Name: 6278-73-5|4-(Benzo[d]thiazol-2-yl)aniline|97%
Brand: Ambeed
SKU: A158766
Price: 12.0 USD
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1
[ 22868-34-4 ]
[ 6278-73-5 ]

Yield	Reaction Conditions	Operation in experiment
100%	With hydrogen In ethanol at 20℃; for 2h;
97%	With tin(ll) chloride In ethanol for 4h; Heating;
97%	With water; tin(ll) chloride In ethanol for 4h; Heating / reflux;	2.b (b) 2-(4-Aminophenyl)benzothiazole (20) (b) 2-(4-Aminophenyl)benzothiazole (20) A mixture of 2-(4-nitrophenyl)benzothiazole (105 mg, 0.40 mmol) and tin(II) chloride dihydrate (205 mg, 0.91 mmol) in ethanol (20 ML) was refluxed under N2 for 4 hrs.After removing ethanol by vacuum evaporation.The residue was dissolved into ethyl acetate (20 ml), and washed with NaOH solution (1N, 320 ml) and water (320 ml), dried and evaporated to dryness to give 102 mg (97%) of the product

94%	With palladium 10% on activated carbon; hydrogen In dichloromethane at 25℃; for 4h; Inert atmosphere;
94%	With palladium 10% on activated carbon; hydrogen In dichloromethane at 20℃; for 4h;	General Procedure for the Syntheses of 2-(4-Aminophenyl)benzothiazole (6a-6j) General procedure: To a solution of 2-(4-nitrophenyl)benzothiazole (1 g, 3.9 mmol) in CH2Cl2 (30 ml) was added 10% Pd/C (0.1 g) under hydrogen at room temperature for 4 h. The resulting solution was concentrated and subjected to flash chromatography (CH2Cl2) to give the corresponding compounds 6. RRN 78 2-(4-Aminophenyl)benzothiazole (6a) (0089) yellow solid; 94% yield; mp 130-132° C.; 1H NMR (CDCl3, 400 MHz) δ7.99 (m, 1H), 7.89 (m, 2H), 7.84 (m, 1H), 7.44 (m, 1H), 7.32 (m, 1H), 6.72 (dt, J=4.2 and 2.0 Hz, 2H), 4.00 (bs, NH2); 13C NMR (CDCl3,100 MHz) δ168.5, 154.2, 149.2, 134.6, 129.1, 126.0, 124.4, 123.9, 122.5, 121.4, 114.8; HRMS (ESI, m/z) for C13H10N2S calcd 226.0565. found 226.0567; Anal. calcd for C13H10N2S: C, 69.00; H, 4.45; N, 12.38. Found C, 69.01; H, 4.69; N, 12.29.
90%	With tin(ll) chloride In ethanol for 4h; Heating;
90%	With tin(ll) chloride In ethanol for 6h; Inert atmosphere; Reflux;	2 2-(4-aminophenyl)benzo[d]thiazole (2) A mixture of 2-(4-nitrophenyl)benzo[d]thiazole (1) (0.015 mol) and stannous chloride (0.075 mol) in absolute ethanol (50 ml) was stirred and refluxed under nitrogen for 6 h. After evaporation of ethanol, ethyl acetate was added to the residue and the organic layer was washed with 2 M aqueous NaOH (3 * 100 ml) and water (2 * 100 ml) and dried with Na2SO4. The solvent was removed under reduced pressure. The crude product was crystallized from ethanol to afford 2-(4-aminophenyl)benzo[d]thiazole (2). The progress of reaction and purity of compound was checked by TLC using TEF (5:4:1) as mobile phase. Pale yellow solid; Yield: 90%; M.P.: 155-157°C; IR (KBr, cm-1): 3458 (N-H), 3180 (Ar C-H), 1642 (C=N), 1602 (C=C); 1H NMR (CDCl3, 300MHz) δ (ppm): 8.03-8.00 (d, 1H, H-4, J=9Hz), 7.93-7.90 (d, 2H, H-2′ & H-6′, J=9Hz), 7.88-7.85 (d, 1H, H-7, J=9Hz), 7.49-7.44 (t, 1H, H-5, J=7.5Hz), 7.36-7.31 (t, 1H, H-6, J=7.5Hz), 6.77-6.74 (d, 2H, H-3′ & H-5′, J=9Hz), 4.02 (bs, 2H, NH2, D2O exchangeable); ESI-MS (m/z): 226.11 (M+); Anal. calcd. for C13H10N2S: C, 69.00; H, 4.45; N, 12.38. Found: C, 69.23; H, 4.47; N, 12.41.
80%	With hydrogenchloride; iron In methanol; water at 90℃; for 7h;
78.76%	With tin(II) chloride dihdyrate In ethanol Inert atmosphere;	3.5. General procedure for synthesis of 6,7-substituted-2-(4-aminophenyl)benzo[ d ]thiazole (4a-f) General procedure: A mixture of an appropriately substituted-2-(4-nitrophenyl) benzo[ d ]thiazole (one of 3a - f , 0.015 mol) and tin (II) chloride di- hydrate (0.075 mol) in 50 mL boiling ethanol was stirred under ni- trogen environment for 3-5 h. The excess ethanol was removed by vacuum evaporation using rota-evaporator and the residue formed was successively extracted with 75 ml of ethyl acetate (3 times). The combined organic fraction was further thoroughly washed first with 50 mL of 2 M aqueous NaOH (3 times) followed by 50 mL of distilled water (2 times). To the resultant organic fraction, anhy- drous Na 2 SO 4 was added, filtered, and the filtrate was evaporated in-vacuum to yield the desired compounds 4a-f .
67%	With zinc; hydrazinium monoformate In methanol at 20℃; for 44h;
65.2%	With tin(II) chloride hydrate In ethanol for 5h; Reflux;
63%	With hydrogenchloride; iron In ethanol; water Reflux;	General procedure: Iron powder (3-4 mmol) and 6 N HCl solution (1 ml) were added to the solution of the nitro derivatives (1 mmol) in EtOH (5 ml) and the mixture was heated to reflux under nitrogen for 3-5 h. After cooling to room temperature, the suspension was diluted with EtOAc (20 ml); a solution of 6 M NaOH (20 ml) was added until basic pH and the layers were separated. The aqueous layer was extracted with AcOEt(2 X 20 ml) and the combined organic layers were washed with brine,dried over anhydrous Na2SO4, filtered and evaporated under vacuum.The crude product was purified by chromatography on silica gel(eluent: EtOAc/Hexane 6:4 v/v or CHCl3/MeOH 9.5:0.5 v/v to 9:1 v/v)or triturated with diethyl ether.
	With hydrogenchloride; tin(ll) chloride
	With hydrogenchloride; tin(ll) chloride
	With tin; sulfuric acid
214 mg	Stage #1: 2-(4-nitrophenyl)benzothiazole With tin(II) chloride dihdyrate In methanol for 5h; Reflux; Stage #2: With sodium hydrogencarbonate
	With iron; ammonium chloride In ethanol; water for 2h; Reflux;
	In dichloromethane	1 General Procedure for the Syntheses of 2-(4-Aminophenyl)benzothiazole (6a-6j) General Procedure for the Syntheses of 2-(4-Aminophenyl)benzothiazole (6a-6j) To a solution of 2-(4-nitrophenyl)benzothiazole (1 g, 3.9 mmol) in CH2Cl2 (30 ml) was added 10% Pd/C (0.1 g) under hydrogen at room temperature for 4 h. The resulting solution was concentrated and subjected to flash chromatography (CH2Cl2) to give the corresponding compounds 6.
	With ethanol; tin(ll) chloride for 3h; Reflux;
	With tin(II) chloride dihdyrate In ethanol for 2h; Reflux;	d. Method D. General Method for the Reduction of Substituted 2-(4- Nitrophenyl)benzothiazoles 10a-d General procedure: To a solution of substituted 2-(4-nitrophenyl)benzothiazoles (3 g, 8.66 mmol) in ethanol, tin(II) chloride dihydrate (25.98 mmol) was added and refluxed it for 2 h. The solvent was removed under vacuum and the resulting oil taken up in ethyl acetate (75 mL) was quenched with aq NaHCO3 solution. The resulting organic layer was separated and evaporated to leave a residue of the amine which was purified by column chromatography (eluent ethylacetate/hexane). For compounds 10a-c the products were authenticated by comparing the 1H NMR values and melting points with the literature values.
	With iron; ammonium chloride In ethanol; water for 1h; Reflux;	4.1.2. General procedure for the preparation of compounds 15a-15h and 16a-16t General procedure: Compound 12 (1.0 equiv) was suspended in EtOH/H2O (v/v:3:1), and iron powder (10.0 equiv) and NH4Cl (3.0 equiv) were added. The suspension was heated to reflux for 1 h with vigorous stirring. The precipitate was separated by filtration and washing with ethanol. The filtrates were evaporated and the resulting oil was added to cold saturated NaHCO3 followed by extracted with acetic ether. The combined organic layers were dried (MgSO4), filtered and the filtrate was concentrated under reduced pressure. The crude amide (13) was used for the next reaction without further purification. A solutionof 13 (1.0 equiv) and 14 (1.0 equiv) in chloroform was heated at 60 C for 2 h. The reaction mixture was purifiedby silica gel chromatography to give 15a-15h and 16a-16t as solid.
	With palladium 10% on activated carbon; hydrogen In dichloromethane at 25℃;

Reference： [1]Current Patent Assignee: SANTEN PHARMACEUTICAL CO LTD - WO2006/22442, 2006, A1 Location in patent: Page/Page column 56
[2]Mathis, Chester A.; Bacskai, Brian J.; Kajdasz, Stephen T.; McLellan, Megan E.; Frosch, Matthew P.; Hyman, Bradley T.; Holt, Daniel P.; Wang, Yanming; Huang, Guo-Feng; Debnath, Manik L.; Klunk, William E. [Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 3, p. 295 - 298]
[3]Current Patent Assignee: COMMONWEALTH SYSTEM OF HIGHER EDUCATION - US2003/236391, 2003, A1 Location in patent: Page 16
[4]Location in patent: experimental part Hu, Wan-Ping; Chen, Yin-Kai; Liao, Chao-Cheng; Yu, Hsin-Su; Tsai, Yi-Min; Huang, Shu-Mei; Tsai, Feng-Yuan; Shen, Ho-Chuan; Chang, Long-Sen; Wang, Jeh-Jeng [Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 16, p. 6197 - 6207]
[5]Current Patent Assignee: KAOHSIUNG MEDICAL UNIVERSITY - US8592603, 2013, B2 Location in patent: Page/Page column 13
[6]Stevens, Malcolm F. G.; Shi, Dong-Fang; Castro, Angeles [Journal of the Chemical Society. Perkin transactions I, 1996, # 1, p. 83 - 94] Shi, Dong-Fang; Bradshaw, Tracey D.; Wrigley, Samantha; McCall, Carol J.; Lelieveld, Peter; Fichtner, Iduna; Stevens, Malcolm F. G. [Journal of Medicinal Chemistry, 1996, vol. 39, # 17, p. 3375 - 3384]
[7]Afzal, Obaid; Akhtar, Md Sayeed; Kumar, Suresh; Ali, Md Rahmat; Jaggi, Manu; Bawa, Sandhya [European Journal of Medicinal Chemistry, 2016, vol. 121, p. 318 - 330]
[8]Flipo, Marion; Willand, Nicolas; Lecat-Guillet, Nathalie; Hounsou, Candide; Desroses, Matthieu; Leroux, Florence; Lens, Zoé; Villeret, Vincent; Wohlkönig, Alexandre; Wintjens, René; Christophe, Thierry; Kyoung Jeon, Hee; Locht, Camille; Brodin, Priscille; Baulard, Alain R; Déprez, Benoit [Journal of Medicinal Chemistry, 2012, vol. 55, # 14, p. 6391 - 6402]
[9]Bolakatti, Girish; Palkar, Mahesh; Katagi, Manjunatha; Hampannavar, Girish; Karpoormath, Rajshekhar V.; Ninganagouda, Shilpa; Badiger, Arvind [Journal of Molecular Structure, 2021, vol. 1227]
[10]Bellina, Fabio; Calandri, Chiara; Cauteruccio, Silvia; Rossi, Renzo [Tetrahedron, 2007, vol. 63, # 9, p. 1970 - 1980]
[11]Shekfeh, Suhaib; Çalışkan, Burcu; Fischer, Katrin; Yalçın, Tansu; Garscha, Ulrike; Werz, Oliver; Banoglu, Erden [ChemMedChem, 2019, vol. 14, # 2, p. 273 - 281]
[12]Agamennone, Mariangela; Caradonna, Alessia; Di Pizio, Antonella; Laghezza, Antonio; Loiodice, Fulvio; Luisi, Grazia; Piemontese, Luca; Tortorella, Paolo [Bioorganic and medicinal chemistry, 2019]
[13]Rivier; Zeltner [Helvetica Chimica Acta, 1937, vol. 20, p. 691,699]
[14]Kiprianow et al. [Ukrainskij Khimicheskij Zhurnal, 1954, vol. 20, p. 204,209][Chem.Abstr., 1955, p. 12834]
[15]Kanaoka; Machida; Ban; Takamitsu [Chemical and pharmaceutical bulletin, 1967, vol. 15, # 11, p. 1738 - 1743]
[16]Location in patent: experimental part Kamal, Ahmed; Reddy, K. Srinivasa; Khan, M. Naseer A.; Shetti, Rajesh V.C.R.N.C.; Ramaiah, M. Janaki; Pushpavalli; Srinivas, Chatla; Pal-Bhadra, Manika; Chourasia, Mukesh; Sastry, G. Narahari; Juvekar, Aarti; Zingde, Surekha; Barkume, Madan [Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 13, p. 4747 - 4761]
[17]Location in patent: scheme or table Lin, Guo-Wu; Wang, Yue; Jin, Qiao-Mei; Yang, Tao-Tao; Song, Jie-Mei; Lu, Yi; Huang, Qing-Jie; Song, Ke; Zhou, Jun; Lu, Tao [Inorganica Chimica Acta, 2012, vol. 382, # 1, p. 35 - 42]
[18]Current Patent Assignee: KAOHSIUNG MEDICAL UNIVERSITY - US2012/215154, 2012, A1
[19]Pan, Jinhe; Mason, Neale S.; Debnath, Manik L.; Mathis, Chester A.; Klunk, William E.; Lin, Kuo-Shyan [Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 6, p. 1720 - 1726]
[20]Kamal, Ahmed; Faazil, Shaikh; Ramaiah, M. Janaki; Ashraf, Md.; Balakrishna; Pushpavalli; Patel, Nibedita; Pal-Bhadra, Manika [Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 20, p. 5733 - 5739]
[21]Xu, Ying; Wang, Ning-Yu; Song, Xue-Jiao; Lei, Qian; Ye, Ting-Hong; You, Xin-Yu; Zuo, Wei-Qiong; Xia, Yong; Zhang, Li-Dan; Yu, Luo-Ting [Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 15, p. 4333 - 4343]
[22]Senadi, Gopal Chandru; Liao, Chieh-Ming; Kuo, Kung-Kai; Lin, Jian-Cheng; Chang, Long-Sen; Wang, Jeh Jeng; Hu, Wan-Ping [MedChemComm, 2016, vol. 7, # 6, p. 1151 - 1158]

2
[ 6278-73-5 ]
[ 52214-61-6 ]

Yield	Reaction Conditions	Operation in experiment
78%	Stage #1: 2-(4-aminophenyl)benzothiazole With hydrogenchloride; sodium nitrite In water at 0℃; for 0.5h; Stage #2: With sodium azide In water at 20℃;	2.2.2. General procedure for the synthesis of azido benzoxazoles 6-7 General procedure: In a 50 mL round bottom flask under an ice bath containing 2.0 mmol of the benzazole precursors 4-5 (2.0 mmol) and a HCl:H2O (3:1) solution (15 mL) it was added dropwise a NaNO2 (0.166 g, 2.4 mmol) solution (1 mL). The reaction mixture was stirred under ice bath for 30 min. After this time, NaN3 was added (0.260 g, 4.0 mmol). The reaction mixture was stirred at room temperature for 2 h. After this time, the solution was neutralized with NH4OH, extracted with ethyl acetate (3 × 20 mL) and concentrated under reduced pressure to yield the respective product.
	(i) (diazotation), (ii) NaN₃; Multistep reaction;
	With hydrogenchloride; sodium azide; sodium nitrite 1.) 0-5 deg C, 20 min, 2.) 0-5 deg C, 2 h; Yield given. Multistep reaction;

With hydrogenchloride; sodium azide; sodium nitrite In water at 0 - 5℃;

Reference： [1]Gil, Eduarda S.; da Silva, Cláudia B.; Nogara, Pablo A.; da Silveira, Carolina H.; da Rocha, João B.T.; Iglesias, Bernardo A.; Lüdtke, Diogo S.; Gonçalves, Paulo F.B.; Rodembusch, Fabiano S. [Journal of Molecular Liquids, 2020, vol. 297]
[2]Skripnik,L.I. et al. [Chemistry of Heterocyclic Compounds, 1971, vol. 7, p. 183 - 186][Khimiya Geterotsiklicheskikh Soedinenii, 1971, vol. 7, p. 201 - 204]
[3]Stevens, Malcolm F. G.; Shi, Dong-Fang; Castro, Angeles [Journal of the Chemical Society. Perkin transactions I, 1996, # 1, p. 83 - 94]
[4]Senadi, Gopal Chandru; Liao, Chieh-Ming; Kuo, Kung-Kai; Lin, Jian-Cheng; Chang, Long-Sen; Wang, Jeh Jeng; Hu, Wan-Ping [MedChemComm, 2016, vol. 7, # 6, p. 1151 - 1158]

3
[ 150-13-0 ]
[ 137-07-5 ]
[ 6278-73-5 ]

Yield	Reaction Conditions	Operation in experiment
90%	Stage #1: 4-amino-benzoic acid; 2-amino-benzenethiol at 220℃; for 4h; Inert atmosphere; Stage #2: With potassium carbonate In water at 20℃;
90%	With polyphosphoric acid at 200℃; for 5h;
87%	With melamine formaldehyde resin supported sulfuric acid Microwave irradiation;	Compounds IIIa-IIIg (general procedure). General procedure: To a solution of o-aminothiophenol (Ia-Id, 5 mmol) and (un)substituted p-aminobenzoic acid (IIa-IIe, 10 mmol) in diethyl ether (10 mL) was added MFR-supported sulfuric acid (IIIg). The slurry was mixed thoroughly and the solvent was removed by rotary evaporation. The resulting solid was irradiated in a MW oven at 900 W for 6-8 min. On completion of the process, the reaction mixture was cooled down to room temperature and ethanol (20 mL) was added. The suspended resin was isolated by filtration and washed with diethyl ether. The filtrate was concentrated under reduced pressure and subjected to chromatography on silica gel to afford the products IIIa-IIIj.

86%	With polyphosphoric acid at 195℃;
84%	With PPA at 220℃; for 4h;
82%	With polyphosphoric acid for 0.5h; Microwave irradiation;
78%	With polyphosphoric acid for 10h; Reflux;
66%	Stage #1: 4-amino-benzoic acid With polyphosphoric acid at 220℃; Stage #2: 2-amino-benzenethiol at 220℃; for 8h;
64%	With PPA at 180℃; for 4h;
64%	Stage #1: 4-amino-benzoic acid; 2-amino-benzenethiol With PPA at 180℃; for 4h; Stage #2: With sodium carbonate
64%	With polyphosphoric acid at 220℃; for 4h;	1 4.1.4.1 4-(Benzo[d]thiazol-2-yl)aniline (6a) General procedure: A mixture of 2-aminothiophenol (1equiv) and different substituted amino-carboxylic acids (4-aminobenzoic acid, 4-aminophenylacetic acid, 4-(aminomethyl)benzoic acid, 4-aminobutyric acid and 4-aminohexanoic acid) (1equiv) in polyphosphoric acid (15g) was stirred at 220°C for 4h. The resulting brown oil was dissolved in 5M NaOH (50mL) to obtain basic yellow solution and this solution was extracted with DCM (2×30mL). The total organic phase was then extracted with 0.1N HCl (2×30mL) and afterwards washed DCM (50mL). The aqueous phase was basified to pH ∼10-12 with 5M NaOH, and it was extracted with DCM (2×30mL). The total organic phase was dried over anhydrous Na2SO4, and the solvent evaporated. The brown oil obtained was treated with HCl-saturated methanol until pH ∼1, the solution was evaporated, and the residue was recrystallized from acetonitrile.
64%	With polyphosphoric acid at 220℃; for 4h;
63%	With polyphosphoric acid at 170℃; for 5h;	2.2.1. General procedure for the synthesis of amino benzoxazoles 4-5 General procedure: An equimolarmixture of o-aminophenol (1) (2.4 g, 22.0mmol) or oaminothiophenol (2) (2.7mL, 22.0mmol) and p-aminobenzoic acid (3) (3.0 g, 22.0mmol) in polyphosphoric acid (20 mL)was stirred at 170 °C for 5 h. After cooling, the mixture was poured onto ice under vigorous stirring. The solution was neutralized with NaHCO3. The precipitate was filtered, washed with water and dried at 60 °C. The solid was purified by column chromatography using dichloromethane as eluent [40].
60%	With PPA at 220℃; for 4h;
58%	With PPA at 230℃; for 4h;
57%	With PPA at 220℃; for 4h;
57%		I.a 2-(4-aminophenyl)benzothiazole (Compound CJM 126) (a) In one particular example, 2-(4-aminophenyl)benzothiazole (Compound CJM 126) was prepared in 57% yield from 2-aminothiophenol and 4-aminobenzoic acid using synthetic Route A, the final product being crystallized from methanol as pale yellow needle crystals having a melting point 155°-157° C. (aqueous solubility about 3.8 μg/ml).
57%	With (1S,2R)-(+)-norphedrine; sodium hydrogencarbonate	1 2-(4'-Aminophenyl)benzothiazole (CJM126) Example 1 2-(4'-Aminophenyl)benzothiazole (CJM126) A stirrable paste prepared by mixing 2-aminothiophenol (9.39 g, 0.075 mol) and 4-aminobenzoic acid (10.29 g, 0.075 mol) with PPA (120 g) was heated to 230° C. for 4 hours, cooled and poured into a large volume of 10% sodium bicarbonate solution (about 1000 ml). The solid was collected by filtration, washed with water and dried. Recrystallisation from methanol gave pale yellow needed crystals (9.65 g, 57%), m.p. 155-157° C.
50%	Stage #1: 4-amino-benzoic acid With polyphosphoric acid at 150℃; Inert atmosphere; Stage #2: 2-amino-benzenethiol at 220℃; for 9h; Inert atmosphere;	2.2.1.1 2-(4-aminophenyl)benzothiazole, 1 2-(4-Aminophenyl)benzothiazole 1 and N-(4′-benzothiazol-2-yl-phenyl)-2-chloroacetamide 2, were synthesized as reported previously with some modifications [18]. For 1, 40 ml of polyphosphoric acid were placed in a 250 mL round bottom flask and heated to 150 °C. In the meantime, p-aminobenzoic acid (9.59 g, 70.0 mmol) was transferred into the flask in aliquots and the contents were stirred to dissolve the aminobenzoic acid. A thick pasty brown mass was obtained after the complete addition of the acid. To this mixture was added o-aminothiophenol (8.75 g, 70.0 mmol) whereupon a vigorous reaction took place and the mixture turned into a black viscous mass. The contents were heated to 220 °C for 9 h, cooled to 100 °C and then carefully poured into a beaker containing ice/water mixture. The oily product thus obtained slowly solidified upon standing (2 h) and the mixture was allowed to stir to obtain a light yellow product. This was filtered and washed with water (2 × 100 mL). The precipitate was then suspended in a solution of sodium bicarbonate (50 g/500 ml of water) and stirred vigorously for 2 h. A light greenish product remained in suspension which was filtered, washed with water (2 × 100 mL) and dried under vacuum for 48 h. The product was further purified by re-crystallization using methanol to yield dark yellow needles of 2-aminophenylbenzothiazole 1. Yield: 8.00 g, 35.2 mmol, 50%. Selected IR bands ν (cm-1) (KBr pellet): 3429s, 3178s, 1636s, 1604m, 1475s, 1433m, 1312m, 1250m, 1228m, 1182m, 1159m, 963m, 827s, 760s. 1H NMR (400 MHz) (d6-DMSO), δ ppm: 8.02-7.98 (m, 2H), 7.77-7.73 (d, 2H, J = 8.0 Hz), 7.45-7.44 (t, 1H), 7.36-7.31 (t, 1H), 6.69-6.65 (d, 2H, J = 8.0 Hz), 5.89 (s, 2H); ESI MS (+ mode): calculated: 226, found: 227 [M+H]+.
49%	With PPA at 220℃; for 16h;
40%	With PPA at 180℃; for 4h;
	With PPA at 200℃;
	With PPA at 210℃; for 4h; Yield given;
	With PPA at 220℃;
	With PPA at 140℃; for 24h;
	With iodine for 0.166667h;
	With PPA
	With PPA at 185℃;
	With PPA at 185℃; for 5h;
	With PPA at 220℃; for 10h;
	With polyphosphoric acid at 220℃;
	With PPA at 180℃;
	With polyphosphoric acid at 220℃; for 3h;
	With polyphosphoric acid at 145℃;
	With polyphosphoric acid at 125℃; for 0.583333h; Microwave irradiation;
	With polyphosphoric acid for 4h; Heating;
	With PPA
	With polyphosphoric acid at 220℃; Reflux;
	With polyphosphoric acid for 4h;	General Procedure for the Synthesis of 2-(4-aminobenzyl/phenyl)benzothiazole (3) General procedure: General Procedure for the Synthesis of 2-(4-aminobenzyl/phenyl)benzothiazole (3)2-(4-aminobenzyl/phenyl)benzothiazole (3) were preparedby heating 1 mmol o-aminothiophenol (1) with 1mmol p-aminobenzoic acid / p-aminophenylacetic acid(2) in 2.4 g polyphosphoric acid and stirring for 4 h(Scheme 1). After then the residue was poured into icewatermixture and neutralized with excess of 10 % NaOHsolution. The precipitate was boiled with activated charcoalin ethanol and then, filtered and recrystallized inethanol (m.p.(3a) = 155-157 C, m.p.(3b) = 93-94 C).23,25
	With polyphosphoric acid at 220℃;
	With polyphosphoric acid at 200℃;
	With polyphosphoric acid at 220℃;
10.8 g	With polyphosphoric acid at 195℃; for 5h; Inert atmosphere;	1-31.1 1) Intermediate Material 30-1 (2-(4-aminophenyl)benzothiazole) Synthesis In 200mL four-neck flask containing 2-aminothiophenol 6.26g (0.05mol) of 4-amino benzoic acid and 6.86g (0.05mol) of the raw material composition and 125g polyphosphoric acid as a solvent, while a nitrogen stream (5mL / min) while stirring with a magnetic stirring heating the inner temperature reached 195 °C for about 5 hours reaction. After termination of the reaction, the reaction solution was poured into 3M aqueous sodium hydroxide solution is carried out about 1L crystallization. The desired product precipitated were filtered, the filter cake was washed with water 500ml with distilled water to about. The obtained wet cake was dried at 40 °C 12 hours to obtain an intermediate raw material 30-1 (2-(4-aminophenyl)benzothiazole) 10.8 g of (relative to the 2-aminothiophenol yield: 95.3mol%).
	With polyphosphoric acid at 160℃;
	With polyphosphoric acid Heating;
	With polyphosphoric acid
	With polyphosphoric acid at 200℃; for 3h;
	With polyphosphoric acid at 220℃; for 0.5h;
	With polyphosphoric acid at 180 - 220℃;
	With polyphosphoric acid at 170℃; for 3h; Inert atmosphere;	4.1.1. General procedure for synthesis of compounds 1, 6-18, 20-22,24-27, 30-40 General procedure: Polyphosphoric acid (10 g) was added to the mixture of 2-aminophenols(or 2-aminothiols or 2-phenylenediamines) 2 (7-9 mmol,1.0 eq) and carboxylic acids 3 (1.0 eq) at room temperature and heatedto 170 °C (dissolution of reactants in polyphosphoric acid and effectivestirring was observed at elevated temperatures). The reaction mixturewas stirred at 170 °C for 3 h and was then allowed to cool to roomtemperature. The viscous reaction mixture was slowly diluted by icewater(200 mL), neutralized (to pH 7) by saturated solution of NaHCO3and extracted with multiple portions of ethyl acetate (3×50 mL). Thecombined organic extracts were washed with brine (50 mL), dried oversodium sulfate (30 g), filtered and concentrated to yield compounds 4in 24-91% yields as colored solids.

Reference： [1]Zhang, Yong; Chen, Li-Yuan; Yin, Wen-Xing; Yin, Jun; Zhang, Shi-Bing; Liu, Chang-Lin [Dalton Transactions, 2011, vol. 40, # 18, p. 4830 - 4833]
[2]Location in patent: experimental part Lin, Guo-Wu; Wang, Yue; Jin, Qiao-Mei; Yang, Tao-Tao; Song, Jie-Mei; Lu, Yi; Huang, Qing-Jie; Song, Ke; Zhou, Jun; Lu, Tao [Inorganica Chimica Acta, 2012, vol. 382, # 1, p. 35 - 42]
[3]Lei, Yingjie; Wu, Xinshi; Zhang, Guochun; Ai, Cuiling [Russian Journal of General Chemistry, 2015, vol. 85, # 3, p. 679 - 682]
[4]Padie, Clement; Zeitler, Kirsten [New Journal of Chemistry, 2011, vol. 35, # 5, p. 994 - 997]
[5]Phoon, Chee Wee; Ng, Poh Yong; Ting, Anthony E.; Yeo, Su Ling; Sim, Mui Mui [Bioorganic and Medicinal Chemistry Letters, 2001, vol. 11, # 13, p. 1647 - 1650]
[6]Yurttaş, Leyla; Tay, Funda; Demirayak, Şeref [Journal of Enzyme Inhibition and Medicinal Chemistry, 2015, vol. 30, # 3, p. 458 - 465]
[7]Ali, Rashid; Gupta, Ramesh C.; Dwivedi, Sushil K.; Misra, Arvind [New Journal of Chemistry, 2018, vol. 42, # 14, p. 11746 - 11754]
[8]Venkatachalam; Stimson; Bhalla; Pierens; Reutens [Journal of labelled compounds and radiopharmaceuticals, 2014, vol. 57, # 9, p. 566 - 573]
[9]Serdons; Verduyckt; Cleynhens; Terwinghe; Mortelmans; Bormans; Verbruggen [Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 22, p. 6086 - 6090]
[10]Location in patent: experimental part Serdons, Kim; Verduyckt; Cleynhens; Bormans; Verbruggen [Journal of labelled compounds and radiopharmaceuticals, 2008, vol. 51, # 10, p. 357 - 367]
[11]Keri, Rangappa S.; Quintanova, Catarina; Marques, Sérgio M.; Esteves, A. Raquel; Cardoso, Sandra M.; Santos, M. Amélia [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 15, p. 4559 - 4569]
[12]Mourtas, Spyridon; Mavroidi, Barbara; Marazioti, Antonia; Kannavou, Maria; Sagnou, Marina; Pelecanou, Maria; Antimisiaris, Sophia G. [Biomacromolecules, 2020, vol. 21, # 12, p. 4685 - 4698]
[13]Gil, Eduarda S.; da Silva, Cláudia B.; Nogara, Pablo A.; da Silveira, Carolina H.; da Rocha, João B.T.; Iglesias, Bernardo A.; Lüdtke, Diogo S.; Gonçalves, Paulo F.B.; Rodembusch, Fabiano S. [Journal of Molecular Liquids, 2020, vol. 297]
[14]Tzanopoulou, Stamatia; Pirmettis, Ioannis C.; Patsis, George; Paravatou-Petsotas, Maria; Livaniou, Evangelia; Papadopoulos, Minas; Pelecanou, Maria [Journal of Medicinal Chemistry, 2006, vol. 49, # 18, p. 5408 - 5410]
[15]Varma, Rajendra S.; Chauhan, Sudha; Prasad, C. R. [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1988, vol. 27, # 1-12, p. 438 - 442]
[16]Shi, Dong-Fang; Bradshaw, Tracey D.; Wrigley, Samantha; McCall, Carol J.; Lelieveld, Peter; Fichtner, Iduna; Stevens, Malcolm F. G. [Journal of Medicinal Chemistry, 1996, vol. 39, # 17, p. 3375 - 3384]
[17]Current Patent Assignee: CANCER RESEARCH UK - US5874431, 1999, A
[18]Current Patent Assignee: CANCER RESEARCH UK - US6034246, 2000, A
[19]Barreto, José; Venkatachalam, Taracad K.; Joshi, Tanmaya; Kreher, Ute; Forsyth, Craig M.; Reutens, David; Spiccia, Leone [Polyhedron, 2013, vol. 52, p. 128 - 138]
[20]Wang, Y.; Klunk, W. E.; Huang, G.-F.; Debnath, M. L.; Holt, D. P.; Mathis, C. A. [Journal of labelled compounds and radiopharmaceuticals, 2001, vol. 44, p. S239 - S241]
[21]Location in patent: scheme or table Chu, Taiwei; Li, Zejun; Wang, Xiangyun [Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 3, p. 658 - 661]
[22]Dey, Krishna Joy; Dogra, Sneh K. [Bulletin of the Chemical Society of Japan, 1991, vol. 64, # 10, p. 3142 - 3152]
[23]Stevens, Malcolm F. G.; Shi, Dong-Fang; Castro, Angeles [Journal of the Chemical Society. Perkin transactions I, 1996, # 1, p. 83 - 94]
[24]Chua, Mei-Sze; Shi, Dong-Fang; Wrigley, Samantha; Bradshaw, Tracey D.; Hutchinson, Ian; Shaw, P. Nicholas; Barrett, David A.; Stanley, Lesley A.; Stevens, Malcolm F. G. [Journal of Medicinal Chemistry, 1999, vol. 42, # 3, p. 381 - 392]
[25]Billeau; Chatel; Robin; Faure; Galy [Magnetic Resonance in Chemistry, 2006, vol. 44, # 1, p. 102 - 105]
[26]Gupta, Sayan Dutta; Singh, Hemendra Pratap; Moorthy [Synthetic Communications, 2007, vol. 37, # 24, p. 4327 - 4329]
[27]Location in patent: scheme or table Shaban, Mohamed A.; Al Badry, Ossama M.; Kamal, Aliaa M.; El-Gawad, Mohamd Abd El Wahap Abd [Journal of Chemical Research, 2008, # 12, p. 715 - 718]
[28]Location in patent: body text Tasler, Stefan; Mueller, Oliver; Wieber, Tanja; Herz, Thomas; Krauss, Rolf; Totzke, Frank; Kubbutat, Michael H.G.; Schaechtele, Christoph [Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 5, p. 1349 - 1356]
[29]Tasler, Stefan; Mueller, Oliver; Wieber, Tanja; Herz, Thomas; Pegoraro, Stefano; Saeb, Wael; Lang, Martin; Krauss, Rolf; Totzke, Frank; Zirrgiebel, Ute; Ehlert, Jan E.; Kubbutat, Michael H.G.; Schaechtele, Christoph [Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 18, p. 6728 - 6737]
[30]Location in patent: scheme or table Venkatachalam, Taracad K.; Pierens, Gregory K.; Reutens, David C. [Magnetic Resonance in Chemistry, 2010, vol. 48, # 3, p. 210 - 218]
[31]Location in patent: scheme or table Tzanopoulou, Stamatia; Sagnou, Marina; Paravatou-Petsotas, Maria; Gourni, Eleni; Loudos, George; Xanthopoulos, Stavros; Lafkas, Daniel; Kiaris, Hippokratis; Varvarigou, Alexandra; Pirmettis, Ioannis C.; Papadopoulos, Minas; Pelecanou, Maria [Journal of Medicinal Chemistry, 2010, vol. 53, # 12, p. 4633 - 4641]
[32]Location in patent: scheme or table Nagarajan, Arasampattu S.; Kathirvelan; Pramesh; Reddy, Boreddy S R. [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2010, vol. 49, # 12, p. 1662 - 1666]
[33]Location in patent: scheme or table Kamal, Ahmed; Kumar, B. Ashwini; Suresh, Paidakula; Shankaraiah, Nagula; Kumar, M. Shiva [Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 1, p. 350 - 353]
[34]Location in patent: body text Chernienko; Nikiforova; Rudaya; Ramsh; Shamanin [Russian Journal of Organic Chemistry, 2011, vol. 47, # 10, p. 1604 - 1605]
[35]Location in patent: scheme or table Tay, Funda; Yurttas, Leyla; Demirayak, Seref [Journal of Enzyme Inhibition and Medicinal Chemistry, 2012, vol. 27, # 4, p. 515 - 520]
[36]Bolelli, Kayhan; Yalcin, Ismail; Ertan-Bolelli, Tugba; Özgen, Selda; Kaynak-Onurdag, Fatma; Yildiz, Ilkay; Aki, Esin [Medicinal Chemistry Research, 2012, vol. 21, # 11, p. 3818 - 3825]
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[38]Singh, Sushil K.; Singh, Meenakshi; Singh, Sudhir K.; Gangwar, Mayank; Nath, Gopal [RSC Advances, 2014, vol. 4, # 36, p. 19013 - 19023]
[39]Yilmaz, Serap; Yalcin, Ismail; Kaynak-Onurdag, Fatma; Ozgen, Selda; Yildiz, Ilkay; Aki, Esin [Croatica Chemica Acta, 2013, vol. 86, # 2, p. 223 - 231]
[40]Pierens; Venkatachalam; Reutens [Magnetic Resonance in Chemistry, 2014, vol. 52, # 8, p. 453 - 459]
[41]Kumar, G. Jagadeesh; Kumar, S. Naveen; Thummuri, Dinesh; Adari, Lavanya Bindu Sree; Naidu; Srinivas, Kolupula; Rao, V. Jayathirtha [Medicinal Chemistry Research, 2015, vol. 24, # 12, p. 3991 - 4001]
[42]Singh, Meenakshi; Singh, Sudhir Kumar; Gangwar, Mayank; Nath, Gopal; Singh, Sushil K. [Medicinal Chemistry Research, 2016, vol. 25, # 2, p. 263 - 282] Singh, Meenakshi; Kumar Singh, Sudhir; Gangwar, Mayank; Sellamuthu, Satheeshkumar; Nath, Gopal; Singh, Sushil K. [Letters in drug design and discovery, 2016, vol. 13, # 5, p. 429 - 437]
[43]Current Patent Assignee: NIPPON SHOKUBAI CO LTD - CN105503699, 2016, A Location in patent: Paragraph 0497; 0498
[44]Lu, Fengxian; Hu, Rui; Wang, Shuangqing; Guo, Xudong; Yang, Guoqiang [RSC Advances, 2017, vol. 7, # 7, p. 4196 - 4202]
[45]El-Arab, Elham Ezz; El-Said; Amine; Moharram [Egyptian Journal of Chemistry, 2016, vol. 59, # 6, p. 967 - 984]
[46]El-Arab, Elham Ezz; El-Said; Amine; Moharram [Egyptian Journal of Chemistry, 2016, vol. 59, # 6, p. 967 - 984]
[47]Belal, Amany; Abdelgawad, Mohamed A. [Research on Chemical Intermediates, 2017, vol. 43, # 7, p. 3859 - 3872]
[48]Narva, Suresh; Chitti, Surendar; Amaroju, Suresh; Goud, Sridhar; Alvala, Mallika; Bhattacharjee, Debanjan; Jain, Nishant; Kondapalli Venkata Gowri, Chandra Sekhar [Journal of Heterocyclic Chemistry, 2019, vol. 56, # 2, p. 520 - 532]
[49]Philoppes, John N.; Lamie, Phoebe F. [Bioorganic Chemistry, 2019, vol. 89]
[50]Ankenbruck, Nicholas; Kumbhare, Rohan; Naro, Yuta; Thomas, Meryl; Gardner, Laura; Emanuelson, Cole; Deiters, Alexander [Bioorganic and Medicinal Chemistry, 2019, vol. 27, # 16, p. 3735 - 3743]

4
[ 6278-73-5 ]
2-(4'Amino-3', 5'-dibromophenyl) benzothiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	With bromine; acetic acid at 25 - 80℃; for 2h;

Reference： [1]Shi, Dong-Fang; Bradshaw, Tracey D.; Wrigley, Samantha; McCall, Carol J.; Lelieveld, Peter; Fichtner, Iduna; Stevens, Malcolm F. G. [Journal of Medicinal Chemistry, 1996, vol. 39, # 17, p. 3375 - 3384]

5
[ 6278-73-5 ]
[ 178804-06-3 ]

Yield	Reaction Conditions	Operation in experiment
91%	With sodium perborate; acetic acid; potassium bromide at 20℃; for 22h;
79%	With bromine In dichloromethane at -5℃; for 0.0333333h;
79.1%	With bromine In dichloromethane	6 2-(4'-amino-3'-bromophenyl)benzothiazole (DF209) 2-(4'-amino-3'-bromophenyl)benzothiazole (DF209) To a solution of 2-(4'-aminophenyl) benzothiazole (0.45 g, 1.99 mmol) in CH2 Cl2 (50 ml) was added a solution of bromine (0.32 g, 1.99 mmol) in CH2 Cl2 (10 ml) at -5° C. After the reaction mixture had been stirred still at -5° C. for 2 minutes, it was poured into ice-water (400 ml). The resulting mixture was stirred for 40 minutes at room temperature. The organic layer was separated, washed with 10% aqueous sodium thiosulfate (50 ml2) and water (60 ml2), dried (MgSO4) and concentrated. The residue was chromatographed on a silica gel column, eluding with ethyl acetate-hexane (1:3), to give pale yellow crystals (0.48 g, 79.1%), m.p. 160.0-161.4° C.

75%	With bromine In dichloromethane at -5℃; for 0.0333333h;
	With bromine In dichloromethane at -5℃;

Reference： [1]Karlsson, H. Jonas; Bergqvist, Mattias H.; Lincoln, Per; Westman, Gunnar [Bioorganic and Medicinal Chemistry, 2004, vol. 12, # 9, p. 2369 - 2384]
[2]Shi, Dong-Fang; Bradshaw, Tracey D.; Wrigley, Samantha; McCall, Carol J.; Lelieveld, Peter; Fichtner, Iduna; Stevens, Malcolm F. G. [Journal of Medicinal Chemistry, 1996, vol. 39, # 17, p. 3375 - 3384]
[3]Current Patent Assignee: CANCER RESEARCH UK - US6034246, 2000, A
[4]Location in patent: scheme or table Kamal, Ahmed; Kumar, B. Ashwini; Suresh, Paidakula; Shankaraiah, Nagula; Kumar, M. Shiva [Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 1, p. 350 - 353]
[5]Chua, Mei-Sze; Shi, Dong-Fang; Wrigley, Samantha; Bradshaw, Tracey D.; Hutchinson, Ian; Shaw, P. Nicholas; Barrett, David A.; Stanley, Lesley A.; Stevens, Malcolm F. G. [Journal of Medicinal Chemistry, 1999, vol. 42, # 3, p. 381 - 392]

6
[ 6278-73-5 ]
[ 162374-60-9 ]

Yield	Reaction Conditions	Operation in experiment
70%	With Iodine monochloride; acetic acid at 25℃; for 1.5h;
64%	With Iodine monochloride; acetic acid In dichloromethane
	With Iodine monochloride; acetic acid at 25℃;

Reference： [1]Shi, Dong-Fang; Bradshaw, Tracey D.; Wrigley, Samantha; McCall, Carol J.; Lelieveld, Peter; Fichtner, Iduna; Stevens, Malcolm F. G. [Journal of Medicinal Chemistry, 1996, vol. 39, # 17, p. 3375 - 3384]
[2]Wang, Y.; Klunk, W. E.; Huang, G.-F.; Debnath, M. L.; Holt, D. P.; Mathis, C. A. [Journal of labelled compounds and radiopharmaceuticals, 2001, vol. 44, p. S239 - S241]
[3]Chua, Mei-Sze; Shi, Dong-Fang; Wrigley, Samantha; Bradshaw, Tracey D.; Hutchinson, Ian; Shaw, P. Nicholas; Barrett, David A.; Stanley, Lesley A.; Stevens, Malcolm F. G. [Journal of Medicinal Chemistry, 1999, vol. 42, # 3, p. 381 - 392]

7
[ 6278-73-5 ]
[ 98-88-4 ]
N-(4-(benzo[d]thiazol-2-yl)phenyl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	With pyridine for 2h; Heating;
82.2%	In pyridine; dichloromethane	23 2-(4'-Benzamidophenyl)benzothiazole (DF131) Example 23 2-(4'-Benzamidophenyl)benzothiazole (DF131) This is an example of a benzoyl derivative. A mixture of 2-(4'-aminophenyl)benzothiazole (0.3 g, 1.32 mmol) and benzoyl chloride (0.3 ml) in pyridine (8 ml) was stirred at reflux for 2 hours, then cooled and poured into water (100 ml). The precipitate formed was filtered off, washed with water and dissolved in hot dichloromethane (12 ml). The resulting solution was cooled in an ice-bath and the solid was filtered off. The filtrate was evaporated and the residue was recrystallized from dichloromethane-methanol to give a white powder (0.36 g, 82.2%), m.p. 227.1-228.5° C.
67%	With triethylamine In tetrahydrofuran at 0 - 20℃; Inert atmosphere;	General procedure: Triethylamine (2 mmol) was added to the solution of aniline derivatives(1 mmol) in anhydrous THF and the appropriate acyl chloride(1.1-2 mmol) was added at 0 °C. The resulting mixture was stirred at room temperature under nitrogen atmosphere for 3-12 h, the eluent was evaporated in vacuo, the residue was partitioned between EtOAc and 2 M NaOH solution. The combined organic layers were washed with NH4Cl ss, brine, dried over anhydrous Na2SO4, filtered, and evaporated under reduced pressure. The residue was purified by chromatography on silica gel (eluent: Hexane/ EtOAc 8:2 → 6:4 v/v).

Reference： [1]Chua, Mei-Sze; Shi, Dong-Fang; Wrigley, Samantha; Bradshaw, Tracey D.; Hutchinson, Ian; Shaw, P. Nicholas; Barrett, David A.; Stanley, Lesley A.; Stevens, Malcolm F. G. [Journal of Medicinal Chemistry, 1999, vol. 42, # 3, p. 381 - 392]
[2]Current Patent Assignee: CANCER RESEARCH UK - US6034246, 2000, A
[3]Agamennone, Mariangela; Caradonna, Alessia; Di Pizio, Antonella; Laghezza, Antonio; Loiodice, Fulvio; Luisi, Grazia; Piemontese, Luca; Tortorella, Paolo [Bioorganic and medicinal chemistry, 2019]

8
[ 6278-73-5 ]
[ 79-04-9 ]
[ 182274-80-2 ]

Yield	Reaction Conditions	Operation in experiment
92%	With potassium carbonate In dichloromethane at 10℃; for 2h;	3 N-(4-(benzo[d]thiazol-2-yl)phenyl)-2-chloroacetamide (3) To a solution of 2-(4-aminophenyl)benzo[d]thiazole (2) (0.016 mol) in DCM (30 ml), powdered anhydrous K2CO3 (1 g) was added. Chloroacetyl chloride (0.03 mol) was added drop wise with constant stirring at 10 °C. The reaction mixture was stirred further for 2 h. After evaporation of DCM, water was added to the residue and stirred for 20 min. The precipitate thus obtained was filtered, washed with water and dried. The crude product was crystallized from ethanol. The progress of reaction and purity of compound was checked by TLC using TEF (5:4:1) as mobile phase. White solid; Yield: 92%; M.P.: 143-145°C; IR (KBr, cm-1): 3327 (N-H), 3094 (Ar C-H), 1670 (C=O), 1595 (C=N), 1523 (C=C), 761 (C-Cl); 1H NMR (DMSO-d6, 300MHz) δ (ppm): 10.60 (s, 1H, NH, D2O exchangeable), 8.11-8.00 (m, 4H, H-4, H-7, H-2′ & H-6′), 7.81-7.78 (d, 2H, H-3′ & H-5′, J=9Hz), 7.54-7.49 (t, 1H, H-5, J=7.5Hz), 7.45-7.40 (t, 1H, H-6, J=7.5Hz), 4.30 (s, 2H, CH2); 13C NMR (DMSO-d6, 125MHz) δ (ppm): 167.22 (C-2), 165.52 (C=O), 154.19 (C-9), 141.73 (C-4′), 134.74 (C-8), 128.70 (C-1′), 128.51 (C-2′ & C-6′), 127.00 (C-5), 125.86 (C-6), 123.03 (C-4), 122.84 (C-7), 120.01 (C-3′ & C-5′), 44.11 (CH2); ESI-MS (m/z): 302.18 (M+), 304.18 (M++2); Anal. calcd. For C15H11ClN2OS: C, 59.50; H, 3.66; N, 9.25. Found: C, 59.56; H, 3.57; N, 9.18.
91%	In N,N-dimethyl acetamide at 0 - 20℃;
86%	With triethylamine In acetone for 4h; Reflux;

86%	With triethylamine In tetrahydrofuran; N,N-dimethyl-formamide for 1h;
76%	With triethylamine In dichloromethane at 0 - 20℃; for 1.5h;
64%	With triethylamine In dichloromethane at 20℃; for 48h; Inert atmosphere;	2.2.1.2 N-(4′-benzothiazol-2-yl-phenyl)-2-chloroacetamide, [18] 2 In a 250 mL round bottom flask was placed 2-(4-aminophenyl)benzothiazole (2.36 g, 10.3 mmol) and 60 mL of anhydrous methylene chloride. The contents were stirred; however, the solid did not completely dissolve at this stage. Using a dry syringe, 2 mL of triethylamine was introduced into the flask and the solution became homogenous dissolving the benzothiazole compound. To the clear solution, chloroacetylchloride (1 mL) was slowly added, causing a vigorous exothermic reaction and the evolution of fumes during the course of addition. A white insoluble precipitate formed in the flask on stirring for 48 h, which was collected by filtration, washed with ether and dried in vacuum (1.20 g). The filtrate was treated with 20 mL of 5 M HCl, the organic layer separated, dried over anhydrous sodium sulfate and subsequently filtered. Removal of solvent left a residue which was triturated with 50 mL of diethyl ether. The insoluble material was filtered and dried in vacuum to yield 0.80 g of a brown colored powder. Both solids were re-crystallized in 96% ethanol, resulting in a combined yield of 2.00 g, 64%. The NMR spectrum confirmed both products to be compound 2. Selected IR bands ν (cm-1) (KBr pellet): 3317s, 1675vs, 1599s, 1528s, 1482m, 1435m, 1409m, 1314m, 1285m, 1252m, 1228m, 1192m, 1116m, 963m, 846m, 828m, 754s. 1H NMR (400 MHz) (d6-DMSO), δ ppm: 10.76 (br, 1H), 8.10-7.98 (m, 4H), 7.80-7.78 (d, 2H, J = 8.0 Hz), 7.52-7.50 (t, 1H), 7.43-7.40 (t, 1H), 4.25 (s, 2H). 13C NMR (100 MHz) (d6-DMSO), δ ppm: 167.4, 165.7, 154.7, 141.9, 134.9, 128.7, 127.2, 125.9, 123.2, 122.9, 120.2, 44.2. ESI MS (+mode): calculated: 302.5 [M+], found: 303 [M+H+].
	In benzene for 0.5h; Heating; Yield given;
	With triethylamine In dichloromethane at 0 - 20℃;
	With triethylamine In N,N-dimethyl-formamide
	With potassium carbonate In tetrahydrofuran at 20℃; for 18h;
	With potassium carbonate In acetone at 57℃; for 24h; Inert atmosphere; Schlenk technique;
	In benzene for 0.5h; Reflux;
	With triethylamine In dichloromethane at 0 - 20℃; Inert atmosphere;
	In toluene at 90℃; for 2h; Inert atmosphere;	General procedure: Further, compounds 4 (0.35-0.50 mmol, 1.0 eq) were heated withchloroacetyl chloride (3.0 eq) in anhydrous toluene (10 mL) to 90 °C for2 h. This reaction mixture was concentrated under reduced pressureand the residue was triturated with diethyl ether (10 mL). The productwas filtered and subsequently washed with multiple portions of diethylether (3×5 mL) and dried to recover colored solids. The solids werevigorously stirred in a saturated solution of NaHCO3 (10 mL) for30 min, acidified to neutral pH by aqueous 1M HCl solution and thenextracted with multiple portions of ethyl acetate (5×10 mL) until theaqueous layer turns colorless. The combined organic extracts werewashed with brine (10 mL), dried over sodium sulfate (10 g), were filteredand concentrated to yield pure amides 5 as colored solids in70-90% yield.
1.5 g	In acetone for 2h; Reflux;	5 Example 5: Compound Ie(R₁= H, R₂= H, R₃=) Synthesis Dissolve 4-(benzothiazol-2-yl)aniline (1g, 4.42mmol) in acetone (20mL), slowly add dropwise a solution of chloroacetyl chloride (500mg, 4.42mmol) in acetone (10mL), and react under reflux 2h.Cool down to room temperature and filter to obtain 1.5g of yellow solid chlorine; The chlorinated substance (300mg, 0.99mmol) was dissolved in DMF (4mL), piperidine (94mg, 1.09mmol) and potassium carbonate (276mg, 1.98mmol) were added and reacted at 60°C for 4h.Add water, extract with dichloromethane, wash with saturated brine, separate the layers, dry with anhydrous sodium sulfate, filter, and remove the solvent.The crude product was subjected to silica gel column chromatography (eluent: dichloromethane) to obtain 225 mg of white solid compound Ie.

Reference： [1]Afzal, Obaid; Akhtar, Md Sayeed; Kumar, Suresh; Ali, Md Rahmat; Jaggi, Manu; Bawa, Sandhya [European Journal of Medicinal Chemistry, 2016, vol. 121, p. 318 - 330]
[2]Flipo, Marion; Willand, Nicolas; Lecat-Guillet, Nathalie; Hounsou, Candide; Desroses, Matthieu; Leroux, Florence; Lens, Zoé; Villeret, Vincent; Wohlkönig, Alexandre; Wintjens, René; Christophe, Thierry; Kyoung Jeon, Hee; Locht, Camille; Brodin, Priscille; Baulard, Alain R; Déprez, Benoit [Journal of Medicinal Chemistry, 2012, vol. 55, # 14, p. 6391 - 6402]
[3]Location in patent: experimental part Lin, Guo-Wu; Wang, Yue; Jin, Qiao-Mei; Yang, Tao-Tao; Song, Jie-Mei; Lu, Yi; Huang, Qing-Jie; Song, Ke; Zhou, Jun; Lu, Tao [Inorganica Chimica Acta, 2012, vol. 382, # 1, p. 35 - 42]
[4]Yurttaş, Leyla; Tay, Funda; Demirayak, Şeref [Journal of Enzyme Inhibition and Medicinal Chemistry, 2015, vol. 30, # 3, p. 458 - 465]
[5]Tzanopoulou, Stamatia; Pirmettis, Ioannis C.; Patsis, George; Paravatou-Petsotas, Maria; Livaniou, Evangelia; Papadopoulos, Minas; Pelecanou, Maria [Journal of Medicinal Chemistry, 2006, vol. 49, # 18, p. 5408 - 5410]
[6]Barreto, José; Venkatachalam, Taracad K.; Joshi, Tanmaya; Kreher, Ute; Forsyth, Craig M.; Reutens, David; Spiccia, Leone [Polyhedron, 2013, vol. 52, p. 128 - 138]
[7]Chua, Mei-Sze; Shi, Dong-Fang; Wrigley, Samantha; Bradshaw, Tracey D.; Hutchinson, Ian; Shaw, P. Nicholas; Barrett, David A.; Stanley, Lesley A.; Stevens, Malcolm F. G. [Journal of Medicinal Chemistry, 1999, vol. 42, # 3, p. 381 - 392]
[8]Pelecanou, M.; Pirmettis, I.; Patsis, G.; Tsoukalas, C.; Tzanopoulou, S.; Papadopoulos, M. [Journal of labelled compounds and radiopharmaceuticals, 2003, vol. 46, p. S25 - S25]
[9]Location in patent: scheme or table Tzanopoulou, Stamatia; Sagnou, Marina; Paravatou-Petsotas, Maria; Gourni, Eleni; Loudos, George; Xanthopoulos, Stavros; Lafkas, Daniel; Kiaris, Hippokratis; Varvarigou, Alexandra; Pirmettis, Ioannis C.; Papadopoulos, Minas; Pelecanou, Maria [Journal of Medicinal Chemistry, 2010, vol. 53, # 12, p. 4633 - 4641]
[10]Location in patent: scheme or table Tay, Funda; Yurttas, Leyla; Demirayak, Seref [Journal of Enzyme Inhibition and Medicinal Chemistry, 2012, vol. 27, # 4, p. 515 - 520]
[11]Pan, Jinhe; Mason, Neale S.; Debnath, Manik L.; Mathis, Chester A.; Klunk, William E.; Lin, Kuo-Shyan [Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 6, p. 1720 - 1726]
[12]Kim, Hee-Kyung; Kang, Min-Kyoung; Jung, Ki-Hye; Kang, Sun-Hee; Kim, Yeoun-Hee; Jung, Jae-Chang; Lee, Gang Ho; Chang, Yongmin; Kim, Tae-Jeong [Journal of Medicinal Chemistry, 2013, vol. 56, # 20, p. 8104 - 8111]
[13]Lamie, Phoebe F.; Philoppes, John N. [Medicinal Chemistry Research, 2017, vol. 26, # 6, p. 1228 - 1240]
[14]Narva, Suresh; Chitti, Surendar; Amaroju, Suresh; Goud, Sridhar; Alvala, Mallika; Bhattacharjee, Debanjan; Jain, Nishant; Kondapalli Venkata Gowri, Chandra Sekhar [Journal of Heterocyclic Chemistry, 2019, vol. 56, # 2, p. 520 - 532]
[15]Ankenbruck, Nicholas; Kumbhare, Rohan; Naro, Yuta; Thomas, Meryl; Gardner, Laura; Emanuelson, Cole; Deiters, Alexander [Bioorganic and Medicinal Chemistry, 2019, vol. 27, # 16, p. 3735 - 3743]
[16]Current Patent Assignee: Shanghai Institute of Materia Medica (in: CAS); CHINESE ACADEMY OF SCIENCES; EAST CHINA NORMAL UNIVERSITY - CN113620903, 2021, A Location in patent: Paragraph 0092-0093

9
[ 6278-73-5 ]
[ 15761-38-3 ]
(S)-{1-[4-(benzothiazol-2-yl)-phenylcarbamoyl]-ethyl}-carbamic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With WSC*HCl; benzotriazol-1-ol In dichloromethane at 20℃; for 48h;
75%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 24h;	5.1.8 General procedure for the preparation of the Boc-protected derivatives 15-17 General procedure: To a stirred solution of the amine 9a or 9b (1 equiv) in CH2Cl2 was added 1-ethyl-3-(3-dimethylamino)propylcarbodiimide·HCl (EDAC) (0.6 equiv), 1-hydroxybenzotriazole (HOBt) (0.6 equiv) and the relevant t-Boc protected amino acid (0.6 equiv). The mixture was allowed to stir at room temperature (24 h) and a further 0.6 equiv of each reagent was added. The mixture was then allowed to stir at room temperature (4 days) and the solvent was evaporated giving the crude product.

Reference： [1]Hutchinson, Ian; Jennings, Sharon A.; Vishnuvajjala, B. Rao; Westwell, Andrew D.; Stevens, Malcolm F.G. [Journal of Medicinal Chemistry, 2002, vol. 45, # 3, p. 744 - 747]
[2]Cellier, Marie; Fazackerley, Elizabeth; James, Arthur L.; Orenga, Sylvain; Perry, John D.; Turnbull, Graeme; Stanforth, Stephen P. [Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 4, p. 1250 - 1261]

10
[ 6278-73-5 ]
[ 2483-46-7 ]
(S)-{5-tert-butoxycarbonylamino-5-[4-(benzothiazol-2-yl)-phenylcarbamoyl]-pentyl}-carbamic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	With WSC*HCl; benzotriazol-1-ol In dichloromethane at 20℃; for 48h;

Reference： [1]Hutchinson, Ian; Jennings, Sharon A.; Vishnuvajjala, B. Rao; Westwell, Andrew D.; Stevens, Malcolm F.G. [Journal of Medicinal Chemistry, 2002, vol. 45, # 3, p. 744 - 747]

11
[ 2516-40-7 ]
[ 214360-73-3 ]
[ 6278-73-5 ]

Reference： [1]Tetrahedron Letters,2003,vol. 44,p. 8535 - 8537

12
[ 95-16-9 ]
[ 106-40-1 ]
[ 6278-73-5 ]

Yield	Reaction Conditions	Operation in experiment
68%	With caesium carbonate; copper(I) bromide In N,N-dimethyl-formamide at 150℃; for 3h;

Reference： [1]Alagille, David; Baldwin, Ronald M.; Tamagnan, Gilles D. [Tetrahedron Letters, 2005, vol. 46, # 8, p. 1349 - 1351]

13
[ 95-16-9 ]
[ 131818-17-2 ]
[ 6278-73-5 ]
(4-benzothiazol-2-yl-phenyl)-carbamic acid <i>tert</i>-butyl ester [ No CAS ]

Reference： [1]Tetrahedron Letters,2005,vol. 46,p. 1349 - 1351

14
[ 6278-73-5 ]
[ 74-88-4 ]
[ 10205-56-8 ]
(4-(benzo[d]thiazole-2′-yl)-N-methylaniline) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1: 10% 2: 16.7%	With potassium carbonate In dimethyl sulfoxide at 100℃; for 16h;	2.c (c) 2-(4-Methylaminophenyl)benzothiazole (21) and 2-(4-dimethylaminophenyl)benzothiazole (23) (c) 2-(4-Methylaminophenyl)benzothiazole (21) and 2-(4-dimethylaminophenyl)benzothiazole (23) A mixture of 2-(4-aminophenyl)benzothiazole 20 (15 mg, 0.066 mmol), MeI (9.4 mg, 0.066 mg) and K2CO3 (135 mg, 0.81 mmol) in DMSO (anhydrous, 0.5 ml) was heated at 100° C. for 16 hrs.The reaction mixture was purified by reverse phase TLC (MeOH:H2O=6:1) to give 1.5 mg (10%) of 2-(4-methylminophenyl)benzothiazole 21 and 2.5 mg (16.7%) of 2-(4-dimethylaminophenyl)benzothiazole 23.

Reference： [1]Current Patent Assignee: COMMONWEALTH SYSTEM OF HIGHER EDUCATION - US2003/236391, 2003, A1 Location in patent: Page 16

15
N-t-butyloxycarbonyl-DL-alanine [ No CAS ]
[ 6278-73-5 ]
2-(4'-aminophenyl)benzothiazole alanyl amide hydrochloride salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: N-t-butyloxycarbonyl-DL-alanine; 2-(4-aminophenyl)benzothiazole With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 216h; Stage #2: With hydrogenchloride In dichloromethane at 25℃; for 2h;	22 2-(4'-Aminophenyl)benzothiazole (7.75 mmol) was dissolved in dichloromethane (100 ml) and stirred at room temperature. To this solution was added 1-ethyl-3-(3'-dimethylaminopropyl)carbodiimide hydrochloride (2.3 mmol), HOBt (2.3 mmol) and Boc protected alanine (2.3 mmol). After stirring for 24 hrs a further 2.3 mmol of each reactant was added, and stirring continued for a further 24 hrs. This procedure was repeated twice more and stirring continued for a further 3 days, until a clear solution formed. The solvent was removed under vacuum and the resulting oil purified by column chromatography (2% methanol/dichloromethane). Recrystallisation from ethanol gave a white solid. [00160] The Boc protected amino acid derivative thus obtained (3.5 mmol) was dissolved in dichloromeihane (20 ml). Dry HCl gas was bubbled through the solution to saturate it, then the reaction mixture was stirred for a further 2 hrs at 25° C. The precipitate was filtered from solution and washed with dichloromethane (10 ml), to leave a bright yellow crystalline solid. [00161] mp 258-259° C.; MS (AP) m/z 298 (M+1).

Reference： [1]Current Patent Assignee: CANCER RESEARCH UK - US6858633, 2005, B1 Location in patent: Page column 18-19

16
[ 6278-73-5 ]
[ 10205-56-8 ]

Yield	Reaction Conditions	Operation in experiment
1.5 mg (10%)	With potassium carbonate In dimethyl sulfoxide	c (b) A mixture of 2-(4-aminophenyl)benzothiazole 20 (15 mg, 0.066 mmol), Mel (9.4 mg, 0.066 mg) and K2CO3(135 mg, 0.81 mmol) in DMSO (anhydrous, 0.5 ml) was heated at 100° C. for 16 hrs. The reaction mixture was purified by reverse phase TLC (MeOH:H2O=6:1) to give 1.5 mg (10%) of 2-(4-methylminophenyl)benzothiazole 21 and 2.5 mg (16.7%) of 2-(4-dimethylaminophenyl)benzothiazole 23.

Reference： [1]Current Patent Assignee: COMMONWEALTH SYSTEM OF HIGHER EDUCATION - US2002/133019, 2002, A1

17
[ 6278-73-5 ]
2-(4-Aminophenyl)benzothiazole methanesulphonic acid salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	With methanesulfonic acid In ethyl acetate	2-(4-Aminophenyl)benzothiazole methanesulphonic acid salt 2-(4-Aminophenyl)benzothiazole methanesulphonic acid salt To a solution of 2-(4-aminophenyl)benzothiazole (0.5 g, 2.21 mmol) in ethyl acetate (65 ml) was added dropwise methanesulphonic acid (0.215 g, 2.21 mmol) at room temperature. The reaction mixture was stirred for 30 minutes. The product was collected and washed with hot ethyl acetate to give a pale yellow powder (0.67 g, 94%), m.p. 261°-262° C.; vmax /cm-1 3422, 2880, 2633, 1598, 1487, 1322, 1220, 1149, 1043, 967, 780, 755, 561; δH (DMSO-d6) 8.10(1H, d, J7.9, 4-H), 8.00(3H, m, 7, 2', 6'-H), 7.52(1H, t, J7.3, 5-H), 7.42(1H, t, J7.5, 6-H), 7.06(2H, d, J8.5, 3', 5'-H), 5.72(3H, br s, NH3+), 2.41(3H, s, CH3).

Reference： [1]Current Patent Assignee: CANCER RESEARCH UK - US5874431, 1999, A

18
[ 6278-73-5 ]
[ 144-55-8 ]
2-(4'Amino-3', 5'-dibromophenyl) benzothiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	With bromine In dichloromethane; acetic acid	8 2-(4'Amino-3', 5'-dibromophenyl) benzothiazole (126) Example 8 2-(4'Amino-3', 5'-dibromophenyl) benzothiazole (126) To a solution of 2-(4'-aminophenyl)benzothiazole (0.6 g, 2,65 mmol) in 15 ml of acetic acid was added dropwise a solution of bromine (0.98 g, 6.1 mmol) in 10 ml of acetic acid at room temperature. The resulting mixture was stirred at 80° C. for 2 hours. After evaporation of acetic acid, 150 ml of 10% aqueous NaHCO3 was added, followed by 150 ml of dichloromethane. The organic phase was washed with aqueous sodium thiosulphate (250 ml) and water (280 ml) and dried over MgSO4. Solvent was evaporated and the residue, adsorbed onto silica gel, was chromatographed using EtOCa-hexane (1:5.5) as the eluant to give a pale yellow powder (0.7 g, 78%), mp 200.7-202.6° C.; IR 3469, 3373, 1608, 1464, 1431, 1396, 1309, 1223, 754 cm-1; δH (CLCl3)8.16(s, 2H, 2',6'-H), 8.04(d, 1H, J=8.0 Hz, 4-H), 7.89(d, 1H, J=7,7 Hz, 7-H), 7.50(dt, 1H, J=1.3, 7.7 Hz, 5-H), 7.38(dt, 1H), J=1.2. 7,6 Hz, 6-H), 4.92(br s 2H, NH2); δC (CDCl3) 165.8(C), 144.6(C), 135.1(C), 131.2 (2CH, C-2', 6'), 126.8 (CH), 125.6(C), 125.5(CH), 122.0 (CH), 108.9(2C, C-3', 5'); m/z 384 (M+), 305(m-Br), 224 (M+2, -Br), 196.