℃; for 2h;

Reference： [1]Current Patent Assignee: Sumitomo Chemical (w/o Dongwoo Fine-Chem); SUMITOMO CHEMICAL COMPANY LIMITED - EP1172356, 2002, A1 Location in patent: Page 8

47
C₈H₆N₄O₄ [ No CAS ]
[ 16133-49-6 ]

Yield	Reaction Conditions	Operation in experiment
4.1 g	Stage #1: C₈H₆N₄O₄ With acetic acid In water Reflux; Stage #2: With sodium hydrogencarbonate In water at 20℃; for 1h;

Reference： [1]Location in patent: experimental part Zhang, Yong Jian; Wei, Hao; Zhang, Wanbin [Tetrahedron, 2009, vol. 65, # 7, p. 1281 - 1286]

48
[ 69986-21-6 ]
[ 16133-49-6 ]
[ 843615-26-9 ]

Yield	Reaction Conditions	Operation in experiment
31%	Stage #1: 5-methoxy-2-nitroaniline With potassium <i>tert</i>-butylate In N,N-dimethyl acetamide for 1h; Stage #2: 2-[p-(chlorosulfonyl)phenoxy]acetamide In N,N-dimethyl acetamide for 1.5h;	2-(4-[(5-Methoxy-2-nitrophenyl)amino]sulfonyl}phenoxy)acetamide (Intermediate A60) 5-methoxy-2-nitrophenylamine (Intermediate A59, 5.1 g, 0.030 mol) was dissolved in N,N-dimethylacetamide (150 mL). Potassium t-butoxide (4.0 g, 0.034 mol) was added to the mixture and stirred for 1 hr. Sulfonyl chloride (10.0 g, 0.035 mol) was then added and the reaction mixture stirred for 1.5 hr. The product was crystallized by slow addition of water to the reaction mixture. The solid was collected and dried in vacuo to give 6.6 g of a brown solid. The solid was recrystallized from acetone to give 3.5 g (31%) of the title compound.

Reference： [1]Current Patent Assignee: ALEVIUM PHARMACEUTICALS - US2005/38076, 2005, A1 Location in patent: Page/Page column 26

49
[ 1258399-08-4 ]
[ 16133-49-6 ]
[ 1258399-52-8 ]

Yield	Reaction Conditions	Operation in experiment
100%	With potassium phosphate In toluene at 100℃; Inert atmosphere;	41 Reference Example 41 methyl { (3S) -6- [ { (3S) -7- [ (5-methoxy-2-nitrophenyl) amino] -2, 3- dihydro-l-benzofuran-3-yl } (trifluoroacetyl) amino] -2, 3-dihydro- 1-benzofuran-3-yl } acetate; [0343]To a solution of methyl [ (3S) -6-{ [ (3S) -7-bromo-2, 3- dihydro-1-benzofuran-3-yl] (trifluoroacetyl) amino } -2, 3-dihydro- l-benzofuran-3-yl] acetate (150 mg, 0.300 mmol) and 5-methoxy- 2-nitroaniline (55.5 mg, 0.330 mmol) and tripotassium phosphate (127 mg, 0.600 mmol) in toluene (1.5 mL) were added under an argon atmosphere tris (dibenzylideneacetone) dipalladium (0) (13.7 mg, 0.015 inmol) and dicyclohexyl [2' , 4' , 6' -tri (propan-2-yl) biphenyl-2- yl]phosphane (14.3 mg, 0.030 iranol), and the mixture was stirred at 1000C overnight. The reaction mixture was cooled to room temperature, filtered through celite, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 95:5 - 60:40) to give the title compound (181 mg, yield 100%) as a yellow oil. MS m/z 588 (M + H)+.

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - WO2010/143733, 2010, A1 Location in patent: Page/Page column 143-144

50
[ 16133-49-6 ]
[ 20628-18-6 ]

Yield	Reaction Conditions	Operation in experiment
	With acetic anhydride at 120℃; for 16h;	C.1 A solution of 5-methoxy-2-nitroaniline (C-I) (25 g, 150 mmol, 1.0 eq) in acetic anhydride (45 ml, 480 mmol, 3.1 eq) was heated at 120 °C for 16 hours. The reaction mixture was cooled to room temperature, poured into water (500 ml) and the resulting precipitate was collected by filtration and dissolved in chloroform (250 ml). The organic layer was washed with water (250 ml) and brine (100 ml), then dried over sodium sulfate and concentrated to yield N-(5-methoxy- 2-nitrophenyl)acetamide (C-2) as a yellow solid. 1H NMR (400 MHz, DMSO): δ 10.30 (s, 1 H); 8.04 (d, J = 9.3 Hz, 1 H); 7.53 (d, J = 2.8 Hz, I H); 6.87 (dd, J - 9.3, 2.8 Hz, 1 H); 3.86 (s, 3 H); 2.13 (s, 3 H). LRMS m/z (M+H) 210.9 found, 21 1.1 required.

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2009/140163, 2009, A1 Location in patent: Page/Page column 53-54

51
[ 16133-49-6 ]
[ 100-07-2 ]
C₁₅H₁₄N₂O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine In tetrahydrofuran at 20℃;	5.1.2. General procedure for the synthesis of the benzanilide derivatives of set I General procedure: To a solution of 10 mmol appropriate o-nitroaniline in 50 ml pyridine was quickly added the appropriate benzoyl chloride. The reaction was stirred for 5-20 h at room temperature. Afterwards the reaction mixture was purged into ice water and the formed solid was isolated and recrystallized.

Reference： [1]Location in patent: experimental part Brunhofer, Gerda; Granig, Walter H.; Studenik, Christian R.; Erker, Thomas [Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 2, p. 994 - 1001]

52
[ 16133-49-6 ]
5-bromo-2-iodo-4-methoxyaniline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: N-Bromosuccinimide / acetonitrile / 0 °C 1.2: 24 h / 0 - 20 °C 2.1: sulfuric acid / acetonitrile / -20 °C 2.2: 0.5 h 2.3: -20 °C 3.1: hydrogenchloride; iron(II) chloride tetrahydrate; iron / ethanol; water / 80 °C / Inert atmosphere
	Multi-step reaction with 3 steps 1.1: trifluoroacetic acid; N-Bromosuccinimide / acetonitrile / 16.5 h / 0 - 20 °C 2.1: sulfuric acid; sodium nitrite / water; acetonitrile / 0.75 h / -10 °C 2.2: 0.83 h / -10 °C 3.1: ammonium chloride; iron / water; ethanol / 2.5 h / 60 - 90 °C
	Multi-step reaction with 3 steps 1: N-Bromosuccinimide / acetonitrile / Inert atmosphere; Reflux 2: sodium nitrite; sulfuric acid / water; acetonitrile / 0.5 h / -20 °C / Inert atmosphere 3: iron; hydrogenchloride / ethanol / 2 h / 80 °C

Multi-step reaction with 3 steps 1.1: trifluoroacetic acid; N-Bromosuccinimide / acetonitrile / 16.5 h / 0 - 20 °C 2.1: sulfuric acid; sodium nitrite / acetonitrile; water / 0.75 h / -10 °C 2.2: 0.83 h / -10 °C 3.1: ammonium chloride; iron / ethanol; water / 2.5 h / 60 - 90 °C

Reference： [1]Sheibani, Esmaeil; Waernmark, Kenneth [Organic and Biomolecular Chemistry, 2012, vol. 10, # 10, p. 2059 - 2067]
[2]Current Patent Assignee: ANTABIO SAS - EP3628666, 2020, A1
[3]Current Patent Assignee: SKYHAWK THERAPEUTICS INC - WO2020/163541, 2020, A1
[4]Current Patent Assignee: ANTABIO SAS - WO2021/191240, 2021, A1

53
[ 16133-49-6 ]
1-bromo-4-iodo-2-methoxy-5-nitrobenzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: N-Bromosuccinimide / acetonitrile / 0 °C 1.2: 24 h / 0 - 20 °C 2.1: sulfuric acid / acetonitrile / -20 °C 2.2: 0.5 h 2.3: -20 °C
	Multi-step reaction with 2 steps 1.1: trifluoroacetic acid; N-Bromosuccinimide / acetonitrile / 16.5 h / 0 - 20 °C 2.1: sulfuric acid; sodium nitrite / water; acetonitrile / 0.75 h / -10 °C 2.2: 0.83 h / -10 °C
	Multi-step reaction with 2 steps 1: N-Bromosuccinimide / acetonitrile / Inert atmosphere; Reflux 2: sodium nitrite; sulfuric acid / water; acetonitrile / 0.5 h / -20 °C / Inert atmosphere

Multi-step reaction with 2 steps 1.1: trifluoroacetic acid; N-Bromosuccinimide / acetonitrile / 16.5 h / 0 - 20 °C 2.1: sulfuric acid; sodium nitrite / acetonitrile; water / 0.75 h / -10 °C 2.2: 0.83 h / -10 °C

Reference： [1]Sheibani, Esmaeil; Waernmark, Kenneth [Organic and Biomolecular Chemistry, 2012, vol. 10, # 10, p. 2059 - 2067]
[2]Current Patent Assignee: ANTABIO SAS - EP3628666, 2020, A1
[3]Current Patent Assignee: SKYHAWK THERAPEUTICS INC - WO2020/163541, 2020, A1
[4]Current Patent Assignee: ANTABIO SAS - WO2021/191240, 2021, A1

54
[ 16133-49-6 ]
[ 40608-76-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 2620 - 2623

55
[ 16133-49-6 ]
[ 41292-65-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 2620 - 2623

56
[ 16133-49-6 ]
[ 4887-80-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 2620 - 2623

57
[ 1400820-08-7 ]
[ 16133-49-6 ]
[ 1400820-18-9 ]

Yield	Reaction Conditions	Operation in experiment
	With palladium diacetate; caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In toluene at 100℃; for 16h; Inert atmosphere;	Regioselective preparation of C-3 substituted benzotriazoles General procedure: (Chloropyrazin-2-yl)imino-triphenyl-λ5-phosphane (12, 12 g, 30.78 mmol), 5-fluoro-2-nitroaniline (4.81 g, 30.78 mmol), cesium carbonate (21.06 g, 64.65 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (3.56 g, 6.16 mmol) and diacetoxypalladium (0.691 g, 3.08 mmol) were suspended in toluene (120 mL). The reaction was degased, purged with argon and heated to 100°C overnight. The resulting suspension was cooled to room temperature and concentrated to dryness. The residue was stirred in CH2Cl2/MeOH 50/50 for 15 minutes, filtered and washed with CH2Cl2. Filtrate was concentrated to dryness. The crude product was absorbed on silica gel and purified by flash chromatography on silica gel eluting with 50 to 75% dichloromethane in petroleum ether. The solvent was evaporated to dryness to afford N-(5-fluoro-2-nitrophenyl)-3-[(triphenyl-λ5-phosphanylidene)amino]pyrazin-2-amine.

Reference： [1]Delouvrié, Bénédicte; Germain, Hervé; Harris, Craig S.; Lamorlette, Maryannick; Lebraud, Honorine; Nguyen, Ha Thi Hoang; Noisier, Anais; Ouvry, Gilles [Tetrahedron Letters, 2012, vol. 53, # 40, p. 5380 - 5384]

58
[ 16133-49-6 ]
[ 7597-22-0 ]
[ 1421518-21-9 ]

Yield	Reaction Conditions	Operation in experiment
77%	With palladium diacetate; caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,4-dioxane at 150℃; for 0.75h; Sealed tube; Microwave irradiation;	General procedure for Buchwald-Hartwig Reactions General procedure: To a degassed suspension of 5 (0.50 g, 1.8 mmol), Cs2CO3 (0.80 g, 2.5 mmol) and 4- or 5-methoxy-2-nitroaniline (0.35 g, 2.1 mmol) in 1,4-dioxane (15 mls) was added Pd(OAc)2 (0.004 g, 0.018 mmol), Xantphos(0.010 g, 0.018 mmol) and water (1.5 ml). This was exposed to microwave irradiation in a sealed tube at 150°C for 45 minutes, partitioned between water and dichloromethane, extracted a further two times into dichloromethane, dried over Na2SO4 and concentrated in vacuo to give the crude product. The crude product was then purified via column chromatography using chloroform/ethyl acetate (6:1) as eluent.

Reference： [1]Miller, Michelle S.; Pinson, Jo-Anne; Zheng, Zhaohua; Jennings, Ian G.; Thompson, Philip E. [Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 3, p. 802 - 805]

59
[ 108-89-4 ]
[ 16133-49-6 ]
[ 84123-78-4 ]

Yield	Reaction Conditions	Operation in experiment
69%	With iron; sulfur at 160℃; for 24h; Inert atmosphere;

Reference： [1]Nguyen, Thanh Binh; Ermolenko, Ludmila; Al-Mourabit, Ali [Journal of the American Chemical Society, 2013, vol. 135, # 1, p. 118 - 121]

60
[ 16133-49-6 ]
[ 122-51-0 ]
[ 4887-80-3 ]

Yield	Reaction Conditions	Operation in experiment
85%	With iron; ytterbium(III) triflate at 75℃; for 3h;

Reference： [1]Wang, Fen; Tran-Dubé, Michelle; Scales, Stephanie; Johnson, Sarah; McAlpine, Indrawan; Ninkovic, Sacha [Tetrahedron Letters, 2013, vol. 54, # 31, p. 4054 - 4057]

61
[ 16133-49-6 ]
[ 64-04-0 ]
[ 77093-88-0 ]
[ 123464-57-3 ]

Yield	Reaction Conditions	Operation in experiment
1: 56% 2: 30%	With iron(III) chloride hexahydrate; sulfur In neat (no solvent) at 120℃; for 24h; Inert atmosphere;

Reference： [1]Nguyen, Thanh Binh; Retailleau, Pascal; Al-Mourabit, Ali [Organic Letters, 2013, vol. 15, # 20, p. 5238 - 5241]

62
[ 188290-36-0 ]
[ 16133-49-6 ]
2-(5-methoxy-2-nitrophenyl)thiophene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With isopentyl nitrite for 2.5h; Heating;	Preparation of 2-(5-methoxy-2-nitrophenyl)thiophene (9) A mixture of methoxy nitro aniline 4 (6.0 g; 35.7 mmol), isoamyl nitrite (7.6 mL; 74.4 mmol) and thiophene (81 mL; 1.0 mol) was heated to boiling for 2.5 h. After cooling, thiophene was evaporated and the crude product purified by column chromatography (silica gel, hexane/ethyl acetate 4/1) and crystallization from methanol. 7.1 g (85%) of 9 was isolated

Reference： [1]Lo, Cheikh; Doucoure, Baba Issa; Aaron, Jean-Jacques; Svoboda, Jiri; Kozmik, Václav; Brochon, Jean-Claude; Henry, Etienne; Maurel, François; Capochichi, Martine [Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2014, vol. 120, p. 47 - 54]

63
[ 16133-49-6 ]
[ 100-46-9 ]
6‐methoxy‐2‐phenyl‐1H-benzoimidazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	With iron(III) chloride hexahydrate In neat (no solvent) at 140℃; for 24h; Inert atmosphere;

Reference： [1]Nguyen, Thanh Binh; Bescont, Julie Le; Ermolenko, Ludmila; Al-Mourabit, Ali [Organic Letters, 2013, vol. 15, # 24, p. 6218 - 6221]

64
[ 16133-49-6 ]
(4-bromo-2,6-difluorophenyl)methanamine [ No CAS ]
N-(4-bromo-2,6-difluorobenzyl)-5-methoxy-2-nitroaniline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80.1%	With N-ethyl-N,N-diisopropylamine In acetonitrile at 130 - 150℃; for 16h;	123.A Step A: N-(4-Bromo-2,6-difluorobenzyl)-5-methoxy-2-nitroaniline Step A: N-(4-Bromo-2,6-difluorobenzyl)-5-methoxy-2-nitroaniline A mixture of 5-methoxy-2-nitroaniline (513 mg, 3 mmol), 4-bromo-2,6-difluorobenzyl amine (616 g, 3 mmol), DIPEA (1.55 mL, 9 mmol) and acetonitrile (10 mL) was heated to 130-150° Celsius for 16 h. The mixture was then cooled to RT and concentrated to dryness. To the residue was added H2O (100 mL) and the resulting solid was collected by filtration and dried to afford the title compound (900 mg, 80.1%).

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - US2014/275029, 2014, A1 Location in patent: Paragraph 0530

65
[ 16133-49-6 ]
C₅H₆F₂O₃ [ No CAS ]
C₁₂H₁₂F₂N₂O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: C₅H₆F₂O₃ With pyridine; dmap; chloro-trimethyl-silane In dichloromethane at 18 - 28℃; for 2.5h; Stage #2: With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide at 0 - 20℃; for 1.5h; Stage #3: 5-methoxy-2-nitroaniline With pyridine In dichloromethane; N,N-dimethyl-formamide at 0 - 20℃;	C4.B.3 Step 3. Preparation of C4-6 Step 3. Preparation of C4-6: The hydroxy acid C4-5 (27.7 g, 182.1 mmol) was added to 1 L flask equipped with a temperature probe and overhead stirring. DCM (280 mL), DMAP (2.0 g, 16.5 mmol) and pyridine (29.4 mL, 364.1 mmol) were added to the substrate at 20-25 °C. TMSCI (46.0 mL, 364.1 mmol) was added over 1 h at a rate to maintain the internal temperature between 18-28 °C. The slurry was then stirred for 1 .5 h at 20 °C. The reaction was cooled to 0 ° and treated with DMF (0.1 mL) and (COCI)2 (15.6 mL, 182.1 mmol) that was added as a rate to maintain the internal temperature below 10 °C. This slurry was stirred for 1 h at 0 °C and 30 min at 20 °C. The internal temperature of the slurry was then decreased to 0 °C and pyridine (20.0 mL, 248.3 mmol) was added while keeping the internal temperature below 10 °C. Upon addition of pyridine, large solids formed and increased agitation was necessary. 5-Methoxy-2- nitroaniline (27.8 g, 165.5 mmol) was added in portions, while keeping the internal temperature below 10 °C. After the addition is complete the reaction temperature was raised to 20 °C. Upon reaction completion (monitored by UPLC) the slurry was filtered and the solids were washed with DCM. The DCM solution was washed with 1 M HCI and then slurried with silica gel for 15 min. The slurry was filtered and washed with DCM. HCI in MeOH (prepared from MeOH and AcCI (1 .3 equiv) at 0 °C) was added and the reaction monitored by UPLC until complete. The DCM solution was neutralized with saturated aqueous NaHCO3. The aqueous layer was extracted with DCM and the combined DCM layers were concentrated to a foam. The foam was taken up in DCM and warmed to 35 °C. Heptane was added slowly, seed was added and the slurry was agitated for 30 min. Heptane was added slowly over 1 h, the slurry was aged for 1 h and then cooled to 25 °C over 1 h. The slurry was agitated for 2 h, filtered and washed with DCM/Heptane (1 :3 mix) to produce of C4-6. 1 H-NMR (400 MHz, CDCI3): 1 1 .64 (s, 1 H), 8.36 (d, J = 2.3 Hz, 1 H), 8.20 (d, J = 9.4 Hz, 1 H), 6.69 (dd, J = 9.4, 2.1 Hz, 1 H), 6.19 - 5.95 (m, 1 H), 5.78 (br-d, J = 17.4 Hz, 1 H), 5.58 (d, J = 1 1 .1 Hz, 1 H), 4.53 (t, J = 10.2 Hz, 1 H), 3.90 (s, 3H)

Reference： [1]Current Patent Assignee: GILEAD SCIENCES INC - WO2014/145095, 2014, A1 Location in patent: Page/Page column 110-112

66
[ 64-18-6 ]
[ 16133-49-6 ]
[ 4887-80-3 ]

Yield	Reaction Conditions	Operation in experiment
93%	With palladium 10% on activated carbon; triethylamine at 150℃; for 0.0833333h; Microwave irradiation;

Reference： [1]Zhu, Kaicheng; Hao, Jian-Hong; Zhang, Cheng-Pan; Zhang, Jiajun; Feng, Yiqing; Qin, Hua-Li [RSC Advances, 2015, vol. 5, # 15, p. 11132 - 11135]

67
[ 16133-49-6 ]
[ 100-51-6 ]
6‐methoxy‐2‐phenyl‐1H-benzoimidazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%	With sodium sulfide hydrate; iron(III) chloride hexahydrate at 140℃; for 24h; Inert atmosphere;	Redox Condensation Reaction of o-Nitroanilines 1 with Benzyl Alcohols 2 or vic-Diols 5; General Procedure General procedure: A 20-mL test-tube equipped with a magnetic stirring bar was charged with o-nitroaniline 1 (2.5 mmol, 1 equiv), alcohol 2 or 5 (3 mmol, 1.2equiv), Na2S·nH2O (≥60%, 130 mg, 1 mmol, 40 mol%) and FeCl3·6H2O(7 mg, 0.025 mmol, 1 mol%). The resulting mixture was stirred for 24h under an argon atmosphere at the indicated temperature (see Schemes 2 and 3 and Table 2). After cooling to r.t., the mixture was purified in different ways. (i) For NH benzimidazole products, the mixture was washed with CH2Cl2 (3 × 2 mL) then dissolved in MeOH.The MeOH solution was filtered through a short pad of silica gel. The filtrate was concentrated in vacuo to afford the NH benzimidazole product. Further purification by column or recrystallization was carried out if necessary. (ii) For N-methyl-2-phenylbenzimidazole 3ha and quinoxalines 5, the crude mixture was dissolved in a minimum volume of CH2Cl2 and purified by column chromatography (silica gel or alumina, heptane-EtOAc, EtOAc, EtOAc-MeOH, hexane-Et2O). We noted that some 13C NMR signals of NH-benzimidazoles are missing or difficult to observe.
39%	With cobalt acetylacetonate; sodium t-butanolate In 1,4-dioxane at 135℃; for 24h; Sealed tube; Inert atmosphere;

Reference： [1]Nguyen, Thanh Binh; Ermolenko, Ludmila; Al-Mourabit, Ali [Synthesis, 2015, vol. 47, # 12, p. 1741 - 1748]
[2]Das, Sanju; Mallick, Samrat; De Sarkar, Suman [Journal of Organic Chemistry, 2019, vol. 84, # 18, p. 12111 - 12119]

68
[ 16133-49-6 ]
(5-methoxy-2-nitrophenyl)hydrazine hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50%	Stage #1: 5-methoxy-2-nitroaniline With hydrogenchloride; sodium nitrite In water at 0 - 20℃; for 1h; Stage #2: With hydrogenchloride; tin(II) chloride dihdyrate In water at 0 - 20℃; for 2h;	14 To a stirred mixture of 5-methoxy-2-nitroaniline (5g, 29.7 mmol) in HC1 (cone. 12.9 mL) at 0°C was added drop wise a solution of NaN02 (2.05 g, 29.7 mmol) in H20 (8 mL). The internal temperature was kept below 5°C. After addition, the mixture was allowed to warm up to room temperature in 1 h. The mixture was cooled to 0°C and a solution of SnCl2 FontWeight="Bold" FontSize="10" 2H20 (20.13 g, 89.2 mmol) in HC1 (cone. 13 mL) was added slowly dropwise. After addition, it was stirred at room temperature for 2 h. The resulting yellow solid was collected by filtration and washed with cold (0°C) 6 N HC1. After drying in vacuum oven, it gave 3.245 g (yield 50%) of brown solid as aryl hydrazine 25. MS: [M+H20+Na] = 224. In a separate flask, a mixture of diethyl 1,3-acetonediacrboxylate (2.426 g, 12 mmol) and diethoxymethyl acetate (1.946 g, 12 mmol) was heated under microwave radiation at 100°C for 1 h. The reaction mixture was concentrated in vacuo, and residual volatile component was co-distilled off with toluene (5ml) in vacuo to give condensation product 26, which was used directly in the next step.
50%	Stage #1: 5-methoxy-2-nitroaniline With hydrogenchloride; sodium nitrite In water at 0 - 20℃; for 1h; Stage #2: With hydrogenchloride; tin(II) chloride dihdyrate In water at 0 - 20℃; for 2h;	14 Example 14: Synthesis of Compound 7: To a stirred mixture of 5-methoxy-2-nitroaniline (5g, 29.7 mmol) in HC1 (cone. 12.9 mL) at 0°C was added drop wise a solution of NaN02 (2.05 g, 29.7 mmol) in H20 (8 mL). The internal temperature was kept below 5°C. After addition, the mixture was allowed to warm up to room temperature in 1 h. The mixture was cooled to 0°C and a solution of SnCl2 2H20 (20.13 g, 89.2 mmol) in HC1 (cone. 13 mL) was added slowly dropwise. After addition, it was stirred at room temperature for 2 h. The resulting yellow solid was collected by filtration and washed with cold (0°C) 6 N HC1. After drying in vacuum oven, it gave 3.245 g (yield 50%) of brown solid as aryl hydrazine 25. MS: [M+H20+Na] = 224. In a separate flask, a mixture of diethyl l,3-acetonediacrboxylate (2.426 g, 12 mmol) and diethoxymethyl acetate (1.946 g, 12 mmol) was heated under microwave radiation at l00°C for 1 h. The reaction mixture was concentrated in vacuo, and residual volatile component was co-distilled off with toluene (5ml) in vacuo to give condensation product 26, which was used directly in the next step.
3.245 g	Stage #1: 5-methoxy-2-nitroaniline With hydrogenchloride; sodium nitrite In water at 0 - 20℃; for 1h; Stage #2: With tin(II) chloride dihdyrate In water at 0 - 20℃; for 2h;	14 To a stirred mixture of 5-methoxy-2-nitroaniline (5g, 29.7 mmol) in HC1 (cone.12.9 mL) at 0°C was added drop wise a solution of NaNO2 (2.05 g, 29.7 mmol) in H20 (8mL). The internal temperature was kept below 5°C. After addition, the mixture was allowed to warm up to room temperature in 1 h. The mixture was cooled to 0°C and a solution of SnC12•2H20 (20.13 g, 89.2 mmol) in HC1 (cone. 13 mL) was added slowly dropwise. After addition, it was stirred at room temperature for 2 h. The resulting yellowsolid was collected by filtration and washed with cold (0°C) 6 N HC1. After drying in vacuum oven, it gave 3.245 g (yield 50%) of brown solid as aryl hydrazine 25. MS:[M+H20+Na] = 224. In a separate flask, a mixture of diethyl 1,3-acetonediacrboxylate (2.426 g, 12 mmol) and diethoxymethyl acetate (1.946 g, 12 mmol) was heated under microwave radiation at 100°C for 1 h. The reaction mixture was concentrated in vacuo,and residual volatile component was co-distilled off with toluene (5m1) in vacuo to give condensation product 26, which was used directly in the next step.

4.342 g

Stage #1: 5-methoxy-2-nitroaniline With hydrogenchloride; sodium nitrite In water at 0 - 20℃; for 1h; Stage #2: With hydrogenchloride; tin(II) chloride dihdyrate In water at 0 - 20℃; for 2h;

14 Synthesis of Compound 7 To a stirred mixture of 5-methoxy-2-nitroaniline (5 g, 29.7 mmol) in HC1 (conc. 12.9 mE) at 00 C. was added drop wise a solution of NaNO2 (2.05 g, 29.7 mmol) in H20 (8 mE). The internal temperature was kept below 5° C. After addition, the mixture was allowed to warm up to room temperature in 1 h. The mixture was cooled to 00 C. and a solution of SnC12.2H20 (20.13 g, 89.2 mmol) in HC1 (conc.13 mE) was added slowly dropwise. Afier addition, it was stirred at room temperature for 2 h. The resulting yellowsolid was collected by filtration and washed with cold (0° C.) 6 N HC1. After drying in vacuum oven, it gave 3.245 g (yield50%) of brown solid as aryl hydrazine 25. MS: [M+H20+ Na]=224. In a separate flask, a mixture of diethyl 1,3- acetonediacrboxylate (2.426 g, 12 mmol) and diethoxymethyl acetate (1.946 g, 12 mmol) was heated under microwave radiation at 100° C. for 1 h. The reaction mixture was concentrated in vacuo, and residual volatile component was co-distilled oil with toluene (5 ml) in vacuo to give condensation product 26, which was used directly in the next step.

Reference： [1]Current Patent Assignee: AGENEBIO; HAGER BIOSCIENCES - WO2015/95783, 2015, A1 Location in patent: Paragraph 0261
[2]Current Patent Assignee: AGENEBIO - WO2019/246300, 2019, A1 Location in patent: Paragraph 330
[3]Current Patent Assignee: AGENEBIO; HAGER BIOSCIENCES - WO2016/205739, 2016, A1 Location in patent: Paragraph 0281
[4]Current Patent Assignee: AGENEBIO; HAGER BIOSCIENCES - US2018/170941, 2018, A1 Location in patent: Paragraph 1174

69
[ 16133-49-6 ]
C₁₅H₁₅N₃O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: hydrogenchloride; sodium nitrite / water / 1 h / 0 - 20 °C 1.2: 2 h / 0 - 20 °C 2.1: ethanol / 24 h / 20 °C / Molecular sieve 3.1: hydrogen; palladium 10% on activated carbon / ethanol / 18 h
	Multi-step reaction with 4 steps 1.1: hydrogenchloride; sodium nitrite / water / 1 h / 0 - 20 °C 1.2: 2 h / 0 - 20 °C 2.1: ethanol / 24 h / 20 °C / Molecular sieve 3.1: hydrogen; palladium 10% on activated carbon / ethanol / 18 h 4.1: toluene-4-sulfonic acid / para-xylene / 20 h / 140 °C
	Multi-step reaction with 4 steps 1.1: hydrogenchloride; sodium nitrite / water / 1 h / 0 - 20 °C 1.2: 2 h / 0 - 20 °C 2.1: ethanol / 24 h / 20 °C / Molecular sieve 3.1: palladium 10% on activated carbon; hydrogen / ethanol / 18 h 4.1: toluene-4-sulfonic acid / water; para-xylene / 20 h / 140 °C

	Multi-step reaction with 3 steps 1.1: hydrogenchloride; sodium nitrite / water / 1 h / 0 - 20 °C 1.2: 2 h / 0 - 20 °C 2.1: ethanol / 24 h / 20 °C / Molecular sieve 3.1: palladium 10% on activated carbon; hydrogen / ethanol / 18 h
	Multi-step reaction with 4 steps 1.1: hydrogenchloride; sodium nitrite / water / 1 h / 0 - 20 °C 1.2: 2 h / 0 - 20 °C 2.1: ethanol / 24 h / 20 °C / Molecular sieve 3.1: palladium 10% on activated carbon; hydrogen / ethanol / 18 h 4.1: toluene-4-sulfonic acid / para-xylene / 20 h / 140 °C
	Multi-step reaction with 4 steps 1.1: sodium nitrite; hydrogenchloride / water / 1 h / 0 - 20 °C 1.2: 2 h / 0 - 20 °C 2.1: ethanol / 24 h / 20 °C / Molecular sieve 3.1: palladium 10% on activated carbon; hydrogen / ethanol / 18 h 4.1: toluene-4-sulfonic acid / water; para-xylene / 20 h / 140 °C

Reference： [1]Current Patent Assignee: AGENEBIO; HAGER BIOSCIENCES - WO2015/95783, 2015, A1
[2]Current Patent Assignee: AGENEBIO; HAGER BIOSCIENCES - WO2015/95783, 2015, A1
[3]Current Patent Assignee: AGENEBIO; HAGER BIOSCIENCES - WO2016/205739, 2016, A1
[4]Current Patent Assignee: AGENEBIO; HAGER BIOSCIENCES - US2018/170941, 2018, A1
[5]Current Patent Assignee: AGENEBIO; HAGER BIOSCIENCES - US2018/170941, 2018, A1
[6]Current Patent Assignee: AGENEBIO - WO2019/246300, 2019, A1

70
[ 16133-49-6 ]
C₁₃H₁₃N₃O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: hydrogenchloride; sodium nitrite / water / 1 h / 0 - 20 °C 1.2: 2 h / 0 - 20 °C 2.1: ethanol / 24 h / 20 °C / Molecular sieve 3.1: hydrogen; palladium 10% on activated carbon / ethanol / 18 h 4.1: diisobutylaluminium hydride / dichloromethane; hexane / 0.83 h / -78 - 20 °C
	Multi-step reaction with 5 steps 1.1: hydrogenchloride; sodium nitrite / water / 1 h / 0 - 20 °C 1.2: 2 h / 0 - 20 °C 2.1: ethanol / 24 h / 20 °C / Molecular sieve 3.1: hydrogen; palladium 10% on activated carbon / ethanol / 18 h 4.1: toluene-4-sulfonic acid / para-xylene / 20 h / 140 °C 5.1: diisobutylaluminium hydride / dichloromethane; hexane / 0.83 h / -78 - 20 °C
	Multi-step reaction with 5 steps 1.1: hydrogenchloride; sodium nitrite / water / 1 h / 0 - 20 °C 1.2: 2 h / 0 - 20 °C 2.1: ethanol / 24 h / 20 °C / Molecular sieve 3.1: palladium 10% on activated carbon; hydrogen / ethanol / 18 h 4.1: toluene-4-sulfonic acid / water; para-xylene / 20 h / 140 °C 5.1: diisobutylaluminium hydride / dichloromethane; hexane / 1 h / -78 - 20 °C

	Multi-step reaction with 4 steps 1.1: hydrogenchloride; sodium nitrite / water / 1 h / 0 - 20 °C 1.2: 2 h / 0 - 20 °C 2.1: ethanol / 24 h / 20 °C / Molecular sieve 3.1: palladium 10% on activated carbon; hydrogen / ethanol / 18 h 4.1: diisobutylaluminium hydride / dichloromethane; hexane / 1 h / -78 - 20 °C
	Multi-step reaction with 5 steps 1.1: hydrogenchloride; sodium nitrite / water / 1 h / 0 - 20 °C 1.2: 2 h / 0 - 20 °C 2.1: ethanol / 24 h / 20 °C / Molecular sieve 3.1: palladium 10% on activated carbon; hydrogen / ethanol / 18 h 4.1: toluene-4-sulfonic acid / para-xylene / 20 h / 140 °C 5.1: diisobutylaluminium hydride / dichloromethane; hexane / 1 h / -78 - 20 °C
	Multi-step reaction with 5 steps 1.1: sodium nitrite; hydrogenchloride / water / 1 h / 0 - 20 °C 1.2: 2 h / 0 - 20 °C 2.1: ethanol / 24 h / 20 °C / Molecular sieve 3.1: palladium 10% on activated carbon; hydrogen / ethanol / 18 h 4.1: toluene-4-sulfonic acid / water; para-xylene / 20 h / 140 °C 5.1: diisobutylaluminium hydride / dichloromethane; hexane / 0.83 h / -78 - 20 °C

Reference： [1]Current Patent Assignee: AGENEBIO; HAGER BIOSCIENCES - WO2015/95783, 2015, A1
[2]Current Patent Assignee: AGENEBIO; HAGER BIOSCIENCES - WO2015/95783, 2015, A1
[3]Current Patent Assignee: AGENEBIO; HAGER BIOSCIENCES - WO2016/205739, 2016, A1
[4]Current Patent Assignee: AGENEBIO; HAGER BIOSCIENCES - US2018/170941, 2018, A1
[5]Current Patent Assignee: AGENEBIO; HAGER BIOSCIENCES - US2018/170941, 2018, A1
[6]Current Patent Assignee: AGENEBIO - WO2019/246300, 2019, A1

71
[ 16133-49-6 ]
C₁₃H₁₂BrN₃O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: hydrogenchloride; sodium nitrite / water / 1 h / 0 - 20 °C 1.2: 2 h / 0 - 20 °C 2.1: ethanol / 24 h / 20 °C / Molecular sieve 3.1: hydrogen; palladium 10% on activated carbon / ethanol / 18 h 4.1: diisobutylaluminium hydride / dichloromethane; hexane / 0.83 h / -78 - 20 °C 5.1: carbon tetrabromide / N,N-dimethyl-formamide / 1 h / 20 °C
	Multi-step reaction with 6 steps 1.1: hydrogenchloride; sodium nitrite / water / 1 h / 0 - 20 °C 1.2: 2 h / 0 - 20 °C 2.1: ethanol / 24 h / 20 °C / Molecular sieve 3.1: hydrogen; palladium 10% on activated carbon / ethanol / 18 h 4.1: toluene-4-sulfonic acid / para-xylene / 20 h / 140 °C 5.1: diisobutylaluminium hydride / dichloromethane; hexane / 0.83 h / -78 - 20 °C 6.1: carbon tetrabromide / N,N-dimethyl-formamide / 1 h / 20 °C
	Multi-step reaction with 6 steps 1.1: hydrogenchloride; sodium nitrite / water / 1 h / 0 - 20 °C 1.2: 2 h / 0 - 20 °C 2.1: ethanol / 24 h / 20 °C / Molecular sieve 3.1: palladium 10% on activated carbon; hydrogen / ethanol / 18 h 4.1: toluene-4-sulfonic acid / water; para-xylene / 20 h / 140 °C 5.1: diisobutylaluminium hydride / dichloromethane; hexane / 1 h / -78 - 20 °C 6.1: carbon tetrabromide; triphenylphosphine / N,N-dimethyl-formamide / 1 h / 20 °C

	Multi-step reaction with 5 steps 1.1: hydrogenchloride; sodium nitrite / water / 1 h / 0 - 20 °C 1.2: 2 h / 0 - 20 °C 2.1: ethanol / 24 h / 20 °C / Molecular sieve 3.1: palladium 10% on activated carbon; hydrogen / ethanol / 18 h 4.1: diisobutylaluminium hydride / dichloromethane; hexane / 1 h / -78 - 20 °C 5.1: carbon tetrabromide; triphenylphosphine / N,N-dimethyl-formamide / 1 h / 20 °C
	Multi-step reaction with 6 steps 1.1: hydrogenchloride; sodium nitrite / water / 1 h / 0 - 20 °C 1.2: 2 h / 0 - 20 °C 2.1: ethanol / 24 h / 20 °C / Molecular sieve 3.1: palladium 10% on activated carbon; hydrogen / ethanol / 18 h 4.1: toluene-4-sulfonic acid / para-xylene / 20 h / 140 °C 5.1: diisobutylaluminium hydride / dichloromethane; hexane / 1 h / -78 - 20 °C 6.1: carbon tetrabromide; triphenylphosphine / N,N-dimethyl-formamide / 1 h / 20 °C
	Multi-step reaction with 6 steps 1.1: sodium nitrite; hydrogenchloride / water / 1 h / 0 - 20 °C 1.2: 2 h / 0 - 20 °C 2.1: ethanol / 24 h / 20 °C / Molecular sieve 3.1: palladium 10% on activated carbon; hydrogen / ethanol / 18 h 4.1: toluene-4-sulfonic acid / water; para-xylene / 20 h / 140 °C 5.1: diisobutylaluminium hydride / dichloromethane; hexane / 0.83 h / -78 - 20 °C 6.1: carbon tetrabromide; triphenylphosphine / N,N-dimethyl-formamide / 1 h / 20 °C

Reference： [1]Current Patent Assignee: AGENEBIO; HAGER BIOSCIENCES - WO2015/95783, 2015, A1
[2]Current Patent Assignee: AGENEBIO; HAGER BIOSCIENCES - WO2015/95783, 2015, A1
[3]Current Patent Assignee: AGENEBIO; HAGER BIOSCIENCES - WO2016/205739, 2016, A1
[4]Current Patent Assignee: AGENEBIO; HAGER BIOSCIENCES - US2018/170941, 2018, A1
[5]Current Patent Assignee: AGENEBIO; HAGER BIOSCIENCES - US2018/170941, 2018, A1
[6]Current Patent Assignee: AGENEBIO - WO2019/246300, 2019, A1

72
[ 16133-49-6 ]
C₁₃H₁₁N₃O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: hydrogenchloride; sodium nitrite / water / 1 h / 0 - 20 °C 1.2: 2 h / 0 - 20 °C 2.1: ethanol / 24 h / 20 °C / Molecular sieve 3.1: hydrogen; palladium 10% on activated carbon / ethanol / 18 h 4.1: diisobutylaluminium hydride / dichloromethane; hexane / 0.83 h / -78 - 20 °C 5.1: sulfur trioxide pyridine complex; dimethyl sulfoxide; triethylamine / dichloromethane / 1 h / 20 °C
	Multi-step reaction with 6 steps 1.1: hydrogenchloride; sodium nitrite / water / 1 h / 0 - 20 °C 1.2: 2 h / 0 - 20 °C 2.1: ethanol / 24 h / 20 °C / Molecular sieve 3.1: hydrogen; palladium 10% on activated carbon / ethanol / 18 h 4.1: toluene-4-sulfonic acid / para-xylene / 20 h / 140 °C 5.1: diisobutylaluminium hydride / dichloromethane; hexane / 0.83 h / -78 - 20 °C 6.1: sulfur trioxide pyridine complex; dimethyl sulfoxide; triethylamine / dichloromethane / 1 h / 20 °C
	Multi-step reaction with 6 steps 1.1: hydrogenchloride; sodium nitrite / water / 1 h / 0 - 20 °C 1.2: 2 h / 0 - 20 °C 2.1: ethanol / 24 h / 20 °C / Molecular sieve 3.1: palladium 10% on activated carbon; hydrogen / ethanol / 18 h 4.1: toluene-4-sulfonic acid / water; para-xylene / 20 h / 140 °C 5.1: diisobutylaluminium hydride / dichloromethane; hexane / 1 h / -78 - 20 °C 6.1: triethylamine; sulfur trioxide pyridine complex / dimethyl sulfoxide; dichloromethane / 1 h / 20 °C

	Multi-step reaction with 5 steps 1.1: hydrogenchloride; sodium nitrite / water / 1 h / 0 - 20 °C 1.2: 2 h / 0 - 20 °C 2.1: ethanol / 24 h / 20 °C / Molecular sieve 3.1: palladium 10% on activated carbon; hydrogen / ethanol / 18 h 4.1: diisobutylaluminium hydride / dichloromethane; hexane / 1 h / -78 - 20 °C 5.1: sulfur trioxide pyridine complex; triethylamine / dimethyl sulfoxide; dichloromethane
	Multi-step reaction with 6 steps 1.1: hydrogenchloride; sodium nitrite / water / 1 h / 0 - 20 °C 1.2: 2 h / 0 - 20 °C 2.1: ethanol / 24 h / 20 °C / Molecular sieve 3.1: palladium 10% on activated carbon; hydrogen / ethanol / 18 h 4.1: toluene-4-sulfonic acid / para-xylene / 20 h / 140 °C 5.1: diisobutylaluminium hydride / dichloromethane; hexane / 1 h / -78 - 20 °C 6.1: sulfur trioxide pyridine complex; triethylamine / dimethyl sulfoxide; dichloromethane
	Multi-step reaction with 6 steps 1.1: sodium nitrite; hydrogenchloride / water / 1 h / 0 - 20 °C 1.2: 2 h / 0 - 20 °C 2.1: ethanol / 24 h / 20 °C / Molecular sieve 3.1: palladium 10% on activated carbon; hydrogen / ethanol / 18 h 4.1: toluene-4-sulfonic acid / water; para-xylene / 20 h / 140 °C 5.1: diisobutylaluminium hydride / dichloromethane; hexane / 0.83 h / -78 - 20 °C 6.1: triethylamine; sulfur trioxide pyridine complex / dimethyl sulfoxide; dichloromethane / 1 h / 20 °C

Reference： [1]Current Patent Assignee: AGENEBIO; HAGER BIOSCIENCES - WO2015/95783, 2015, A1
[2]Current Patent Assignee: AGENEBIO; HAGER BIOSCIENCES - WO2015/95783, 2015, A1
[3]Current Patent Assignee: AGENEBIO; HAGER BIOSCIENCES - WO2016/205739, 2016, A1
[4]Current Patent Assignee: AGENEBIO; HAGER BIOSCIENCES - US2018/170941, 2018, A1
[5]Current Patent Assignee: AGENEBIO; HAGER BIOSCIENCES - US2018/170941, 2018, A1
[6]Current Patent Assignee: AGENEBIO - WO2019/246300, 2019, A1

73
[ 16133-49-6 ]
C₁₉H₁₇N₃O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: hydrogenchloride; sodium nitrite / water / 1 h / 0 - 20 °C 1.2: 2 h / 0 - 20 °C 2.1: ethanol / 24 h / 20 °C / Molecular sieve 3.1: hydrogen; palladium 10% on activated carbon / ethanol / 18 h 4.1: diisobutylaluminium hydride / dichloromethane; hexane / 0.83 h / -78 - 20 °C 5.1: sulfur trioxide pyridine complex; dimethyl sulfoxide; triethylamine / dichloromethane / 1 h / 20 °C 6.1: tetrahydrofuran / 0.5 h / 0 °C
	Multi-step reaction with 7 steps 1.1: hydrogenchloride; sodium nitrite / water / 1 h / 0 - 20 °C 1.2: 2 h / 0 - 20 °C 2.1: ethanol / 24 h / 20 °C / Molecular sieve 3.1: hydrogen; palladium 10% on activated carbon / ethanol / 18 h 4.1: toluene-4-sulfonic acid / para-xylene / 20 h / 140 °C 5.1: diisobutylaluminium hydride / dichloromethane; hexane / 0.83 h / -78 - 20 °C 6.1: sulfur trioxide pyridine complex; dimethyl sulfoxide; triethylamine / dichloromethane / 1 h / 20 °C 7.1: tetrahydrofuran / 0.5 h / 0 °C
	Multi-step reaction with 7 steps 1.1: hydrogenchloride; sodium nitrite / water / 1 h / 0 - 20 °C 1.2: 2 h / 0 - 20 °C 2.1: ethanol / 24 h / 20 °C / Molecular sieve 3.1: palladium 10% on activated carbon; hydrogen / ethanol / 18 h 4.1: toluene-4-sulfonic acid / water; para-xylene / 20 h / 140 °C 5.1: diisobutylaluminium hydride / dichloromethane; hexane / 1 h / -78 - 20 °C 6.1: triethylamine; sulfur trioxide pyridine complex / dimethyl sulfoxide; dichloromethane / 1 h / 20 °C 7.1: tetrahydrofuran / 0.5 h / 0 °C

	Multi-step reaction with 6 steps 1.1: hydrogenchloride; sodium nitrite / water / 1 h / 0 - 20 °C 1.2: 2 h / 0 - 20 °C 2.1: ethanol / 24 h / 20 °C / Molecular sieve 3.1: palladium 10% on activated carbon; hydrogen / ethanol / 18 h 4.1: diisobutylaluminium hydride / dichloromethane; hexane / 1 h / -78 - 20 °C 5.1: sulfur trioxide pyridine complex; triethylamine / dimethyl sulfoxide; dichloromethane 6.1: tetrahydrofuran
	Multi-step reaction with 7 steps 1.1: hydrogenchloride; sodium nitrite / water / 1 h / 0 - 20 °C 1.2: 2 h / 0 - 20 °C 2.1: ethanol / 24 h / 20 °C / Molecular sieve 3.1: palladium 10% on activated carbon; hydrogen / ethanol / 18 h 4.1: toluene-4-sulfonic acid / para-xylene / 20 h / 140 °C 5.1: diisobutylaluminium hydride / dichloromethane; hexane / 1 h / -78 - 20 °C 6.1: sulfur trioxide pyridine complex; triethylamine / dimethyl sulfoxide; dichloromethane 7.1: tetrahydrofuran
	Multi-step reaction with 7 steps 1.1: sodium nitrite; hydrogenchloride / water / 1 h / 0 - 20 °C 1.2: 2 h / 0 - 20 °C 2.1: ethanol / 24 h / 20 °C / Molecular sieve 3.1: palladium 10% on activated carbon; hydrogen / ethanol / 18 h 4.1: toluene-4-sulfonic acid / water; para-xylene / 20 h / 140 °C 5.1: diisobutylaluminium hydride / dichloromethane; hexane / 0.83 h / -78 - 20 °C 6.1: triethylamine; sulfur trioxide pyridine complex / dimethyl sulfoxide; dichloromethane / 1 h / 20 °C 7.1: tetrahydrofuran / 0.5 h / 0 °C

Reference： [1]Current Patent Assignee: AGENEBIO; HAGER BIOSCIENCES - WO2015/95783, 2015, A1
[2]Current Patent Assignee: AGENEBIO; HAGER BIOSCIENCES - WO2015/95783, 2015, A1
[3]Current Patent Assignee: AGENEBIO; HAGER BIOSCIENCES - WO2016/205739, 2016, A1
[4]Current Patent Assignee: AGENEBIO; HAGER BIOSCIENCES - US2018/170941, 2018, A1
[5]Current Patent Assignee: AGENEBIO; HAGER BIOSCIENCES - US2018/170941, 2018, A1
[6]Current Patent Assignee: AGENEBIO - WO2019/246300, 2019, A1

74
[ 16133-49-6 ]
C₁₉H₁₇N₃O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1.1: hydrogenchloride; sodium nitrite / water / 1 h / 0 - 20 °C 1.2: 2 h / 0 - 20 °C 2.1: ethanol / 24 h / 20 °C / Molecular sieve 3.1: hydrogen; palladium 10% on activated carbon / ethanol / 18 h 4.1: diisobutylaluminium hydride / dichloromethane; hexane / 0.83 h / -78 - 20 °C 5.1: sulfur trioxide pyridine complex; dimethyl sulfoxide; triethylamine / dichloromethane / 1 h / 20 °C 6.1: tetrahydrofuran / 0.5 h / 0 °C 7.1: triethylsilane; trifluoroacetic acid / dichloromethane / 1 h / 20 °C
	Multi-step reaction with 8 steps 1.1: hydrogenchloride; sodium nitrite / water / 1 h / 0 - 20 °C 1.2: 2 h / 0 - 20 °C 2.1: ethanol / 24 h / 20 °C / Molecular sieve 3.1: hydrogen; palladium 10% on activated carbon / ethanol / 18 h 4.1: toluene-4-sulfonic acid / para-xylene / 20 h / 140 °C 5.1: diisobutylaluminium hydride / dichloromethane; hexane / 0.83 h / -78 - 20 °C 6.1: sulfur trioxide pyridine complex; dimethyl sulfoxide; triethylamine / dichloromethane / 1 h / 20 °C 7.1: tetrahydrofuran / 0.5 h / 0 °C 8.1: triethylsilane; trifluoroacetic acid / dichloromethane / 1 h / 20 °C
	Multi-step reaction with 8 steps 1.1: hydrogenchloride; sodium nitrite / water / 1 h / 0 - 20 °C 1.2: 2 h / 0 - 20 °C 2.1: ethanol / 24 h / 20 °C / Molecular sieve 3.1: palladium 10% on activated carbon; hydrogen / ethanol / 18 h 4.1: toluene-4-sulfonic acid / water; para-xylene / 20 h / 140 °C 5.1: diisobutylaluminium hydride / dichloromethane; hexane / 1 h / -78 - 20 °C 6.1: triethylamine; sulfur trioxide pyridine complex / dimethyl sulfoxide; dichloromethane / 1 h / 20 °C 7.1: tetrahydrofuran / 0.5 h / 0 °C 8.1: triethylsilane; trifluoroacetic acid / dichloromethane / 1 h / 20 °C

	Multi-step reaction with 7 steps 1.1: hydrogenchloride; sodium nitrite / water / 1 h / 0 - 20 °C 1.2: 2 h / 0 - 20 °C 2.1: ethanol / 24 h / 20 °C / Molecular sieve 3.1: palladium 10% on activated carbon; hydrogen / ethanol / 18 h 4.1: diisobutylaluminium hydride / dichloromethane; hexane / 1 h / -78 - 20 °C 5.1: sulfur trioxide pyridine complex; triethylamine / dimethyl sulfoxide; dichloromethane 6.1: tetrahydrofuran 7.1: trifluoroacetic acid; triethylsilane / dichloromethane / 1 h / 20 °C
	Multi-step reaction with 8 steps 1.1: hydrogenchloride; sodium nitrite / water / 1 h / 0 - 20 °C 1.2: 2 h / 0 - 20 °C 2.1: ethanol / 24 h / 20 °C / Molecular sieve 3.1: palladium 10% on activated carbon; hydrogen / ethanol / 18 h 4.1: toluene-4-sulfonic acid / para-xylene / 20 h / 140 °C 5.1: diisobutylaluminium hydride / dichloromethane; hexane / 1 h / -78 - 20 °C 6.1: sulfur trioxide pyridine complex; triethylamine / dimethyl sulfoxide; dichloromethane 7.1: tetrahydrofuran 8.1: trifluoroacetic acid; triethylsilane / dichloromethane / 1 h / 20 °C
	Multi-step reaction with 8 steps 1.1: sodium nitrite; hydrogenchloride / water / 1 h / 0 - 20 °C 1.2: 2 h / 0 - 20 °C 2.1: ethanol / 24 h / 20 °C / Molecular sieve 3.1: palladium 10% on activated carbon; hydrogen / ethanol / 18 h 4.1: toluene-4-sulfonic acid / water; para-xylene / 20 h / 140 °C 5.1: diisobutylaluminium hydride / dichloromethane; hexane / 0.83 h / -78 - 20 °C 6.1: triethylamine; sulfur trioxide pyridine complex / dimethyl sulfoxide; dichloromethane / 1 h / 20 °C 7.1: tetrahydrofuran / 0.5 h / 0 °C 8.1: triethylsilane; trifluoroacetic acid / dichloromethane / 1 h / 20 °C

Reference： [1]Current Patent Assignee: AGENEBIO; HAGER BIOSCIENCES - WO2015/95783, 2015, A1
[2]Current Patent Assignee: AGENEBIO; HAGER BIOSCIENCES - WO2015/95783, 2015, A1
[3]Current Patent Assignee: AGENEBIO; HAGER BIOSCIENCES - WO2016/205739, 2016, A1
[4]Current Patent Assignee: AGENEBIO; HAGER BIOSCIENCES - US2018/170941, 2018, A1
[5]Current Patent Assignee: AGENEBIO; HAGER BIOSCIENCES - US2018/170941, 2018, A1
[6]Current Patent Assignee: AGENEBIO - WO2019/246300, 2019, A1

75
[ 16133-49-6 ]
C₂₄H₂₂N₄O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 10 steps 1.1: hydrogenchloride; sodium nitrite / water / 1 h / 0 - 20 °C 1.2: 2 h / 0 - 20 °C 2.1: ethanol / 24 h / 20 °C / Molecular sieve 3.1: hydrogen; palladium 10% on activated carbon / ethanol / 18 h 4.1: toluene-4-sulfonic acid / para-xylene / 20 h / 140 °C 5.1: diisobutylaluminium hydride / dichloromethane; hexane / 0.83 h / -78 - 20 °C 6.1: sulfur trioxide pyridine complex; dimethyl sulfoxide; triethylamine / dichloromethane / 1 h / 20 °C 7.1: tetrahydrofuran / 0.5 h / 0 °C 8.1: triethylsilane; trifluoroacetic acid / dichloromethane / 1 h / 20 °C 9.1: trichlorophosphate; N-ethyl-N,N-diisopropylamine / acetonitrile / 2 h / 0 °C 9.2: 18 h / 0 - 80 °C 10.1: potassium <i>tert</i>-butylate / N,N-dimethyl-formamide / 1 h / -50 °C 10.2: 2 h / -50 - 10 °C
	Multi-step reaction with 9 steps 1.1: hydrogenchloride; sodium nitrite / water / 1 h / 0 - 20 °C 1.2: 2 h / 0 - 20 °C 2.1: ethanol / 24 h / 20 °C / Molecular sieve 3.1: hydrogen; palladium 10% on activated carbon / ethanol / 18 h 4.1: diisobutylaluminium hydride / dichloromethane; hexane / 0.83 h / -78 - 20 °C 5.1: sulfur trioxide pyridine complex; dimethyl sulfoxide; triethylamine / dichloromethane / 1 h / 20 °C 6.1: tetrahydrofuran / 0.5 h / 0 °C 7.1: triethylsilane; trifluoroacetic acid / dichloromethane / 1 h / 20 °C 8.1: trichlorophosphate; N-ethyl-N,N-diisopropylamine / acetonitrile / 2 h / 0 °C 8.2: 18 h / 0 - 80 °C 9.1: potassium <i>tert</i>-butylate / N,N-dimethyl-formamide / 1 h / -50 °C 9.2: 2 h / -50 - 10 °C
	Multi-step reaction with 10 steps 1.1: hydrogenchloride; sodium nitrite / water / 1 h / 0 - 20 °C 1.2: 2 h / 0 - 20 °C 2.1: ethanol / 24 h / 20 °C / Molecular sieve 3.1: palladium 10% on activated carbon; hydrogen / ethanol / 18 h 4.1: toluene-4-sulfonic acid / water; para-xylene / 20 h / 140 °C 5.1: diisobutylaluminium hydride / dichloromethane; hexane / 1 h / -78 - 20 °C 6.1: triethylamine; sulfur trioxide pyridine complex / dimethyl sulfoxide; dichloromethane / 1 h / 20 °C 7.1: tetrahydrofuran / 0.5 h / 0 °C 8.1: triethylsilane; trifluoroacetic acid / dichloromethane / 1 h / 20 °C 9.1: N-ethyl-N,N-diisopropylamine; trichlorophosphate / acetonitrile / 2 h / 0 °C 9.2: 18 h / 80 °C 10.1: potassium <i>tert</i>-butylate / N,N-dimethyl-formamide / 1 h / -50 °C 10.2: 2 h / 10 °C

	Multi-step reaction with 10 steps 1.1: hydrogenchloride; sodium nitrite / water / 1 h / 0 - 20 °C 1.2: 2 h / 0 - 20 °C 2.1: ethanol / 24 h / 20 °C / Molecular sieve 3.1: palladium 10% on activated carbon; hydrogen / ethanol / 18 h 4.1: toluene-4-sulfonic acid / para-xylene / 20 h / 140 °C 5.1: diisobutylaluminium hydride / dichloromethane; hexane / 1 h / -78 - 20 °C 6.1: sulfur trioxide pyridine complex; triethylamine / dimethyl sulfoxide; dichloromethane 7.1: tetrahydrofuran 8.1: trifluoroacetic acid; triethylsilane / dichloromethane / 1 h / 20 °C 9.1: N-ethyl-N,N-diisopropylamine; trichlorophosphate / acetonitrile / 2 h / 0 °C 9.2: 18 h / 80 °C 10.1: potassium <i>tert</i>-butylate / N,N-dimethyl-formamide / 1 h / -50 °C 10.2: 2 h / 10 °C
	Multi-step reaction with 9 steps 1.1: hydrogenchloride; sodium nitrite / water / 1 h / 0 - 20 °C 1.2: 2 h / 0 - 20 °C 2.1: ethanol / 24 h / 20 °C / Molecular sieve 3.1: palladium 10% on activated carbon; hydrogen / ethanol / 18 h 4.1: diisobutylaluminium hydride / dichloromethane; hexane / 1 h / -78 - 20 °C 5.1: sulfur trioxide pyridine complex; triethylamine / dimethyl sulfoxide; dichloromethane 6.1: tetrahydrofuran 7.1: trifluoroacetic acid; triethylsilane / dichloromethane / 1 h / 20 °C 8.1: N-ethyl-N,N-diisopropylamine; trichlorophosphate / acetonitrile / 2 h / 0 °C 8.2: 18 h / 80 °C 9.1: potassium <i>tert</i>-butylate / N,N-dimethyl-formamide / 1 h / -50 °C 9.2: 2 h / 10 °C
	Multi-step reaction with 10 steps 1.1: sodium nitrite; hydrogenchloride / water / 1 h / 0 - 20 °C 1.2: 2 h / 0 - 20 °C 2.1: ethanol / 24 h / 20 °C / Molecular sieve 3.1: palladium 10% on activated carbon; hydrogen / ethanol / 18 h 4.1: toluene-4-sulfonic acid / water; para-xylene / 20 h / 140 °C 5.1: diisobutylaluminium hydride / dichloromethane; hexane / 0.83 h / -78 - 20 °C 6.1: triethylamine; sulfur trioxide pyridine complex / dimethyl sulfoxide; dichloromethane / 1 h / 20 °C 7.1: tetrahydrofuran / 0.5 h / 0 °C 8.1: triethylsilane; trifluoroacetic acid / dichloromethane / 1 h / 20 °C 9.1: trichlorophosphate; N-ethyl-N,N-diisopropylamine / acetonitrile / 2 h / 0 °C 9.2: 18 h / 80 °C 10.1: potassium <i>tert</i>-butylate / N,N-dimethyl-formamide / 1 h / -50 °C 10.2: 2 h / -50 - 10 °C

Reference： [1]Current Patent Assignee: AGENEBIO; HAGER BIOSCIENCES - WO2015/95783, 2015, A1
[2]Current Patent Assignee: AGENEBIO; HAGER BIOSCIENCES - WO2015/95783, 2015, A1
[3]Current Patent Assignee: AGENEBIO; HAGER BIOSCIENCES - WO2016/205739, 2016, A1
[4]Current Patent Assignee: AGENEBIO; HAGER BIOSCIENCES - US2018/170941, 2018, A1
[5]Current Patent Assignee: AGENEBIO; HAGER BIOSCIENCES - US2018/170941, 2018, A1
[6]Current Patent Assignee: AGENEBIO - WO2019/246300, 2019, A1

76
N-(5-methoxy-2-nitrophenyl)pyrimidin-2-amine [ No CAS ]
[ 16133-49-6 ]

Yield	Reaction Conditions	Operation in experiment
72%	Stage #1: N-(5-methoxy-2-nitrophenyl)pyrimidin-2-amine With triethylsilane; trifluoroacetic acid at 50℃; Inert atmosphere; Stage #2: With acetic acid; hydrazine In methanol at 20℃; Inert atmosphere; regioselective reaction;

Reference： [1]Pawar, Govind Goroba; Brahmanandan, Abhilashamole; Kapur, Manmohan [Organic Letters, 2016, vol. 18, # 3, p. 448 - 451]

77
[ 16133-49-6 ]
3-bromopyridine-4-carbonyl chloride hydrochloride [ No CAS ]
3-bromo-N-(5-methoxy-2-nitrophenyl)pyridine-4-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.5 g	Stage #1: 3-bromopyridine-4-carbonyl chloride hydrochloride With triethylamine In dichloromethane at 20℃; Inert atmosphere; Stage #2: 5-methoxy-2-nitroaniline With triethylamine In dichloromethane at 0 - 20℃; for 23.5h; Inert atmosphere; Stage #3: With potassium carbonate In methanol; dichloromethane at 20℃; for 1.5h; Inert atmosphere;	1.2 Step 2, Method 4: 3-Bromo-N-(4-methoxy-2-nitrophenyl)pyridine-4-carboxamide Step 2, Method 4: 3-Bromo-iV-(4-methoxy-2-nitrophenyl)pyridine-4-carboxamide[0154] 3-Bromopyridine-4-carbonyl chloride hydrochloride (2.27 g, 8.83 mmol) was dissolved in dichloromethane (20 mL) with stirring under nitrogen at room temperature and cooled to 0 °C. 5-Methoxy-2-nitroaniline (1.35 g, 8.03 mmol) was added followed by triethylamine (2.35 mL, 16.9 mmol). The reaction mixture was then stirred at 0 °C to room temperature for 23.5 hours then potassium carbonate (1.1 g, 8.03 mmol) and methanol (5 mL) were added. The reaction mixture was stirred at room temperature for 1.5 hours and concentrated. The residue was dissolved in dichloromethane (20 mL) and washed with water (20 mL), 10% aqueous citric acid (20 mL), saturated aqueous sodium hydrogen carbonate (20 mL) and brine (20 mL). The organic solution was dried over magnesium sulphate, filtered and concentrated. Purification by FCC (silica, 0-50% ethyl acetate in heptane) gave the title compound 1.50 g (53% yield) as an off-white solid. δΗNMR (500 MHz, chloroform) 10.54 (s, 1H), 8.89 (s, 1H), 8.77 (d, J = 9.3 Hz, 1H), 8.69 (d, J = 4.9 Hz, 1H), 7.73 (d, J = 3.0 Hz, 1H), 7.52 (d, J = 4.8 Hz, 1H), 7.32 (dd, J = 9.3, 3.0 Hz, 1H), 3.90 (s, 3H).Tr(METCR1278) = 1.83 min, (ES+) (M+H)+352/354.
	With triethylamine In dichloromethane at 0 - 20℃; for 90h; Inert atmosphere;

Reference： [1]Current Patent Assignee: CHDI FOUNDATION - WO2016/33460, 2016, A1 Location in patent: Paragraph 0154
[2]Prime, Michael E.; Liu, Longbin; Lee, Matt R.; Khetarpal, Vinod; Brown, Christopher J.; Johnson, Peter D.; Miranda-Azpiazu, Patricia; Chen, Xuemei; Clark-Frew, Daniel; Coe, Samuel; Davis, Randall; Dickie, Anthony; Ebneth, Andreas; Esposito, Simone; Gadouleau, Elise; Gai, Xinjie; Galan, Sebastien; Green, Samantha; Greenaway, Catherine; Giles, Paul; Halldin, Christer; Hayes, Sarah; Herbst, Todd; Herrmann, Frank; Heßmann, Manuela; Jia, Zhisheng; Kiselyov, Alexander; Kotey, Adrian; Krulle, Thomas; Mangette, John E.; Marston, Richard W.; Menta, Sergio; Mills, Matthew R.; Monteagudo, Edith; Nag, Sangram; Nibbio, Martina; Orsatti, Laura; Schaertl, Sabine; Scheich, Christoph; Sproston, Joanne; Stepanov, Vladimir; Svedberg, Marie; Takano, Akihiro; Taylor, Malcolm; Thomas, Wayne; Toth, Miklós; Vaidya, Darshan; Vanräs, Katarina; Weddell, Derek; Wigginton, Ian; Wityak, John; Mrzljak, Ladislav; Munoz-Sanjuan, Ignacio; Bard, Jonathan A.; Dominguez, Celia [Journal of Medicinal Chemistry, 2020, vol. 63, # 15, p. 8608 - 8633]

78
[ 16133-49-6 ]
2-(methylthio)benzo[d]oxazole-6-carbaldehyde [ No CAS ]
5-methoxy-N-((2-(methylthio)benzo[d]oxazol-6-yl)methyl)-2-nitroaniline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With sodium tris(acetoxy)borohydride; trifluoroacetic acid In dichloromethane at 0 - 5℃; for 2h;	152.1 Step 1: To a solution of 5-methoxy-2-nitroaniline (500 mg, 2.99 mmol) and TFA (3.07 mL) in DCM (15 mL) at5 °C was added NaBH(OAc)3 (1.9 g, 8.97 mmol). To the resulting mixture at 0 °C was added dropwise a solution of2-(methylthio)benzo[d]oxazole-6-carbaldehyde (630 mg, 3.29 mmol) in DCM (10 mL) and . the mixture was stirred at 0°C for 2 h. The reaction mixture was diluted with DCM and washed with H2O, aq NaHCO3 and brine. The organic layerwas dried over Na2SO4 and concentrated under reduced pressure to give 5-methoxy-N-((2-(methylthio)benzo[d]oxazol-6-yl)methyl)-2-nitro aniline as a light brown solid (1.06 g, 100%). 1H NMR (300 MHz, DMSO-d6) δ 8.90 (t, 1H), 8.04 (d,J= 8.7 Hz, 1H), 7.68 (s, 1H), 7.60 (d, J= 8.4 Hz, 1H), 7.41 (d, J= 7.5 Hz, 1H), 6.28-6.32 (m, 2H), 4.73 (d, J= 6 Hz, 2H),3.72 (s,3H), 2.74 (s, 3H). LCMS (ESI) m/z 345 (M+H)+.

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP2766359, 2016, B1 Location in patent: Paragraph 0849

79
[ 16133-49-6 ]
5-(1-(3,5-dichloropyridin-4-yl)ethoxy)-1H-indazole-3-carbaldehyde [ No CAS ]
5-(1-(3,5-dichloropyridin-4-yl)ethoxy)-3-(5-methoxy-1H-benzo-[d]imidazol-2-yl)-1H-indazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
58%	Stage #1: 5-methoxy-2-nitroaniline With palladium 10% on activated carbon; hydrogen In methanol at 20℃; for 2h; Stage #2: 5-(1-(3,5-dichloropyridin-4-yl)ethoxy)-1H-indazole-3-carbaldehyde With sulfur In N,N-dimethyl-formamide at 90℃; for 2h; Inert atmosphere;

Reference： [1]Yan, Wei; Wang, Xinyi; Dai, Yang; Zhao, Bin; Yang, Xinying; Fan, Jun; Gao, Yinglei; Meng, Fanwang; Wang, Yuming; Luo, Cheng; Ai, Jing; Geng, Meiyu; Duan, Wenhu [Journal of Medicinal Chemistry, 2016, vol. 59, # 14, p. 6690 - 6708]

80
[ 67-56-1 ]
[ 16133-49-6 ]
[ 5809-23-4 ]
C₂₅H₂₄N₃O₅⁽¹⁺⁾ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	Stage #1: 5-methoxy-2-nitroaniline; 2'-Carboxy-4-diethylamino-2-hydroxybenzophenon In methanesulfonic acid at 90℃; for 12h; Stage #2: methanol With sulfuric acid for 24h; Reflux;	2.2. The preparation of 1 2-(4-Diethylamino-2-hydroxybenzoyl) benzoic acid [13] (1.43 g, 4.6 mmol) and 5-methoxy-2-nitrophenylamine (0.70 g, 4.2 mmol) were combined in methanesulfonic acid (2.0 mL) in a sealed flask and heated at 90 °C for 12 h. The reaction was poured into stirred ice water, its pH was adjusted to 7-8 with 1.0 M sodium hydroxide aqueous solution, and the mixture was stirred for 20 min. Then, the mixture was extracted with CH2Cl2 (3 * 50 mL). The organic layers were dried over Na2SO4 and evaporated to give the crude product. Then, the crude product refluxed in methanol (10.0 mL) with concentrated sulfuric acid (2.0 mL) for 24 h. The reaction was poured into stirred ice water, its pH was adjusted to 7-8 with 1.0 M sodium hydroxide aqueous solution, and the mixture was stirred for 20 min. Then, the mixture was extracted with CH2Cl2 (3 * 50 mL). The organic layers were dried over Na2SO4 and evaporated to give the crude product. The crude product was purified by silica gel column chromatography (SiO2, CH2Cl2/EtOH, gradient) to obtain a red solid 1 in 75% yield (1.4 g); m.p. 248-249 °C. HRMS: m/z [M + H]+ = 446.1710; Calcd: 446.1717; 1H NMR (DMSO-d6, 400 MHz, ppm): 8.31 (d, J = 8.0 Hz, 1H), 7.97 (t, J = 8.0 Hz, 1H), 7.89 (t, J = 8.0 Hz, 1H), 7.78 (s, 1H), 7.56 (d, J = 8.0 Hz, 1H), 7.23-7.20 (m, 2H), 7.15 (s, 1H), 7.03 (d, J = 8.8 Hz, 1H), 3.81-3.75 (m, 4H), 3.62 (s, 2H), 3.37 (s, 2H), 1.28 (t, J = 6.0 Hz, 3H), 1.21 (t, J = 6.0 Hz, 3H); 13C NMR (DMSO-d6, 100 MHz, ppm): 165.86 159.99, 158.93, 158.76, 156.74, 151.70, 134.35, 133.49, 133.16, 132.11, 131.97, 131.47, 130.33, 117.95, 116.53, 112.90, 103.08, 98.47, 53.73, 53.52, 47.87, 47.24, 14.05, 13.32.

Reference： [1]Liu, Chang; Jiao, Xiaojie; He, Song; Zhao, Liancheng; Zeng, Xianshun [Dyes and Pigments, 2017, vol. 138, p. 23 - 29]

81
[ 696-59-3 ]
[ 16133-49-6 ]
[ 59194-26-2 ]

Reference： [1]Journal of Organic Chemistry,2017,vol. 82,p. 3491 - 3499
[2]Organic and Biomolecular Chemistry,2017,vol. 15,p. 7157 - 7164

82
[ 16133-49-6 ]
[ 78-84-2 ]
5-methoxy-2-nitro-N-(2-methyl-1-propen-1-yl)benzenamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
37%	In dichloromethane at 20℃; for 48h; Inert atmosphere; Molecular sieve;	3 3.3. 5-Methoxy-2-nitro-N-(2-methyl-1-propen-1-yl)benzenamine (24) To a solution of 5-methoxy-2-nitrobenzenamine (1.00 g, 5.95 mmol) with 2-methylpropanal (515 mg, 7.14 mmol) in dichloromethane (DCM, 12 mL) at ambient temperature under a nitrogen atmosphere was added 4 Å molecular sieves (3 g, activated by heating at 120 °C under vacuum overnight, then stored under nitrogen). The reaction mixture was allowed to sit without agitation or stirring for 48 h. The mixture was then filtered and the sieves were washed with DCM (20 mL). The filtrate was concentrated under reduced pressure and the resulting residue was purified by chromatography (hexane/EtOAc, 9:1) to give 24 (484 mg, 2.18 mmol, 37%) as a red solid. mp = 83-84 °C; 1H NMR (600 MHz, CDCl3) δ 9.86 (d, J = 7.2 Hz, 1H), 8.14 (d, J = 9.6 Hz, 1H), 6.32 (d, J = 3.0 Hz, 1H), 6.29 (dd, J = 9.6, 2.4 Hz, 1H), 6.20 (dpent, J = 9.6, 1.2 Hz, 1H), 3.88 (s, 3H), 1.83 (s, 3H), 1.80 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 165.7, 143.5, 129.0, 126.0, 119.0, 118.0, 106.1, 95.0, 55.7, 22.5, 16.8; IR (ATR) 2923, 1616, 1585, 1497, 1239 cm-1; HRMS (ESI) calcd for C11H14N2O3Na (M + Na+) 245.0902, found 245.0896.
	Molecular sieve;

Reference： [1]Ansari, Nurul H.; Jordan, Arica L.; Söderberg, Björn C.G. [Tetrahedron, 2017, vol. 73, # 32, p. 4811 - 4821]
[2]Ansari, Nurul H.; Söderberg, Björn C.G. [Tetrahedron Letters, 2017, vol. 58, # 50, p. 4717 - 4720]

83
[ 16133-49-6 ]
3-(2,6-dichloro-3,5-dimethoxyphenyl)-7-chloro-2H-pyrano[3,2-c]pyridine-2-one [ No CAS ]
C₂₃H₁₇Cl₂N₃O₇ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	With tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; caesium carbonate; XPhos In toluene at 110℃; for 4h; Inert atmosphere;	95 100 mL round bottom flask95A (200 mg, 0.517 mmol),95B (261 mg, 1.55 mmol)Pd2 (dba) 3 (48 mg, 0.052 mmol)X-phos (49 mg, 0.103 mmol), cesium carbonate (505 mg, 1.55 mmol), toluene (12 mL), bubbled with nitrogen for 15 min, reacted under nitrogen for 4 h in an oil bath at 110 ° C, cooled to room temperature, The mixture was washed with dichloromethane and methanol (5: 1). The filtrate was combined and the solvent was evaporated. The resulting residue was purified by column chromatography (dichloromethane: methanol 500: 1) to give 95C as a yellow solid (190 mg, 71.0%).

Reference： [1]Current Patent Assignee: CHENGDU RONGKE BOHAI TECH - CN106810559, 2017, A Location in patent: Paragraph 0433-0435

84
[ 49844-90-8 ]
[ 16133-49-6 ]
N-(5-methoxy-2-nitrophenyl)-2-(methylthio)pyrimidin-4-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	Stage #1: 5-methoxy-2-nitroaniline With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 1h; Stage #2: 4-Chloro-2-methylthiopyrimidine In N,N-dimethyl-formamide; mineral oil for 2h;	2-1 Production example 2-1 ; N- (5-methoxy-2-nitrophenyl) -2- (methylthio)Pyrimidin-4-amine (15) 4-Methoxy 2-nitrobenzenamine (Compound 14; 4.6 g, 27.11 mmol) was dissolved in DMF (136 ml) and 60% NaH (1.63 g) was slowly added at 0 ° C. After stirring for 1 hour, 4-chloro-2- (methylthio) pyrimidine (4355 mg, 17.85 mmol) was added and stirred for about 2 hours. Thereafter, the solvent was poured into ice water to precipitate out, and the precipitated reaction product was filtered to obtain Compound 15 (6 g, 77%).
	With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; for 2h;

Reference： [1]Current Patent Assignee: HANYANG UNIVERSITY - KR101840674, 2018, B1 Location in patent: Paragraph 0376-0379
[2]Jun, Joon-Hong; Baek, Ji-Hyun; Yang, Song-Yi; Moon, Hyung-Woo; Kim, Hye-Jin; Cho, Hyun-Wook; Hah, Jung-Mi [International Journal of Molecular Sciences, 2021, vol. 22, # 20]

85
[ 16133-49-6 ]
3,3-diethoxypropanoyl chloride [ No CAS ]
C₁₂H₁₄N₂O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine In dichloromethane at 20℃; for 24h;	General procedure for the preparation of 5-methyl-8-nitroquinolin-2(1H)-one 26, 6-methyl-8-nitroquinolin-2 (1H)-one 27 [37], 7-methyl-8-nitroquinolin-2 (1H)-one 28, 5-methoxy-8-nitroquinolin-2 (1H)-one 29, 6-methoxy-8-nitroquinolin-2 (1H)-one 30 [38] and 7-methoxy-8-nitroquinolin-2(1H)-one 31. General procedure: In a first step, according to a previously reported procedure [21], 1.2 equiv. of 3,3′-diethoxyacryloyl chloride (prepared from ethyl 3,3′-diethoxypropionate by successive saponification and reaction with SOCl2) was reacted at rt with 1 equiv. of the appropriate nitroaniline derivative in dichloromethane, in the presence of 2 equiv. of pyridine. The reaction mixtures were then poured into water and extracted three times with dichloromethane. The organic layers were washed with brine, dried over anhydrous Na2SO4 and evaporated in vacuo. In a second step, each crude residue was reacted with 98% sulfuric acid and stirred at rt for 3-4 h (monitored by TLC). The reaction mixtures were then poured into ice, neutralized with K2CO3 and extracted three times with dichloromethane. The organic layers were washed with water, dried over anhydrous Na2SO4 and evaporated in vacuo. The final crude residues were purified by chromatography on silica gel. 5-methyl-8-nitroquinolin-2(1H)-one 26 (C10H8N2O3) was purified by chromatography on silica gel using cyclohexane/ethyl acetate (90/10) as eluent, isolated and recrystallized in acetonitrile to yield a pale brown solid (46%, 2.39 mol, 490 mg).

Reference： [1]Pedron, Julien; Boudot, Clotilde; Hutter, Sébastien; Bourgeade-Delmas, Sandra; Stigliani, Jean-Luc; Sournia-Saquet, Alix; Moreau, Alain; Boutet-Robinet, Elisa; Paloque, Lucie; Mothes, Emmanuelle; Laget, Michèle; Vendier, Laure; Pratviel, Geneviève; Wyllie, Susan; Fairlamb, Alan; Azas, Nadine; Courtioux, Bertrand; Valentin, Alexis; Verhaeghe, Pierre [European Journal of Medicinal Chemistry, 2018, vol. 155, p. 135 - 152]

86
[ 16133-49-6 ]
[ 292638-85-8 ]
[ 142010-17-1 ]

Yield	Reaction Conditions	Operation in experiment
77%	With palladium diacetate; toluene-4-sulfonic acid In methanol at 60℃; for 1.5h; Inert atmosphere;

Reference： [1]Faggyas, Réka J.; Grace, Megan; Williams, Lewis; Sutherland, Andrew [Journal of Organic Chemistry, 2018, vol. 83, # 20, p. 12595 - 12608]

87
[ 16133-49-6 ]
[ 54197-64-7 ]

Reference： [1]Journal of Organic Chemistry,2018,vol. 83,p. 12595 - 12608

88
[ 16133-49-6 ]
[ 1196074-43-7 ]

Reference： [1]Patent: WO2009/140163,2009,A1

89
[ 75-15-0 ]
[ 16133-49-6 ]
[ 37052-78-1 ]

Yield	Reaction Conditions	Operation in experiment
72%	Stage #1: 5-methoxy-2-nitroaniline With palladium 10% on activated carbon; ammonium formate In methanol at 55℃; for 4h; Stage #2: carbon disulfide With potassium hydroxide In ethanol; water at 70℃;	1.2 Step 2: Preparation of 5-methoxy-1H-benzo[d]imidazole-2(3H)-thione Dissolve 1.0 g of 5-methoxy-2-nitroaniline in 20 ml of methanol and add 100 mg of 10% palladium on carbon.3.7 g of ammonium formate, heated to 55 ° C and heated and stirred for 4 hours,The reaction was stopped, filtered after cooling, washed several times with methanol, and the filtrate was concentrated to dryness.Then dissolve it in 20 ml of ethanol, add 5 ml of carbon disulfide, 336 mg of potassium hydroxide (dissolved in 3 ml of water), and warm to 70 ° C and stir overnight.The reaction solution was sparged, dissolved in water, filtered, and the filter cake was washed several times with water.A brown solid of 774 mg was obtained in a yield of 72%.

Reference： [1]Current Patent Assignee: CHINESE ACADEMY OF SCIENCES; Shanghai Institute of Materia Medica (in: CAS) - CN108689946, 2018, A Location in patent: Paragraph 0073; 0081; 0082; 0083

90
[ 16133-49-6 ]
[ 586-78-7 ]
(5-methoxyl-2-nitrophenyl)(4-nitrophenyl)amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.7 g	With tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; sodium t-butanolate; XPhos In toluene at 90℃; for 3h; Inert atmosphere;	25.1; 26.1; 27.1 Step 1: Preparation of (5-methoxyl-2-nitro-phenyl)-(4- nitro-phenyl)-amine Under a nitrogen atmosphere, 2-nitro-5-methoxylaniline (1.5 g, 8.92 mmol), p-bromonitrobenzene (3.6 g, 17mmol), Xphos (425 mg), Pd2(dba)3 (408 mg) and sodium tert-butoxide (1.71 g, 17.8 mmol) were dissolved in 30 ml oftoluene, and the mixture was heated to 90°C and reacted for 3 hours. After the reaction solution was cooled to roomtemperature, 100 ml of dichloromethane was added and the mixture was stirred at room temperature for 5 minutes, andthen filtered and the filtrate was concentrated under a reduced pressure. The residues were purified via column chromatography(eluent: petroleum ether/ethyl acetate) to give 1.7 g of (5-methoxyl-2-nitro-phenyl)-(4-nitro-phenyl)-aminenas a red black solid.

Reference： [1]Current Patent Assignee: ANCUREALL PHARMACEUTICAL SHANGHAI - EP3424924, 2019, A1 Location in patent: Paragraph 0149; 0150; 0154; 0155; 0161; 0162

91
[ 16133-49-6 ]
[ 1008361-65-6 ]

Reference： [1]Patent: CN109020957,2018,A

92
[ 88-67-5 ]
[ 16133-49-6 ]
2-[(5-methoxy-2-nitrophenyl)amino]benzoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%	With copper(l) iodide; potassium carbonate In N,N-dimethyl-formamide at 120℃; for 3h;

Reference： [1]Tryniszewski, Michał; Bujok, Robert; Cmoch, Piotr; Gańczarczyk, Roman; Kulszewicz-Bajer, Irena; Wróbel, Zbigniew [Journal of Organic Chemistry, 2019, vol. 84, # 4, p. 2277 - 2286]

93
[ 16133-49-6 ]
[ 75-07-0 ]
[ 577969-59-6 ]

Yield	Reaction Conditions	Operation in experiment
70%	With hydrogenchloride In water at 0 - 80℃; for 1.15h;	6-Methoxy-2-methyl-8-nitroquinoline (D-TDMQ31). General procedure: Toa solution of 4-methoxy-2-nitroaniline (C-TDMQ31,Scheme 2, R6 OCH3) in HCl (12 M, 10 mL) at 0 C, acetaldehydewas added dropwise under stirring. The reactionmedium was kept at 0 C for 15 min, gradually increased to80 C, and then stirred at 80 C for 1 h. The resultingmixture was poured into ice-cold water and neutralizedwith aqueous ammonium hydroxide. After extraction withCH2Cl2, the organic phase was dried over MgSO4, filtered,and concentrated under reduced pressure. The crude mixture was purified by silica gel flash column chromatography(ethyl acetate/hexane, 1/20, v/v). After evaporationof the eluent, D-TDMQ31 was obtained as a yellow solid (41%).

Reference： [1]Huang, Ju; Nguyen, Michel; Liu, Yan; Robert, Anne; Meunier, Bernard [Comptes Rendus Chimie, 2019, vol. 22, # 5, p. 419 - 427]

94
[ 16133-49-6 ]
[ 100-52-7 ]
6‐methoxy‐2‐phenyl‐1H-benzoimidazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With 1,4-diaza-bicyclo[2.2.2]octane; sulfur at 130℃; for 10h;	General Procedure General procedure: To a round-bottomed flask equipped with a magnetic stirrer was sequentially added o-nitrophenol or o-nitroaniline (1 mmol), aldehyde (1 mmol), sulfur (3 mmol, 96 mg), and DABCO (1,4-diazabicyclo-[2.2.2]octane; 1 mmol, 112 mg). The reaction mixture was stirred at 130 °C for 2 h under air. Upon completion, the reaction mixture was dissolved in EtOAc, and the residual sulfur was removed. The crude mixture was purified by a silica gel column (petroleum ether/EtOAc, from 95:5 to 90:10) to give the expected product.
9%	With cobalt acetylacetonate; sodium t-butanolate In 1,4-dioxane at 135℃; for 24h; Sealed tube; Inert atmosphere;

Reference： [1]Dang, Minh-Huy Dinh; Nguyen, Linh Ho Thuy; Tran, Phuong Hoang [Synthesis, 2020, vol. 52, # 11, p. 1687 - 1694]
[2]Das, Sanju; Mallick, Samrat; De Sarkar, Suman [Journal of Organic Chemistry, 2019, vol. 84, # 18, p. 12111 - 12119]

95
[ 16133-49-6 ]
[ 513-85-9 ]
[ 6637-22-5 ]

Yield	Reaction Conditions	Operation in experiment
95%	With cesiumhydroxide monohydrate In toluene at 150℃; for 24h; Inert atmosphere; Sealed tube;	2.4 Direct synthesis of quinoxaline from nitroamine General procedure: In an oven dried 9mL screw cap tube a magnetic stir-bar, nitroamine (0.5mmol), vicinal diol (2.5mmol), CsOH.H2O (0.125mmol), Co-phen/C-800 (1.5mol%) and toluene (2.5mL) were added under argon atmosphere. Then, the tube was sealed and placed in a preheated oil bath at 150°C for 24h. After completion of the reaction, the tube was allowed to cool at room temperature. Next, the solvent was evaporated under reduced pressure. Finally, the quinoxaline was purified by silica gel column chromatography using ethyl acetate/hexane as eluent.
82%	With sodium hydroxide In toluene at 120℃; for 3h; Inert atmosphere; Sealed tube; Green chemistry;

Reference： [1]Panja, Dibyajyoti; Paul, Bhaskar; Balasubramaniam, Bhuvaneshwari; Gupta, Raju K.; Kundu, Sabuj [Catalysis Communications, 2020, vol. 137]
[2]Wang, Yan-Bing; Shi, Linlin; Zhang, Xiaojie; Fu, Lian-Rong; Hu, Weinan; Zhang, Wenjing; Zhu, Xinju; Hao, Xin-Qi; Song, Mao-Ping [Journal of Organic Chemistry, 2021, vol. 86, # 1, p. 947 - 958]

96
[ 16133-49-6 ]
[ 110-13-4 ]
2-(2,5-dimethyl-1H-pyrrol-1-yl)-4-methoxynitrobenzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56%	With acetic acid at 170℃; for 0.333333h;	1 Example 1 5-Methoxy-2-nitro-1-benzenamine (168 mg, 1.0 mmol), 2,5-hexanedione (342 mg, 3.0 mmol), acetic acid (3.0 mL) were added to Biotage's 5 mL snap cap reaction vial. In addition, after mounting the aluminum cap, heating and stirring were carried out at 170 ° C. for 20 minutes in a microwave reactor.After cooling to room temperature and concentration under reduced pressure, the residue obtained was purified by silica gel column chromatography (Biotage KP-SIL 10 g, 5% → 10% ethyl acetate / hexane, eluted with 15 column volumes) to give the title compound, 2 -(2,5-Dimethyl-1H-pyrrol-1-yl) -4-methoxy-1-nitrobenzene was obtained as an orange oil (139.3 mg, yield 56%).

Reference： [1]Current Patent Assignee: HOKKAIDO UNIVERSITY; LILAC PHARMA - JP2020/50635, 2020, A Location in patent: Paragraph 0062; 0063

97
1,2-diphenyl-1,2-ethanediol [ No CAS ]
[ 16133-49-6 ]
[ 26832-42-8 ]

Yield	Reaction Conditions	Operation in experiment
46%	With cesiumhydroxide monohydrate In 5,5-dimethyl-1,3-cyclohexadiene at 160℃; for 24h; Inert atmosphere;	4 Example 4Preparation of 6-methoxy-2,3-diphenylquinoxaline from 5-methoxy-6-nitroaniline and 2-hydroxy-2-phenylphenethyl alcohol Add 5-methoxy-6-nitroaniline (84.075mg, 0.5mmol) to the reaction tube in sequence,2-hydroxy-2-phenylphenethyl alcohol (187.5mg, 1.75equiv),Cesium hydroxide monohydrate (83.96mg, 0.5mmol) was evacuated and filled with nitrogen,Then heat and stir at 160 for 24h,After the reaction was monitored by TLC or GC-MS, the product was separated and purified by column chromatography.The separation yield was 46%.

Reference： [1]Current Patent Assignee: YANGZHOU UNIVERSITY - CN111116496, 2020, A Location in patent: Paragraph 0034-0037

98
[ 16133-49-6 ]
[ 123-11-5 ]
[ 30458-48-1 ]

Yield	Reaction Conditions	Operation in experiment
68%	With 1,4-diaza-bicyclo[2.2.2]octane; sulfur at 130℃; for 10h;	General Procedure General procedure: To a round-bottomed flask equipped with a magnetic stirrer was sequentially added o-nitrophenol or o-nitroaniline (1 mmol), aldehyde (1 mmol), sulfur (3 mmol, 96 mg), and DABCO (1,4-diazabicyclo-[2.2.2]octane; 1 mmol, 112 mg). The reaction mixture was stirred at 130 °C for 2 h under air. Upon completion, the reaction mixture was dissolved in EtOAc, and the residual sulfur was removed. The crude mixture was purified by a silica gel column (petroleum ether/EtOAc, from 95:5 to 90:10) to give the expected product.

Reference： [1]Dang, Minh-Huy Dinh; Nguyen, Linh Ho Thuy; Tran, Phuong Hoang [Synthesis, 2020, vol. 52, # 11, p. 1687 - 1694]

99
[ 67-56-1 ]
[ 16133-49-6 ]
[ 4887-80-3 ]

Yield	Reaction Conditions	Operation in experiment
99%	With iron; ammonium chloride at 68 - 70℃; for 48h; Inert atmosphere;	1 In a 10mL reaction tube, add 50.4mg (0.3mmol) of 5-methoxy-2-nitroaniline,Reduced iron powder 92.2mg (1.65mmol), ammonium chloride 88.3mg (1.65mmol),Under nitrogen protection, add 5 mL of anhydrous methanol with a syringe, and heat and stir at 68-70°C for 48 hours.The reaction was cooled to room temperature and quenched with 5 mL of saturated aqueous sodium bicarbonate solution.Suction filtered through diatomaceous earth, the filtrate was extracted with dichloromethane (10 mL×3), and the organic phases were combined,After drying and concentrating, 44.0 mg of the target compound was obtained with a yield of 99%.
98%	With iron; ammonium chloride at 70℃; for 48h; Schlenk technique; Inert atmosphere; regioselective reaction;

Reference： [1]Current Patent Assignee: CHINA AGRICULTURAL UNIVERSITY - CN111704579, 2020, A Location in patent: Paragraph 0044-0048
[2]An, Jie; Lai, Zemin; Li, Hengzhao; Peng, Mengqi; Sun, Yanhao; Yan, Zihan; Yang, Ruoyan; Zhang, Yuntong [Green Chemistry, 2022, vol. 24, # 2, p. 748 - 753]

100
[ 591-50-4 ]
[ 16133-49-6 ]
[ 36242-53-2 ]

Yield	Reaction Conditions	Operation in experiment
	With copper(l) iodide; 1,10-Phenanthroline; potassium carbonate In N,N-dimethyl-formamide at 80℃; for 12h;	1.1; 2.1; 3.1 Example 2 (1) Combine 5-methoxy-2-nitroaniline (3.87g, 0.023mol), iodobenzene (5.71g, 0.028mol), CuI (0.44g, 0.0023mol),O-phenanthroline (0.46g, 0.0023mol) and potassium carbonate (6.36g, 0.046mol) were dissolved in 50ml DMF, and reacted under reflux at 80°C for 12h;Then it was cooled to room temperature, DMF in the system was recovered by rotary evaporation, and column chromatography was performed with ethyl acetate: petroleum ether=1:20 (V:V) as the eluent to obtain intermediate product A;

Reference： [1]Current Patent Assignee: LUOYANG INSTITUTE OF SCIENCE AND TECHNOLOGY; ZHENGZHOU UNIVERSITY - CN111875634, 2020, A Location in patent: Paragraph 0052-0053; 0057-0058; 0062-0063

101
[ 16133-49-6 ]
[ 119-52-8 ]
[ 36305-66-5 ]

Yield	Reaction Conditions	Operation in experiment
98%	With sodium hydroxide In toluene at 120℃; for 3h; Inert atmosphere; Sealed tube; Green chemistry;

Reference： [1]Wang, Yan-Bing; Shi, Linlin; Zhang, Xiaojie; Fu, Lian-Rong; Hu, Weinan; Zhang, Wenjing; Zhu, Xinju; Hao, Xin-Qi; Song, Mao-Ping [Journal of Organic Chemistry, 2021, vol. 86, # 1, p. 947 - 958]

102
[ 16133-49-6 ]
[ 552-86-3 ]
2,3-di(furan-2-yl)-6-methoxyquinoxaline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	With sodium hydroxide In toluene at 120℃; for 3h; Inert atmosphere; Sealed tube; Green chemistry;

Reference： [1]Wang, Yan-Bing; Shi, Linlin; Zhang, Xiaojie; Fu, Lian-Rong; Hu, Weinan; Zhang, Wenjing; Zhu, Xinju; Hao, Xin-Qi; Song, Mao-Ping [Journal of Organic Chemistry, 2021, vol. 86, # 1, p. 947 - 958]

103
[ 124-38-9 ]
[ 16133-49-6 ]
[ 4887-80-3 ]

Yield	Reaction Conditions	Operation in experiment
92%	With palladium 10% on activated carbon; phenylsilane; 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine In acetonitrile at 70℃; for 15h;

Reference： [1]Phatake, Vishal V.; Bhanage, Bhalchandra M. [Tetrahedron Letters, 2021, vol. 68]

104
[ 93-56-1 ]
[ 16133-49-6 ]
[ 77093-88-0 ]
[ 123464-57-3 ]

Yield	Reaction Conditions	Operation in experiment
1: 60% 2: 38%	With trimethylamine-N-oxide; tricarbonyl(η⁴-1,3-bis(trimethylsilyl)-4,5,6,7-tetrahydro-2H-inden-2-one)iron In toluene at 150℃; for 24h; Green chemistry;

Reference： [1]Chun, Simin; Hong, Junhwa; Hong, Suckchang; Lee, Seok Beom; Oh, Dong-Chan; Putta, Ramachandra Reddy [RSC Advances, 2021, vol. 11, # 30, p. 18225 - 18230]

105
[ 81644-23-7 ]
[ 16133-49-6 ]
1-(5-methoxy-2-nitrophenyl)-1H-pyrrole-3-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	Stage #1: 2,5-dimethoxytetrahydrofuran-3-carbonitrile; 5-methoxy-2-nitroaniline In 1,4-dioxane for 0.333333h; Reflux; Stage #2: With hydrogenchloride In 1,4-dioxane; water for 0.333333h; Reflux;

Reference： [1]Grillo, Alessandro; Fezza, Filomena; Chemi, Giulia; Colangeli, Roberto; Brogi, Simone; Fazio, Domenico; Federico, Stefano; Papa, Alessandro; Relitti, Nicola; Di Maio, Roberto; Giorgi, Gianluca; Lamponi, Stefania; Valoti, Massimo; Gorelli, Beatrice; Saponara, Simona; Benedusi, Mascia; Pecorelli, Alessandra; Minetti, Patrizia; Valacchi, Giuseppe; Butini, Stefania; Campiani, Giuseppe; Gemma, Sandra; Maccarrone, Mauro; Di Giovanni, Giuseppe [ACS Chemical Neuroscience, 2021, vol. 12, # 9, p. 1716 - 1736]

106
[ 16133-49-6 ]
[ 50777-76-9 ]
C₂₆H₂₁N₂O₂P [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
43%	With sodium dithionite In ethanol; water at 75℃; for 5h;
43%	With sodium dithionite In ethanol; water at 75℃; for 5h;
43%	With sodium dithionite In ethanol; water for 5h; Reflux;	Synthesis of HL1 General procedure: The 2-nitroaniline (0.71g, 5mmol), 2-(diphenylphosphino)benzaldehyde (1.74g, 6mmol) and sodium hydrosulfite (3.48g, 20mmol) in a mixture of the ethanol and water (v/v=5:1) were refluxed for 5h. The reaction mixture was filtered to remove the precipitated base. Then, the filtrate was concentrated under reduced pressure to remove the mixture of ethanol and water, and then extracted with ethyl acetate. The crude product was purified by silica gel column chromatography using dichloromethane/ethyl acetate (10:1) as the eluent to afford HL1 as a white solid (0.93g, 47% yield).

Reference： [1]Du, Chenxia; Liu, Chunmei; Peng, Zhengchun; Wang, Weigao; Zhang, Bin; Zhang, Han [Journal of Materials Chemistry C, 2021, vol. 9, # 30, p. 9627 - 9636]
[2]Du, Chenxia; Liu, Chunmei; Yin, Guojie; Zhang, Bin; Zhang, Han [Dalton Transactions, 2021, vol. 50, # 46, p. 17319 - 17327]
[3]Du, Chenxia; Liu, Chunmei; Zhang, Bin; Zhang, Han [Journal of Organometallic Chemistry, 2022, vol. 960]

107
[ 64-17-5 ]
[ 16133-49-6 ]
[ 4887-81-4 ]

Yield	Reaction Conditions	Operation in experiment
87%	With iron; ammonium chloride at 70℃; for 48h; Schlenk technique; Inert atmosphere; regioselective reaction;

Reference： [1]An, Jie; Lai, Zemin; Li, Hengzhao; Peng, Mengqi; Sun, Yanhao; Yan, Zihan; Yang, Ruoyan; Zhang, Yuntong [Green Chemistry, 2022, vol. 24, # 2, p. 748 - 753]

108
[ 811-98-3 ]
[ 16133-49-6 ]
6-methoxy-1H-benzo[d]imidazole-2-d [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	With iron; ammonium chloride at 70℃; for 48h; Schlenk technique; Inert atmosphere; regioselective reaction;

Reference： [1]An, Jie; Lai, Zemin; Li, Hengzhao; Peng, Mengqi; Sun, Yanhao; Yan, Zihan; Yang, Ruoyan; Zhang, Yuntong [Green Chemistry, 2022, vol. 24, # 2, p. 748 - 753]

109
[ 16133-49-6 ]
5-((R)-1-(3,5-dichloropyridin-4-yl)ethoxy)-3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole [ No CAS ]
5-((R)-1-(3,5-dichloropyridin-4-yl)ethoxy)-N-(5-methoxy-2-nitrophenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
37%	With tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; Cs₂CO₃; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In toluene at 90℃; Inert atmosphere;

Reference： [1]Shao, Min; Chen, Xiaojuan; Yang, Fang; Song, Xiaojuan; Zhou, Yang; Lin, Qianmeng; Fu, Ying; Ortega, Raquel; Lin, Xiaojing; Tu, Zhengchao; Patterson, Adam V.; Smaill, Jeff B.; Chen, Yongheng; Lu, Xiaoyun [Journal of Medicinal Chemistry, 2022, vol. 65, # 6, p. 5113 - 5133]

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	16133-49-6	MDL No. :	MFCD00179573
Formula :	C₇H₈N₂O₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	QEHVRGACCVLLNN-UHFFFAOYSA-N
M.W :	168.15	Pubchem ID :	85300
Synonyms :		Chemical Name :	5-Methoxy-2-nitrophenylamine

Num. heavy atoms :	12
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.14
Num. rotatable bonds :	2
Num. H-bond acceptors :	3.0
Num. H-bond donors :	1.0
Molar Refractivity :	46.16
TPSA :	81.07 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) :	-6.01 cm/s

Log Po/w (iLOGP) :	1.28
Log Po/w (XLOGP3) :	1.86
Log Po/w (WLOGP) :	1.19
Log Po/w (MLOGP) :	0.05
Log Po/w (SILICOS-IT) :	-1.04
Consensus Log Po/w :	0.67

[ CAS No. 16133-49-6 ] {[proInfo.proName]}

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[ 16133-49-6 ] Synthesis Path-Upstream 1~13

[ 16133-49-6 ] Synthesis Path-Downstream 1~109

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[ 16133-49-6 ]

Aryls

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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) :	-2.29
Solubility :	0.858 mg/ml ; 0.0051 mol/l
Class :	Soluble
Log S (Ali) :	-3.18
Solubility :	0.11 mg/ml ; 0.000655 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-1.54
Solubility :	4.85 mg/ml ; 0.0288 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	3.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.86

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280	UN#:	N/A
Hazard Statements:	H317	Packing Group:	N/A
GHS Pictogram:

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

[ CAS No. 16133-49-6 ] {[proInfo.proName]}

Quality Control of [ 16133-49-6 ]

Related Doc. of [ 16133-49-6 ]

Product Details of [ 16133-49-6 ]

Calculated chemistry of [ 16133-49-6 ] Expand+

Physicochemical Properties

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Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 16133-49-6 ]

Application In Synthesis of [ 16133-49-6 ]

[ 16133-49-6 ] Synthesis Path-Upstream 1~13

[ 16133-49-6 ] Synthesis Path-Downstream 1~109

Technical Information

Related Functional Groups of [ 16133-49-6 ]

Aryls

Ethers

Amines

Nitroes

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

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Environmental hazards

Inquiry

Related Functional Groups of
[ 16133-49-6 ]