Name: 570-23-0|3-Aminosalicylic acid|95%
Brand: Ambeed
SKU: A810773
Price: 18.0 USD
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1
[ 128-93-8 ]
[ 570-23-0 ]
2-hydroxy-3-(4-methylamino-9,10-dioxo-9,10-dihydro-[1]anthrylamino)-benzoic acid [ No CAS ]

Reference： [1]Patent: DE638835,1934,C
Fortschr. Teerfarbenfabr. Verw. Industriezweige,vol. 23,p. 973
Fortschr. Teerfarbenfabr. Verw. Industriezweige,vol. 23,p. 973

2
[ 85-38-1 ]
[ 570-23-0 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogen;palladium 10% on activated carbon; In ethanol; under 2250.23 Torr; for 6h;	Synthesis of Example 4<strong>[85-38-1]3-Nitrosalicylic acid</strong> (1.0 g, 5.46 mmol) is dissolved in absolute ethanol (60 mL) and hydrogenated at 3 Bar for 6 hours using 10% palladium on activated charcoal (116 mg) as the catalyst. The suspension is filtered through Celite and the solvent removed under reduced pressure to give compound 4-1.Yield: 600 mgES mass spectrum: [M+H]+ = 154Retention time: 0.28 min (UPLC method 2)
	With hydrogen;palladium-on-charcoal; In ethanol; under 2250.23 Torr; for 6h;	<strong>[85-38-1]3-Nitrosalicylic acid</strong> (1.0 g, 5.46 mmol) is dissolved in absolute ethanol (60 mL) and hydrogenated at 3 Bar for 6 hours using 10% palladium on activated charcoal (116 mg) as the catalyst. The suspension is filtered through Celite and the solvent removed under reduced pressure to give compound 4-1.Yield: 600 mgES mass spectrum: [M+H]+=154Retention time: 0.28 min (HPLC method 2)

Reference： [1]Organic Letters,2016,vol. 18,p. 2395 - 2398
[2],1933,vol. 3,p. 391,397, 400
Chemisches Zentralblatt,1935,vol. 106,p. 226
[3]Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences,1965,vol. 261,p. 167
[4]Journal fur praktische Chemie (Leipzig 1954),1890,vol. <2> 42,p. 551
[5]Journal fur praktische Chemie (Leipzig 1954),1900,vol. <2>61,p. 533
[6]Justus Liebigs Annalen der Chemie,1879,vol. 195,p. 37
[7]Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistry,2011,vol. 41,p. 590 - 597
[8]Patent: WO2012/80456,2012,A1 .Location in patent: Page/Page column 37
[9]Patent: US2012/329773,2012,A1 .Location in patent: Page/Page column 17

3
[ 64-17-5 ]
[ 570-23-0 ]
[ 42059-80-3 ]
3-(3-carboxy-2-hydroxyphenyl)aminomethylene-2-ethoxy-6-nitrochroman-4-one [ No CAS ]

Reference： [1]Tetrahedron,2001,vol. 57,p. 3455 - 3464
[2]Tetrahedron,2001,vol. 57,p. 3455 - 3464

4
[ 570-23-0 ]
[ 17422-74-1 ]
[ 67-63-0 ]
3-(3-carboxy-2-hydroxyphenyl)aminomethylene-2-i-propyloxychroman-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%	With toluene-4-sulfonic acid at 20℃; for 12h;

Reference： [1]Stankovičová, Henrieta; Lácová, Margita; Gáplovský, Anton; Chovancová, Jarmila; Prónayová, Nad'A [Tetrahedron, 2001, vol. 57, # 16, p. 3455 - 3464]

5
[ 570-23-0 ]
[ 42248-31-7 ]
3-(3-carboxy-2-hydroxyphenyl)aminomethylene-6-chloro-2-hydroxychroman-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With toluene-4-sulfonic acid for 3h; Heating;

Reference： [1]Stankovičová, Henrieta; Lácová, Margita; Gáplovský, Anton; Chovancová, Jarmila; Prónayová, Nad'A [Tetrahedron, 2001, vol. 57, # 16, p. 3455 - 3464]

6
[ 2905-62-6 ]
[ 570-23-0 ]
3-(3,5-dichloro-benzoylamino)-2-hydroxy-benzoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine In tetrahydrofuran

Reference： [1]Razavi, Hossein; Palaninathan, Satheesh K.; Powers, Evan T.; Wiseman, R. Luke; Purkey, Hans E.; Mohamedmohaideen, Nilofar N.; Deechongkit, Songpon; Chiang, Kyle P.; Dendle, Maria T. A.; Sacchettini, James C.; Kelly, Jeffery W. [Angewandte Chemie - International Edition, 2003, vol. 42, # 24, p. 2758 - 2761]

7
[ 570-23-0 ]
[ 129714-97-2 ]
3-(3,5-difluoro-benzoylamino)-2-hydroxy-benzoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine In tetrahydrofuran

Reference： [1]Razavi, Hossein; Palaninathan, Satheesh K.; Powers, Evan T.; Wiseman, R. Luke; Purkey, Hans E.; Mohamedmohaideen, Nilofar N.; Deechongkit, Songpon; Chiang, Kyle P.; Dendle, Maria T. A.; Sacchettini, James C.; Kelly, Jeffery W. [Angewandte Chemie - International Edition, 2003, vol. 42, # 24, p. 2758 - 2761]

8
[ 570-23-0 ]
[ 2251-65-2 ]
2-hydroxy-3-(3-trifluoromethyl-benzoylamino)-benzoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine In tetrahydrofuran

Reference： [1]Razavi, Hossein; Palaninathan, Satheesh K.; Powers, Evan T.; Wiseman, R. Luke; Purkey, Hans E.; Mohamedmohaideen, Nilofar N.; Deechongkit, Songpon; Chiang, Kyle P.; Dendle, Maria T. A.; Sacchettini, James C.; Kelly, Jeffery W. [Angewandte Chemie - International Edition, 2003, vol. 42, # 24, p. 2758 - 2761]

9
[ 570-23-0 ]
[ 98-88-4 ]
3-benzamido-2-hydroxybenzoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine In tetrahydrofuran

Reference： [1]Razavi, Hossein; Palaninathan, Satheesh K.; Powers, Evan T.; Wiseman, R. Luke; Purkey, Hans E.; Mohamedmohaideen, Nilofar N.; Deechongkit, Songpon; Chiang, Kyle P.; Dendle, Maria T. A.; Sacchettini, James C.; Kelly, Jeffery W. [Angewandte Chemie - International Edition, 2003, vol. 42, # 24, p. 2758 - 2761]

10
[ 570-23-0 ]
[ 18063-02-0 ]
3-(2,6-difluoro-benzoylamino)-2-hydroxy-benzoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine In tetrahydrofuran

Reference： [1]Razavi, Hossein; Palaninathan, Satheesh K.; Powers, Evan T.; Wiseman, R. Luke; Purkey, Hans E.; Mohamedmohaideen, Nilofar N.; Deechongkit, Songpon; Chiang, Kyle P.; Dendle, Maria T. A.; Sacchettini, James C.; Kelly, Jeffery W. [Angewandte Chemie - International Edition, 2003, vol. 42, # 24, p. 2758 - 2761]

11
[ 570-23-0 ]
[ 4659-45-4 ]
3-(2,6-dichloro-benzoylamino)-2-hydroxy-benzoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine In tetrahydrofuran

Reference： [1]Razavi, Hossein; Palaninathan, Satheesh K.; Powers, Evan T.; Wiseman, R. Luke; Purkey, Hans E.; Mohamedmohaideen, Nilofar N.; Deechongkit, Songpon; Chiang, Kyle P.; Dendle, Maria T. A.; Sacchettini, James C.; Kelly, Jeffery W. [Angewandte Chemie - International Edition, 2003, vol. 42, # 24, p. 2758 - 2761]

12
[ 570-23-0 ]
[ 312-94-7 ]
2-hydroxy-3-(2-trifluoromethyl-benzoylamino)-benzoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine In tetrahydrofuran

Reference： [1]Razavi, Hossein; Palaninathan, Satheesh K.; Powers, Evan T.; Wiseman, R. Luke; Purkey, Hans E.; Mohamedmohaideen, Nilofar N.; Deechongkit, Songpon; Chiang, Kyle P.; Dendle, Maria T. A.; Sacchettini, James C.; Kelly, Jeffery W. [Angewandte Chemie - International Edition, 2003, vol. 42, # 24, p. 2758 - 2761]

13
[ 570-23-0 ]
5-(4-chlorophenyl)-3-methyl-2-(methylthio)-1,3,4-thiadiazolium perchlorate [ No CAS ]
3-[5-(4-chloro-phenyl)-3-methyl-3<i>H</i>-[1,3,4]thiadiazol-2-ylideneamino]-2-hydroxy-benzoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In ethanol at 40 - 80℃;

Reference： [1]Vergne, Fabrice; Bernardelli, Patrick; Lorthiois, Edwige; Pham, Nga; Proust, Emmanuelle; Oliveira, Chrystelle; Mafroud, Abdel-Kader; Royer, Frederique; Wrigglesworth, Roger; Schellhaas, Jennifer; Barvian, Mark; Moreau, François; Idrissi, Moulay; Tertre, Anita; Bertin, Bernadette; Coupe, Magali; Berna, Patrick; Soulard, Patricia [Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 18, p. 4607 - 4613]

14
[ 570-23-0 ]
[ 60100-09-6 ]
[ 17968-71-7 ]

Yield	Reaction Conditions	Operation in experiment
90%	at 150℃; for 0.5h;
2.47 g	at 150℃; for 0.5h; Inert atmosphere;

Reference： [1]Pettit, George R.; Smith, Thomas H.; Feng, Song; Knight, John C.; Tan, Rui; Pettit, Robin K.; Hinrichs, Peter A. [Journal of Natural Products, 2007, vol. 70, # 7, p. 1073 - 1083]
[2]Chevalier, Arnaud; Zhang, Yanmin; Khdour, Omar M.; Hecht, Sidney M. [Organic Letters, 2016, vol. 18, # 10, p. 2395 - 2398]

15
[ 570-23-0 ]
N-(5-s-butyl-8,13-diisobutyl-2,10,10,16-tetramethyl-3,6,9,11,14,18-hexaoxo-1,4,12,15-tetraoxa-7-azacyclooctadec-17-yl)-3-formylamino-2-hydroxybenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: 90 percent / 0.5 h / 150 °C 2: 79 percent / NaHCO₃ / dimethylformamide / 15 h / 23 °C 3: 95 percent / K₂CO₃ / dimethylformamide / 15 h / 60 °C 4: 79 percent / aq. LiOH / tetrahydrofuran; methanol / 18 h / 23 °C 5: 61 percent / 1-hydroxybenzotriazole; EDCI; N-methylmorpholine / dimethylformamide / 11 h / 23 °C 6: 82 percent / H₂ / Pd/C / ethyl acetate / 2 h / 23 °C

Reference： [1]Pettit, George R.; Smith, Thomas H.; Feng, Song; Knight, John C.; Tan, Rui; Pettit, Robin K.; Hinrichs, Peter A. [Journal of Natural Products, 2007, vol. 70, # 7, p. 1073 - 1083]

16
[ 64-17-5 ]
[ 570-23-0 ]
[ 172092-29-4 ]

Yield	Reaction Conditions	Operation in experiment
46%	at 20℃; for 3h;	32 A solution of 3-amino salicylic acid (0.75g, 4.9 mmol) in EtOH (30 ml) and concentrated H2SO4 (5 ml) was stirred at room temperature for 3h. After concentration in vacuo, the residue was diluted with water, treated with solid K2CO3 and extracted with EtOAc. After drying over Na2SO4, concentration of the organic phase in vacuo afforded a brown oil 0.41 g (46%). MS: m/z (MH+) =182. 1H-NMR (400 MHz, CDCl3): δ (ppm): 7.25 (d, 1H), 6.88 (d, 1H), 6.71 (t, 1H), 4.37 (q, 2H), 1.41 (t, 3H).

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - EP1228043, 2005, B1 Location in patent: Page/Page column 13
[2]Current Patent Assignee: MEIJI HOLDINGS CO., LTD - EP1180514, 2002, A1 Location in patent: Example 70

17
[ 67-56-1 ]
[ 570-23-0 ]
[ 35748-34-6 ]

Yield	Reaction Conditions	Operation in experiment
85.1%	In dimethyl sulfoxide at 0 - 60℃; for 24h;	23.1 (1) Preparation of 2-hydroxy-3-aminobenzoic acid methyl ester Add 2-hydroxy-3-aminobenzoic acid (8.0 g) to anhydrous methanol (80 mL),Slowly add dichlorosulfoxide (15 mL) at 0 ° C.The reaction was carried out at 60 ° C for 24h.After the reaction was completed, the solvent was concentrated under reduced pressure,Adjust the pH to neutral with an aqueous sodium bicarbonate solution,Then, 100 mL of dichloromethane was added to the reaction solution for extraction.It was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by silica gel column chromatography.7.4 g of a solid product was obtained with a yield of 85.1%.
45%	With sulfuric acid at 0 - 70℃; for 12h; Inert atmosphere;	2.12 Synthesis of methyl 3-amino-2-hydroxybenzoate (XVII):XVIITo a stirred solution of 3-amino-2-hydroxybenzoic acid XII (0.5 g, 3.26 mmol) in MeOH (15 ml) was added sulfuric acid (1 ml) at 0°C under nitrogen atmosphere and the resulting mixture was heated at 70°C for 12 h. After completion of reaction, the reaction mixture was cooled, concentrated, washed with saturated NaHCC>3 solution and extracted with ethyl acetate. The organic layer was dried over Na2S04 and evaporated under reduced pressure to afford product XVII in 45% yield.
25.9%	With sulfuric acid for 55h; Heating / reflux;	8.1 [Example 8] 2-(4-Isobutoxy-3-nitrophenyl)benzoxazole-7-carboxylic acid; (1) Methyl 3-aminosalicylate (1) methyl 3-aminosalicylate 3-Aminosalicylic acid (690 mg, 4.51 mmol), methanol (45 ML), and conc. sulfuric acid (0.9 ML) were mixed, and heated for 55 hours under reflux.. The methanol was distilled off under reduced pressure.. To the residue was added cooled water.. The aqueous residue was made alkaline by addition of aqueous saturated sodium hydrogen carbonate under cooling with ice.. Thus precipitated crystalline product were collected by filtration, washed with two portions of water, and dried in vacuo at 40°C for 40 min., to give 710 mg of a pale pink crystalline product.. The product was suspended in chloroform (35 ML), and insolubles were removed by filtration.. The filtrate was dried over sodium sulfate and then concentrated under reduced pressure to give 181 mg (yield 25.9%) of the desired compound in the form of a brown crystalline product. 1H NMR (CDCl3, 400 MHz) δ: 3.88 (2H, broad s), 3, 94 (3H, s), 6.71 (1H, dd, J=8Hz, 8Hz), 6.87 (1H, d, J=8Hz), 7.24 (1H, m), 10.88 (1H, s).

19%

With thionyl chloride at 20℃; for 22h; Heating / reflux;

392.A EXAMPLE 392; 3-[(2-Chlorobenzoyl)Amino]-2-[(2-Chlorophenyl)Methoxy]Benzoic Acid EXAMPLE 392 3-[(2-Chlorobenzoyl)Amino]-2-[(2-Chlorophenyl)Methoxy]Benzoic Acid A mixture of thionyl chloride (1.15 ML, 15.8 mmol) and methanol (20.0 ML) was stirred at room temperature for 30 min then treated with 3-amino-2-hydroxybenzoic acid (1.5 g, 9.79 mmol).The reaction mixture was stirred at room temperature for 2 h, refluxed for 20 h, cooled and concentrated.The crude product was partitioned between EtOAc (100 ML) and 5% NAHCO3 solution (65 ML), back-extracting the aqueous phase with EtOAc (4*100 ML).The organic phase was washed with water (2*20 ML) and brine (20 ML), dried (MgSO4), filtered and concentrated to give a dark red solid (381 mg, 19%).

Reference： [1]Current Patent Assignee: TIANJIN GUDUI BIOPHARMA TECH; GUDUI BIOPHARMA TECH - CN110857285, 2020, A Location in patent: Paragraph 0213-0217
[2]Current Patent Assignee: SERVIER MONDE - WO2011/72174, 2011, A1 Location in patent: Page/Page column 146-147
[3]Current Patent Assignee: NIPPON CHEMIPHAR CO LTD - EP1452528, 2004, A1 Location in patent: Page 18
[4]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - US2003/225091, 2003, A1 Location in patent: Page 71

18
[ 570-23-0 ]
[ 622-58-2 ]
[ 721422-50-0 ]

Yield	Reaction Conditions	Operation in experiment
90%	With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 3h;	1.A A. General Synthesis Of 3-Substituted-Amido, -Ureido and -Thioureido Analogs of Salicylic Acid To a solution of 3-AMINOSALICYLIC acid 1 (0.05 g, 0.326 MMOL) and DIEA (227 PI, 1.63 MMOL) in dry dichloromethane (2 ml) was added P-TOLYL isocyanate (82.2 ul, 0.652 MMOL) at rt, and the mixture was stirred for 3 hrs. The mixture was then quenched by addition of 10% water in methanol and stirred at rt for 1 hr. The mixture was concentrated under reduced pressure, the residue was diluted with 0.5 M NAOH and then extracted twice with ether. The aqueous layer was acidified with concentrated HCI and extracted with ethyl acetate. The organic layers were combined, washed with brine and dried over anhydrous sodium sulfate. The solvent was evaporated in vacuo to provide structure 2 (X = O and R = 4-methylphenyl) in 90% yield. The purity of the product was checked by LC/MS. H NMR (500 MHz, CD30D) 8 8.26 (d, J = 8.1 Hz, 1H), 7.51 (d, J = 8.1 Hz, 1H), 7.31 (d, J = 6.8 Hz, 2H), 7.10 (d, J = 8.2 Hz, 2H), 6.87 (t, J = 8.1 Hz, 1H), 2.29 (s, 3H); MS (calculated FOR C5H15N204) 287.1 [M + H] +, found 287.0.

Reference： [1]Current Patent Assignee: MITOKOR - WO2004/58683, 2004, A2 Location in patent: Page 23

19
[ 473733-69-6 ]
[ 570-23-0 ]
[ 473730-92-6 ]

Yield	Reaction Conditions	Operation in experiment
90%	With N-ethyl-N,N-diisopropylamine In ethanol Heating / reflux;	2.15 Preparative Example 2.15 The cyclobutenedione intermediate from Preparative Example 87 (200 mg), DIEA(100 ul), 3-aminosalicylic acid (120 mg) and EtOH (4 ml) were combined and heated to reflux overnight to give the title compound (90%, MH+= 367).
90%	With N-ethyl-N,N-diisopropylamine In ethanol Heating / reflux;	2.15 Preparative example 2.15 The cyclobutenedione intermediate from Preparative Example 87 (200 mg), DIEA (100 ul), 3-aminosalicylic acid (120 mg) and EtOH (4 ml) were combined and heated to reflux overnight to give the title compound (90%, MH+=367).

Reference： [1]Current Patent Assignee: MERCK & CO INC; LIGAND PHARMACEUTICALS INC - US2004/147559, 2004, A1 Location in patent: Page 71
[2]Current Patent Assignee: MERCK & CO INC; LIGAND PHARMACEUTICALS INC - US2004/106794, 2004, A1 Location in patent: Page 69

20
[ 570-23-0 ]
[ 31450-67-6 ]

Yield	Reaction Conditions	Operation in experiment
	In 5,5-dimethyl-1,3-cyclohexadiene	17.c 8-Trifluoromethyl-10H-dibenzo[b,f][1,4]oxazepin-11-one (Formula 2, X=O, R1=CF3) (c) The aminosalicylic acid (17.3 g, 58.2 mmol) was refluxed in 150 ml of xylene for 24 hours with continuous removal of water. The xylene was removed, and the residue was recrystallized from methanol to provide 8-trifluoromethyl-10H-dibenzo[b,f][1,4]oxazepin-11-one as a white solid, mp 246-247° C., 1H NMR (DMSO-d6), δ 7.38-7.66 (m, 7H), 10.7 (s, 1H, NH).

Reference： [1]Current Patent Assignee: CENTRE FOR ADDICTION AND MENTAL HEALTH - US2003/135042, 2003, A1

21
[ 277299-70-4 ]
[ 570-23-0 ]
3-[1-(3,4-dimethylphenyl)-5-hydroxy-3-methyl-1H-pyrazol-4-yl]azo}-2-hydroxybenzoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
32%		EXAMPLE 10 Preparation of 3-[1-(3,4-Dimethylphenyl)-5-hydroxy-3-methyl-1H-pyrazol-4-yl]azo}-2-hydroxybenzoic Acid Following the procedure of Example 1, except substituting <strong>[277299-70-4]1-(3,4-dimethylphenyl)-3-methyl-3-pyrazolin-5-one</strong> for 3-methyl-1-(4-methylphenyl)-3-pyrazolin-5-one and 3-amino-2-hydroxybenzoic acid for 4-amino-3-hydroxybenzoic acid, the title compound was prepared as an orange solid (0.40 g, 32%). 1H NMR (400 MHz, d6-DMSO) delta 7.83 (m, 2H), 7.59 (d, J=7.8 Hz, 1H), 7.50 (d, J=7.8 Hz, 1H), 7.09 (d, J=8.0Hz, 1H), 6.60 (t, J=7.8 Hz, 1H), 2.29 (s, 3H), 2,24 (s, 3H), 2.21 (s, 3H).

Reference： [1]Patent: US6642265,2003,B1

22
[ 570-23-0 ]
[ 67127-88-2 ]

Yield	Reaction Conditions	Operation in experiment
	With formaldehyd; ammonia In hydrogenchloride; acetic acid	R.17 REFERENCE EXAMPLE 17 REFERENCE EXAMPLE 17 A suspension of 3-aminosalicylic acid (5.0 g) in acetic acid (75 ml) was treated with hydrochloric acid (2N), slowly with shaking, until complete solution was achieved. The solution was then treated with aqueous formaldehyde solution (40% w/v; 20 ml) and 5% palladium on charcoal catalyst (2.0 g), and the mixture was hydrogenated at 25° C. and at atmospheric pressure for 18 hours. The catalyst was filtered off, the filtrate was evaporated in vacuo, and the resulting residue was dissolved in hydrochloric acid (2N; 100 ml) and then the solution was adjusted to pH 5 by treatment with concentrated aqueous ammonia solution. The mixture was left to stand for 24 hours in the refrigerator. The precipitate was then collected to give 3-dimethylaminosalicylic acid (3.0 g), m.p. 273°-277° C. (with decomposition).

Reference： [1]Current Patent Assignee: SANOFI - US4146631, 1979, A

23
[ 915702-47-5 ]
[ 570-23-0 ]
3-([2'-(acetylamino)-4'-methyl-4,5'-bi-1,3-thiazol-2-yl]carbonyl}amino)-2-hydroxybenzoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
42%	With triethylamine In tetrahydrofuran; dichloromethane at 20℃;	20 2'-Acetylamino-4'-methyl-[4,5']bithiazolyl-2-carbonyl chloride, prepared as in Step I of Example 13, described above, (106.5 mg; 0.35 mmol; 1 eq.), is dissolved in THF (8 ml) and DCM (4 ml). 3 -Aminosalicylic acid (TCI-US) (54.05 mg; 0.35 mmol; 1 eq.) and triethylamine (97 μl; 0.70 mmol; 2 eq.) are added and the mixture is stirred overnight at it. Solvents are evaporated and the crude product is crystallyzed in MeOH, filtrated, affording Compound (20) as a yellow solid (61 mg; 42%).Potassium salt of 2'-(acetylamino)4-'-methyl-N-[4-(1H-tetrazol-5-yl)phenyl]-4,5'-bi-1,3-thiazole-2-carboxamide, Compound (20), is prepared by dissolving the parent compound (58.3 mg; 0.14 mmol; 1 eq.) in THF (2 ml) and water (2 ml). Potassium hydroxide 0.5 N solution (279 μl; 0.50 M; 0.14 mmol; 1 eq.) is added. The mixture is stirred 10 min at it, filtered through cotton and is lyophilized. Potassium salt of compound (20) is isolated as a yellow solid (58 mg, 91%). 1H NMR (DMSO-d6, 300 MHz) δ 2.16 (s, 3H), 2.55 (s, 3H), 6.47 (t, J = 8 Hz, 1H), 7.39 (dd, J = 8 Hz, J = 2 Hz, 1H), 8.07 (s, IH), 8.18 (dd, J = 8, 2 Hz, 1H), 9.97 (s, 1H), 12.19 (s, 1H). M (ESI): 417.1; M+(ESI): 419.1. HPLC (method A), Rt: 1.50 min (purity: 92.3%).

Reference： [1]Current Patent Assignee: MERCK KGAA - WO2006/125805, 2006, A1 Location in patent: Page/Page column 85-86

24
[ 570-23-0 ]
[ 78-39-7 ]
[ 52395-92-3 ]

Yield	Reaction Conditions	Operation in experiment
	With toluene-4-sulfonic acid for 5h; Heating / reflux;	A.9 A solution of 3-amino-2-hydroxy-benzoic acid (9.40 mmol) and PTSA(0.34 mmol) in triethyl orthoacetate (5.77 niL) is heated to reflux for 5h and concentrated in vacuo. The residue is washed with ether and dried in vacuo to give the desired product which is used without further purification. LC-MS: tR = 0.67 min; [M+H]+ = 178.0.
	for 5h; Heating / reflux;	A.9 A solution of 3-amino-2-hydroxy-benzoic acid (9.40 mmol) and p-toluenesulfonic acid monohydrate (0.34 mmol) in triethyl orthoacetate (5.77 mL) is heated to reflux for 5h and concentrated in vacuo. The residue is washed with ether and dried in vacuo to give the desired product which is used without further purification. LC-MS: tR = 0.67 min; [M+H]+ = 178.0.
	With toluene-4-sulfonic acid at 100℃; for 5h;	190.A Part A: Preparation of 2-methylbenzo[d]oxazole-7-carboxylic acid A vial was charged with 3-amino-2-hydroxybenzoic acid (0.5 g, 3.26 mmol) in triethylorthoacetate (2 mL) and p-toluenesulfonic acid (20 mg). The reaction mixture was heated for 5 hours at 100° C. The reaction mixture was concentrated in vaccuo and the residue (0.55 g) was used as such in the next reaction. MS m/z 178 (M+H)

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2008/81399, 2008, A2 Location in patent: Page/Page column 78
[2]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2009/16560, 2009, A2 Location in patent: Page/Page column 83
[3]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - US2007/60589, 2007, A1 Location in patent: Page/Page column 88

25
[ 28966-81-6 ]
[ 570-23-0 ]
[ 879000-21-2 ]

Yield	Reaction Conditions	Operation in experiment
40%	With Et₃N In methanol; ethanol suspn. of acid and Et3N in MeOH added to stirred suspn. of complex in EtOH, refluxed for 1 h; filtered, pptd. with water, centrifuged, washed with water, dried over silica gel; elem. anal.;

Reference： [1]Quintal, Susana M.O.; Félix, Vitor; Drew, Michael G.B.; Nogueira, Helena I.S. [Polyhedron, 2006, vol. 25, # 3, p. 753 - 758]

26
[ 570-23-0 ]
[ 149-73-5 ]
7-Benzoxazolecarboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	for 20h; Heating / reflux;	A.8 A solution of 3-amino-2-hydroxy-benzoic acid (12.5 mmol) in trimethyl orthoformate (19.2 mL) is heated to reflux for 2Oh and concentrated in vacuo. The residue is washed three times with hot MeOH, the filtrates are combined and the solvent is removed in vacuo to give the desired product which is used without further purification. 1H-NMR (DMSO- d6): δ = 13.4 (bs, IH) ; 8.87 (s, IH) ; 8.08 (d, J = 8.0 Hz, IH); 7.96 (d, J = 7.5 Hz, IH); 7.52 (t, J = 7.9 Hz, IH).
	for 20h; Heating / reflux;	A.8 A solution of 3-amino-2-hydroxy-benzoic acid (12.5 mmol) in trimethyl ortho formate (19.2 mL) is heated to reflux for 2Oh and concentrated in vacuo. The residue is washed three times with hot MeOH, the filtrates are combined and the solvent is removed in vacuo to give the desired product which is used without further purification. 1H-NMR (DMSO-d6): δ = 13.4 (bs, IH) ; 8.87 (s, IH) ; 8.08 (d, J = 8.0 Hz, IH); 7.96 (d, J = 7.5 Hz, IH); 7.52 (t, J = 7.9 Hz, IH).
460mg	Reflux; Inert atmosphere;

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2008/81399, 2008, A2 Location in patent: Page/Page column 77
[2]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2009/16560, 2009, A2 Location in patent: Page/Page column 82
[3]Current Patent Assignee: SHANGHAI MEIYUE BIOTECHNOLOGY DEV - CN111560012, 2020, A Location in patent: Paragraph 0099-0102

27
[ 570-23-0 ]
[ 4349-62-6 ]
[ 18107-18-1 ]
methyl 2-(2-hydroxy-phenyl)-benzooxazole-7-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 3-aminosalicylic acid; 2-benzyloxybenzoyl chloride In xylene at 20℃; Heating / reflux; Stage #2: With toluene-4-sulfonic acid In water; xylene at 20℃; for 12h; Heating / reflux; Stage #3: diazomethyl-trimethyl-silane In water; xylene at 0℃;	Compound 2.16: Methyl 2-(2-Hydroxy-phenyl)-benzooxazole-7-carboxylate. To a solution of 2-benzyloxybenzoic acid dry CH2Cl2 was added to 1 ml of freshly distilled oxalyl chloride. After stirring for 10 minutes, 1 drop of DMF was added to the reaction mixture. The reaction mixture was stirred for 2 hours at room temperature and the solvent was removed by evaporation. The resultant yellow oil was dried under vacuum for 3 hours. The yellow oil was then dissolved in 5 ml of dry xylenes and transferred via cannula to a solution of 3-aminosalacylic acid (g, 31.5 mmol) in xylenes. The mixture was stirred at room temperature for 1 h, then heated to reflux overnight. After the reaction mixture had cooled to room temperature, p-toluenesulfonic acid monohydrate (475 mg, 2.5 mmol) was added and the mixture heated to reflux for an additional 12 h. The reaction mixture was cooled to 0° C. and treated with an excess of TMSCHN2. The product was purified by column chromatography (20% EtOAc in hexane) to give a light yellow solid (42 mg, 36%): 1H NMR δ 4.04 (s, 3H, CH3), 7.00 (m, 1H), 7.10 (d, 1H, J=8.4 Hz), 7.4-7.5 (m, 2H), 7.87 (dd, 1H, J=8.1, 1.2 Hz), 7.97 (dd, 1H, J=7.5, 1.2 Hz), 8.06 (dd, 1H, J=8.1, 1.2 Hz); CIMS m/z 270 (MH+); HRMS m/z calc'd for C15H12NO4: 270.0763, found 270.0766.

Reference： [1]Current Patent Assignee: THE UNIVERSITY OF TEXAS SYSTEM - US2005/4188, 2005, A1 Location in patent: Page 9-10

28
[ 309933-10-6 ]
[ 570-23-0 ]
[ 309932-03-4 ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine In tetrahydrofuran at 20℃; for 16h;

Reference： [1]Location in patent: experimental part Lum, Robert T.; Cheng, Mingshan; Cristobal, Cristina P.; Goldfine, Ira D.; Evans, Joseph L.; Keck, James G.; Macsata, Robert W.; Manchem, Vara Prasad; Matsumoto, Yukiharu; Park, Sophia J.; Rao, Sandhya S.; Robinson, Louise; Shi, Songyuan; Spevak, Wayne R.; Schow, Steven R. [Journal of Medicinal Chemistry, 2008, vol. 51, # 19, p. 6173 - 6187]

29
[ 98-01-1 ]
[ 570-23-0 ]
[ 1175710-41-4 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 3-aminosalicylic acid With tetrafluoroboric acid; sodium nitrite In water at 0℃; Stage #2: furfural With copper dichloride In water; acetone at 20℃;

Reference： [1]Location in patent: scheme or table Rajamaki, Suvi; Innitzer, Anna; Falciani, Chiara; Tintori, Cristina; Christ, Frauke; Witvrouw, Myriam; Debyser, Zeger; Massa, Silvio; Botta, Maurizio [Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 13, p. 3615 - 3618]

30
[ 570-23-0 ]
[ 586-75-4 ]
[ 1236010-61-9 ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine In toluene at 70℃; for 1h;	4.4A EXAMPLE 4 ; 2-(4-bromophenyl)-l ,3-benzoxazole-7-carboxamideEXAMPLE 4A 3-(4-bromobenzamido)-2-hydroxybenzoic acid A suspension of 3-amino-2-hydroxybenzoic acid (1.5 g) in toluene (50 niL) and pyridine (2 rnL) was treated with 4-bromobenzoyl chloride (2.58 g) and the mixture was heated at 7O0C for 1 hour. The mixture was cooled and filtered. The solid was washed with ethyl acetate, stirred in water for 15 minutes, filtered and dried to afford the title compound.

Reference： [1]Current Patent Assignee: ABBOTT LABORATORIES INC - WO2010/83220, 2010, A1 Location in patent: Page/Page column 31-32

31
[ 570-23-0 ]
[ 78-39-7 ]
ethyl 2-methylbenzoxazole-7-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With toluene-4-sulfonic acid at 100℃; for 18h;	72.A [0510] Step A: A solution of 3-amino-2-hydroxybenzoic acid (1 g, 6.53 mmol), triethylorthoacetate (4 mL), and P-toluenesulfonic acid (40 mg) was heated at 100 °C for 18 hours. The reaction was concentrated in vacuo and the crude product was purified by flash column chromatography on silica gel with hexanes and EtOAc (30%) to afford ethyl 2-methylbenzo[d]oxazole-7-carboxylate (743) (1.27 g, 95%).
95%	With toluene-4-sulfonic acid at 100℃; for 18h;	72.A [0502] Step A: A solution of 3-amino-2-hydroxybenzoic acid (1 g, 6.53 mmol), triethylorthoacetate (4 rnL), and P-toluenesulfonic acid (40 mg) was heated at 100 0C for 18 hours. The reaction was concentrated in vacuo and the crude product was purified by flash column chromatography on silica gel with hexanes and EtOAc (30%) to afford ethyl 2- methylbenzo[d]oxazole-7-carboxylate (743) (1.27 g, 95%).

Reference： [1]Current Patent Assignee: CYMABAY THERAPEUTICS, INC. - WO2011/159297, 2011, A1 Location in patent: Page/Page column 145
[2]Current Patent Assignee: CYMABAY THERAPEUTICS, INC. - WO2010/80537, 2010, A1 Location in patent: Page/Page column 119

32
[ 570-23-0 ]
[ 403-43-0 ]
[ 906095-16-7 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 3-aminosalicylic acid; 4-fluorobenzoyl chloride With pyridine In dichloromethane at 20℃; Stage #2: With toluene-4-sulfonic acid In toluene Reflux;

Reference： [1]Location in patent: scheme or table Yang, Zhicai; Fairfax, David J.; Maeng, Jun-Ho; Masih, Liaqat; Usyatinsky, Alexander; Hassler, Carla; Isaacson, Soshanna; Fitzpatrick, Kevin; Deorazio, Russell J.; Chen, Jianqing; Harding, James P.; Isherwood, Matthew; Dobritsa, Svetlana; Christensen, Kevin L.; Wierschke, Jonathan D.; Bliss, Brian I.; Peterson, Lisa H.; Beer, Cathy M.; Cioffi, Christopher; Lynch, Michael; Rennells, W. Martin; Richards, Justin J.; Rust, Timothy; Khmelnitsky, Yuri L.; Cohen, Marlene L.; Manning, David D. [Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 22, p. 6538 - 6541]

33
[ 570-23-0 ]
[ 98-88-4 ]
[ 131862-24-3 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 3-aminosalicylic acid; benzoyl chloride With pyridine In dichloromethane at 20℃; Stage #2: With toluene-4-sulfonic acid In toluene Reflux;

Reference： [1]Location in patent: scheme or table Yang, Zhicai; Fairfax, David J.; Maeng, Jun-Ho; Masih, Liaqat; Usyatinsky, Alexander; Hassler, Carla; Isaacson, Soshanna; Fitzpatrick, Kevin; Deorazio, Russell J.; Chen, Jianqing; Harding, James P.; Isherwood, Matthew; Dobritsa, Svetlana; Christensen, Kevin L.; Wierschke, Jonathan D.; Bliss, Brian I.; Peterson, Lisa H.; Beer, Cathy M.; Cioffi, Christopher; Lynch, Michael; Rennells, W. Martin; Richards, Justin J.; Rust, Timothy; Khmelnitsky, Yuri L.; Cohen, Marlene L.; Manning, David D. [Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 22, p. 6538 - 6541]

34
[ 570-23-0 ]
[ 122-01-0 ]
[ 906095-19-0 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 3-aminosalicylic acid; 4-chloro-benzoyl chloride With pyridine In dichloromethane at 20℃; Stage #2: With toluene-4-sulfonic acid In toluene Reflux;

Reference： [1]Location in patent: scheme or table Yang, Zhicai; Fairfax, David J.; Maeng, Jun-Ho; Masih, Liaqat; Usyatinsky, Alexander; Hassler, Carla; Isaacson, Soshanna; Fitzpatrick, Kevin; Deorazio, Russell J.; Chen, Jianqing; Harding, James P.; Isherwood, Matthew; Dobritsa, Svetlana; Christensen, Kevin L.; Wierschke, Jonathan D.; Bliss, Brian I.; Peterson, Lisa H.; Beer, Cathy M.; Cioffi, Christopher; Lynch, Michael; Rennells, W. Martin; Richards, Justin J.; Rust, Timothy; Khmelnitsky, Yuri L.; Cohen, Marlene L.; Manning, David D. [Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 22, p. 6538 - 6541]

35
[ 570-23-0 ]
[ 100-07-2 ]
[ 906095-18-9 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 3-aminosalicylic acid; 4-methoxy-benzoyl chloride With pyridine In dichloromethane at 20℃; Stage #2: With toluene-4-sulfonic acid In toluene Reflux;

Reference： [1]Location in patent: scheme or table Yang, Zhicai; Fairfax, David J.; Maeng, Jun-Ho; Masih, Liaqat; Usyatinsky, Alexander; Hassler, Carla; Isaacson, Soshanna; Fitzpatrick, Kevin; Deorazio, Russell J.; Chen, Jianqing; Harding, James P.; Isherwood, Matthew; Dobritsa, Svetlana; Christensen, Kevin L.; Wierschke, Jonathan D.; Bliss, Brian I.; Peterson, Lisa H.; Beer, Cathy M.; Cioffi, Christopher; Lynch, Michael; Rennells, W. Martin; Richards, Justin J.; Rust, Timothy; Khmelnitsky, Yuri L.; Cohen, Marlene L.; Manning, David D. [Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 22, p. 6538 - 6541]

36
[ 617-89-0 ]
[ 570-23-0 ]
[ 1332325-54-8 ]

Yield	Reaction Conditions	Operation in experiment
30%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃; for 6.5h; Inert atmosphere;	5.2.18. N-(4-Fluorobenzyl)-2,3-dihydroxybenzamide (5a) General procedure: A solution of 2,3-dihydroxybenzoic acid (154 mg, 1 mmol), EDCI (380 mg, 2 mmol), DIPEA (2 mmol), and HOBt (290 mg, 2 mmol) in dry THF (15 mL) was stirred at rt under N2. To this solution was added 90% (4-fluorophenyl)methanamine (0.152 mL, 1.2 mmol). The reaction mixture was stirred for 6.5 h at rt. After removal of most of THF, 20 mL of EtOAc was added to the residue. The solution was washed by 1 N HCl, satd NH4Cl and dried over Na2SO4. The concentration provided the residue which was purified by chromatography using petroleum ether/ethyl acetate (1:1) as eluent to give compound 5a as a white solid (51 mg, 57% yield).

Reference： [1]Location in patent: experimental part Fan, Xing; Zhang, Feng-Hua; Al-Safi, Rasha I.; Zeng, Li-Fan; Shabaik, Yumna; Debnath, Bikash; Sanchez, Tino W.; Odde, Srinivas; Neamati, Nouri; Long, Ya-Qiu [Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 16, p. 4935 - 4952]

37
[ 935518-09-5 ]
[ 570-23-0 ]
[ 1338065-60-3 ]

Yield	Reaction Conditions	Operation in experiment
51%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 0 - 20℃;	11.i'; 64 3-amino-2-hydroxybenzoic acid (1 g, 6.5 mmol) was dissolved in 20 ml of DMF and at 0°C EDCI (1.4 g, 1.2equiv.), hydroxybenzotriazole (1 g, 1.2equiv.) and amine 2c (2 g, 1.2equiv.) were added. The mixture was stirred at rt for 20 hours. The solvent was evaporated and the crude was dissolved in AcOEt (30 ml) and washed with water (1 X 20 ml) and brine. The organic phase was dried over sodium sulfate and concentrated under vacuum. The purification of the crude residue by chromatographic column using AcOEt 1 / petroleum ether 9 as eluant gave 1.3 g of a beige solid. Yield = 51% [M+1] 393.4 (C20H22F3N3O2 requires 393.4).
51%	With N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In N,N-dimethyl-formamide at 0 - 20℃; for 20h;	64 Example 64: N-(4-(trifluoromethyl)-2-(piperidin-1-yl)benzyl)-3,4-dihydro-3-oxo-2H-benzo[b][1,4]oxazine-8-carboxamide (scheme 11) Preparation of N-(4-(trifluoromethyl)-2-(piperidin-1-yl)benzyl)-3-amino-2-hydroxybenzamide 24b 3-amino-2-hydroxybenzoic acid (1 g, 6.5 mmol) was dissolved in 20 ml of DMF and at 0°C EDCI (1.4 g, 1.2equiv.), hydroxybenzotriazole (1 g, 1.2equiv.) and amine 2c (2 g, 1.2equiv.) were added. The mixture was stirred at rt for 20 hours. The solvent was evaporated and the crude was dissolved in AcOEt (30 ml) and washed with water (1 X 20 ml) and brine. The organic phase was dried over sodium sulfate and concentrated under vacuum. The purification of the crude residue by chromatographic column using AcOEt 1 / petroleum ether 9 as eluant gave 1.3 g of a beige solid. Yield = 51% [M+1] 393.4 (C20H22F3N3O2 requires 393.4).

Reference： [1]Current Patent Assignee: SERENTRIX - WO2011/120604, 2011, A1 Location in patent: Page/Page column 97; 98; 136
[2]Current Patent Assignee: SERENTRIX - EP2377850, 2011, A1 Location in patent: Page/Page column 31

38
[ 570-23-0 ]
[ 55341-62-3 ]
[ 1133971-01-3 ]

Yield	Reaction Conditions	Operation in experiment
95%	Stage #1: 3-aminosalicylic acid; 9-oxo-9H-fluorene-1-carbonyl chloride With triethylamine In dichloromethane at 0 - 20℃; for 4h; Stage #2: With hydrogenchloride In dichloromethane; water	5.1.4. General procedure for the amide bond formation via acid chloride General procedure: To a stirred solution of amine (1.1 mmol, 1.1 equiv) and 0.46 mL triethylamine (3.3 mmol, dissolved in 2 mL dry CH2Cl2 at 0 °C, was added dropwise a solution of acid chloride (1 mmol, 1 equiv) in 2 mL dry CH2Cl2. Stirring was continued at 0 °C for 1 h and at room temperature for 3 h. The reaction mixture was diluted with 2-5 mL CH2Cl2, and acidified by 2 N HCl until pH 4. The precipitate was filtered, washed with H2O, CH2Cl2, and dried to give moderate-to-good yields (64-95%).

Reference： [1]Location in patent: experimental part Chen, Deliang; Ma, Lili; Kanalas, John J.; Gao, Jian; Pawlik, Jennifer; Jimenez, Maria Estrella; Walter, Mary A.; Peterson, Johnny W.; Gilbertson, Scott R.; Schein, Catherine H. [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 1, p. 368 - 376]

39
[ 570-23-0 ]
5-chloro-3-methylbenzo[b]thiophene-2-sulfonyl chloride [ No CAS ]
[ 1365721-38-5 ]

Yield	Reaction Conditions	Operation in experiment
72%	In 1,4-dioxane; water at 35℃; for 120h;	134 A solution of 5-chloro-3-methyl-benzothiophene-2-sulfonyl chloride (17 mg, 0.060 mmol) and 3-aminosalicylic acid (14 mg, 0.090 mmol) in 1200 μΙ_, of water/dioxane (1 :6) was shaken at 35 °C for 5 days. The product was purified by reversed phase chromatography (ACE C8,5μϖι, 21x50mm, flow 25 ml/min, gradient: 0.1% TFA in water/MeCN over 6 minutes). The title compound was obtained in 72% yield (17.2 mg). 1H NMR (500 MHz, DMSO-i ) δ ppm 2.48 (s, 3 H) 6.85 (t, J=7.92 Hz, 1 H) 7.46 (dd, J=7.69, 1.64 Hz, 1 H) 7.55 (dd, J=8.66, 2.05 Hz, 1 H) 7.63 (dd, J=7.92, 1.64 Hz, 1 H) 8.00 (dd, J=2.05, 0.47 Hz, 1 H) 8.04 (dd, J=8.66, 0.47 Hz, 1 H) 10.17 (br. s., 1 H). MS (ESI+) m/z 398 [M+H]+.

Reference： [1]Current Patent Assignee: KANCERA AB - WO2012/35171, 2012, A2 Location in patent: Page/Page column 111

40
4-bromo-5-chlorothiophen-2-yl-sulfonyl chloride [ No CAS ]
[ 570-23-0 ]
[ 1365722-00-4 ]

Yield	Reaction Conditions	Operation in experiment
53%	In 1,4-dioxane; water at 20℃; for 672h;	A solution of 3 -aminosalicylic acid (0.17 g, 1.11 mmol) and 3-bromo-2-chlorothiophene-5- sulfonyl chloride (0.33 g, 1.11 mmol) in aqueous dioxane (20 mL, 95:5 dioxane/water) was stirred at room temperature for 4 weeks. The pH of the reaction mixture was adjusted to about 9 using 1M Na2C03 and then EtOAc (200 mL) and water(100 mL) were added. The organic phase was removed and the aqueous phase washed with more EtOAc. The pH of the aqueous phase was adjusted to about 3 with concentrated phosphoric acid and EtOAc (200 mL) was added. The aqueous phase was removed and the organic phase was washed with 1 M HCl and brine, dried over MgS04, filtered and concentrated. The brown residue was recrystallized from aqueous MeOH at 60 °C. The precipitate was collected by filtration and dried over night. The title compound was obtained in 53% yield (0.24 g). 1H MR (500 MHz, MeOH-i¾) δ ppm 6.92 (t, J=7.93 Hz, 1 H) 7.34 (s, 1 H) 7.65 (dd, J=7.93, 1.59 Hz, 1 H) 7.75 (dd, J=7.93, 1.59 Hz, 1 H). MS (ESI+) m/z 412 [M+H]+.

Reference： [1]Current Patent Assignee: KANCERA AB - WO2012/35171, 2012, A2 Location in patent: Page/Page column 57

41
[ 570-23-0 ]
[ 5231-87-8 ]
[ 1383453-62-0 ]

Yield	Reaction Conditions	Operation in experiment
38%	In ethanol at 50 - 70℃; for 27.5h;	4.1 3-(2-Ethoxy-3,4-dioxocyclobut-1-enylamino)-2-hydroxybenzoic acid Step 1 3-(2-Ethoxy-3,4-dioxocyclobut-1-enylamino)-2-hydroxybenzoic acid A mixture of 1.68 g (11 mmol, 1.1 eq) of 3-aminosalicylic acid and 1.70 g (10 mmol, 1 eq) of 3,4-diethoxy-3-cyclobutene-1,2-dione in 15 ml of ethanol was heated at 50° C. for three and a half hours, then at 60° C. for 20 hours (66% product formed) and at 70° C. for 4 hours (55% product formed). The reaction medium was filtered and the filtrate was chromatographed on silica gel (column puriFlash IR50SI-120G, Spot II) eluted with dichloromethane/methanol (gradient). The solid was taken up with a little ethyl acetate, filtered and dried under vacuum at 55° C. 1.04 g of 3-(2-ethoxy-3,4-dioxocyclobut-1-enylamino)-2-hydroxy-benzoic acid were obtained in the form of a yellow-beige solid. Yield=38%.
	Stage #1: 3-aminosalicylic acid; 3,4-diethoxy-3-cyclobuten-1,2-dione With triethylamine In ethanol for 1h; Reflux; Stage #2: With sodium hydroxide In water; ethyl acetate Stage #3: With hydrogenchloride In water	36 Synthesis of Example 364-1Compound 4-1 (480 mg, 3.13 mmol), 3,4-diethoxy3-cyclobutene-l,2-dione (557 μ, 3.76 mmol) and triethylamine (1 mL) are dissolved in ethanol (5 mL) and the mixture refluxed for 1 hour. The solvent is removed, and the residue partitioned between 1 M aqueous NaOH solution and ethyl acetate. The aqueous phase is washed three times with ethyl acetate, acidified to pH 2 with concentrated HCl solution and extracted three times with DCM. The combined DCM extracts were dried and the solvent removed under reduced pressure to give compound 36-1.Yield: 570 mgES mass spectrum: [M+H]+ = 270
	Stage #1: 3-aminosalicylic acid; 3,4-diethoxy-3-cyclobuten-1,2-dione With triethylamine In ethanol for 1h; Reflux; Stage #2: With water; sodium hydroxide In ethyl acetate Stage #3: With hydrogenchloride In water; ethyl acetate	Compound 4-1 (480 mg, 3.13 mmol), 3,4-diethoxy-3-cyclobutene-1,2-dione (557 μL, 3.76 mmol) and triethylamine (1 mL) are dissolved in ethanol (5 mL) and the mixture refluxed for 1 hour. The solvent is removed, and the residue partitioned between 1 M aqueous NaOH solution and ethyl acetate. The aqueous phase is washed three times with ethyl acetate, acidified to pH 2 with concentrated HCl solution and extracted three times with DCM. The combined DCM extracts were dried and the solvent removed under reduced pressure to give compound 36-1.Yield: 570 mgES mass spectrum: [M+H]+=270Retention time HPLC: 0.65 min (HPLC method 2)

Reference： [1]Current Patent Assignee: Eqt Partners AB; Galderma (in: EQT Partners) - US2014/309208, 2014, A1 Location in patent: Paragraph 0136; 0137
[2]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - WO2012/80456, 2012, A1 Location in patent: Page/Page column 83
[3]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - US2012/329773, 2012, A1 Location in patent: Page/Page column 38

42
[ 570-23-0 ]
C₁₃H₈ClFN₂O₄ [ No CAS ]
[ 1383453-29-9 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 3-aminosalicylic acid; C₁₃H₈ClFN₂O₄ With pyridine In dichloromethane for 72h; Stage #2: With hydrogenchloride In dichloromethane; water	4 4-Nitrophenylchloroformate (868 mg, 4.31 mmol) is dissolved in dry dichloromethane (10 mL) and cooled to 0 °C. A solution of 2-chloro-3-fluoroaniline (627 mg, 4.31 mmol) and pyridine (355 4.48 mmol) in dry DCM (10 mL) is added dropwise and the mixture stirred for 15 minutes.Compound 4- 1 (600 mg, 3.92 mmol) is added followed by pyridine (1.2 mL, 15.1 mmol) and the mixture stirred for 3 days. The mixture is shaken with 0.2 M HCl solution and the phases allowed to separate. The organic phase is dried and the solvent removed. The residue is triturated with diethyl ether to give compound 4-2.Yield: 850 mgES mass spectrum: [M+H]+ = 325Retention time: 1.19 min (UPLC method 1)

Reference： [1]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - WO2012/80456, 2012, A1 Location in patent: Page/Page column 37

43
[ 570-23-0 ]
[ 21397-08-0 ]
[ 7693-46-1 ]
[ 1383453-29-9 ]

Yield	Reaction Conditions	Operation in experiment
		4-Nitrophenylchloroformate (868 mg, 4.31 mmol) is dissolved in dry dichloromethane (10 mL) and cooled to 0 C. A solution of <strong>[21397-08-0]2-chloro-3-fluoroaniline</strong> (627 mg, 4.31 mmol) and pyridine (355 muL 4.48 mmol) in dry DCM (10 mL) is added dropwise and the mixture stirred for 15 minutes. Compound 4-1 (600 mg, 3.92 mmol) is added followed by pyridine (1.2 mL, 15.1 mmol) and the mixture stirred for 3 days. The mixture is shaken with 0.2 M HCl solution and the phases allowed to separate. The organic phase is dried and the solvent removed. The residue is triturated with diethyl ether to give compound 4-2.Yield: 850 mgES mass spectrum: [M+H]+=325Retention time: 1.19 min (HPLC method 1)

Reference： [1]Patent: US2012/329773,2012,A1 .Location in patent: Page/Page column 17

44
[ 141-82-2 ]
[ 570-23-0 ]
[ 264260-07-3 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: malonic acid With naphthalene; trichlorophosphate at 150℃; for 0.5h; Stage #2: 3-aminosalicylic acid for 0.5h; Heating;	Experimental details The synthesis of the quinoline derivative was done by [24] adding corresponding anilines (0.20 ml) and malonic acid (0.18 mol). Naphthalene (0.12 mol) and malonic acid (0.18 mol) were melted under stirring at temperature control (<150 C) to avoid decarboxylationof the acid. POCl3 (0.36 mol) was then added dropwise over30 min and aminosalicylic acid (0.1 mol) was then added. The resulting mixture was heated for 30 min and allowed to cool. Water (100 ml) was added to the warm mixture and the solution was alkalized with 20% NaOH to pH 9. After cooling on ice precipitated naphthalene, it was filtered and the filtrate was acidified to pH 2. The product was filtered again and crystallized from acetic acid.

Reference： [1]Ulahannan, Rajeev T.; Panicker, C. Yohannan; Varghese, Hema Tresa; Van Alsenoy; Musiol, Robert; Jampilek, Josef; Anto [Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2014, vol. 121, p. 404 - 414]

45
[ 298-14-6 ]
[ 95-55-6 ]
[ 570-23-0 ]

Yield	Reaction Conditions	Operation in experiment
	With 2,3-dihydroxybenzoate decarboxylase from Aspergillus oryzae In aq. phosphate buffer at 30℃; for 24h; Enzymatic reaction; regioselective reaction;

Reference： [1]Wuensch, Christiane; Gross, Johannes; Steinkellner, Georg; Lyskowski, Andrzej; Gruber, Karl; Glueck, Silvia M.; Faber, Kurt [RSC Advances, 2014, vol. 4, # 19, p. 9673 - 9679]

46
[ 570-23-0 ]
[ 2843-26-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 0.5 h / 150 °C / Inert atmosphere 2: (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate / N,N-dimethyl-formamide / 0 °C / Inert atmosphere