Name: 86-48-6|1-Hydroxy-2-naphthoic acid|98%
Brand: Ambeed
SKU: A155867
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1
[ 77-78-1 ]
[ 86-48-6 ]
[ 948-03-8 ]

Yield	Reaction Conditions	Operation in experiment
100%	With lithium hydroxide In tetrahydrofuran for 1h; Heating;
95.9%	Stage #1: 1-hydroxy-2-naphthoic acid With lithium hydroxide In tetrahydrofuran for 0.5h; Stage #2: dimethyl sulfate In tetrahydrofuran for 3h; Heating;
95%	Stage #1: 1-hydroxy-2-naphthoic acid With triethylamine In acetone for 0.25h; Inert atmosphere; Stage #2: dimethyl sulfate In acetone at 55℃; for 12h; Inert atmosphere;

	With sodium carbonate
	Stage #1: 1-hydroxy-2-naphthoic acid With lithium hydroxide monohydrate In tetrahydrofuran at 20℃; for 0.5h; Inert atmosphere; Stage #2: dimethyl sulfate In tetrahydrofuran for 3h; Inert atmosphere; Reflux;	1.1 Step 1: Synthesis of methyl 1-hydroxy-2-naphthoate, compound 2 To a stirred solution of 1-hydroxy-2-naphthoic acid (5.0 g, 27 mmol) in THF (25 mL) atroom temperature was added lithium hydroxide monohydrate (1.1 g, 27 mmol). The mixture wasstirred for 30 minutes, afterwhich dimethyl sulfate (2.54 mL, 26.6 mmol) was added. The mixture was then refluxed for 3 hours, cooled to ambient temperature and concentrated in vacuo. The residue was diluted with saturated aqueous NaHCO3 and extracted with diethyl ether. The organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo, providingthe titled compound.
	Stage #1: 1-hydroxy-2-naphthoic acid With lithium hydroxide In tetrahydrofuran at 20℃; for 0.5h; Stage #2: dimethyl sulfate In tetrahydrofuran for 3h; Reflux;	1.1 Step 1 : Preparation of methyl 1 -hydroxy -2-naphthoate, Compound 2: To a solution of l-hydroxy-2-naphthoic acid (15 g, 80 mmol) in THF (80 mL) at room temperature was added LiOH (3.3 g, 80 mmol). The mixture was stirred for 30 minutes and was treated with dimethyl sulfate (15 mL, 159 mmol). The mixture was refluxed for 3 hours, cooled to room temperature, and the volatiles removed under reduced pressure. Aqueous saturated NaHCCb (100 mL) was added and the mixture was extracted with diethyl ether (3 x 300 mL). The combined organic extracts were dried with sodium sulfate, filtered, and concentrated under reduced pressure to afford the title compound, which gave a proton NMR spectra consistent with theory
	With tetrabutylammomium bromide; potassium carbonate In dichloromethane; water at 24℃;	Step 2. Preparation of 1-Hydroxynaphthalene-2-carboxylic acid methyl ester A 3 L jacketed reactor equipped with mechanical stirring, thermocouple, static nitrogen line, and addition funnel was charged with 1-hydroxynaphthalene-2-carboxylic acid (86.8 g, 461.3 mmol, 1 eq), tetrabutylammonium bromide (14.9 g, 46.1 mmol, 0.10 eq), and dichloromethane (1.74 L, 20 V). The resulting gray slurry was stirred while charging a solution of potassium carbonate (191.2 g, 1.38 moles, 3.0 eq) in H2O (434 mL, 5 V). Charged dimethyl sulfate (52.7 mL, 553.5 mmol, 1.20 eq) using an addition funnel and stirred at 24 °C for 4.5 h then charged additional dimethylsulfate (8.8 mL, 92.3 mmol, 0.20 eq). Stirred at 24 °C until in- process HPLC indicated complete reaction (< 0.5 A% SM). Separated the layers. Charged 2 M NH3 in MeOH (553.5 mL, 1.11 moles, 2.40 eq) and stirred at 23 °C for about 1 h until in-process NMR indicated no remaining dimethylsulfate. Washed with H2O (4 x 1 L). Dried with MgSO4. Removed the solvent in vacuo using a 40 °C bath. Dried the brown solids for an additional 1 h under high vacuum at room temperature to obtain 94.9 g of 1-hydroxy-naphthalene-2-carboxylic acid methyl ester as a soft brown solid (100.4 % yield, 98.7 A% HPLC).

Reference： [1]Chakraborti, Asit K.; Basak, Anindita; Grover, Vikas [Journal of Organic Chemistry, 1999, vol. 64, # 21, p. 8014 - 8017]
[2]Broyles, David A.; Carpenter, Barry K. [Organic and Biomolecular Chemistry, 2005, vol. 3, # 9, p. 1757 - 1767]
[3]Brockway, Anthony J.; González-López, Marcos; Fettinger, James C.; Shaw, Jared T. [Journal of Organic Chemistry, 2011, vol. 76, # 9, p. 3515 - 3518]
[4]Kauffmann; Egner [Chemische Berichte, 1913, vol. 46, p. 3786]
[5]Current Patent Assignee: MERCK & CO INC - WO2017/160670, 2017, A1 Location in patent: Page/Page column 28; 29; 30
[6]Current Patent Assignee: MERCK & CO INC - WO2018/5249, 2018, A1 Location in patent: Page/Page column 34; 35; 45
[7]Current Patent Assignee: SANOFI - WO2021/113808, 2021, A1 Location in patent: Page/Page column 69; 70; 71

2
[ 108-95-2 ]
[ 86-48-6 ]
[ 132-54-7 ]

Reference： [1]Chemische Berichte,1887,vol. 20,p. 2700
[2]Patent: DE43713,

3
[ 67-56-1 ]
[ 86-48-6 ]
[ 948-03-8 ]

Yield	Reaction Conditions	Operation in experiment
90%	With sulfuric acid
90%	With sulfuric acid
82%	With sulfuric acid Reflux;

80%	With sulfuric acid at 80℃; for 8h;	1-Hydroxy-naphthalene-2-carboxylic acid methylester II 1-Hydroxy-naphthalene-2-carboxylic acid (0.9 g, 5 mM) was dissolved in methanol and 1ml concentrated H2SO4 was added slowly with continuous stirring. The reaction mixture was refluxed at 80 °C for 8 h. The solvent was then evaporated under reduced pressure and a brown solid mass was extracted with ethylacetate (3 x 20 ml). The organic layer was washed several times with water and dried over anhydrous Na2SO4, and finally the solvent was removed under reduced pressure that gave a brown solid product II; yield 80% (Scheme 1).
80%	With sulfuric acid at 100℃; for 24h;
79%	With sulfuric acid for 48h; Inert atmosphere; Reflux;
74.4%	With sulfuric acid Reflux;	3-(1) 2L round bottom 1-hydroxy-2-naphthalic acid (50g, 266mmol) to the reactor flask, into 1000ml of methanol, 100ml of sulfuric acid was stirred for 100 hr reflux. After completion of the reaction monitored by TLC was cooled at room temperature. The solution was extracted with dichloromethane and concentrated under reduced pressure and then water. The organic layer was separated, by crystallization into a large excess After concentration under reduced pressure heptane obtained (40g, 74.4%)
72.6%	With sulfuric acid for 100h; Reflux;	3-1 Synthesis of intermediate 3-a 2L round bottom flask reactor, 1-hydroxy-2-naphthalic acid (50g, 266mmol), put into 1000ml of methanol, 100ml of sulfuric acid was stirred for 100 hours strring under reflux. After completion of the reaction monitored by TLC was cooled at room temperature. The solution was extracted with dichloromethane and concentrated under reduced pressure and then water. After treatment with anhydrous magnesium sulfate, the organic layer was separated by filtration, and then concentrated under reduced pressure to an excess of heptane crystallization put intermediates 3-a> (39g, 72.6%) was obtained.
72.6%	With sulfuric acid In methanol for 100h; Reflux;	7-1 synthesis of intermediate 7-a 2L round bottom flask reactor1-hydroxy-2-naphthalic acid (50g, 266mmol),Methanol 1000ml,Sulfuric acid was added 100ml100 hours stirring under reflux.After completion of the reaction monitored by TLC was cooled at room temperature. The solution was extracted with dichloromethane and concentrated under reduced pressure and then water. The organic layer was separated and the excess into the crystallization process after filtration over anhydrous magnesium sulfate, and then concentrated under reduced pressure heptane (39g, 72.6%) was obtained.
72.6%	With sulfuric acid for 100h; Reflux;	2-(1) Synthesis of Intermediate 2-a 2L A round bottom flask reactor was charged with 1-hydroxy 2-naphthalic acid (50 g, 266 mmol) 1000 ml of methanol and 100 ml of sulfuric acid were added, and the mixture was stirred under reflux for 100 hours. The reaction was terminated by TLC and then cooled to room temperature. The solution was concentrated under reduced pressure and then extracted with dichloromethane and water. The organic layer was separated, dried over anhydrous magnesium sulfate, filtered, concentrated under reduced pressure, and recrystallized from heptane to obtain Intermediate 2-a. (39 g, 72.6%).
72.6%	With sulfuric acid for 100h; Reflux;	3-1 Synthesis of Intermediate 3-a 1-hydroxy-2-naphthalenedicarboxylic acid (50 g, 266 mmol) was charged in a 2 L round bottom flask reactor,Methanol 1000 ml, sulfuric acid 100 ml, and refluxed for 100 hours.The TLC was used to confirm the end of the reaction and then cooled to room temperature. The solution was concentrated under reduced pressure and extracted with dichloromethane and water.And the organic layer was separated and subjected to an anhydrous treatment using magnesium sulfate, followed by filtration,After concentration under reduced pressure, excess heptane was charged and crystallized to obtain (39 g, 72.6%).
72.6%	With sulfuric acid for 100h; Reflux;	5-1 Synthesis of Intermediate 5-a In a 2-L round-bottom flask reactor, 1 -hydroxy2-naphthalic acid (50 g, 266 mmol), methanol (1000 ml), and sulfuric acid (100 ml) were stirred together for 100 hrsunder reflux. The completion of the reaction was confirmedby TLC before the reaction mixture was cooled to roomtemperature. The mixture was concentrated in a vacuum andextracted with dichloromethane and watet The organic layerwas isolated, dried over magnesium sulfate, and filtered. The filtrate was concentrated in a vacuum and crystallized in an excess of heptane to afford Intermediate 5-a (39 g, 72.6%).
72.6%	With sulfuric acid for 100h; Reflux;	3.1 Synthesis Example 3-(1): Synthesis of Intermediate 3-a In a 2-L round-bottom flask reactor, 1-hydroxy 2-naphthalic acid (50 g, 266 mmol), methanol (1000 ml), and sulfuric acid (100 ml) were stirred together for 100 hrs under reflux. The completion of the reaction was confirmed by TLC before the reaction mixture was cooled to room temperature. The mixture was concentrated in a vacuum and extracted with dichloromethane and water. The organic layer was isolated, dried over magnesium sulfate, and filtered. The filtrate was concentrated at a reduced pressure and crystallized in an excess of heptane to afford (39 g, 72.6%).
72.6%	With sulfuric acid for 100h; Reflux;	7.7-1 Synthesis Example 7- (1): Synthesis of Intermediate 7-a According to Scheme 50, intermediate 7-a was synthesized:1-hydroxy 2-naphthalic acid (50 g, 266 mmol) in a 2 L round bottom flask reactor,1000 ml of methanol and 100 ml of sulfuric acid were added thereto, and the mixture was stirred under reflux for 100 hours.After confirming the reaction termination by TLC, the mixture was cooled to room temperature. The solution was concentrated under reduced pressure and extracted with dichloromethane and water.The organic layer was separated, anhydrous treated with magnesium sulfate, filteredAfter concentration under reduced pressure, heptane was added in excess and crystallized to obtain an intermediate 7-a> (39 g, 72.6%).
69%	With sulfuric acid for 100h; Reflux;	1 Synthesis of A1 1-Hydroxy 2-naphthalic acid (50 g, 266 mmol), methanol (1000 ml) and sulfuric acid (100 ml) were placed and heated under reflux and stirring for 100 hours. After confirming the termination of the reaction, the solution was cooled to room temperature, concentrated under reduced pressure, and extracted with methylene chloride and water. The organic layer was separated, dried over anhydrous magnesium sulfate, filtered, concentrated under reduced pressure, and solidified by adding hexane in an excess amount to obtain A1 (33 g, 69%)
35%	With thionyl chloride at 0 - 65℃; for 48h; Inert atmosphere;	Esterification of carboxylic acids Ia-VIIa: General procedure: Method B: To a solution of the corresponding acid (21.87 mmol) in MeOH (35 mL) at 0 °C, SOCl2 (15.86 mL, 218.75 mmol) was added dropwiseover a period of 10 min. Once the addition was finished, the reaction wasallowed to warm to rt and subsequently heated to 65°C for a period of 18 hours.After this time, MeOH and the excess of SOCl2 were removed undervacuum. The residue obtained was dissolved in DCM and a saturated solution ofNaHCO3 (40 mL) was added until no evolution of gas was observed. Theaqueous solution was extracted with DCM (3 x 40 mL) and the combined organicphases were dried over Na2SO4 and concentrated undervacuum to afford the desired compound with enough purity to be used in the nextreaction without further purification.
35%	With thionyl chloride at 0 - 65℃; for 48h; Inert atmosphere;
32%	With sulfuric acid for 44h; Reflux;
	With sulfuric acid
	With sulfuric acid for 24h; Heating;
	With protic acid
	With sulfuric acid Reflux;
1.117 g	With thionyl chloride at 0 - 65℃; for 18h;

Reference： [1]Hoque, Md. Najbul; Basu, Arghya; Das, Gopal [Journal of Fluorescence, 2014, vol. 24, # 2, p. 411 - 416]
[2]Bouchet, Samuel; Linot, Camille; Ruzic, Dusan; Agbaba, Danica; Fouchaq, Benoit; Roche, Joëlle; Nikolic, Katarina; Blanquart, Christophe; Bertrand, Philippe [ACS Medicinal Chemistry Letters, 2019, vol. 10, # 6, p. 863 - 868]
[3]Haberhauer, Gebhard; Semleit, Nina [Organic Letters, 2021, vol. 23, # 24, p. 9635 - 9639]
[4]Hoque, Md. Najbul; Basu, Arghya; Das, Gopal [Supramolecular Chemistry, 2014, vol. 26, # 5-6, p. 392 - 402]
[5]Yu, Rongrong; Chen, Xingyu; Martin, Stephen F.; Wang, Zhiqian [Organic Letters, 2017, vol. 19, # 7, p. 1808 - 1811]
[6]Location in patent: experimental part Dean, Melissa A.; Hitchcock, Shawn R. [Tetrahedron Asymmetry, 2010, vol. 21, # 20, p. 2471 - 2478]
[7]Current Patent Assignee: HODOGAYA CHEMICAL CO LTD - KR2015/128583, 2015, A Location in patent: Paragraph 0302-0308
[8]Current Patent Assignee: HODOGAYA CHEMICAL CO LTD - KR2015/130206, 2015, A Location in patent: Paragraph 0499-0504
[9]Current Patent Assignee: SFC CO LTD - KR2016/13678, 2016, A Location in patent: Paragraph 0529-0535
[10]Current Patent Assignee: HODOGAYA CHEMICAL CO LTD - KR2017/86011, 2017, A Location in patent: Paragraph 0304; 0305-0310
[11]Current Patent Assignee: HODOGAYA CHEMICAL CO LTD - CN107207454, 2017, A Location in patent: Paragraph 0254; 0255; 0256; 0258; 0259
[12]Current Patent Assignee: HODOGAYA CHEMICAL CO LTD - US2017/342318, 2017, A1 Location in patent: Paragraph 0202; 0203
[13]Current Patent Assignee: HODOGAYA CHEMICAL CO LTD - US2018/233669, 2018, A1 Location in patent: Paragraph 0191-0192
[14]Current Patent Assignee: SFC CO LTD - KR2019/111856, 2019, A Location in patent: Paragraph 0529-0535
[15]Current Patent Assignee: LG CHEM CO.,LTD. - KR2018/75914, 2018, A Location in patent: Paragraph 0277-0280
[16]Nolla-Saltiel, Roberto; Robles-Marín, Elvis; Porcel, Susana [Tetrahedron Letters, 2014, vol. 55, # 32, p. 4484 - 4488]
[17]Carrillo-Arcos, Ulises A.; Rojas-Ocampo, Jonathan; Porcel, Susana [Dalton Transactions, 2015, vol. 45, # 2, p. 479 - 483]
[18]Krogsgaard-Larsen, Niels; Delgar, Claudia G.; Koch, Karina; Brown, Patricia M. G. E.; Møller, Charlotte; Han, Liwei; Huynh, Tri H. V.; Hansen, Stinne W.; Nielsen, Birgitte; Bowie, Derek; Pickering, Darryl S.; Kastrup, Jette Sandholm; Frydenvang, Karla; Bunch, Lennart [Journal of Medicinal Chemistry, 2017, vol. 60, # 1, p. 441 - 457]
[19]Schmitt; Burkard [Chemische Berichte, 1887, vol. 20, p. 2700]
[20]Catalan, Javier; Del Valle, Juan C.; Palomar, Jose; Diaz, Cristina; De Paz, Jose L. G. [Journal of Physical Chemistry A, 1999, vol. 103, # 50, p. 10921 - 10934]
[21]Wessig, Pablo; Mller, Gunnar [Australian Journal of Chemistry, 2008, vol. 61, # 8, p. 569 - 572]
[22]Al-Mughaid, Hussein; Al-Zoubi, Raed M.; Khazaaleh, Maha; Grindley, T. Bruce [Carbohydrate Research, 2017, vol. 446-447, p. 76 - 84]
[23]Carrillo-Arcos, Ulises A.; Porcel, Susana [Organic and Biomolecular Chemistry, 2018, vol. 16, # 11, p. 1837 - 1842]

4
[ 64-17-5 ]
[ 86-48-6 ]
[ 33950-71-9 ]

Yield	Reaction Conditions	Operation in experiment
93%	With pyridine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In toluene at 20℃; for 7.5h; Inert atmosphere;	3-1 Synthesis of (3-1) of 1-hydroxy-2-carboxylate Under an argon atmosphere, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (9.2 g), pyridine (9.7 mL of) in toluene (199 ml) was added dropwise Add 1-hydroxy-naphthoic acid (7.5g) and ethanol (148 mL) was stirred at room temperature for 7.5 hours.Under reduced pressure from the resulting reaction mixture was distilled to remove the solvent, and the resulting residue was dissolved in dichloromethane, the dichloromethane layer was washed successively with 5% hydrochloric acid and saturated brine, dried over anhydrous sodium sulfate, reduced in The solvent was removed by distillation pressure.The resulting residue was purified by silica gel chromatography to obtain 1-hydroxy-2-naphthoic acid ethyl ester (7.98g).The yield was 93%.
	With sulfuric acid
	Stage #1: 1-hydroxy-2-naphthoic acid With thionyl chloride Stage #2: ethanol With triethylamine

With sulfuric acid Reflux;

- Route B (R1 = aryl) General procedure: Note: hydrazine and carbon disulphide used during this procedure have to be handled withcaution.The carboxylic compound was first converted into its ethyl ester by refluxing in absoluteethanol in the presence of a few drops of H2SO4. The ester was then treated overnight withhydrazine hydrate (2 to 4 equiv.) without solvent at 120 °C. Evaporation of excess hydrazineyielded the corresponding hydrazide compound. The hydrazide, solubilized in absolute ethanol,was treated with CS2 (5 equiv.) in the presence of KOH (1.7 equiv.) at 85 °C for 3 h. Water wasadded and pH was adjusted to 2-3 with 1N HCl. The formed precipitate was collected byfiltration and washed with water, yielding the 1,3,4-oxadiazol-thione, which was used withoutfurther purification. Finally, the preceding compound was treated with hydrazine hydrate (10equiv.) in absolute ethanol at 100 °C overnight in a sealed tube. After evaporation of excesshydrazine, the residue was purified on a silica gel column to yield the final compound.

Reference： [1]Current Patent Assignee: IDEMITSU KOSAN CO LTD - CN105431407, 2016, A Location in patent: Paragraph 0231
[2]Schmitt; Burkard [Chemische Berichte, 1887, vol. 20, p. 2700]
[3]Cappelli, Andrea; Anzini, Maurizio; Vomero, Salvatore; Mennuni, Laura; Makovec, Francesco; Doucet, Edith; Hamon, Michel; Menziani; De Benedetti, Pier G.; Giorgi, Gianluca; Ghelardini, Carla; Collina, Simona [Bioorganic and Medicinal Chemistry, 2002, vol. 10, # 3, p. 779 - 801]
[4]Baud, Damien; Bebrone, Carine; Becker, Katja; Benvenuti, Manuela; Cerboni, Giulia; Chelini, Giulia; Cutolo, Giuliano; De Luca, Filomena; Docquier, Jean-Denis; Feller, Georges; Fischer, Marina; Galleni, Moreno; Gavara, Laurent; Gresh, Nohad; Kwapien, Karolina; Legru, Alice; Mangani, Stefano; Mercuri, Paola; Pozzi, Cecilia; Sannio, Filomena; Sevaille, Laurent; Tanfoni, Silvia; Verdirosa, Federica; Berthomieu, Dorothée; Bestgen, Benoît; Frère, Jean-Marie; Hernandez, Jean-François [European Journal of Medicinal Chemistry, 2020, vol. 208]

5
[ 2832-19-1 ]
[ 86-48-6 ]
4-[(2-chloro-acetylamino)-methyl]-1-hydroxy-[2]naphthoic acid [ No CAS ]

Reference： [1]Helvetica Chimica Acta,1931,vol. 14,p. 355,357

6
[ 140-95-4 ]
[ 86-48-6 ]
1,1'-dihydroxy-4,4'-(3-oxo-2,4-diaza-pentanediyl)-di-[2]naphthoic acid [ No CAS ]

Reference： [1]Helvetica Chimica Acta,1931,vol. 14,p. 355,357

7
[ 86-48-6 ]
[ 38077-69-9 ]

Yield	Reaction Conditions	Operation in experiment
	With chloroform; phosphorus pentachloride; Petroleum ether
	With thionyl chloride
	With thionyl chloride; Petroleum ether

	With thionyl chloride In chloroform Heating;
	With thionyl chloride; N,N-dimethyl-formamide In n-heptane at 60℃;
	With thionyl chloride In N,N-dimethyl-formamide; benzene	I.a EXAMPLE I a. Dry 1-hydroxy-2-naphthoic acid (50 gms., 0.266 mole) was suspended in 350 ml. dry benzene in a flame-dried 1 liter 1-neck round bottom flask under an air condenser and drying tube. Thionyl chloride (31.7 gms., 0.266 mole) was added in one portion followed by 1.5 ml. dry N,N-dimethylformamide. The reaction mixture was stirred magnetically 2-3 days at room temperature. Insoluble material (6.5 gms.) was removed by filtration, and the yellow-tan filtrate was evaporated to dryness to give pale yellow 1-hydroxy-2-naphthoyl chloride, m. p. 87°-88° C.
	With thionyl chloride In n-heptane; N,N-dimethyl-formamide for 4h; Reflux;
	With oxalyl dichloride In dichloromethane at 20℃; for 2h;
	With thionyl chloride In dichloromethane at 40℃; for 1h;
	With thionyl chloride In N,N-dimethyl-formamide; benzene	I.a EXAMPLE I a. Dry 1-hydroxy-2-naphthoic acid (50 gms., 0.266 mole) was suspended in 350 ml. dry benzene in a flame-dried 1 liter 1-neck round bottom flask under an air condenser and drying tube. Thionyl chloride (31.7 gms., 0.266 mole) was added in one portion followed by 1.5 ml. dry N,N-dimethylformamide. The reaction mixture was stirred magnetically 2-3 days at room temperature. Insoluble material (6.5 gms.) was removed by filtration, and the yellow-tan filtrate was evaporated to dryness to give pale yellow 1-hydroxy-2-naphthoyl chloride, m.p. 87°-88° C.
	With thionyl chloride; N,N-dimethyl-formamide In dichloromethane at 25℃; for 12h;	Method B General procedure: Thionyl chloride (1.46 mL, 20.0 mmol) was added to a suspension of salicylic acid (4.0 mmol) in DCM (20 mL), followed by a catalytic amount of DMF (0.80 mmol). The reaction mixture was stirred overnight at room temperature. The solvent and residual thionyl chloride were removed under reduced pressure and the crude residue was used immediately without further purification. The crude was resuspended in DCM (20 mL), 4-aminobenzonitrile (945 mg, 8.0 mmol) was added and the reaction mixture was stirred overnight at room temperature. The mixture was diluted with DCM, washed with 1M HCl solution, brine, dried (MgSO4) and evaporated to dryness under reduced pressure. Chromatography (hexanes in ethyl acetate 0-100%) afford the salicylamides.
	With phosphorus trichloride Microwave irradiation;

Reference： [1]Anschuetz,R. [Chemische Berichte, 1897, vol. 30, p. 222] Anschuetz,R.; Weber; Runkel [Justus Liebigs Annalen der Chemie, 1906, vol. 346, p. 361]
[2]Meyer,H. [Monatshefte fur Chemie, 1901, vol. 22, p. 785][Monatshefte fuer Chemie, 1904, vol. 25, p. 478]
[3]Pianka; Barany [Journal of the Chemical Society, 1948, p. 309]
[4]Vansdadia; Vikani; Rarekh [Journal of the Indian Chemical Society, 1988, vol. 65, # 11, p. 782 - 783]
[5]Van Zandt, Michael C.; Sibley, Evelyn O.; McCann, Erin E.; Combs, Kerry J.; Flam, Brenda; Sawicki, Diane R.; Sabetta, Al; Carrington, Anne; Sredy, Janet; Howard, Eduardo; Mitschler, Andre; Podjarny, Alberto D. [Bioorganic and Medicinal Chemistry, 2004, vol. 12, # 21, p. 5661 - 5675]
[6]Current Patent Assignee: PLR IP HOLDINGS, LLC - US4010168, 1977, A
[7]Location in patent: experimental part Kurteva, Vanya B.; Antonov, Liudmil M.; Nedeltcheva, Daniela V.; Crochet, Aurélien; Fromm, Katharina M.; Nikolova, Rositsa P.; Shivachev, Boris L.; Nikiforova, Maya S. [Dyes and Pigments, 2012, vol. 92, # 3, p. 1266 - 1277]
[8]Schrader, Florian C.; Glinca, Serghei; Sattler, Julia M.; Dahse, Hans-Martin; Afanador, Gustavo A.; Prigge, Sean T.; Lanzer, Michael; Mueller, Ann-Kristin; Klebe, Gerhard; Schlitzer, Martin [ChemMedChem, 2013, vol. 8, # 3, p. 442 - 461]
[9]Wang, Shengzheng; Fang, Kun; Dong, Guoqiang; Chen, Shuqiang; Liu, Na; Miao, Zhenyuan; Yao, Jianzhong; Li, Jian; Zhang, Wannian; Sheng, Chunquan [Journal of Medicinal Chemistry, 2015, vol. 58, # 16, p. 6678 - 6696]
[10]Current Patent Assignee: PLR IP HOLDINGS, LLC - US4056539, 1977, A
[11]Chae, Hee-Don; Cox, Nick; Capolicchio, Samanta; Lee, Jae Wook; Horikoshi; Kam, Sharon; Ng, Andrew A.; Edwards, Jeffrey; Butler, Tae-León; Chan, Justin; Lee, Yvonne; Potter, Garrett; Capece, Mark C.; Liu, Corey W.; Wakatsuki, Soichi; Smith, Mark; Sakamoto, Kathleen M. [Bioorganic and Medicinal Chemistry Letters, 2019, vol. 29, # 16, p. 2307 - 2315]
[12]Campos, Ludmila E.; Garibotto, Francisco M.; Angelina, Emilio; Kos, Jiri; Tomašič, Tihomir; Zidar, Nace; Kikelj, Danijel; Gonec; Marvanova, Pavlina; Mokry, Petr; Jampilek; Alvarez, Sergio E.; Enriz, Ricardo D. [Bioorganic Chemistry, 2019, vol. 91]

8
[ 86-48-6 ]
[ 5813-37-6 ]

Yield	Reaction Conditions	Operation in experiment
99%	With bromine In acetic acid at 20℃;
99%	With bromine; acetic acid at 20℃;
92%	With bromine In acetic acid at 20℃; Inert atmosphere;	93.1 Bromine (6.1 mL, 120 mmol) was added to a solution of 1 -hydroxys- naphthoic acid (compound 66, 18.9 g, 100 mmol) in glacial acetic acid (250 mL). The mixture was stirred at room temperature overnight. The resulting solid was filtered and dried in vacuo to yield the title compound (24.6 g, 92 %) as a white solid.1H NMR (400 MHz, DMSO-d6) δ 8.31 (d, J = 8.4 Hz, IH), 8.04 (d, J = 8.4 Hz, IH), 7.96 (s, IH), 7.82 (t, J= 7.2 Hz, IH), 7.67 (t, J= 7.2 Hz, IH);MH+ 267.

92%	With bromine; acetic acid at 20℃; Inert atmosphere;	8.1 Step 1: 4-Bromo-l-hydroxy-2-naphthoic acid (18)Bromine (6.1 mL, 120 mmol) was added to a solution of naphthoic acid 17 (18.9 g, 100 mmol) in glacial acetic acid (250 mL). The mixture was stirred at room temperature overnight. The resulting solid was filtered and dried in vacuo to provide the titled compound 18 (24.7 g, 92%) as a white solid.1H NMR (400 MHz, DMSO-i 6) δ 8.31 (d, J= 8.4 Hz, 1H), 8.04 (d, J= 8.4 Hz, 1H),7.96 (s, 1H), 7.82 (t, J= 7.2 Hz, 1H), 7.67 (t, J= 7.2 Hz, 1H); MH+ 267.
	With bromine; acetic acid
	With bromine In chloroform for 16h;	4-Bromo-1-hydroxy-naphthalene-2-carboxylic acidTo a solution of 2.50 g 1-hydroxy-2-naphthoic acid in 50 ml chloroform a solution of 0.68 ml bromine in 5 ml chloroform was added dropwise. After 16 h the reaction was concentrated to yield 3.40 g 4-bromo-1-hydroxy-naphthalene-2-carboxylic acid. C1 1 H7BrO3 (267.08, LCMS (ESI): 268.95 (MH+).
	With bromine In acetic acid at 20℃;	182a.1 The title compound was prepared according to a literature procedure published in J. Med. Chem. 2001, 44, 1815.
	With bromine In acetic acid for 72h;	1 To a solution of l-hydroxy-2 -naphthoic acid (10.2 g, 53.9 mmol) in 100 mL of acetic acid was added bromine (6.60 mL, 53.9 mmol) dropwise. After 72 hours, the reaction was filtered and the filter cake was washed with acetic acid (40 mL) and hexanes (150 mL) to provide 4-bromo- l-hydroxy-2 -naphthoic acid that gave a proton NMR spectra consistent with theory

Reference： [1]Mach, Robert H.; Hammond, Philip S.; Huang, Yunsheng; Yang, Biao; Xu, Yueping; Cheney, Jason T.; Freeman, Rebekah; Luedtke, Robert R. [Medicinal Chemistry Research, 1999, vol. 9, # 6, p. 355 - 373]
[2]Huang; Luedtke; Freeman; Wu; Mach [Journal of Medicinal Chemistry, 2001, vol. 44, # 11, p. 1815 - 1826]
[3]Current Patent Assignee: GREEN CROSS HOLDINGS CORPORATION - WO2010/147430, 2010, A2 Location in patent: Page/Page column 110
[4]Current Patent Assignee: GREEN CROSS HOLDINGS CORPORATION - WO2011/159067, 2011, A2 Location in patent: Page/Page column 53
[5]Weil [Chemische Berichte, 1911, vol. 44, p. 3060]
[6]Current Patent Assignee: SANOFI - WO2008/409, 2008, A1 Location in patent: Page/Page column 156
[7]Current Patent Assignee: AMGEN INC - WO2006/44823, 2006, A2 Location in patent: Page/Page column 183
[8]Current Patent Assignee: MERCK & CO INC - WO2011/149801, 2011, A1 Location in patent: Page/Page column 32

9
[ 86-48-6 ]
[ 5409-15-4 ]

Yield	Reaction Conditions	Operation in experiment
	With methanol durch Chlorieren;
	With acetic acid durch Chlorieren;
	With bismuth(III) chloride; sulfuryl dichloride; diethyl ether

	With sulfuryl dichloride In chloroform at 20℃; for 8h;	4-Chloro-1 -hydroxy-naphthalene^-carboxylic acidTo a suspension of 30.0 g i-Hydroxy-naphthalene-2-carboxylic acid in 600 ml chloroform a mixture of 14.9 ml sulfuryl chloride and 20 ml chloroform was added dropwise. After stirring the reation for 8 h at room temperature the precipitated product was isolated by filtration, washed with dichloromethane and recrystallized from isopropanol/water to yield 25.1 g of 4-chloro-1-hydroxy-naphthalene-2-carboxylic acid as off-white solid.C1 1 H7CIO3 (222.63, LCMS (ESI): 223.00 (MH+).
	With sulfuryl dichloride In chloroform at 20℃; for 8h;	4-Chloro-1-hydroxy-naphthalene-2-carboxylic acid To a suspension of 30.0 g i-Hydroxy-naphthalene-2-carboxylic acid in 600 ml chloroform a mixture of 14.9 ml sulfuryl chloride and 20 ml chloroform was added dropwise. After stirring the reation for 8 h at room temperature the precipitated product was isolated by filtration, washed with dichloromethane and recrystallized from isopropanol/water to yield 25.1 g of 4-chloro-1-hydroxy-naphthalene-2-carboxylic acid as off-white solid.C1 1 H7CIO3 (222.63, LCMS (ESI): 223.00 (MH+).

Reference： [1]Reissert [Chemische Berichte, 1911, vol. 44, p. 867] Weil; Heerdt [Chemische Berichte, 1922, vol. 55, p. 230] Weil [Chemische Berichte, 1911, vol. 44, p. 3060]
[2]Reissert [Chemische Berichte, 1911, vol. 44, p. 867] Weil; Heerdt [Chemische Berichte, 1922, vol. 55, p. 230] Weil [Chemische Berichte, 1911, vol. 44, p. 3060]
[3]Airan; Shah [Journal of the University of Bombay, Science: Physical Sciences, Mathematics, Biological Sciences and Medicine, 10, Tl 5A <1942> 131, 133]
[4]Current Patent Assignee: SANOFI - WO2008/407, 2008, A1 Location in patent: Page/Page column 60
[5]Current Patent Assignee: SANOFI - WO2008/409, 2008, A1 Location in patent: Page/Page column 155-156

10
[ 86-48-6 ]
[ 103986-80-7 ]

Yield	Reaction Conditions	Operation in experiment
72%	With chloro(1,5-cyclooctadiene)rhodium(I) dimer In methanol at 40℃; for 12h; Inert atmosphere; regioselective reaction;
	With hydrogenchloride; Pt/Al₂O₃; colloid; acetic acid Hydrogenation;
	With acetic acid; platinum Hydrogenation;

With sodium hydroxide; aluminum nickel

Reference： [1]He, Yuan; Tang, Jinghua; Luo, Meiming; Zeng, Xiaoming [Organic Letters, 2018, vol. 20, # 14, p. 4159 - 4163]
[2]Hueckel; Goth [Chemische Berichte, 1924, vol. 57, p. 1290]
[3]Hueckel; Goth [Chemische Berichte, 1924, vol. 57, p. 1290]
[4]Papa; Schwenk; Breiger [Journal of Organic Chemistry, 1949, vol. 14, p. 366,369]

11
[ 137-07-5 ]
[ 86-48-6 ]
[ 76995-70-5 ]

Yield	Reaction Conditions	Operation in experiment
84%	Stage #1: 2-amino-benzenethiol; 1-hydroxy-2-naphthoic acid In toluene at 90℃; Stage #2: With phosphorus trichloride In toluene at 60℃; for 2h; Reflux;
72%	With triphenyl phosphite; tetrabutylammomium bromide at 120℃; for 1h;	2. General procedure General procedure: A mixture of 1.55 g (5 mmol) of triphenyl phosphite (TPP), 1.66-2.25 g (5-7 mmol) of tetrabutylammonium bromide (TBAB), 0.625 g (5 mmol) of 2-aminothiophenol, and the corresponding substituted benzoic acid (5 mmol) in a 25 mL round bottomed flask was placed in an oil bath. The solution was stirred (15-60 minutes depending on the type of acid used) at 120oC. The product precipitated from the viscous solution by adding MeOH, and the resulting solid was filtered off and washed with cold MeOH to give the desired benzothiazole.
61%	With phosphorus trichloride In toluene for 4h; Heating;

61.5 g

With PPA at 120 - 170℃; for 9h; Inert atmosphere;

1 1) operation: to the ground with argon protection with mechanical mixing, condenser,Thermometer 2000ml three bottles of argon (30ml / min) 30min followed by adding 95g 2-mercaptoaniline,65.1 g of 1-naphthol-2-carboxylic acid, 696 g of PPA,Open the heating to 120 after the opening to continue to heat up to 160 ~ 170 between the incubation reaction after 9h every 2h sampling time,The reaction was stopped until the starting material 2-mercaptoaniline LC 80% (this reaction was about 9 h,Raw materials 2 - mercaptoaniline = 0.8296%Main content of 2-naphthol benzothiazole LC = 86.0820%, see Figure 1), 2) Post-processing:Step 1) The reaction solution was cooled to 120 ° C while the reaction solution was slowly poured into the stirred 4 L ice-water mixture, and the mixture was stirred for 2 hours, allowed to stand for 3 hours, filtered and drained. The filter cake was washed with 500 ml / To neutral (PH about 7),The filter cake was dried and dried by vacuum drying (-0.08 MPa ~ -0.09 MPa, 75 ° C, 10 h) to give 149 g of a grayish green solid (2-naphthol benzothiazole LC = 89.2094%, see Figure 2).Solid with 935ml toluene reflux (100 ~ 108 ) for 2h and then cooled to 90 (6 to 13 ° C) for 8 to 10 hours, and the mixture was dried and dried, and the filtrate was concentrated under reduced pressure (-0.08 MPa to -0.09 MPa, 65 ° C) to about 400 ml.Filter powder (-0.08MPa ~ -0.09MPa, 75 , 8h) to get 99g products (the main content of 2-naphthol benzothiazole LC = 98.1055%See Figure 3) (toluene to remove the solid in the water and purification); product added 2178ml dichloromethane dissolved at 36 ° C, began to over the insulation column, column liquid concentration under pressure (-0.06MPa, 35-40 ) To the remaining about 400ml to stop the concentration of concentrated liquid at room temperature (6 ~ 13 ) placed 8 ~ 10h filter, dry,(-0.08MPa ~ -0.09MPa, 75 , 6h) to get 86.5g product (main content 2-naphthol benzothiazole LC = 99.6145%, see Figure 4);(35 ~ 40 ) for 1h, stirring at room temperature (6 ~ 13 ) for 3h after filtration, dry, filter cake vacuum drying (-0.08MPa ~ -0.09 MPa, 75 ° C, 8 h) to give 61.5 g of product.Samples were taken until the product 2-naphthol benzothiazole LC> 99.9% (2-mercaptoaniline was not detected,Main content of 2-naphthol benzothiazole LC = 99.9786%, see Figure 5);

Reference： [1]Kiprof, Paul; Carlson, Jeffrey C.; Anderson, Derrick R.; Nemykin, Victor N. [Dalton Transactions, 2013, vol. 42, # 42, p. 15120 - 15132]
[2]Meghdadi, Soraia; Amirnasr, Mehdi; Ford, Peter C. [Tetrahedron Letters, 2012, vol. 53, # 51, p. 6950 - 6953]
[3]Anthony, Kevin; Brown, Robert G.; Hepworth, John D.; Hodgson, Kevin W.; May, Bernadette; West, Michael A. [Journal of the Chemical Society. Perkin transactions II, 1984, p. 2111 - 2118]
[4]Current Patent Assignee: XI'AN MANARECO NEW MATERIALS CO LTD - CN106892880, 2017, A Location in patent: Paragraph 0028-0031

12
[ 74-88-4 ]
[ 86-48-6 ]
[ 6039-59-4 ]

Yield	Reaction Conditions	Operation in experiment
100%	With potassium carbonate In acetone Reflux;	10 Synthesis of intermediate 30 50.0 g (0.265 mol) of 1-hydroxy-2-naphthoic acid, 110.2 g (0.797 mol) of potassium carbonate (K2CO3) and 1050 mL of acetone were placed in a 2 L 1-necked flask, 151 g (1.06 mol) was slowly added dropwise and then refluxed. After completion of the reaction, the inorganic matter was removed by filtration, and the solvent was removed by concentration under reduced pressure. The concentrate was extracted twice with EA, washed with saturated brine, dried over anhydrous MgSO 4 and concentrated under reduced pressure to obtain 57.45 g (yield: 100%) of a red oil compound (Intermediate (30)).
96%	With potassium carbonate In acetone Reflux;
95%	With potassium carbonate In acetone for 18h; Reflux;	STEP-1: Synthesis of 1-methoxy-naphthalene-2-carboxylic acid methyl ester. The suspension of 1-hydroxy-naphthalene-2-carboxylic acid (25g, 133 mmol), potassium carbonate (55 g, 399 mmol), and methyl iodide (76g, 532 mmol) in acetone (600 ml) were refluxed for 18 h. After completion of reaction, the reaction mixture was cooled at room temperature. The solid material was filtered off. The filtrate was concentrated; work up with ethyl acetate (500 ml), washed with aqueous NaHCO3 solution, dried, concentrated to afford 1-methoxy-naphthalene-2-carboxylic acid methyl ester (27 g, 95%). 1H-NMR (CDCl3, 500 MHz) d3.93 (s, 3H), 3.99 (s, 3H), 7.19 (s, 1H), 7.36 (m, 1H), 7.50 (m, 1H), 7.72 (d,J = 6.2 Hz, 1H), 7.80 (d, J = 6.2 Hz, 1H), 8.29 (s, 1H).

92.4%	Stage #1: 1-hydroxy-2-naphthoic acid With sodium hydride In N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: methyl iodide In N,N-dimethyl-formamide at 20℃; for 72h;
89%	With sodium hydride In N,N-dimethyl-formamide at 60℃; for 4h;
88.7%	With potassium carbonate In N,N-dimethyl-formamide at 40℃;	76 Synthesis of Intermediate 3a Dissolve 1-hydroxy-2-naphthoic acid (5g, 26,57mmol) in 15ml DMF solution,Add potassium carbonate (11.02g, 79.71mmol), iodomethane (6.62ml, 106.28mmol) in sequence,The reaction was reacted overnight at 40 degrees, and the reaction was monitored by TLC to end.The reaction solution was poured into water, extracted twice with ethyl acetate, washed with saturated sodium chloride solution,It was dried over anhydrous sodium sulfate, and subjected to silica gel column chromatography (PE / EA = 20/1) to obtain intermediate 3a (5.1 g, 88.7%).
85%	In acetone at 55℃;
84%	With potassium carbonate In acetone for 13h; Heating;
44%	With potassium carbonate In acetone for 16h; Reflux;	methyl 1-methoxynaphthalene-2-carboxylate To a solution of 1-hydroxynaphthalene-2-carboxylic acid (10.0 g, 53.1 mmol) and potassium carbonate (22.0 g, 159 mmol) in acetone (200 ml) was added iodomethane (13 ml, 210 mmol) at room temperature. The reaction mixture was refluxed for 16 hours. The mixture was filtered through a pad of celite and the filtrate was concentrated to give a residue. The residue was purified by column chromatography (1000 mesh, petroleum ether: ethyl acetate = 100: 1 to 50:1) to give methyl 1-methoxy-2-naphthoate (5.00 g, 44% yield) as yellow oil. (1791) LC-MS (Method C): Rt = 0.930 min; MS (ESIpos): m/z = 217.1 [M+H]+. (1792) 1H NMR (400 MHz, DMSO-d6): d [ppm] = 8.19 (d, 1H), 7.99 (d, 1H), 7.78-7.50 (m, 2H), 7.69- 7.62 (m, 2H), 3.97 (s, 3H), 3.90 (s, 3H).
	With sodium hydride In N,N-dimethyl-formamide
	With potassium hydroxide; sodium chloride In <i>N</i>-methyl-acetamide	1.1 Methyl 1-methoxy-2-naphthoate (Compound CCXVIII) Step 1 Methyl 1-methoxy-2-naphthoate (Compound CCXVIII) Over a 15 minute period, 149 g. (2.7 moles) of ground potassium hydroxide is added to 180 g. (0.96 mole) of 1-hydroxy-2-naphthoic acid in 2.5 l. of dimethylformamide (during the course of which the temperature rises to 32° C.). The reaction mixture is stirred at 20°-25° C. for 16 hours and at 50° C. for 2 hours and cooled to 40° C. 387 g. (2.7 moles) of methyl iodide is added, and the reaction mixture is stirred at 40°-50° C. for 4 hours. 4 l. of saturated sodium chloride solution is added, and the mixture is extracted with diethyl ether. The diethyl ether extract is dried over anhydrous sodium sulfate and evaporated at reduced pressure to obtain the crude product as a light brown oil (255 g.).
	With potassium carbonate In acetone at 70℃; for 24h;	1. Methyl 1-methoxynaphthalene-2-carboxylate (2) A mixture of 1-hydroxy-2-naphthoic acid (2.00 g, 10.63 mmol), K2CO3 (5.87 g, 42.51 mmol) and methyl iodide (2.7 mL, 42.51 mmol) in acetone (43 mL) were stirred and heated at 70oC in Schlenk tube for 24 hours. The reaction was cooled to room temperature and then K2CO3 was filtered out. The filtrate was concentrated under reduced pressure to give the desired ester 2 as brown oils. The crude ester was used in the next step without purification.

Reference： [1]Current Patent Assignee: SAMSUNG ELECTRONICS CO.,LTD.; LAPTO CO LTD; Samsung Display (in: Samsung) - KR2019/25788, 2019, A Location in patent: Paragraph 0182-0184
[2]Location in patent: scheme or table Kongkathip, Ngampong; Pradidphol, Narathip; Hasitapan, Komkrit; Grigg, Ronald; Kao, Wei-Chun; Hunte, Carola; Fisher, Nicholas; Warman, Ashley J.; Biagini, Giancarlo A.; Kongsaeree, Palangpon; Chuawong, Pitak; Kongkathip, Boonsong [Journal of Medicinal Chemistry, 2010, vol. 53, # 3, p. 1211 - 1221]
[3]Ganguly, Aniruddha; Ghosh, Soumen; Kar, Samiran; Guchhait, Nikhil [Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2015, vol. 143, p. 72 - 80]
[4]Tojo, Kenta; Arisawa, Tatsuya; Yasutake, Mikio; Aoki, Yoshio; Teninuma, Daiyo [Chemistry Letters, 2008, vol. 37, # 9, p. 930 - 931]
[5]Hattori, Tetsutaro; Hotta, Hiroki; Suzuki, Takatsugu; Miyano, Sotaro [Bulletin of the Chemical Society of Japan, 1993, vol. 66, # 2, p. 613 - 622]
[6]Current Patent Assignee: FUDAN UNIVERSITY; Shanghai Institute of Materia Medica (in: CAS); CHINESE ACADEMY OF SCIENCES - CN110903224, 2020, A Location in patent: Paragraph 0377-0380
[7]Lin, Zechao; Fan, Heli; Zhang, Qi; Peng, Xiaohua [Journal of Organic Chemistry, 2018, vol. 83, # 16, p. 8815 - 8826]
[8]Kongkathip, Ngampong; Kongkathip, Boonsong; Siripong, Pongpun; Sangma, Chak; Luangkamin, Suwaporn; Niyomdecha, Momad; Pattanapa, Suppachai; Piyaviriyagul, Suratsawadee; Kongsaeree, Palangpon [Bioorganic and Medicinal Chemistry, 2003, vol. 11, # 14, p. 3179 - 3191]
[9]Current Patent Assignee: BAYER AG - WO2021/13978, 2021, A1 Location in patent: Page/Page column 266; 267
[10]Van Veldhuizen, Joshua J.; Garber, Steven B.; Kingsbury, Jason S.; Hoveyda, Amir H. [Journal of the American Chemical Society, 2002, vol. 124, # 18, p. 4954 - 4955]
[11]Current Patent Assignee: Sandoz (in: Novartis); NOVARTIS AG - US4686237, 1987, A
[12]Kongkathip, Boonsong; Akkarasamiyo, Sunisa; Hasitapan, Komkrit; Sittikul, Pichamon; Boonyalai, Nonlawat; Kongkathip, Ngampong [European Journal of Medicinal Chemistry, 2013, vol. 60, p. 271 - 284]

13
[ 86-48-6 ]
[ 7469-77-4 ]

Reference： [1]Chemical and pharmaceutical bulletin,1979,vol. 27,p. 816 - 820
[2]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,1985,vol. 24,p. 233 - 235
[3]Synthesis,2005,p. 2479 - 2481
[4]Synthetic Communications,1994,vol. 24,p. 859 - 869

14
[ 6742-26-3 ]
[ 108-93-0 ]
sodium [ No CAS ]
[ 53440-12-3 ]
[ 22440-38-6 ]
[ 1081-27-2 ]
[ 86-48-6 ]

Reference： [1]Chemische Berichte,1924,vol. 57,p. 1290

15
[ 106-47-8 ]
[ 86-48-6 ]
[ 50729-12-9 ]

Yield	Reaction Conditions	Operation in experiment
75%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	14 4.1.14. N-(4-Chlorophenyl)-1-hydroxynaphthalene-2-carboxamide (5c) General procedure: 4.1.1. General procedure for synthesis of N-(substituted phenyl)-1-hydroxynaphthalene-2-carboxamides 1-8c. 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 °C, using infrared flask-surface control of temperature, for 15min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. Studied compounds 1-8c are presented in Table 1 .
	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	General Procedure for Synthesis of N-(substituted phenyl)-1-hydroxynaphthalene-2-carboxamides 1-24 General procedure: 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 °C, using infrared flask-surface control of temperature, for 15 min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. All the studied compounds are presented in Table 1.
	With phosphorus trichloride In chlorobenzene Microwave irradiation;

Reference： [1]Gonec, Tomas; Kos, Jiri; Zadrazilova, Iveta; Pesko, Matus; Keltosova, Stanislava; Tengler, Jan; Bobal, Pavel; Kollar, Peter; Cizek, Alois; Kralova, Katarina; Jampilek, Josef [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 21, p. 6531 - 6541]
[2]Vaillancourt, Valerie A; Cudahy, Michele M.; Staley, Sandra A.; Brideau, Roger J.; Conrad, Steven J.; Knechtel, Mary L.; Oien, Nancee L.; Wieber, Janet L.; Yagi, Yoshihiko; Wathen, Michael W. [Bioorganic and Medicinal Chemistry Letters, 2000, vol. 10, # 18, p. 2079 - 2081]
[3]Gonec, Tomas; Kos, Jiri; Pesko, Matus; Dohanosova, Jana; Oravec, Michal; Liptaj, Tibor; Kralova, Katarina; Jampilek, Josef [Molecules, 2017, vol. 22, # 10]
[4]Gajdár, Július; Tsami, Konstantina; Michnová, Hana; Goněc, Tomáš; Brázdová, Marie; Soldánová, Zuzana; Fojta, Miroslav; Jampílek, Josef; Barek, Jiří; Fischer, Jan [Electrochimica Acta, 2020, vol. 332]

16
[ 312753-06-3 ]
[ 86-48-6 ]
(R)-5-[2-(5,6-diethyl-indan-2-ylamino)-1-hydroxyethyl]-8-hydroxy-1H-quinolin-2-one xinafoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	In butan-1-ol at 20 - 100℃; for 17h;	18 Example 18Preparation of (R)-5-[2-(5.6-diethyl-indan-2-ylamino)-l-hydroxyethyl]-8-hydroxy-lH- quinolin-2-one xinafoate 5.O g (R)-5-[2-(5,6-diethyl-indan-2-ylamino)-l-hydroxyethyl]-8-hydroxy-lH-quinolin-2-one base (12.738 mmoles) and 2.40 g l-hydroxy-2-naphthoic acid (12.626 mmoles) are dissolved in 60 ml n-butanol at 1000C. The solution is allowed to cool. Some seeds are added at 25°C and crystallization takes place slowly. The suspension is stirred for 17 hours at room temperature and then filtered. The crystals are washed with 10 ml n-butanol and dried at 700C and ca. 10 mbar for 20 hours. Yield: 5.57 g beige powder (76%). Elemental analysis:CaIc: 72.40% C; 6.25% H; 4.82% N; 16.53% O Found: 72.16% C; 6.18% H; 4.81% N; 16.47% O

Reference： [1]Current Patent Assignee: Novartis (w/o Sandoz); NOVARTIS AG - WO2008/839, 2008, A1 Location in patent: Page/Page column 26-27

17
[ 62-53-3 ]
[ 86-48-6 ]
[ 13545-65-8 ]

Yield	Reaction Conditions	Operation in experiment
78%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	2 4.1.2 1-Hydroxy-N-phenylnaphthalene-2-carboxamide (1) General procedure: 4.1.1. General procedure for synthesis of N-(substituted phenyl)-1-hydroxynaphthalene-2-carboxamides 1-8c. 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 °C, using infrared flask-surface control of temperature, for 15min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. Studied compounds 1-8c are presented in Table 1 .
59%	Stage #1: 1-hydroxy-2-naphthoic acid With 1,1'-carbonyldiimidazole In tetrahydrofuran at 20℃; for 0.166667h; Stage #2: aniline In tetrahydrofuran Heating; Further stages.;
	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	3.2.1. General Procedure for Synthesis of N-(Alkoxyphenyl)-2-hydroxynaphthalene-1-carboxamides 1-7c and N-(Alkoxyphenyl)-1-hydroxynaphthalene-2-carboxamides 8-14c General procedure: 2-Hydroxynaphthalene-1-carboxylic acid or 1-hydroxynaphthalene-2-carboxylic acid (5.30 mmol) and appropriate alkoxyaniline (5.30 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and reacting mixture was heated in the microwave reactor for 15 min at 130 °C using infrared flask-surface control of temperature. Solvent was evaporated in vacuum; residue solid was washed with 2M HCl and crystallized from aqueous ethanol. If necessary, column chromatography was used for further purification (mobile phase DCM:MeOH 19:1).

	With phosphorus trichloride In chlorobenzene Microwave irradiation;
	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	General Procedure for Synthesis of N-(substituted phenyl)-1-hydroxynaphthalene-2-carboxamides 1-24 General procedure: 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 °C, using infrared flask-surface control of temperature, for 15 min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. All the studied compounds are presented in Table 1.
	With trichlorophosphate In chlorobenzene for 0.25h; Microwave irradiation;

Reference： [1]Gonec, Tomas; Kos, Jiri; Zadrazilova, Iveta; Pesko, Matus; Keltosova, Stanislava; Tengler, Jan; Bobal, Pavel; Kollar, Peter; Cizek, Alois; Kralova, Katarina; Jampilek, Josef [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 21, p. 6531 - 6541]
[2]Kumar, Anil; Narasimhan, Balasubramanian; Kumar, Devinder [Bioorganic and Medicinal Chemistry, 2007, vol. 15, # 12, p. 4113 - 4124]
[3]Gonec, Tomas; Pospisilova, Sarka; Kauerova, Tereza; Kos, Jiri; Dohanosova, Jana; Oravec, Michal; Kollar, Peter; Coffey, Aidan; Liptaj, Tibor; Cizek, Alois; Jampilek, Josef [Molecules, 2016, vol. 21, # 8]
[4]Gonec, Tomas; Kralova, Katarina; Pesko, Matus; Jampilek, Josef [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 9, p. 1881 - 1885] Gajdár, Július; Tsami, Konstantina; Michnová, Hana; Goněc, Tomáš; Brázdová, Marie; Soldánová, Zuzana; Fojta, Miroslav; Jampílek, Josef; Barek, Jiří; Fischer, Jan [Electrochimica Acta, 2020, vol. 332]
[5]Gonec, Tomas; Kos, Jiri; Pesko, Matus; Dohanosova, Jana; Oravec, Michal; Liptaj, Tibor; Kralova, Katarina; Jampilek, Josef [Molecules, 2017, vol. 22, # 10]
[6]Kapustikova, Iva; Bak, Andrzej; Gonec, Tomas; Kos, Jiri; Kozik, Violetta; Jampilek, Josef [Molecules, 2018, vol. 23, # 7]

18
[ 86-48-6 ]
[ 604-44-4 ]

Reference： [1]Chemische Berichte,1911,vol. 44,p. 867

19
[ 35654-56-9 ]
[ 86-48-6 ]
6,7-dimethoxy-4-(1-naphthyloxy)quinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With dmap In 1,2-dichloro-benzene at 150℃; for 2h;	Compound 16: 6,7-Dimethoxy-4-(1-naphthyloxy)quinoline Compound 16: 6,7-Dimethoxy-4-(1-naphthyloxy)quinoline; 4-Chloro-6,7-dimethoxyquinoline (100 mg), 1-hydroxy-2-naphthonic acid (252 mg), and 4-dimethylaminopyridine (164 mg) were suspended in o-dichlorobenzene (3 ml), and the suspension was stirred at 150°C for 2 hr. The reaction solution was cooled to room temperature, water was then added thereto, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was then washed with water and saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed therefrom by distillation under the reduced pressure, and the residue was purified by column chromatography using acetone-chloroform to give the title compound (119 mg, yield 80%). 1H-NMR (CDCl3, 400 MHz): δ 3.96 (s, 6H), 6.22 (d, J = 5.2 Hz, 1H), 7.22 (m, 1H), 7.31 - 7.40 (m, 4H), 7.64 (s, 1H), 7.68 (d, J = 8.0 Hz, 1H), 7.82 (t, J = 8.0 Hz, 2H), 8.31 (d, J = 5.2 Hz, 1H) Mass spectrometric value (ESI-MS, m/z): 332 (M+1)+

Reference： [1]Current Patent Assignee: KIRIN HOLDINGS CO., LTD.; Kyowa Kirin (in: Kirin Holdings) - EP1548008, 2005, A1 Location in patent: Page/Page column 64

20
[ 86-48-6 ]
[ 352662-32-9 ]

Yield	Reaction Conditions	Operation in experiment
90%	With triethylamine; phosphorus trichloride In toluene at 20℃;	1.4 Example 1.4; Preparation of ligand L062-01 by reaction of 1-hydroxy-2-naphthoic acid with phosphorus trichloride to form chloronaphthyldioxaphosphorinone The experiment described below was carried out using the protective gas technique. 18.9 g (0.1 mol) of 1-hydroxy-2-naphthoic acid were weighed into a secured 500 ml Schlenk vessel. The Schlenk vessel was subsequently evacuated, heated to hand heat by means of a hair dryer and, after cooling, argon was admitted. 250 ml of dried toluene were then siphoned in and the mixture was stirred vigorously.100 ml of dried toluene were placed in a second secured 250 ml Schlenk vessel. 30.7 g (0.3 mol)=42.2 ml of triethylamine and 13.9 g (0.1 mol)=8.8 ml of phosphorus trichloride were subsequently introduced by means of a syringe which had been flushed with argon while stirring. The solution obtained was siphoned a little at a time into the naphthoic acid solution at room temperature over a period of 1.5 hours while stirring vigorously. During this addition, the acid slowly dissolved and insoluble ammonium chloride was formed (suspension reaction). The reaction mixture was subsequently stirred until the following morning.The conversion test carried out at this point in example 1.3 could not be carried out since the large amount of ammonium chloride had not settled properly. The ammonium chloride was then firstly filtered off on a frit and washed twice with 100 ml of dried toluene. GC/MS was subsequently carried out on the filtrate obtained in order to check the conversion.To determine the mass of chlorophosphite, all of the toluene was separated off by means of an oil pump vacuum at room temperature using cold traps filled with liquid nitrogen and the product which remained was weighed. For further processing, the defined amount of chlorophosphite was dissolved with stirring in 300 ml of dried toluene and was stored in a refrigerator until used further. The yield was about 90% and the purity determined by means of GC/MS was >99% by mass.
75%	With anhydrous phosphorus trichloride In toluene	1.1 Inventive, Using an Ion Exchanger Example 1.1 Inventive, Using an Ion Exchanger A mixture of 9.5 g (0.05 mol) of 1-hydroxy-2-naphthoic acid and 58 g (approx. 0.1 mol) of Lewatit MP 62 ion exchanger and 250 ml of toluene was stirred vigorously for 30 min, in the course of which the acid is gradually dissolved. Subsequently, a solution of 4.4 ml=6.9 g (0.05 mol) of phosphorus trichloride in 30 ml of toluene was added dropwise at room temperature, in the course of which gentle heat evolution took place. For workup, the solution was decanted from the ion exchanger, the residue was washed twice with approx. 80 ml of dried toluene and the solvent (toluene) was removed in an oil-pump vacuum. The product obtained was a colorless solid. The yield was 75% of theory.
75%	With Lewatit MP-62; phosphorus trichloride In toluene at 20℃;

74.35%

With triethylamine; phosphorus trichloride In toluene at 0 - 20℃;

Reference： [1]Current Patent Assignee: EVONIK INDUSTRIES AG - US2008/188686, 2008, A1 Location in patent: Page/Page column 14
[2]Current Patent Assignee: EVONIK INDUSTRIES AG - US2007/117995, 2007, A1
[3]Current Patent Assignee: EVONIK INDUSTRIES AG - WO2005/63781, 2005, A1 Location in patent: Page/Page column 29-30
[4]Current Patent Assignee: EVONIK INDUSTRIES AG - WO2005/63781, 2005, A1 Location in patent: Page/Page column 30

21
[ 59721-28-7 ]
[ 86-48-6 ]
N,N-dimethyl-carbamoylmethyl p-(p-guanidinobenzoyloxy)phenylacetate xinafoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
99.1%	In water; isopropyl alcohol at 25 - 60℃;	8 Example 8; Xinafoate Form A; A suspension of 3.0 g camostat base (7.53 mmoles) in a mixture of 28 ml isopropanol and 2 ml water is heated to 600C. A solution of 1.44 g l-hydroxy-2-naphthoic acid (7.53 mmoles) in 27 ml isopropanol and 3 ml water is added at constant flow rate over ca 10 min. A clear solution is first observed and crystallization takes then rapidly place. The tick suspension is allowed to cool and gradually diluted with 27 ml isopropanol and 3 ml water. After stirring over night at 25°C the slurry is filtered. The solid is washed first with 10 ml isopropanol / water = 9 / 1 and then with 10 ml isopropanol. The product is dried first 2 h at 25 °C / vacuum and then 20 h at 80°C and ca. 10 mbar.Yield: 4.38 g white powder (99.1 %)Elemental analysis:CaIc: 63.47 % C; 5.15 % H; 9.55 % N; 21.82 % OFound: 62.89 % C; 5.25 % H; 9.37 % N; 22.28 % OWater assay: 0.42 % (m/m) HPLC purity: 98.1 % (a)

Reference： [1]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz); IRM LLC - WO2006/108643, 2006, A2 Location in patent: Page/Page column 25

22
[ 840530-57-6 ]
[ 86-48-6 ]
4-hydroxy-α'-[[[6-(4-phenylbutoxy)hexyl]amino]methyl]-1,3-benzenedirmethanol 1-hydroxy-2-naphthoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	In methanol at 10 - 30℃; for 3h;	7 To a solution of salmeterol (11) in methanol (5 volumes) was added an equimolar methanolic solution of l-hydroxy-2-naphthoic acid at 25-300C. The xinafoate salt (12a) immediately precipitated out. The slurry obtained was stirred further at 10- 200C for 3 hours and the crude salmeterol xinafoate (12a) was isolated. Yield: 116% w/w HPLC purity: 99.50% In order to prepare salmeterol xinafoate having an HPLC purity more than 99.8%, the above material was further purified by crystallization from methanol. Yield: 75% w/w

Reference： [1]Current Patent Assignee: VIATRIS INC - WO2007/45857, 2007, A1 Location in patent: Page/Page column 26-27; Figure 2

23
[ 1044642-88-7 ]
[ 86-48-6 ]
3-(5-methoxy-1H-indol-3-ylmethylene)-N-pentylcarbazimidamide xinafoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82.7%	In isopropyl alcohol at 25 - 70℃; for 20h;	39 Example 39 xinafoate [Show Image] A suspension of 2.0 g base (6.63 mmoles) and 1.25 g 1-hydroxy-2-naphthoic acid (6.63 mmoles) in 30 ml isopropanol is heated at 70°C. The resulting clear solution is allowed to cool. Crystallization takes place after seeding at 30°C. The slurry is stirred at 25°C for 20 h and filtered. The crystals are washed with 20 ml isopropanol and dried for 20 h at 80°C and ca. 10 mbar. Yield: 2.69 g whitish powder (82.7%) Elemental analysis: Calc.: 66.24 % C; 6.38 % H; 14.31 % N; 13.07 % OFound: 66.29 % C; 6.37 % H; 14.33 % N; 13.49 % OWater assay: 0.29 % m/m

Reference： [1]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - EP1939176, 2008, A1 Location in patent: Page/Page column 22

24
[ 59803-98-4 ]
[ 86-48-6 ]
[ 1084892-27-2 ]

Yield	Reaction Conditions	Operation in experiment
87%	In ethanol; n-heptane; at -5 - 65℃;Product distribution / selectivity;	EXAMPLE 11-2; Complex Comprising Brimonidine and 1-Hydroxy-2-Naphthoic AcidIn a three-liter, three-neck round bottom flask equipped with overhead stirrer, heating mantle, condenser, temperature probe, and N2 inlet, 1.25 g of brimonidine (lot BRMB-001 L08) was dissolved in ethanol (500 mL) at 65 C. 1-hydroxy-2-napthoic acid (1.05 eq, 17.9 mL, 0.25M in ethanol) was then added. The resulting solution was stirred for 10 minutes and then cooled to 55 C. Heptane (1 L) was then slowly added maintaining a reaction temperature of 50-55 C. No precipitation was observed. The solution was then seeded [lot PDH-P-37(1)] and cooled to ambient temperature at 20 C./h. At 35 C., precipitation began to thicken. After the reaction had reached ambient temperature, the mixture was further cooled to -5 C. using a MeCN/ice water bath for 2 h. The solids were then filtered and dried under vacuum at ambient temperature for 16 h affording 1.780 g (87% yield) of yellow solids (lot No. PDH-P-38(1)). XRD spectra of this material and another sample (lot JMS-A-22(1)) previously prepared are shown in FIG. 7. The spectra are consistent, indicating that the material was reproduced. A proton NMR spectrum of the sample of lot No. PDH-P-38(1) is shown in FIG. 10.
	at 60 - 70℃;Product distribution / selectivity;	EXAMPLE 10; Preparation of Various Complexes Comprising Brimonidine and Selected CounterionsIn this experiment, various complexes comprising Brimonidine and counterions of one of the following acids were prepared: pamoic acid, capric acid, sebacic acid, hippuric acid, naproxen, 1-hydroxy-2-naphthoic acid, palmitic acid, and stearic acid. Variations of the procedure described in the following disclosure may be made within the skill of a person of ordinary skill in the art without departing from the scope of the present invention. Brimonidine free base in a preselected solvent was heated to about 60-70 C. The organic acid in another portion of the solvent was added into the heated mixture or was included in the original mixture before heating. The heating of the combined mixture was continued for an additional period, which was not critical. In certain embodiments, an antisolvent was added to the combined mixture, preferably at a lower temperature, to effect a precipitation of the complex of brimonidine and the counterion. It may be advantageous to remove a portion of the solvent and antisolvent to assist the precipitation. In certain other embodiments, the heated combined mixture was cooled down to a lower temperature, such as room temperature (or below) to effect the precipitation of the complex of brimonidine and the counterion. The precipitate was then filtered and dried to yield the final complex. The solubility of various complexes in water at the resulting pH is shown in Table 9.

Reference： [1]Patent: US2008/293728,2008,A1 .Location in patent: Page/Page column 9
[2]Patent: US2008/293728,2008,A1 .Location in patent: Page/Page column 9

25
2-[3-[4-(2,2-difluoro-3-oxo-3,4-dihydro-2H-benzo [1,4]oxazin-6-ylamino)-5-fluoro-pyrimidin-2-ylamino]phenoxy]-N-methylacetamide [ No CAS ]
[ 86-48-6 ]
[ 1127890-40-7 ]

Yield	Reaction Conditions	Operation in experiment
80%	In water; butanone at 20 - 55℃; for 18h;	A suspension of 2-{3-[4-(2,2-Difluoro-3-oxo-3,4-dihydro-2H-benzo[1 ,4]oxazin-6- ylamino)5-fluoro-pyrimidin-2-ylamino]phenoxy}N-methyl-acetamide (1.18kg, 2.49 mmol, 1 equiv) in methyl ethyl ketone (MEK) (23.6L, 20ml/g) was heated to 550C, whereupon water (1.18L1 1ml/g) was added, resulting in a solution. The solution was passed through a filter for clarification then held at 550C for 1 hour. The subsequent addition of a pre-formed spec-free solution of 1-hydroxy-2-naphoic acid (515g, 2.74mol, 1.1 equiv) in MEK (4.72L, 4 ml/g) resulted in precipitation of a white solid after ~ 10mins. The reaction was cooled to ambient temp, stirred overnight (18 hours) and then cooled to 50C for 2 hours before filtration. The filtered solid was washed with MEK (2 x 2.36L, 2 x 2ml/g) and' dried under reduced pressure at 5O0C for 16 hours. The product, 2-{3-[4-(2,2-difluoro-3- oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylamino)5-fluoro-pyrimidin-2-ylamino]phenoxy}N- methyl-acetamide 1-hydroxy-2-naphoic acid salt, was isolated as a white solid (1.32kg,When analysed by conventional proton NMR (300MHz, d6-DMSO), the xinafoate salt gives the following spectrum: δ 2.65 (d, J 4.5 Hz, 3H), 4.34, (s, 2H), 6.46-6.52 (m, 1H), 7.10 (t, J 8.0 Hz, 1H), 7.23-7.28 (m, 2H), 7.36-7.41 (m, 2H), 7.45-7.48 (m, 1H), 7.55- 7.62 (m, 2H), 7.64-7.71 (m, 1H), 7.73-7.77 (m, 1H), 7.86-7.95 (m, 2H), 8.14 (d, J 4.0 Hz, 1H), 8.26-8.32 (m, 1H), 9.14 (s, 1H), 9.56 (s, 1H), 11.90-11.96 (m, 1 H).When analysed by differential scanning calorimetry (DSC) (8.588mg of the sample was heated from 25 to 2500C at 200C per minute using a Perkin Elmer Diamond DSC with autosampler and a 4 hole side wall vented aluminium pan and lid with nitrogen flow gas), the xinafoate salt shows a sharp endothermic melting peak at 2330C +/- 20C. The DSC trace is shown in Figure 1.When characterised by powder X-ray diffraction (PXRD), the xinafoate salt gives the pattern shown in Figure 2. The characteristic peaks are given in Table 1 below. The main characteristic peaks are at 8.0, 8.9, 11.6, 24.5 and 27.7 degrees two theta (+ 0.1 degree).Table 1 - Characteristic PXRD peaksThe powder X-ray diffraction pattern was determined using a Bruker-AXS Ltd D4 powder X-ray d iff racto meter fitted with an automatic sample changer, a theta-theta goniometer, automatic beam divergence slit, and a PSD Vantec-1 detector. The sample was prepared for analysis by mounting on a low background silicon wafer specimen mount. The specimen was rotated whilst being irradiated with copper K-alphai X-rays (wavelength = 1.5406 Angstroms) with the X-ray tube operated at 40kV/30mA. The analyses were performed with the goniometer running in continuous mode set for a 0.2 second count per 0.018° step over a two theta range of 2° to 55°. Peaks were selected manually using Bruker-AXS Ltd evaluation software. The data were collected at 210C.As will be appreciated by the skilled person, the relative intensities of the various peaks within Table 1 given below may vary due to a number of factors such as for example orientation effects of crystals in the X-ray beam or the purity of the material being analysed or the degree of crystallinity of the sample. The peak positions may also shift for variations in sample height but the peak positions will remain substantially as defined in given Table 1. The skilled person will also appreciate that measurements using a different wavelength will result in different shifts according to the Bragg equation - nλ = 2d sin θ. Such alternative PXRD patterns generated by use of alternative wavelengths are nevertheless representations of the same material.The main PXRD peaks which have been simulated from a single crystal X-ray analysis are listed in Table 2 below and the corresponding simulated pattern is shown in Figure 3.Table 2 - Characteristic simulated PXRD peaksWhen characterised by Fourier Transform Infra-red (FT-IR) spectroscopy, the xinafoate salt gives the pattern shown in Figure 4. The fingerprint region is shown in expanded form in Figure 5. The characteristic peaks are given in Table 3 below (w = weak, s = strong, m = medium). The main characteristic peaks are 1228 (m), 1152 (m), 1078 (s) and 858 (s). The FT-IR spectrum was acquired using a ThermoNicolet Nexus FTIR spectrometer equipped with a 'DurasampllR' single reflection ATR accessory (diamond surface on zinc selenide substrate) and d-TGS KBr detector. The spectrum was collected at 2cm"1 resolution and a co-addition of 256 scans for all compounds. Happ-Genzel apodization was used. Because the FT-IR spectrum was recorded using single reflection ATR, no sample preparation was required. Using ATR FT-IR will cause the relative intensities of infrared bands to differ from those seen in a transmission FT-IR spectrum using KBr disc or nujol mull sample preparations. Due to the nature of ATR FT-IR, the bands at lower wavenumber are more intense than those at higher wavenumber. Experimental error, unless otherwise noted, was +/- 2 cm"1. Peaks were picked using ThermoNicolet Omnic 6.0a software.When characterised by Fourier Transform Raman spectroscopy, the xinafoate salt gives the pattern shown in Figure 6. The fingerprint region is shown in greater detail in Figure 7. The characteristic peaks are given in Table 4 below (w = weak, s = strong, m = medium). The main characteristic peaks are 1626 (m), 1205 (m), 998 (s), 156 (s) and 91 (S).Table 4 - Characteristic FT-Raman peaks The Raman spectrum was collected using a Bruker Vertex70 with Ram 11 module FT-Raman spectrometer equipped with a 1064nm NdYAG laser and LN-Germanium detector. The spectrum was recorded using 2cm"1 resolution and Blackman-Harris 4- term apodization. Laser power was 30OmW and 2048 co-added scans were collected. Each sample was placed in a glass vial and exposed to the laser radiation. The data is presented as intensity as a function of Raman shift and is corrected for instrument response and frequency dependent scattering using a white light spectrum from a reference lamp. The Bruker Raman Correct function was used to do the correction. (Bruker software - OPUS 6.0). Experimental error, unless otherwise noted, was +/- 2 cm" Peaks were picked using ThermoNicolet Omnic 6.0a softwareWhen characterised by proton decoupled 13C solid state NMR, the xinafoate salt gives the spectrum shown in Figure 8. The characteristic shifts are given in Table 5 below. The main characteristic shifts are 176.8, 159.4, 137.1 , 118.2, 104.9 and 25.4 ppm. Intensities can vary depending on the actual setup of the experimental parameters and the thermal history of the sample and are not therefore necessarily quantitative.Table 5 - Characteristic 13 C solid state NMR shiftsApproximately 80 mg of sample were tightly packed into a 4 mm ZrO2 spinner. The spectrum was collected at ambient conditions on a Bruker-Biospin 4mm BL HFX CPMAS probe positioned into a wide-bore Bruker-Biospin Avance DSX 500 MHz NMR spectrometer. The sample was positioned at the magic angle and spun at 15.0 kHz. The fast spinning speed minimized the intensities of the spinning side bands. The number of scans was adjusted to obtain adequate S/N. The 13C solid state spectrum was collected using a proton decoupled cross-polarization magic angle spinning experiment (CPMAS). A proton decoupling field of approximately 85 kHz was applied. 656 scans were collected with the recycle, delay adjusted to 80 seconds. The spectrum was referenced using an external standard of crystalline adamantane, setting its upfield resonance to 29.5 ppm.When characterised by fluorine solid state NMR, the xinafoate salt gives the spectrum shown in Figure 9. The characteristic shifts are -69.2, -72.4 and -164.0 ppm. Intensities can vary depending on the actual setup of the experimental parameters and the thermal history of the sample and are not therefore necessarily quantitative.The same apparatus was used to acquire the fluorine NMR spectrum as that used to acquire the 13C spectrum. The 19F solid state spectrum was collected using a proton decoupled magic angle spinning (MAS) experiment. The proton decoupling field of approximately 85 kHz was applied and 8 scans were collected. The recycle delay was set to 750s to ensure acquisition of quantitative spectra. Proton longitudinal relaxation times (1H T1) were calculated based on a fluorine detected proton inversion recovery relaxation experiment. Fluorine longitudinal relaxation times (19F T1) were calculated based on a fluorine detected fluorine inversion recovery relaxation experiment. The spectrum was referenced using an external sample of trifluoroacetic acid (50% by volume in H2O), setting its resonance to -76.54 ppm.
1.32 kg	Stage #1: 2-[3-[4-(2,2-difluoro-3-oxo-3,4-dihydro-2H-benzo [1,4]oxazin-6-ylamino)-5-fluoro-pyrimidin-2-ylamino]phenoxy]-N-methylacetamide In water; butanone at 55℃; for 1h; Large scale; Stage #2: 1-hydroxy-2-naphthoic acid In water; butanone at 5 - 20℃; for 18h; Large scale;	XII XII. Working Examples; The following example illustrates preparing the xinafoate salt of N4-[(2,2-difluoro-4H-benzo[1,4]oxazin-3-one)-6-yl]-5-fluoro-N2-[3-(methylaminocarbonylmethyleneoxy)phenyl]-2,4-pyrimidinediamine. A suspension of 2- {3- [4-(2,2-Difluoro-3 -oxo-3,4-dihydro-2H-benzo [1,4] oxazin-6-ylamino)5-fluoro-pyrimidin-2-ylamino]phenoxy}N-methyl-acetamide (1.18 kg, 2.49 mmol, 1 equiv) in methyl ethyl ketone (MEK) (23.6 L, 20 ml/g) was heated to 55° C., whereupon water (1.18L, lml/g) was added, resulting in a solution. The solution was passed through a filter for clarification then held at 55° C. for 1 hour. The subsequent addition of a pre-formed spec-free solution of 1-hydroxy-2-naphthoic acid (515 g, 2.74 mol, 1.1 equiv) in MEK (4.72 L, 4 ml/g) resulted in precipitation of a white solid after approximately 10 minutes. The reaction was cooled to ambient temperature, stirred overnight (18 hours) and then cooled to 5° C. for 2 hours before filtration. The filtered solid was washed with MEK (22.36 L, 22 ml/g) and dried under reduced pressure at 50° C. for 16 hours. The product, 2-{3-[4-(2,2-difluoro-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylamino)5-fluoro-pyrimidin-2-ylamino]phenoxy}N-methyl-acetamide 1-hydroxy-2-napthoic acid salt, was isolated as a white solid (1.32 kg). When analyzed by conventional proton NMR (300 MHz, d6-DMSO), the xinafoate salt gives the following spectrum: δ 2.65 (d, J 4.5 Hz, 3H), 4.34, (s, 2H), 6.46-6.52 (m, 1H), 7.10 (t, J 8.0 Hz, 1H), 7.23-7.28 (m, 2H), 7.36-7.41 (m, 2H), 7.45-7.48 (m, 1H), 7.55-7.62 (m, 2H), 7.64-7.71 (m, 1H), 7.73-7.77 (m, 1H), 7.86-7.95 (m, 2H), 8.14 (d, J 4.0 Hz, 1H), 8.26-8.32 (m, 1H), 9.14 (s, 1H), 9.56 (s, 1H), 11.90-11.96 (m, 1 H).

Reference： [1]Current Patent Assignee: RIGEL PHARMACEUTICALS INC - WO2009/31011, 2009, A2 Location in patent: Page/Page column 20-25
[2]Current Patent Assignee: RIGEL PHARMACEUTICALS INC - US2013/102596, 2013, A1 Location in patent: Paragraph 0165

26
[ 81-11-8 ]
[ 86-48-6 ]
C₃₆H₂₂N₄O₁₂S₂^(2-)*2Na⁽¹⁺⁾ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4,4'-diaminostilbene-2,2'-disulfonic acid With hydrogenchloride; sodium hydroxide; sodium nitrite In water Stage #2: 1-hydroxy-2-naphthoic acid With sodium hydroxide; sodium carbonate In water at 8℃; for 3h;

Reference： [1]Location in patent: experimental part Grad, Maria Elena; Simu, Georgeta Maria; Lupea, Alfa Xenia; Tomas, Stefan; Pascariu, Aurelia [Revue Roumaine de Chimie, 2008, vol. 53, # 2, p. 107 - 111]

27
[ 71125-38-7 ]
[ 86-48-6 ]
[ 1174325-92-8 ]

Yield	Reaction Conditions	Operation in experiment
	In tetrahydrofuran;Product distribution / selectivity;	176 mg of <strong>[71125-38-7]meloxicam</strong> was ground with 94 mg of 1-hydroxy-2-naphthoic acid and 400 muL of THF was added to the solid mixture. The solids gathered after grinding were stored in screw cap vials for subsequent analysis.

Reference： [1]Crystal Growth and Design,2010,vol. 10,p. 4401 - 4413
[2]Patent: US2009/203680,2009,A1 .Location in patent: Page/Page column 10

28
[ 124937-51-5 ]
[ 86-48-6 ]
[ 615255-99-7 ]

Yield	Reaction Conditions	Operation in experiment
84.1%	In acetone at 25℃; Inert atmosphere;	9 Example 9Preparation of tolterodine 1-hydroxy-2-naphthate3.25 g of tolterodine dissolved in 50 mL of acetone was mixed at room temperature (25° C.) with 1.88 g of 1-hydroxy-2-naphthoic acid, which was suspended in 50 mL of acetone, and then stirred for 30 minutes. Acetone in the above mixture was removed by nitrogen reflux apparatus, and when about 10-20 mL of acetone was removed there started to appear a solid precipitate. After stirring the mixture at room temperature (25° C.) for 1 hour, the solid precipitate was filtered and then washed with hexane. The resultant was dried at room temperature (25° C.) for 24 hours and 4.32 g (theoretical yield: 84.1%) of the final product in light brown solid was obtained.
84.1%	In acetone at 25℃;	9 3.25 g of tolterodine dissolved in 50 mL of acetone was mixed at room temperature (25°C) with 1.88 g of 1-hydroxy-2-naphthoic acid, which was suspended in 50 mL of acetone, and then stirred for 30 minutes. Acetone in the above mixture was removed by nitrogen reflux apparatus, and when about 10~20 mL of acetone was removed there started to appear a solid precipitate. After stirring the mixture at room temperature (25°C) for 1 hour, the solid precipitate was filtered and then washed with hexane. The resultant was dried at room temperature (25°C) for 24 hours and 4.32 g(theoretical yield: 84.1%) of the final product in light brown solid was obtained.

Reference： [1]Current Patent Assignee: SK CHEMICALS CO LTD - US2010/331552, 2010, A1 Location in patent: Page/Page column 4
[2]Current Patent Assignee: SK CHEMICALS CO LTD - WO2009/104920, 2009, A1 Location in patent: Page/Page column 10

29
[ 89365-50-4 ]
[ 86-48-6 ]
salmeterol xinafoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94.1%	In acetone; at 30℃; for 0.666667h;	150 g <strong>[89365-50-4]salmeterol</strong> base and 1500 ml acetone were added to a 3 L flask,Warmed to 30 C stirring and dissolved, adding 68g 1-hydroxy-2-naphthoic acid,Stirring for 40 minutes precipitated a white solid, cooled to 5 C, crystallization insulation 3 hours,Suction filtered, washed and dried in vacuo to give <strong>[89365-50-4]salmeterol</strong> xinafoate in 94.1% yield.
69%	In acetone; at 25 - 45℃; for 1.5h;	Example-8: Preparation of <strong>[89365-50-4]Salmeterol</strong> Xinafoate [I]100 g <strong>[89365-50-4]Salmeterol</strong> Base and 400 mL acetone were taken in round bottom flask at 25C. 47.54 g of Xinafoic acid was added and heated to get clear solution at 45C. The reaction mixture was stirred for 30 min and cooled to 25C. After stirring for 1 hour, 700 mL of methyltertbutyl ether was added and reaction mixture was further cooled to 10C and stirred for 2 hours. The product was filtered and washed with 150 mL chilled acetone. The product was dried in vacuum tray dryer for 12 hours at 45C to obtain 100 g (69%) of <strong>[89365-50-4]Salmeterol</strong> Xinafoate (I) with purity greater than 97% by HPLC.
	In diethyl ether; at 20℃; for 16h;	Step 11 N-(2-Hydroxy-2-(4-hydroxy-3-(hydroxymethyl)phenyl)ethyl)-6-(4-phenylbutoxy)hexan-1-aminium 1-hydroxy-2-naphthoate: Acetic acid (5 mL) and water (1 mL) was added to 1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)-2-(6-(4-phenylbutoxy)hexylamino)ethanol (60 mg; 0. 13 mmol; 1. 00 equiv). The solution was stirred at about 70 C. for about 3 hours, and then concentrated in vacuo. The resulting residue was dissolved with water (40 mL), washed with ethyl acetate (20 mL) and ether (20 mL), and then the pH of the aqueous layer was adjusted to 8 with a saturated sodium bicarbonate solution. Following standard extractive workup with ethyl acetate, the crude residue was dissolved in diethyl ether (10 mL). 1-hydroxy-2-naphthoic acid (50 mg; 0.27 mmol; 2.12 equiv) was added and the mixture was stirred at ambient temperature for about 16 hours. The solid was collected by filtration and washed with diethyl ether to give the title compound as white solid (30 mg; 39% yield). 1H NMR (300 MHz, DMSO) delta: 9.43 (s, 1H), 8.49 (s, 2H), 8.20 (d, J=7.8 Hz, 1H), 7.70 (m, 2H), 7.44 (t, J=7.2, 7.8 Hz, 1H), 7.38~7.25 (m, 4H), 7.17 (m, 3H), 7.07 (d, J=8.1 Hz, 1H), 6.96 (s, d, J=8.4 Hz, 1H), 6.77 (d, J=8.1 Hz, 1H), 6.00 (s, 1H), 5.03 (t, J=4.8, 4.8 Hz, 1H), 4.78 (d, J=9.0 Hz, 1H), 4.49 (d, J=4.5 Hz, 2H), 3.34 (m, 4H), 3.07~2.90 (m, 4H), 2.58 (t, J=6.9, 7.8 Hz, 2H), 1.63~1.50 (m, 8H), 1.33 (m, 4H). LC-MS: m/z=416 (MH)+.

20.75 g

Mixture of [89365-50-4]Salmeterol base (30 grams) and methanol (150 mL) were taken in round bottom flaskand stirred for clear solution at 25-30 C. Activated carbon (3.0 grams) was added and stirred for30 minutes at 25-30 C. Filtered the reaction mixture through hyflo bed and washed with methanol(30 mL). 1-hydroxy-2-napthoic acid (13.59 grams) was added to the filtrate at 30±2 C. Stirred the reaction mixture for 1.0 hour at 30±2 C and cooled to 18-22 C. Stirred the reaction mixture for 2.0 hours and the product was filtered, slurry washed with chilled methanol (60 mL). Dried the product in vacuum tray dryer for 12 hours at 40-45 C to obtain of [89365-50-4]Salmeterol Xinafoate (36 grams).; Mixture of?[89365-50-4]Salmeterol Xinafoate (25 grams) and methanol (150 mL) were taken in round bottom flask and heated at 45-50 C to get clear solution. Activated carbon (NoritDarco G60) (1.25 grams) was added and stirred for 15 minutes at 45-50 C. Filtered the reaction mixture was through hyflowbed and washed with methanol (8.33 mL). The filtrate was taken into round bottom flask and heated at 45-50 C to get clear solution. Cooled the reaction mixture slowly to 20±2 C and stirred for 4.0 hours. Filtered the precipitated product and slurry washed with chilled methanol (25 mL). Dried the product in vacuum tray dryer for 12 hours at 40-45 C to obtain pure [89365-50-4]Salmeterol Xinafoate (20.75 grans).1HNMR (DMSO, 300 MHz): 1.29-1.64 (m, 121-1), 2.50-2.58 (m, 2H), 2.91-3.10 (m 4H), 127-3.34(rn, 4H), 4.5 (s 2H), 4.83-4.87 (d 2H), 5.05 (br s 1H), 6.13 (br s IH), 6.77-6.79 (d IH), 7.02-7.08(rn 2H), 7.13-7.18 (m 3K), 7.23-7.28 (m 3K), 7.36-7.40 (m 21-1), 7.43-7.48(m 1H), 7.70-7.79 (m2H), 8.19-8.22 (d 1K), 8.82 (br s IH), 9.52 (br s 1K).MS: m/z = 416 [M+Hj.

Reference： [1]Patent: CN106478432,2017,A .Location in patent: Paragraph 0051; 0057
[2]Patent: WO2012/32546,2012,A2 .Location in patent: Page/Page column 29
[3]Patent: US2010/9950,2010,A1 .Location in patent: Page/Page column 22-23
[4]Organic Process Research and Development,1999,vol. 3,p. 370 - 376
[5]Patent: WO2017/168431,2017,A1 .Location in patent: Page/Page column 15; 16

30
[ 93413-62-8 ]
[ 86-48-6 ]
ODV 1-hydroxy-2-naphthoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60.23%	In water; acetone; at 60 - 65℃; for 0.5h;	O-desmethyl venlafaxine (10 gm; 0.038 mol) was stirred with acetone:water (3.5:1 ) mixture (90 ml). To the reaction mass, 1-hydroxy-2-naphthoic acid (8.14 gm; 0.043 mol) was added. The mixture was heated to 60-650C for 30 minutes. Activated charcoal (1 gm) was added to the reaction mixture and heated to reflux for 30 minutes. The mixture was filtered through hyflo bed and washed with acetone (10 ml). The filtrate was cooled gradually to room temperature and further chilled to 0-50C. The solid obtained was isolated by filtration and washed with chilled acetone to obtain ODV 1-hydroxy-2- naphthoate.The salt obtained was purified by dissolving in acetone:water (3.5:1 ) mixture (84 ml). The mixture was heated to 60-65 for 1 hour. The mixture was cooled gradually to room temperature and further chilled to 0-5C for 30 minutes. The solid was isolated by filtration and further dried in a vacuum oven at 45-500C. Yield: 10.3 gm; Efficiency: 60.23%.

Reference： [1]Patent: WO2011/7136,2011,A2 .Location in patent: Page/Page column 19; 20

31
[ 136236-51-6 ]
[ 86-48-6 ]
[ 1309125-27-6 ]

Yield	Reaction Conditions	Operation in experiment
	In n-heptane; isopropyl alcohol;	Example 11; (Rasagiline 1-hydroxy-2-naftoate) Rasagiline base (0.60 g) was dissolved in 2-propanol (15 ml) then 1-hydroxy-2-naftoic acid (0.66 g) was added. To this solution 20 ml of heptane was slowly added and the solution was left to crystallize, to give rasigaline 1-hydroxy-2-naftoate.
	In isopropyl alcohol;	Rasagiline base (0.60 g) was dissolved in 2-propanol (15 ml) then 1 -hydroxy-2- naftoic acid (0.66 g) was added. To this solution 20 ml of heptane was slowly added and the solution was left to crystallize, to give rasigaline 1 -hydroxy-2-naftoate.

Reference： [1]Patent: EP2325159,2011,A1 .Location in patent: Page/Page column 9
[2]Patent: WO2011/64216,2011,A1 .Location in patent: Page/Page column 19

32
[ 86-48-6 ]
[ 144875-48-9 ]
[ 1313530-20-9 ]

Yield	Reaction Conditions	Operation in experiment
	In methanol;Heating;	Example 1; l-Hydroxy-2 -naphthoic acid (3.1 g) and l-[4-amino-2-(ethoxymethyl)-lH- imidazo[4,5-c]quinolin-l-yl]-2-methylpropan-2-ol (5.2 g) were added with stirring to methanol (100 mL). The resulting mixture was heated until it became a solution. The solution was filtered while hot and the filtrate was cooled to room temperature. The crystals that formed in the filtrate were recovered by vacuum filtration, washed with three portions of methanol (5 mL each), and dried overnight at 50 C. The solid was cooled to room temperature to yield 6.2 g of 4-amino-2-(ethoxymethyl)-l-(2-hydroxy-2- methylpropyl)- lH-imidazo[4,5-c]quinolin-5-ium 1 -hydroxynaphthalene-2-carboxylate as an off-white crystalline solid, mp 181-183 C.1H NMR (700 MHz, DMSO-d6) delta 15.0 (broad s, 2H), 9.28 (broad s, 2H), 8.50 (d, J = 8.5 Hz, 1H), 8.27 (d, J= 8.2 Hz, 1H), 7.91 (d, J= 8.5 Hz, 1H), 7.86 (d, J= 8.2 Hz, 1H), 7.82 (d, J= 7.8 Hz, 1H), 7.70 (t, J= 7.7 Hz, 1H), 7.56 (t, J= 7.5 Hz, 1H), 7.49 (t, J= 7.5 Hz, 1H), 7.48 (t, J= 7.5 Hz, 1H), 7.23 (d, J= 8.9 Hz, 1H), 5.19 (broad s, 2H), 4.99 (broad s, 1H), 4.76 (broad s, 2H), 3.57 (q, J= 6.8 Hz, 2H), 1.21 (broad s, 6H), 1.17 (t, J= 7.0 Hz, 3H).

Reference： [1]Patent: WO2011/84725,2011,A1 .Location in patent: Page/Page column 17-18

33
[ 106-95-6 ]
[ 86-48-6 ]
allyl 1-allyloxy-2-naphthoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With potassium carbonate In acetone at 60℃; for 4h;
80%	With potassium carbonate In acetone at 60℃; for 4h;	18 Allyl ether allyl ester of 1-hydroxy-2-naphthoic acid (24) Allyl ether allyl ester of 1-hydroxy-2-naphthoic acid (24) To a solution of 1-hydroxy-2-napthoic acid (HNAP, 1.04 g, 5.51 mmol) in anhydrous acetone (12 mL) were added ally bromide (1.4 mL, 16.53 mmol) and finely powdered K2CO3 (2.28 g, 16.53 mmol). The mixture was stirred for 4 h at 60° C., and then concentrated under reduced pressure. The residue was partitioned between EtOAc and 1 M HCl. The organic layer was washed with saturated NaHCO3 and brine, dried over MgSO4, filtered, and concentrated by rotary evaporation under reduced pressure. The crude material was purified by silica gel column chromatography (EtOAc/hexane=1:9) to yield the bis-allylation product 24 (1180 mg, 80%). C17H16O3; TLC (EtOAc/hexane=1:9) Rf=0.65; IR νmax (neat) 1722, 1334, 1274, 1233, 1131 cm-1; 1H NMR (400 MHz, CDCl3) δ 8.27-8.24 (1H, m), 7.87 (1H, d, J=8.4 Hz), 7.77-7.27 (1H, m), 7.53 (1H, d, J=8.4 Hz), 7.51-7.47 (2H, m), 6.24-6.17 (1H, m), 6.09-6.02 (1H, m), 5.50-5.40 (2H, m), 5.30-5.25 (2H, m), 4.87-4.84 (2H, m), 4.61-4.62 (2H, m); 13C NMR (100 MHz, CDCl3) δ 165.4, 156.7, 136.4, 133.5, 131.9, 128.5, 128.0, 127.5, 126.3, 126.2, 123.4, 123.3, 119.3, 118.2, 117.4, 76.3, 65.4; ESI-HRMS calcd for C17H17O3: 269.1178, found: m/z 269.1184 [M+H]+.
	With potassium carbonate In acetone at 60℃; for 4h; Inert atmosphere;	4.3.1. 1-(2-Propenoxy)-2-naphthoic acid (10) To a solution of 1-hydroxy-2-napthoic acid 4 (1.04 g, 5.5 mmol) and allyl bromide (1.4 mL, 16.5 mmol) in anhydrous acetone (12 mL) was added finely powdered K2CO3 (2.28 g, 16.5 mmol). The mixture was stirred for 4 h at 60 °C, and then concentrated under reduced pressure. The residue was partitioned between EtOAc and 1 M HCl. The organic layer was washed with saturated NaHCO3 and brine, dried over MgSO4, filtered, and concentrated by rotary evaporation under reduced pressure. The crude material in MeOH (10 mL) was added 1 M NaOH (1 mL), stirred for 4 h at 60 °C, and then concentrated under reduced pressure. The mixture was diluted with water (20 mL), washed with ether, acidified with 1 M HCl, and then extracted with CH2Cl2. The organic layer was dried over MgSO4, filtered, and concentrated by rotary evaporation under reduced pressure. The residue was purified by silica gel column chromatography (EtOAc/hexane = 3:7) to yield the allyl ether 10 (942 mg, 75%). C14H12O3; yellow solid, mp 99-101 °C; TLC (EtOAc/hexane = 3:7) Rf = 0.18; IR νmax (neat) 3455, 1738, 1365, 1232, 1228 cm-1; 1H NMR (400 MHz, CDCl3) δ 8.21 (1H, d, J = 9.6 Hz), 8.03 (1H, d, J = 8.4 Hz), 7.83 (1H, dd, J = 8.4, 1.2 Hz), 7.63 (1H, d, J = 8.8 Hz), 7.60-7.52 (2H, m), 6.28-6.17 (1H, m), 5.50 (1H, dd, J = 17.2, 1.0 Hz), 5.37 (1H, dd, J = 10.4, 1.0 Hz), 4.71 (2H, d, J = 6.0 Hz); 13C NMR (100 MHz, CDCl3) δ 169.2, 157.1, 137.2, 132.5, 128.8, 128.0, 127.8, 126.7, 126.6, 124.3, 123.3, 119.2, 118.2, 77.4; ESI-HRMS (negative mode) calcd for C14H11O3: 227.0708, found: m/z 227.0715 [M-H]-.

Reference： [1]Liu, Kung-Cheng; Fang, Jim-Min; Jan, Jia-Tsrong; Cheng, Ting-Jen R.; Wang, Shi-Yun; Yang, Shi-Ting; Cheng, Yih-Shyun E.; Wong, Chi-Huey [Journal of Medicinal Chemistry, 2012, vol. 55, # 19, p. 8493 - 8501]
[2]Current Patent Assignee: ACADEMIA SINICA - US2013/274229, 2013, A1 Location in patent: Paragraph 0269
[3]Location in patent: experimental part Liu, Kung-Cheng; Lee, Pei-Shan; Wang, Shi-Yun; Cheng, Yih-Shyun E.; Fang, Jim-Min; Wong, Chi-Huey [Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 16, p. 4796 - 4802]

34
[ 175591-23-8 ]
[ 86-48-6 ]
[ 1356394-21-2 ]

Yield	Reaction Conditions	Operation in experiment
89.83%	In isopropyl alcohol at 20℃; for 18h;	b1-3 Example b1-3Salt or Cocrystal of Tapentadol and 1-Hydroxy-2-Naphthoic Acid120 g (0.54 mol) of tapentadol were dissolved in 700 mL of 2-propanol. To this solution, 102.02 g (0.54 mol) of 1-hydroxy-2-naphthoic acid were added as a solid in portions. Then, 100 mL of 2-propanol were added. After complete addition, the resulting suspension was stirred for 18 hours. The crystallized brownish precipitate was then filtered off and dried at 50° C. under reduced pressure (6 mbar) (yield: 199.43 g, 89.83%, melting point (DSC): To=114.9° C., Tp=122.7, ° C., 1.0 J/g; To=157.6° C., Tp=159.9° C., 78.3 J/g). 1H-NMR analysis showed a 1:1-stochiometry of tapentadol and 1-hydroxy-2-naphthoic acid.
89.83%	In isopropyl alcohol for 18h;	b1-3 Example b1-3: salt or cocrystal of tapentadol and 1-hydroxy-2-naphthoic acid120 g (0.54 mol) of tapentadol were dissolved in 700 mL of 2-propanol. To this solution, 102.02 g (0.54 mol) of 1-hydroxy-2-naphthoic acid were added as a solid in portions. Then, 100 mL of 2-propanol were added. After complete addition, the resulting suspension was stirred for 18 hours. The crystallized brownish precipitate was then filtered off and dried at 50°C under reduced pressure (6 mbar) (yield: 199.43 g, 89.83%, melting point (DSC): T0= 114.9 °C, Tp = 122.7, °C, 1.0 J/g; T0= 157.6°C, Tp = 159.9 °C, 78.3 J/g). 1H-NMR analysis showed a 1 :1-stochiometry of tapentadol and 1-hydroxy-2-naphthoic acid

Reference： [1]Current Patent Assignee: Gruenenthal Pharma GmbH & Co. Kommanditgesellschaft - US2012/22117, 2012, A1 Location in patent: Page/Page column 13
[2]Current Patent Assignee: Gruenenthal Pharma GmbH & Co. Kommanditgesellschaft - WO2012/10316, 2012, A1 Location in patent: Page/Page column 36

35
[ 81-16-3 ]
[ 86-48-6 ]
[ 1402066-96-9 ]
1-hydroxy-4-[(1-sulfo-2-naphthalenyl)azo]-2-naphthalenecarboxylic acid disodium salt [ No CAS ]

Reference： [1]Dyes and Pigments,2012,vol. 95,p. 304 - 312

36
[ 1310717-02-2 ]
[ 86-48-6 ]
[ 1400593-10-3 ]

Yield	Reaction Conditions	Operation in experiment
95%	In Isopropyl acetate; water at 60℃;	5 Compound A xinafoate: 3-Cyclopropylcarbonyl-3,6-diazabicyclo[3.1.1 Jheptanes (500 mg, 3.01 mmol) was dissolved in isopropyl acetate (5 mL) at 70°C. Xinafoic acid (626 mg, 3.31 mmol) was suspended in 98:2 isopropyl acetate/water (6.1 mL) at 60°C and added to the solution of free base. The resulting mixture was cooled slowly to 0°C, and the suspended solids were collected by suction filtration and dried under vacuum at ambient temperature for 5 h. An off-white powder was obtained (1.01 g, 95% yield). The sample exhibited a melting point of 177°C and an aqueous solubility of 2.6 img/mL.

Reference： [1]Current Patent Assignee: CATALYST BIOSCIENCES, INC. - WO2012/125518, 2012, A1 Location in patent: Page/Page column 39

37
[ 183321-74-6 ]
[ 86-48-6 ]
[ 1429636-57-6 ]

Yield	Reaction Conditions	Operation in experiment
0.47 g	In ethanol;Reflux;	Into an apparatus 15 ml of ethanol are weighed in under vigorous stirring, whereupon 0.704 g /l .79 millimoles/ of <strong>[183321-74-6]erlotinib</strong> base are dissolved therein under stirring and reflux. To the reaction mixture at this temperature 0.336 g /l .79 millimoles/ of l-hydroxy-2 -naphthoic acid are added under stirring. A dark yellow solution is obtained. The reaction mixture is allowed to cool to room temperature under stirring whereby a slow precipitation of crystals can begin. The reaction mixture is allowed to stand in a refrigerator overnight the precipitated product is filtered and washed with a small amount of cold ethanol and thereafter with tertiary butyl methyl ether.Yield: 0.77 g (74 %)0.700 g of the crude product thus obtained is recrystallized from 10 ml of ethanol. The suspension obtained is allowed to stand in a refrigerator overnight and washed with a small amount of cold isopropanol and thereafter with tertiary butyl methyl ether.Yield: 0.47 g (67 %)Mp.:144.2-147C.Analysis for the Formula C22H23N304 CuH803 (581.63):Calc: C: 68.15 H: 5.37 N: 7.22Found: C: 67.39 H: 5.46 N: 7.22IR (KBr, cm"1): 3258, 1648, 1583, 1439, 1403, 775.?-NMR (DMSO-</6, 500 MHz): 12-10 (b), 9.74 (b, 1H), 8.58 (s, 1H), 8.29 (m, 1H), 8.00 (m, 1H), 7.89 (m, 3H), 7.78 (d, J=8.7 Hz, 1H), 7.65 (m, 1H9, 7.56 (m, 1H), 7.43 (m, 1H), 7.34 (d, J=8.7 Hz, 1H), 7.27 (m, lH), 7.25 (s, 1H), 4.30 (m, 4H), 4.21 (s, 1H), 3.78 (m, 4H), 3.39 (s, 2H), 3.37 (s,3H).13C-NMR (DMSO- e, 125 MHz) 173.06, 160.68, 156.54, 154.14, 152.36, 148.49, 145.53, 139.60, 129.22, 129.05, 127.69, 126.91 , 125.80, 125.28, 125.23, 124.43, 123.22, 123.04, 121.96, 117.88, 108.84, 107.35, 106.93, 103.57, 83.56, 80.73, 70.24, 70.18, 68.60, 68.31 , 58.53, 58.49.

Reference： [1]Patent: WO2013/54147,2013,A2 .Location in patent: Page/Page column 28

38
[ 90-04-0 ]
[ 86-48-6 ]
[ 26675-52-5 ]

Yield	Reaction Conditions	Operation in experiment
73%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	3 4.1.3. 1-Hydroxy-N-(2-methoxyphenyl)naphthalene-2-carboxamide (2a) General procedure: 4.1.1. General procedure for synthesis of N-(substituted phenyl)-1-hydroxynaphthalene-2-carboxamides 1-8c. 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 °C, using infrared flask-surface control of temperature, for 15min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. Studied compounds 1-8c are presented in Table 1 .
	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	3.2.1. General Procedure for Synthesis of N-(Alkoxyphenyl)-2-hydroxynaphthalene-1-carboxamides 1-7c and N-(Alkoxyphenyl)-1-hydroxynaphthalene-2-carboxamides 8-14c General procedure: 2-Hydroxynaphthalene-1-carboxylic acid or 1-hydroxynaphthalene-2-carboxylic acid (5.30 mmol) and appropriate alkoxyaniline (5.30 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and reacting mixture was heated in the microwave reactor for 15 min at 130 °C using infrared flask-surface control of temperature. Solvent was evaporated in vacuum; residue solid was washed with 2M HCl and crystallized from aqueous ethanol. If necessary, column chromatography was used for further purification (mobile phase DCM:MeOH 19:1).
	With phosphorus trichloride In chlorobenzene Microwave irradiation;

With trichlorophosphate In chlorobenzene for 0.25h; Microwave irradiation;

Reference： [1]Gonec, Tomas; Kos, Jiri; Zadrazilova, Iveta; Pesko, Matus; Keltosova, Stanislava; Tengler, Jan; Bobal, Pavel; Kollar, Peter; Cizek, Alois; Kralova, Katarina; Jampilek, Josef [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 21, p. 6531 - 6541]
[2]Gonec, Tomas; Pospisilova, Sarka; Kauerova, Tereza; Kos, Jiri; Dohanosova, Jana; Oravec, Michal; Kollar, Peter; Coffey, Aidan; Liptaj, Tibor; Cizek, Alois; Jampilek, Josef [Molecules, 2016, vol. 21, # 8]
[3]Gonec, Tomas; Kralova, Katarina; Pesko, Matus; Jampilek, Josef [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 9, p. 1881 - 1885] Gajdár, Július; Tsami, Konstantina; Michnová, Hana; Goněc, Tomáš; Brázdová, Marie; Soldánová, Zuzana; Fojta, Miroslav; Jampílek, Josef; Barek, Jiří; Fischer, Jan [Electrochimica Acta, 2020, vol. 332]
[4]Kapustikova, Iva; Bak, Andrzej; Gonec, Tomas; Kos, Jiri; Kozik, Violetta; Jampilek, Josef [Molecules, 2018, vol. 23, # 7]

39
[ 536-90-3 ]
[ 86-48-6 ]
[ 110677-79-7 ]

Yield	Reaction Conditions	Operation in experiment
81%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	4 4.1.4 1-Hydroxy-N-(3-methoxyphenyl)naphthalene-2-carboxamide (2b) General procedure: 4.1.1. General procedure for synthesis of N-(substituted phenyl)-1-hydroxynaphthalene-2-carboxamides 1-8c. 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 °C, using infrared flask-surface control of temperature, for 15min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. Studied compounds 1-8c are presented in Table 1 .
	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	3.2.1. General Procedure for Synthesis of N-(Alkoxyphenyl)-2-hydroxynaphthalene-1-carboxamides 1-7c and N-(Alkoxyphenyl)-1-hydroxynaphthalene-2-carboxamides 8-14c General procedure: 2-Hydroxynaphthalene-1-carboxylic acid or 1-hydroxynaphthalene-2-carboxylic acid (5.30 mmol) and appropriate alkoxyaniline (5.30 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and reacting mixture was heated in the microwave reactor for 15 min at 130 °C using infrared flask-surface control of temperature. Solvent was evaporated in vacuum; residue solid was washed with 2M HCl and crystallized from aqueous ethanol. If necessary, column chromatography was used for further purification (mobile phase DCM:MeOH 19:1).
	With phosphorus trichloride In chlorobenzene Microwave irradiation;

With trichlorophosphate In chlorobenzene for 0.25h; Microwave irradiation;

Reference： [1]Gonec, Tomas; Kos, Jiri; Zadrazilova, Iveta; Pesko, Matus; Keltosova, Stanislava; Tengler, Jan; Bobal, Pavel; Kollar, Peter; Cizek, Alois; Kralova, Katarina; Jampilek, Josef [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 21, p. 6531 - 6541]
[2]Gonec, Tomas; Pospisilova, Sarka; Kauerova, Tereza; Kos, Jiri; Dohanosova, Jana; Oravec, Michal; Kollar, Peter; Coffey, Aidan; Liptaj, Tibor; Cizek, Alois; Jampilek, Josef [Molecules, 2016, vol. 21, # 8]
[3]Gonec, Tomas; Kralova, Katarina; Pesko, Matus; Jampilek, Josef [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 9, p. 1881 - 1885] Gajdár, Július; Tsami, Konstantina; Michnová, Hana; Goněc, Tomáš; Brázdová, Marie; Soldánová, Zuzana; Fojta, Miroslav; Jampílek, Josef; Barek, Jiří; Fischer, Jan [Electrochimica Acta, 2020, vol. 332]
[4]Kapustikova, Iva; Bak, Andrzej; Gonec, Tomas; Kos, Jiri; Kozik, Violetta; Jampilek, Josef [Molecules, 2018, vol. 23, # 7]

40
[ 104-94-9 ]
[ 86-48-6 ]
[ 98621-48-8 ]

Yield	Reaction Conditions	Operation in experiment
78%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	5 4.1.5 1-Hydroxy-N-(4-methoxyphenyl)naphthalene-2-carboxamide (2c) General procedure: 4.1.1. General procedure for synthesis of N-(substituted phenyl)-1-hydroxynaphthalene-2-carboxamides 1-8c. 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 °C, using infrared flask-surface control of temperature, for 15min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. Studied compounds 1-8c are presented in Table 1 .
	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	3.2.1. General Procedure for Synthesis of N-(Alkoxyphenyl)-2-hydroxynaphthalene-1-carboxamides 1-7c and N-(Alkoxyphenyl)-1-hydroxynaphthalene-2-carboxamides 8-14c General procedure: 2-Hydroxynaphthalene-1-carboxylic acid or 1-hydroxynaphthalene-2-carboxylic acid (5.30 mmol) and appropriate alkoxyaniline (5.30 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and reacting mixture was heated in the microwave reactor for 15 min at 130 °C using infrared flask-surface control of temperature. Solvent was evaporated in vacuum; residue solid was washed with 2M HCl and crystallized from aqueous ethanol. If necessary, column chromatography was used for further purification (mobile phase DCM:MeOH 19:1).
	With phosphorus trichloride In chlorobenzene Microwave irradiation;

With trichlorophosphate In chlorobenzene for 0.25h; Microwave irradiation;

Reference： [1]Gonec, Tomas; Kos, Jiri; Zadrazilova, Iveta; Pesko, Matus; Keltosova, Stanislava; Tengler, Jan; Bobal, Pavel; Kollar, Peter; Cizek, Alois; Kralova, Katarina; Jampilek, Josef [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 21, p. 6531 - 6541]
[2]Gonec, Tomas; Pospisilova, Sarka; Kauerova, Tereza; Kos, Jiri; Dohanosova, Jana; Oravec, Michal; Kollar, Peter; Coffey, Aidan; Liptaj, Tibor; Cizek, Alois; Jampilek, Josef [Molecules, 2016, vol. 21, # 8]
[3]Gonec, Tomas; Kralova, Katarina; Pesko, Matus; Jampilek, Josef [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 9, p. 1881 - 1885] Gajdár, Július; Tsami, Konstantina; Michnová, Hana; Goněc, Tomáš; Brázdová, Marie; Soldánová, Zuzana; Fojta, Miroslav; Jampílek, Josef; Barek, Jiří; Fischer, Jan [Electrochimica Acta, 2020, vol. 332]
[4]Kapustikova, Iva; Bak, Andrzej; Gonec, Tomas; Kos, Jiri; Kozik, Violetta; Jampilek, Josef [Molecules, 2018, vol. 23, # 7]

41
[ 95-53-4 ]
[ 86-48-6 ]
[ 110677-77-5 ]

Yield	Reaction Conditions	Operation in experiment
70%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	6 4.1.6 1-Hydroxy-N-(2-methylphenyl)naphthalene-2-carboxamide (3a) General procedure: 4.1.1. General procedure for synthesis of N-(substituted phenyl)-1-hydroxynaphthalene-2-carboxamides 1-8c. 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 °C, using infrared flask-surface control of temperature, for 15min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. Studied compounds 1-8c are presented in Table 1 .
	With phosphorus trichloride In chlorobenzene Microwave irradiation;

Reference： [1]Gonec, Tomas; Kos, Jiri; Zadrazilova, Iveta; Pesko, Matus; Keltosova, Stanislava; Tengler, Jan; Bobal, Pavel; Kollar, Peter; Cizek, Alois; Kralova, Katarina; Jampilek, Josef [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 21, p. 6531 - 6541]
[2]Gajdár, Július; Tsami, Konstantina; Michnová, Hana; Goněc, Tomáš; Brázdová, Marie; Soldánová, Zuzana; Fojta, Miroslav; Jampílek, Josef; Barek, Jiří; Fischer, Jan [Electrochimica Acta, 2020, vol. 332]

42
[ 108-44-1 ]
[ 86-48-6 ]
[ 110677-80-0 ]

Yield	Reaction Conditions	Operation in experiment
70%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	7 4.1.7 1-Hydroxy-N-(3-methylphenyl)naphthalene-2-carboxamide (3b) General procedure: 4.1.1. General procedure for synthesis of N-(substituted phenyl)-1-hydroxynaphthalene-2-carboxamides 1-8c. 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 °C, using infrared flask-surface control of temperature, for 15min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. Studied compounds 1-8c are presented in Table 1 .
	With phosphorus trichloride In chlorobenzene Microwave irradiation;

Reference： [1]Gonec, Tomas; Kos, Jiri; Zadrazilova, Iveta; Pesko, Matus; Keltosova, Stanislava; Tengler, Jan; Bobal, Pavel; Kollar, Peter; Cizek, Alois; Kralova, Katarina; Jampilek, Josef [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 21, p. 6531 - 6541]
[2]Gajdár, Július; Tsami, Konstantina; Michnová, Hana; Goněc, Tomáš; Brázdová, Marie; Soldánová, Zuzana; Fojta, Miroslav; Jampílek, Josef; Barek, Jiří; Fischer, Jan [Electrochimica Acta, 2020, vol. 332]

43
[ 106-49-0 ]
[ 86-48-6 ]
[ 110677-81-1 ]

Yield	Reaction Conditions	Operation in experiment
68%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	8 4.1.8 1-Hydroxy-N-(4-methylphenyl)naphthalene-2-carboxamide (3c) General procedure: 4.1.1. General procedure for synthesis of N-(substituted phenyl)-1-hydroxynaphthalene-2-carboxamides 1-8c. 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 °C, using infrared flask-surface control of temperature, for 15min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. Studied compounds 1-8c are presented in Table 1 .
	With phosphorus trichloride In chlorobenzene Microwave irradiation;

Reference： [1]Gonec, Tomas; Kos, Jiri; Zadrazilova, Iveta; Pesko, Matus; Keltosova, Stanislava; Tengler, Jan; Bobal, Pavel; Kollar, Peter; Cizek, Alois; Kralova, Katarina; Jampilek, Josef [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 21, p. 6531 - 6541]
[2]Gajdár, Július; Tsami, Konstantina; Michnová, Hana; Goněc, Tomáš; Brázdová, Marie; Soldánová, Zuzana; Fojta, Miroslav; Jampílek, Josef; Barek, Jiří; Fischer, Jan [Electrochimica Acta, 2020, vol. 332]

44
[ 348-54-9 ]
[ 86-48-6 ]
N-(2-fluorophenyl)-1-hydroxynaphthalene-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	9 4.1.9 N-(2-Fluorophenyl)-1-hydroxynaphthalene-2-carboxamide (4a) General procedure: 4.1.1. General procedure for synthesis of N-(substituted phenyl)-1-hydroxynaphthalene-2-carboxamides 1-8c. 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 °C, using infrared flask-surface control of temperature, for 15min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. Studied compounds 1-8c are presented in Table 1 .
	With phosphorus trichloride In chlorobenzene Microwave irradiation;

Reference： [1]Gonec, Tomas; Kos, Jiri; Zadrazilova, Iveta; Pesko, Matus; Keltosova, Stanislava; Tengler, Jan; Bobal, Pavel; Kollar, Peter; Cizek, Alois; Kralova, Katarina; Jampilek, Josef [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 21, p. 6531 - 6541]
[2]Gajdár, Július; Tsami, Konstantina; Michnová, Hana; Goněc, Tomáš; Brázdová, Marie; Soldánová, Zuzana; Fojta, Miroslav; Jampílek, Josef; Barek, Jiří; Fischer, Jan [Electrochimica Acta, 2020, vol. 332]

45
[ 372-19-0 ]
[ 86-48-6 ]
N-(3-fluorophenyl)-1-hydroxynaphthalene-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	10 4.1.10. N-(3-Fluorophenyl)-1-hydroxynaphthalene-2-carboxamide (4b) General procedure: 4.1.1. General procedure for synthesis of N-(substituted phenyl)-1-hydroxynaphthalene-2-carboxamides 1-8c. 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 °C, using infrared flask-surface control of temperature, for 15min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. Studied compounds 1-8c are presented in Table 1 .
	With phosphorus trichloride In chlorobenzene Microwave irradiation;

Reference： [1]Gonec, Tomas; Kos, Jiri; Zadrazilova, Iveta; Pesko, Matus; Keltosova, Stanislava; Tengler, Jan; Bobal, Pavel; Kollar, Peter; Cizek, Alois; Kralova, Katarina; Jampilek, Josef [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 21, p. 6531 - 6541]
[2]Gajdár, Július; Tsami, Konstantina; Michnová, Hana; Goněc, Tomáš; Brázdová, Marie; Soldánová, Zuzana; Fojta, Miroslav; Jampílek, Josef; Barek, Jiří; Fischer, Jan [Electrochimica Acta, 2020, vol. 332]

46
[ 371-40-4 ]
[ 86-48-6 ]
N-(4-fluorophenyl)-1-hydroxynaphthalene-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	11 4.1.11 N-(4-Fluorophenyl)-1-hydroxynaphthalene-2-carboxamide (4c). General procedure: 4.1.1. General procedure for synthesis of N-(substituted phenyl)-1-hydroxynaphthalene-2-carboxamides 1-8c. 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 °C, using infrared flask-surface control of temperature, for 15min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. Studied compounds 1-8c are presented in Table 1 .
	With phosphorus trichloride In chlorobenzene Microwave irradiation;

Reference： [1]Gonec, Tomas; Kos, Jiri; Zadrazilova, Iveta; Pesko, Matus; Keltosova, Stanislava; Tengler, Jan; Bobal, Pavel; Kollar, Peter; Cizek, Alois; Kralova, Katarina; Jampilek, Josef [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 21, p. 6531 - 6541]
[2]Gajdár, Július; Tsami, Konstantina; Michnová, Hana; Goněc, Tomáš; Brázdová, Marie; Soldánová, Zuzana; Fojta, Miroslav; Jampílek, Josef; Barek, Jiří; Fischer, Jan [Electrochimica Acta, 2020, vol. 332]

47
[ 95-51-2 ]
[ 86-48-6 ]
[ 50729-10-7 ]

Yield	Reaction Conditions	Operation in experiment
81%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	12 4.1.12. N-(2-Chlorophenyl)-1-hydroxynaphthalene-2-carboxamide (5a) General procedure: 4.1.1. General procedure for synthesis of N-(substituted phenyl)-1-hydroxynaphthalene-2-carboxamides 1-8c. 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 °C, using infrared flask-surface control of temperature, for 15min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. Studied compounds 1-8c are presented in Table 1 .
	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	General Procedure for Synthesis of N-(substituted phenyl)-1-hydroxynaphthalene-2-carboxamides 1-24 General procedure: 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 °C, using infrared flask-surface control of temperature, for 15 min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. All the studied compounds are presented in Table 1.
	With phosphorus trichloride In chlorobenzene Microwave irradiation;

Reference： [1]Gonec, Tomas; Kos, Jiri; Zadrazilova, Iveta; Pesko, Matus; Keltosova, Stanislava; Tengler, Jan; Bobal, Pavel; Kollar, Peter; Cizek, Alois; Kralova, Katarina; Jampilek, Josef [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 21, p. 6531 - 6541]
[2]Gonec, Tomas; Kos, Jiri; Pesko, Matus; Dohanosova, Jana; Oravec, Michal; Liptaj, Tibor; Kralova, Katarina; Jampilek, Josef [Molecules, 2017, vol. 22, # 10]
[3]Gajdár, Július; Tsami, Konstantina; Michnová, Hana; Goněc, Tomáš; Brázdová, Marie; Soldánová, Zuzana; Fojta, Miroslav; Jampílek, Josef; Barek, Jiří; Fischer, Jan [Electrochimica Acta, 2020, vol. 332]

48
[ 108-42-9 ]
[ 86-48-6 ]
[ 50729-11-8 ]

Yield	Reaction Conditions	Operation in experiment
88%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Inert atmosphere;	13 4.1.13. N-(3-Chlorophenyl)-1-hydroxynaphthalene-2-carboxamide (5b) General procedure: 4.1.1. General procedure for synthesis of N-(substituted phenyl)-1-hydroxynaphthalene-2-carboxamides 1-8c. 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 °C, using infrared flask-surface control of temperature, for 15min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. Studied compounds 1-8c are presented in Table 1 .
	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	General Procedure for Synthesis of N-(substituted phenyl)-1-hydroxynaphthalene-2-carboxamides 1-24 General procedure: 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 °C, using infrared flask-surface control of temperature, for 15 min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. All the studied compounds are presented in Table 1.
	With phosphorus trichloride In chlorobenzene Microwave irradiation;

Reference： [1]Gonec, Tomas; Kos, Jiri; Zadrazilova, Iveta; Pesko, Matus; Keltosova, Stanislava; Tengler, Jan; Bobal, Pavel; Kollar, Peter; Cizek, Alois; Kralova, Katarina; Jampilek, Josef [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 21, p. 6531 - 6541]
[2]Gonec, Tomas; Kos, Jiri; Pesko, Matus; Dohanosova, Jana; Oravec, Michal; Liptaj, Tibor; Kralova, Katarina; Jampilek, Josef [Molecules, 2017, vol. 22, # 10]
[3]Gajdár, Július; Tsami, Konstantina; Michnová, Hana; Goněc, Tomáš; Brázdová, Marie; Soldánová, Zuzana; Fojta, Miroslav; Jampílek, Josef; Barek, Jiří; Fischer, Jan [Electrochimica Acta, 2020, vol. 332]

49
[ 615-36-1 ]
[ 86-48-6 ]
N-(2-bromophenyl)-1-hydroxynaphthalene-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	15 4.1.15. N-(2-Bromophenyl)-1-hydroxynaphthalene-2-carboxamide (6a) General procedure: 4.1.1. General procedure for synthesis of N-(substituted phenyl)-1-hydroxynaphthalene-2-carboxamides 1-8c. 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 °C, using infrared flask-surface control of temperature, for 15min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. Studied compounds 1-8c are presented in Table 1 .
	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	General Procedure for Synthesis of N-(substituted phenyl)-1-hydroxynaphthalene-2-carboxamides 1-24 General procedure: 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 °C, using infrared flask-surface control of temperature, for 15 min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. All the studied compounds are presented in Table 1.
	With phosphorus trichloride In chlorobenzene Microwave irradiation;

Reference： [1]Gonec, Tomas; Kos, Jiri; Zadrazilova, Iveta; Pesko, Matus; Keltosova, Stanislava; Tengler, Jan; Bobal, Pavel; Kollar, Peter; Cizek, Alois; Kralova, Katarina; Jampilek, Josef [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 21, p. 6531 - 6541]
[2]Gonec, Tomas; Kos, Jiri; Pesko, Matus; Dohanosova, Jana; Oravec, Michal; Liptaj, Tibor; Kralova, Katarina; Jampilek, Josef [Molecules, 2017, vol. 22, # 10]
[3]Gajdár, Július; Tsami, Konstantina; Michnová, Hana; Goněc, Tomáš; Brázdová, Marie; Soldánová, Zuzana; Fojta, Miroslav; Jampílek, Josef; Barek, Jiří; Fischer, Jan [Electrochimica Acta, 2020, vol. 332]

50
[ 591-19-5 ]
[ 86-48-6 ]
N-(3-bromophenyl)-1-hydroxynaphthalene-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	16 4.1.16. N-(3-Bromophenyl)-1-hydroxynaphthalene-2-carboxamide (6b) General procedure: 4.1.1. General procedure for synthesis of N-(substituted phenyl)-1-hydroxynaphthalene-2-carboxamides 1-8c. 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 °C, using infrared flask-surface control of temperature, for 15min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. Studied compounds 1-8c are presented in Table 1 .
	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	General Procedure for Synthesis of N-(substituted phenyl)-1-hydroxynaphthalene-2-carboxamides 1-24 General procedure: 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 °C, using infrared flask-surface control of temperature, for 15 min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. All the studied compounds are presented in Table 1.
	With phosphorus trichloride In chlorobenzene Microwave irradiation;

Reference： [1]Gonec, Tomas; Kos, Jiri; Zadrazilova, Iveta; Pesko, Matus; Keltosova, Stanislava; Tengler, Jan; Bobal, Pavel; Kollar, Peter; Cizek, Alois; Kralova, Katarina; Jampilek, Josef [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 21, p. 6531 - 6541]
[2]Gonec, Tomas; Kos, Jiri; Pesko, Matus; Dohanosova, Jana; Oravec, Michal; Liptaj, Tibor; Kralova, Katarina; Jampilek, Josef [Molecules, 2017, vol. 22, # 10]
[3]Gajdár, Július; Tsami, Konstantina; Michnová, Hana; Goněc, Tomáš; Brázdová, Marie; Soldánová, Zuzana; Fojta, Miroslav; Jampílek, Josef; Barek, Jiří; Fischer, Jan [Electrochimica Acta, 2020, vol. 332]

51
[ 106-40-1 ]
[ 86-48-6 ]
[ 50729-13-0 ]

Yield	Reaction Conditions	Operation in experiment
81%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	17 4.1.17. N-(4-Bromophenyl)-1-hydroxynaphthalene-2-carboxamide (6c) General procedure: 4.1.1. General procedure for synthesis of N-(substituted phenyl)-1-hydroxynaphthalene-2-carboxamides 1-8c. 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 °C, using infrared flask-surface control of temperature, for 15min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. Studied compounds 1-8c are presented in Table 1 .
	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	General Procedure for Synthesis of N-(substituted phenyl)-1-hydroxynaphthalene-2-carboxamides 1-24 General procedure: 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 °C, using infrared flask-surface control of temperature, for 15 min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. All the studied compounds are presented in Table 1.
	With phosphorus trichloride In chlorobenzene Microwave irradiation;

Reference： [1]Gonec, Tomas; Kos, Jiri; Zadrazilova, Iveta; Pesko, Matus; Keltosova, Stanislava; Tengler, Jan; Bobal, Pavel; Kollar, Peter; Cizek, Alois; Kralova, Katarina; Jampilek, Josef [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 21, p. 6531 - 6541]
[2]Gonec, Tomas; Kos, Jiri; Pesko, Matus; Dohanosova, Jana; Oravec, Michal; Liptaj, Tibor; Kralova, Katarina; Jampilek, Josef [Molecules, 2017, vol. 22, # 10]
[3]Gajdár, Július; Tsami, Konstantina; Michnová, Hana; Goněc, Tomáš; Brázdová, Marie; Soldánová, Zuzana; Fojta, Miroslav; Jampílek, Josef; Barek, Jiří; Fischer, Jan [Electrochimica Acta, 2020, vol. 332]

52
[ 88-17-5 ]
[ 86-48-6 ]
1-hydroxy-N-[2-(trifluoromethyl)phenyl]naphthalene-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	18 4.1.18, 1-Hydroxy-N-[2-(trifluoromethyl)phenyl]naphthalene-2-carboxamide (7a) General procedure: 4.1.1. General procedure for synthesis of N-(substituted phenyl)-1-hydroxynaphthalene-2-carboxamides 1-8c. 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 °C, using infrared flask-surface control of temperature, for 15min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. Studied compounds 1-8c are presented in Table 1 .
	With phosphorus trichloride In chlorobenzene Microwave irradiation;

Reference： [1]Gonec, Tomas; Kos, Jiri; Zadrazilova, Iveta; Pesko, Matus; Keltosova, Stanislava; Tengler, Jan; Bobal, Pavel; Kollar, Peter; Cizek, Alois; Kralova, Katarina; Jampilek, Josef [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 21, p. 6531 - 6541]
[2]Gajdár, Július; Tsami, Konstantina; Michnová, Hana; Goněc, Tomáš; Brázdová, Marie; Soldánová, Zuzana; Fojta, Miroslav; Jampílek, Josef; Barek, Jiří; Fischer, Jan [Electrochimica Acta, 2020, vol. 332]

53
[ 98-16-8 ]
[ 86-48-6 ]
[ 442-30-8 ]

Yield	Reaction Conditions	Operation in experiment
60%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	19 4.1.19. 1-Hydroxy-N-[3-(trifluoromethyl)phenyl]naphthalene-2-carboxamide (7b) General procedure: 4.1.1. General procedure for synthesis of N-(substituted phenyl)-1-hydroxynaphthalene-2-carboxamides 1-8c. 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 °C, using infrared flask-surface control of temperature, for 15min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. Studied compounds 1-8c are presented in Table 1 .
	With phosphorus trichloride In chlorobenzene Microwave irradiation;

Reference： [1]Gonec, Tomas; Kos, Jiri; Zadrazilova, Iveta; Pesko, Matus; Keltosova, Stanislava; Tengler, Jan; Bobal, Pavel; Kollar, Peter; Cizek, Alois; Kralova, Katarina; Jampilek, Josef [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 21, p. 6531 - 6541]
[2]Gajdár, Július; Tsami, Konstantina; Michnová, Hana; Goněc, Tomáš; Brázdová, Marie; Soldánová, Zuzana; Fojta, Miroslav; Jampílek, Josef; Barek, Jiří; Fischer, Jan [Electrochimica Acta, 2020, vol. 332]

54
[ 455-14-1 ]
[ 86-48-6 ]
1-hydroxy-N-[4-(trifluoromethyl)phenyl]naphthalene-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	20 4.1.20. 1-Hydroxy-N-[4-(trifluoromethyl)phenyl]naphthalene-2-carboxamide (7c) General procedure: 4.1.1. General procedure for synthesis of N-(substituted phenyl)-1-hydroxynaphthalene-2-carboxamides 1-8c. 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 °C, using infrared flask-surface control of temperature, for 15min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. Studied compounds 1-8c are presented in Table 1 .
	With phosphorus trichloride In chlorobenzene Microwave irradiation;

Reference： [1]Gonec, Tomas; Kos, Jiri; Zadrazilova, Iveta; Pesko, Matus; Keltosova, Stanislava; Tengler, Jan; Bobal, Pavel; Kollar, Peter; Cizek, Alois; Kralova, Katarina; Jampilek, Josef [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 21, p. 6531 - 6541]
[2]Gajdár, Július; Tsami, Konstantina; Michnová, Hana; Goněc, Tomáš; Brázdová, Marie; Soldánová, Zuzana; Fojta, Miroslav; Jampílek, Josef; Barek, Jiří; Fischer, Jan [Electrochimica Acta, 2020, vol. 332]

55
[ 88-74-4 ]
[ 86-48-6 ]
[ 40388-14-5 ]

Yield	Reaction Conditions	Operation in experiment
74%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Inert atmosphere;	21 4.1.21. 1-Hydroxy-N-(2-nitrophenyl)naphthalene-2-carboxamide (8a) General procedure: 4.1.1. General procedure for synthesis of N-(substituted phenyl)-1-hydroxynaphthalene-2-carboxamides 1-8c. 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 °C, using infrared flask-surface control of temperature, for 15min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. Studied compounds 1-8c are presented in Table 1 .
	With phosphorus trichloride In chlorobenzene Microwave irradiation;

Reference： [1]Gonec, Tomas; Kos, Jiri; Zadrazilova, Iveta; Pesko, Matus; Keltosova, Stanislava; Tengler, Jan; Bobal, Pavel; Kollar, Peter; Cizek, Alois; Kralova, Katarina; Jampilek, Josef [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 21, p. 6531 - 6541]
[2]Gajdár, Július; Tsami, Konstantina; Michnová, Hana; Goněc, Tomáš; Brázdová, Marie; Soldánová, Zuzana; Fojta, Miroslav; Jampílek, Josef; Barek, Jiří; Fischer, Jan [Electrochimica Acta, 2020, vol. 332]

56
[ 99-09-2 ]
[ 86-48-6 ]
[ 71835-65-9 ]

Yield	Reaction Conditions	Operation in experiment
74%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	22 4.1.22. 1-Hydroxy-N-(3-nitrophenyl)naphthalene-2-carboxamide (8b) General procedure: 4.1.1. General procedure for synthesis of N-(substituted phenyl)-1-hydroxynaphthalene-2-carboxamides 1-8c. 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 °C, using infrared flask-surface control of temperature, for 15min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. Studied compounds 1-8c are presented in Table 1 .
	With phosphorus trichloride In chlorobenzene Microwave irradiation;

Reference： [1]Gonec, Tomas; Kos, Jiri; Zadrazilova, Iveta; Pesko, Matus; Keltosova, Stanislava; Tengler, Jan; Bobal, Pavel; Kollar, Peter; Cizek, Alois; Kralova, Katarina; Jampilek, Josef [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 21, p. 6531 - 6541]
[2]Gajdár, Július; Tsami, Konstantina; Michnová, Hana; Goněc, Tomáš; Brázdová, Marie; Soldánová, Zuzana; Fojta, Miroslav; Jampílek, Josef; Barek, Jiří; Fischer, Jan [Electrochimica Acta, 2020, vol. 332]

57
[ 100-01-6 ]
[ 86-48-6 ]
[ 68352-27-2 ]

Yield	Reaction Conditions	Operation in experiment
67%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	23 4.1.23. 1-Hydroxy-N-(4-nitrophenyl)naphthalene-2-carboxamide (8c) General procedure: 4.1.1. General procedure for synthesis of N-(substituted phenyl)-1-hydroxynaphthalene-2-carboxamides 1-8c. 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 °C, using infrared flask-surface control of temperature, for 15min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. Studied compounds 1-8c are presented in Table 1 .
	With phosphorus trichloride In chlorobenzene Microwave irradiation;

Reference： [1]Gonec, Tomas; Kos, Jiri; Zadrazilova, Iveta; Pesko, Matus; Keltosova, Stanislava; Tengler, Jan; Bobal, Pavel; Kollar, Peter; Cizek, Alois; Kralova, Katarina; Jampilek, Josef [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 21, p. 6531 - 6541]
[2]Gajdár, Július; Tsami, Konstantina; Michnová, Hana; Goněc, Tomáš; Brázdová, Marie; Soldánová, Zuzana; Fojta, Miroslav; Jampílek, Josef; Barek, Jiří; Fischer, Jan [Electrochimica Acta, 2020, vol. 332]

58
tert-butyl (3-aminopropyl) carbamate [ No CAS ]
[ 86-48-6 ]
[ 1417803-43-0 ]

Yield	Reaction Conditions	Operation in experiment
69%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 12h;	21 N-3-(Tert-butoxycarbonylamino)propyl 1-hydroxynaphthene-2-carboxamide (34) N-3-(Tert-butoxycarbonylamino)propyl 1-hydroxynaphthene-2-carboxamide (34) To a solution of HNAP (300 mg, 1.60 mmol) in CH2Cl2 (5 mL) was added amine 30 (306 mg, 1.76 mmol), EDCI (334 mg, 1.76 mmol) and 4-dimethylaminopyridine (215 mg, 1.76 mmol). The mixture was stirred at room temperature for 12 h. The resulting solution was washed with 1 M HCl, dried over MgSO4, concentrated under reduced pressure, and purified by flash silica gel column chromatography (hexane to EtOAc/hexane=1:4) to afford the coupling product 34 (378 mg, 69%). C19H24N2O4; TLC (EtOAc/hexane=3:7) R=0.31; red foam; IR νmax (neat) 3356, 2976, 1692, 1619, 1609, 1538, 1392, 1365, 1282 cm-1; 1H NMR (400 MHz, CDCl3) δ 14.16 (1H, s), 8.43 (1H, d, J=8.4 Hz), 7.94 (1H, s), 7.73 (1H, d, J=8.0 Hz), 7.53 (3H, m), 7.25 (1H, d, J=8.8 Hz), 5.22 (1H, s), 3.51 (2H, m), 3.23 (2H, t, J=6.0 Hz), 1.71 (2H, t, J=5.2 Hz), 1.49 (9H, s); 13C NMR (100 MHz, CDCl3) δ 170.7, 160.2, 157.1, 136.0, 128.5, 127.1, 125.4, 123.5, 121.3, 118.0, 106.8, 79.5, 77.0, 36.9, 35.5, 29.8, 28.2 (3*); ESI-HRMS (negative mode) calcd for C19H23N2O4: 343.1658, found: m/z 343.1648 [M-H]-.

Reference： [1]Current Patent Assignee: ACADEMIA SINICA - US2013/274229, 2013, A1 Location in patent: Paragraph 0281

59
[ 641571-10-0 ]
[ 86-48-6 ]
nilotinib 1-hydroxy-2-naphthoic acid salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In water; at 50 - 55℃; for 1h;	Example 10: Preparation of <strong>[641571-10-0]nilotinib</strong> l-hydroxy-2-napthoic acid salt crystalline Form VIII <strong>[641571-10-0]Nilotinib</strong> base (1 g) was suspended in water (20 ml) and heated to 50-55 C. l-Hydroxy-2- napthoic acid was added to it and the content was heated at 50-55 C for 1 h. Methanol (5 ml) was added to the mixture and stirred for 30 min. The content was filtered, washed with water (2 x 2 ml) and dried under vacuum for 1 h at 50-55 C. 1H NMR (400 MHz, DMSO-d6) delta 2.25 (s,3H), 2.41 (s,3H), 7.40-7.92 (m,l lH), 8.23-8.73 (m,8H), 9.24 (s,lH), 9.34(s,lH), 10.70 (s,lH). The salt has a XRPD pattern substantially same as set forth in FIG. 8.

Reference： [1]Patent: WO2016/24289,2016,A2 .Location in patent: Page/Page column 9

60
[ 74-88-4 ]
[ 86-48-6 ]
[ 883-21-6 ]

Yield	Reaction Conditions	Operation in experiment
90%	With potassium carbonate In N,N-dimethyl-formamide at 90℃; for 10h; Cooling with ice;	68.a Preparation of 1-methoxy-2-naphthoic acid Reaction flask was added 2.0 g (10.6 dirty 1) of 1-hydroxy-2-naphthoic acid, 3.68 g (26.6 1 dirty) in dry Of potassium carbonate and 20 ml of DMF dry, stirred, ice bath cooling, 3.4 g (23 3_1) of methyl iodide was slowly added dropwise to the reaction Bottle, heated to 90 ° C for 6 hours. The reaction mixture was poured into water, extracted with dichloromethane, washed with saturated sodium chloride solution The organic layer was washed three times, dried over anhydrous sodium sulfate, and concentrated. The concentrate was dissolved in 10 ml of methanol, was slowly added 6N hydroxide 6.6 ml solution of sodium stirred at room temperature for 5 hours. Extracted three times, the aqueous layer (ice) and acidified with concentrated hydrochloric acid and methylene chloride, To give a white solid which was recrystallized from ethanol to give 1.9 g of white crystals, yield 90%

Reference： [1]Current Patent Assignee: CHINESE ACADEMY OF MEDICAL SCIENCES - CN101602750, 2016, B Location in patent: Paragraph 0439; 0440

61
[ 94-70-2 ]
[ 86-48-6 ]
[ 26639-37-2 ]

Yield	Reaction Conditions	Operation in experiment
55%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	3.2.1. General Procedure for Synthesis of N-(Alkoxyphenyl)-2-hydroxynaphthalene-1-carboxamides 1-7c and N-(Alkoxyphenyl)-1-hydroxynaphthalene-2-carboxamides 8-14c General procedure: 2-Hydroxynaphthalene-1-carboxylic acid or 1-hydroxynaphthalene-2-carboxylic acid (5.30 mmol) and appropriate alkoxyaniline (5.30 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and reacting mixture was heated in the microwave reactor for 15 min at 130 °C using infrared flask-surface control of temperature. Solvent was evaporated in vacuum; residue solid was washed with 2M HCl and crystallized from aqueous ethanol. If necessary, column chromatography was used for further purification (mobile phase DCM:MeOH 19:1).
	With phosphorus trichloride In chlorobenzene Microwave irradiation;
	With trichlorophosphate In chlorobenzene for 0.25h; Microwave irradiation;

Reference： [1]Gonec, Tomas; Pospisilova, Sarka; Kauerova, Tereza; Kos, Jiri; Dohanosova, Jana; Oravec, Michal; Kollar, Peter; Coffey, Aidan; Liptaj, Tibor; Cizek, Alois; Jampilek, Josef [Molecules, 2016, vol. 21, # 8]
[2]Gonec, Tomas; Kralova, Katarina; Pesko, Matus; Jampilek, Josef [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 9, p. 1881 - 1885]
[3]Kapustikova, Iva; Bak, Andrzej; Gonec, Tomas; Kos, Jiri; Kozik, Violetta; Jampilek, Josef [Molecules, 2018, vol. 23, # 7]

62
[ 621-33-0 ]
[ 86-48-6 ]
1-hydroxy-N-(3-ethoxyphenyl)-naphthalene-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	3.2.1. General Procedure for Synthesis of N-(Alkoxyphenyl)-2-hydroxynaphthalene-1-carboxamides 1-7c and N-(Alkoxyphenyl)-1-hydroxynaphthalene-2-carboxamides 8-14c General procedure: 2-Hydroxynaphthalene-1-carboxylic acid or 1-hydroxynaphthalene-2-carboxylic acid (5.30 mmol) and appropriate alkoxyaniline (5.30 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and reacting mixture was heated in the microwave reactor for 15 min at 130 °C using infrared flask-surface control of temperature. Solvent was evaporated in vacuum; residue solid was washed with 2M HCl and crystallized from aqueous ethanol. If necessary, column chromatography was used for further purification (mobile phase DCM:MeOH 19:1).
	With phosphorus trichloride In chlorobenzene Microwave irradiation;
	With trichlorophosphate In chlorobenzene for 0.25h; Microwave irradiation;

Reference： [1]Gonec, Tomas; Pospisilova, Sarka; Kauerova, Tereza; Kos, Jiri; Dohanosova, Jana; Oravec, Michal; Kollar, Peter; Coffey, Aidan; Liptaj, Tibor; Cizek, Alois; Jampilek, Josef [Molecules, 2016, vol. 21, # 8]
[2]Gonec, Tomas; Kralova, Katarina; Pesko, Matus; Jampilek, Josef [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 9, p. 1881 - 1885]
[3]Kapustikova, Iva; Bak, Andrzej; Gonec, Tomas; Kos, Jiri; Kozik, Violetta; Jampilek, Josef [Molecules, 2018, vol. 23, # 7]

63
[ 156-43-4 ]
[ 86-48-6 ]
[ 109883-65-0 ]

Yield	Reaction Conditions	Operation in experiment
56%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	3.2.1. General Procedure for Synthesis of N-(Alkoxyphenyl)-2-hydroxynaphthalene-1-carboxamides 1-7c and N-(Alkoxyphenyl)-1-hydroxynaphthalene-2-carboxamides 8-14c General procedure: 2-Hydroxynaphthalene-1-carboxylic acid or 1-hydroxynaphthalene-2-carboxylic acid (5.30 mmol) and appropriate alkoxyaniline (5.30 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and reacting mixture was heated in the microwave reactor for 15 min at 130 °C using infrared flask-surface control of temperature. Solvent was evaporated in vacuum; residue solid was washed with 2M HCl and crystallized from aqueous ethanol. If necessary, column chromatography was used for further purification (mobile phase DCM:MeOH 19:1).
	With phosphorus trichloride In chlorobenzene Microwave irradiation;
	With trichlorophosphate In chlorobenzene for 0.25h; Microwave irradiation;

Reference： [1]Gonec, Tomas; Pospisilova, Sarka; Kauerova, Tereza; Kos, Jiri; Dohanosova, Jana; Oravec, Michal; Kollar, Peter; Coffey, Aidan; Liptaj, Tibor; Cizek, Alois; Jampilek, Josef [Molecules, 2016, vol. 21, # 8]
[2]Gonec, Tomas; Kralova, Katarina; Pesko, Matus; Jampilek, Josef [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 9, p. 1881 - 1885]
[3]Kapustikova, Iva; Bak, Andrzej; Gonec, Tomas; Kos, Jiri; Kozik, Violetta; Jampilek, Josef [Molecules, 2018, vol. 23, # 7]

64
[ 4469-78-7 ]
[ 86-48-6 ]
1-hydroxy-N-(2-propoxyphenyl)naphthalene-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	3.2.1. General Procedure for Synthesis of N-(Alkoxyphenyl)-2-hydroxynaphthalene-1-carboxamides 1-7c and N-(Alkoxyphenyl)-1-hydroxynaphthalene-2-carboxamides 8-14c General procedure: 2-Hydroxynaphthalene-1-carboxylic acid or 1-hydroxynaphthalene-2-carboxylic acid (5.30 mmol) and appropriate alkoxyaniline (5.30 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and reacting mixture was heated in the microwave reactor for 15 min at 130 °C using infrared flask-surface control of temperature. Solvent was evaporated in vacuum; residue solid was washed with 2M HCl and crystallized from aqueous ethanol. If necessary, column chromatography was used for further purification (mobile phase DCM:MeOH 19:1).
	With phosphorus trichloride In chlorobenzene Microwave irradiation;
	With trichlorophosphate In chlorobenzene for 0.25h; Microwave irradiation;

Reference： [1]Gonec, Tomas; Pospisilova, Sarka; Kauerova, Tereza; Kos, Jiri; Dohanosova, Jana; Oravec, Michal; Kollar, Peter; Coffey, Aidan; Liptaj, Tibor; Cizek, Alois; Jampilek, Josef [Molecules, 2016, vol. 21, # 8]
[2]Gonec, Tomas; Kralova, Katarina; Pesko, Matus; Jampilek, Josef [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 9, p. 1881 - 1885]
[3]Kapustikova, Iva; Bak, Andrzej; Gonec, Tomas; Kos, Jiri; Kozik, Violetta; Jampilek, Josef [Molecules, 2018, vol. 23, # 7]

65
[ 4469-79-8 ]
[ 86-48-6 ]
1-hydroxy-N-(3-propoxyphenyl)naphthalene-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
58%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	3.2.1. General Procedure for Synthesis of N-(Alkoxyphenyl)-2-hydroxynaphthalene-1-carboxamides 1-7c and N-(Alkoxyphenyl)-1-hydroxynaphthalene-2-carboxamides 8-14c General procedure: 2-Hydroxynaphthalene-1-carboxylic acid or 1-hydroxynaphthalene-2-carboxylic acid (5.30 mmol) and appropriate alkoxyaniline (5.30 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and reacting mixture was heated in the microwave reactor for 15 min at 130 °C using infrared flask-surface control of temperature. Solvent was evaporated in vacuum; residue solid was washed with 2M HCl and crystallized from aqueous ethanol. If necessary, column chromatography was used for further purification (mobile phase DCM:MeOH 19:1).
	With phosphorus trichloride In chlorobenzene Microwave irradiation;
	With trichlorophosphate In chlorobenzene for 0.25h; Microwave irradiation;

Reference： [1]Gonec, Tomas; Pospisilova, Sarka; Kauerova, Tereza; Kos, Jiri; Dohanosova, Jana; Oravec, Michal; Kollar, Peter; Coffey, Aidan; Liptaj, Tibor; Cizek, Alois; Jampilek, Josef [Molecules, 2016, vol. 21, # 8]
[2]Gonec, Tomas; Kralova, Katarina; Pesko, Matus; Jampilek, Josef [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 9, p. 1881 - 1885]
[3]Kapustikova, Iva; Bak, Andrzej; Gonec, Tomas; Kos, Jiri; Kozik, Violetta; Jampilek, Josef [Molecules, 2018, vol. 23, # 7]

66
[ 4469-80-1 ]
[ 86-48-6 ]
1-hydroxy-N-(4-propoxyphenyl)naphthalene-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	3.2.1. General Procedure for Synthesis of N-(Alkoxyphenyl)-2-hydroxynaphthalene-1-carboxamides 1-7c and N-(Alkoxyphenyl)-1-hydroxynaphthalene-2-carboxamides 8-14c General procedure: 2-Hydroxynaphthalene-1-carboxylic acid or 1-hydroxynaphthalene-2-carboxylic acid (5.30 mmol) and appropriate alkoxyaniline (5.30 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and reacting mixture was heated in the microwave reactor for 15 min at 130 °C using infrared flask-surface control of temperature. Solvent was evaporated in vacuum; residue solid was washed with 2M HCl and crystallized from aqueous ethanol. If necessary, column chromatography was used for further purification (mobile phase DCM:MeOH 19:1).
	With phosphorus trichloride In chlorobenzene Microwave irradiation;
	With trichlorophosphate In chlorobenzene for 0.25h; Microwave irradiation;

Reference： [1]Gonec, Tomas; Pospisilova, Sarka; Kauerova, Tereza; Kos, Jiri; Dohanosova, Jana; Oravec, Michal; Kollar, Peter; Coffey, Aidan; Liptaj, Tibor; Cizek, Alois; Jampilek, Josef [Molecules, 2016, vol. 21, # 8]
[2]Gonec, Tomas; Kralova, Katarina; Pesko, Matus; Jampilek, Josef [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 9, p. 1881 - 1885]
[3]Kapustikova, Iva; Bak, Andrzej; Gonec, Tomas; Kos, Jiri; Kozik, Violetta; Jampilek, Josef [Molecules, 2018, vol. 23, # 7]

67
[ 4469-81-2 ]
[ 86-48-6 ]
N-(2-butoxyphenyl)-1-hydroxynaphthalene-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	3.2.1. General Procedure for Synthesis of N-(Alkoxyphenyl)-2-hydroxynaphthalene-1-carboxamides 1-7c and N-(Alkoxyphenyl)-1-hydroxynaphthalene-2-carboxamides 8-14c General procedure: 2-Hydroxynaphthalene-1-carboxylic acid or 1-hydroxynaphthalene-2-carboxylic acid (5.30 mmol) and appropriate alkoxyaniline (5.30 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and reacting mixture was heated in the microwave reactor for 15 min at 130 °C using infrared flask-surface control of temperature. Solvent was evaporated in vacuum; residue solid was washed with 2M HCl and crystallized from aqueous ethanol. If necessary, column chromatography was used for further purification (mobile phase DCM:MeOH 19:1).
	With phosphorus trichloride In chlorobenzene Microwave irradiation;
	With trichlorophosphate In chlorobenzene for 0.25h; Microwave irradiation;

Reference： [1]Gonec, Tomas; Pospisilova, Sarka; Kauerova, Tereza; Kos, Jiri; Dohanosova, Jana; Oravec, Michal; Kollar, Peter; Coffey, Aidan; Liptaj, Tibor; Cizek, Alois; Jampilek, Josef [Molecules, 2016, vol. 21, # 8]
[2]Gonec, Tomas; Kralova, Katarina; Pesko, Matus; Jampilek, Josef [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 9, p. 1881 - 1885]
[3]Kapustikova, Iva; Bak, Andrzej; Gonec, Tomas; Kos, Jiri; Kozik, Violetta; Jampilek, Josef [Molecules, 2018, vol. 23, # 7]

68
[ 23079-68-7 ]
[ 86-48-6 ]
N-(3-butoxyphenyl)-1-hydroxynaphthalene-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
58%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	3.2.1. General Procedure for Synthesis of N-(Alkoxyphenyl)-2-hydroxynaphthalene-1-carboxamides 1-7c and N-(Alkoxyphenyl)-1-hydroxynaphthalene-2-carboxamides 8-14c General procedure: 2-Hydroxynaphthalene-1-carboxylic acid or 1-hydroxynaphthalene-2-carboxylic acid (5.30 mmol) and appropriate alkoxyaniline (5.30 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and reacting mixture was heated in the microwave reactor for 15 min at 130 °C using infrared flask-surface control of temperature. Solvent was evaporated in vacuum; residue solid was washed with 2M HCl and crystallized from aqueous ethanol. If necessary, column chromatography was used for further purification (mobile phase DCM:MeOH 19:1).
	With phosphorus trichloride In chlorobenzene Microwave irradiation;
	With trichlorophosphate In chlorobenzene for 0.25h; Microwave irradiation;

Reference： [1]Gonec, Tomas; Pospisilova, Sarka; Kauerova, Tereza; Kos, Jiri; Dohanosova, Jana; Oravec, Michal; Kollar, Peter; Coffey, Aidan; Liptaj, Tibor; Cizek, Alois; Jampilek, Josef [Molecules, 2016, vol. 21, # 8]
[2]Gonec, Tomas; Kralova, Katarina; Pesko, Matus; Jampilek, Josef [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 9, p. 1881 - 1885]
[3]Kapustikova, Iva; Bak, Andrzej; Gonec, Tomas; Kos, Jiri; Kozik, Violetta; Jampilek, Josef [Molecules, 2018, vol. 23, # 7]

69
[ 4344-55-2 ]
[ 86-48-6 ]
N-(4-butoxyphenyl)-1-hydroxynaphthalene-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	3.2.1. General Procedure for Synthesis of N-(Alkoxyphenyl)-2-hydroxynaphthalene-1-carboxamides 1-7c and N-(Alkoxyphenyl)-1-hydroxynaphthalene-2-carboxamides 8-14c General procedure: 2-Hydroxynaphthalene-1-carboxylic acid or 1-hydroxynaphthalene-2-carboxylic acid (5.30 mmol) and appropriate alkoxyaniline (5.30 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and reacting mixture was heated in the microwave reactor for 15 min at 130 °C using infrared flask-surface control of temperature. Solvent was evaporated in vacuum; residue solid was washed with 2M HCl and crystallized from aqueous ethanol. If necessary, column chromatography was used for further purification (mobile phase DCM:MeOH 19:1).
	With phosphorus trichloride In chlorobenzene Microwave irradiation;
	With trichlorophosphate In chlorobenzene for 0.25h; Microwave irradiation;

Reference： [1]Gonec, Tomas; Pospisilova, Sarka; Kauerova, Tereza; Kos, Jiri; Dohanosova, Jana; Oravec, Michal; Kollar, Peter; Coffey, Aidan; Liptaj, Tibor; Cizek, Alois; Jampilek, Josef [Molecules, 2016, vol. 21, # 8]
[2]Gonec, Tomas; Kralova, Katarina; Pesko, Matus; Jampilek, Josef [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 9, p. 1881 - 1885]
[3]Kapustikova, Iva; Bak, Andrzej; Gonec, Tomas; Kos, Jiri; Kozik, Violetta; Jampilek, Josef [Molecules, 2018, vol. 23, # 7]

70
[ 29026-74-2 ]
[ 86-48-6 ]
1-hydroxy-N-[2-(prop-2-yloxy)phenyl]naphthalene-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
49%	With phosphorus trichloride; In chlorobenzene; at 130℃; for 0.25h;Microwave irradiation;	General procedure: 2-Hydroxynaphthalene-1-carboxylic acid or 1-hydroxynaphthalene-2-carboxylic acid (5.30 mmol) and appropriate alkoxyaniline (5.30 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and reacting mixture was heated in the microwave reactor for 15 min at 130 C using infrared flask-surface control of temperature. Solvent was evaporated in vacuum; residue solid was washed with 2M HCl and crystallized from aqueous ethanol. If necessary, column chromatography was used for further purification (mobile phase DCM:MeOH 19:1).

Reference： [1]Molecules,2016,vol. 21
[2]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 1881 - 1885
[3]Molecules,2018,vol. 23

71
[ 41406-00-2 ]
[ 86-48-6 ]
1-hydroxy-N-[3-(prop-2-yloxy)phenyl]naphthalene-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	With phosphorus trichloride; In chlorobenzene; at 130℃; for 0.25h;Microwave irradiation;	General procedure: 2-Hydroxynaphthalene-1-carboxylic acid or 1-hydroxynaphthalene-2-carboxylic acid (5.30 mmol) and appropriate alkoxyaniline (5.30 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and reacting mixture was heated in the microwave reactor for 15 min at 130 C using infrared flask-surface control of temperature. Solvent was evaporated in vacuum; residue solid was washed with 2M HCl and crystallized from aqueous ethanol. If necessary, column chromatography was used for further purification (mobile phase DCM:MeOH 19:1).

Reference： [1]Molecules,2016,vol. 21
[2]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 1881 - 1885
[3]Molecules,2018,vol. 23

72
[ 7664-66-6 ]
[ 86-48-6 ]
1-hydroxy-N-[4-(prop-2-yloxy)phenyl]naphthalene-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66%	With phosphorus trichloride; In chlorobenzene; at 130℃; for 0.25h;Microwave irradiation;	General procedure: 2-Hydroxynaphthalene-1-carboxylic acid or 1-hydroxynaphthalene-2-carboxylic acid (5.30 mmol) and appropriate alkoxyaniline (5.30 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and reacting mixture was heated in the microwave reactor for 15 min at 130 C using infrared flask-surface control of temperature. Solvent was evaporated in vacuum; residue solid was washed with 2M HCl and crystallized from aqueous ethanol. If necessary, column chromatography was used for further purification (mobile phase DCM:MeOH 19:1).

Reference： [1]Molecules,2016,vol. 21
[2]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 1881 - 1885
[3]Molecules,2018,vol. 23

73
[ 52464-53-6 ]
[ 86-48-6 ]
N-[2-(but-2-yloxy)phenyl]-1-hydroxynaphthalene-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	3.2.1. General Procedure for Synthesis of N-(Alkoxyphenyl)-2-hydroxynaphthalene-1-carboxamides 1-7c and N-(Alkoxyphenyl)-1-hydroxynaphthalene-2-carboxamides 8-14c General procedure: 2-Hydroxynaphthalene-1-carboxylic acid or 1-hydroxynaphthalene-2-carboxylic acid (5.30 mmol) and appropriate alkoxyaniline (5.30 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and reacting mixture was heated in the microwave reactor for 15 min at 130 °C using infrared flask-surface control of temperature. Solvent was evaporated in vacuum; residue solid was washed with 2M HCl and crystallized from aqueous ethanol. If necessary, column chromatography was used for further purification (mobile phase DCM:MeOH 19:1).
	With phosphorus trichloride In chlorobenzene Microwave irradiation;
	With trichlorophosphate In chlorobenzene for 0.25h; Microwave irradiation;

Reference： [1]Gonec, Tomas; Pospisilova, Sarka; Kauerova, Tereza; Kos, Jiri; Dohanosova, Jana; Oravec, Michal; Kollar, Peter; Coffey, Aidan; Liptaj, Tibor; Cizek, Alois; Jampilek, Josef [Molecules, 2016, vol. 21, # 8]
[2]Gonec, Tomas; Kralova, Katarina; Pesko, Matus; Jampilek, Josef [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 9, p. 1881 - 1885]
[3]Kapustikova, Iva; Bak, Andrzej; Gonec, Tomas; Kos, Jiri; Kozik, Violetta; Jampilek, Josef [Molecules, 2018, vol. 23, # 7]

74
3-(but-2-yloxy)aniline [ No CAS ]
[ 86-48-6 ]
N-[3-(but-2-yloxy)phenyl]-1-hydroxynaphthalene-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
59%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	3.2.1. General Procedure for Synthesis of N-(Alkoxyphenyl)-2-hydroxynaphthalene-1-carboxamides 1-7c and N-(Alkoxyphenyl)-1-hydroxynaphthalene-2-carboxamides 8-14c General procedure: 2-Hydroxynaphthalene-1-carboxylic acid or 1-hydroxynaphthalene-2-carboxylic acid (5.30 mmol) and appropriate alkoxyaniline (5.30 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and reacting mixture was heated in the microwave reactor for 15 min at 130 °C using infrared flask-surface control of temperature. Solvent was evaporated in vacuum; residue solid was washed with 2M HCl and crystallized from aqueous ethanol. If necessary, column chromatography was used for further purification (mobile phase DCM:MeOH 19:1).
	With phosphorus trichloride In chlorobenzene Microwave irradiation;
	With trichlorophosphate In chlorobenzene for 0.25h; Microwave irradiation;

Reference： [1]Gonec, Tomas; Pospisilova, Sarka; Kauerova, Tereza; Kos, Jiri; Dohanosova, Jana; Oravec, Michal; Kollar, Peter; Coffey, Aidan; Liptaj, Tibor; Cizek, Alois; Jampilek, Josef [Molecules, 2016, vol. 21, # 8]
[2]Gonec, Tomas; Kralova, Katarina; Pesko, Matus; Jampilek, Josef [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 9, p. 1881 - 1885]
[3]Kapustikova, Iva; Bak, Andrzej; Gonec, Tomas; Kos, Jiri; Kozik, Violetta; Jampilek, Josef [Molecules, 2018, vol. 23, # 7]

75
[ 59002-72-1 ]
[ 86-48-6 ]
N-[4-(but-2-yloxy)phenyl]-1-hydroxynaphthalene-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
59%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	3.2.1. General Procedure for Synthesis of N-(Alkoxyphenyl)-2-hydroxynaphthalene-1-carboxamides 1-7c and N-(Alkoxyphenyl)-1-hydroxynaphthalene-2-carboxamides 8-14c General procedure: 2-Hydroxynaphthalene-1-carboxylic acid or 1-hydroxynaphthalene-2-carboxylic acid (5.30 mmol) and appropriate alkoxyaniline (5.30 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and reacting mixture was heated in the microwave reactor for 15 min at 130 °C using infrared flask-surface control of temperature. Solvent was evaporated in vacuum; residue solid was washed with 2M HCl and crystallized from aqueous ethanol. If necessary, column chromatography was used for further purification (mobile phase DCM:MeOH 19:1).
	With phosphorus trichloride In chlorobenzene Microwave irradiation;
	With trichlorophosphate In chlorobenzene for 0.25h; Microwave irradiation;

Reference： [1]Gonec, Tomas; Pospisilova, Sarka; Kauerova, Tereza; Kos, Jiri; Dohanosova, Jana; Oravec, Michal; Kollar, Peter; Coffey, Aidan; Liptaj, Tibor; Cizek, Alois; Jampilek, Josef [Molecules, 2016, vol. 21, # 8]
[2]Gonec, Tomas; Kralova, Katarina; Pesko, Matus; Jampilek, Josef [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 9, p. 1881 - 1885]
[3]Kapustikova, Iva; Bak, Andrzej; Gonec, Tomas; Kos, Jiri; Kozik, Violetta; Jampilek, Josef [Molecules, 2018, vol. 23, # 7]

76
5-(2,5-dimethylphenoxy)-2,2-dimethylpentan-1-amine [ No CAS ]
[ 86-48-6 ]
C₂₆H₃₀O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71.6%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃; for 12h;	25 Example 25: Preparation of Compound 22 0.188 g of 1-hydroxy-2-naphthoic acid was added to 20 mL of dichloromethane,Followed by HOBT 0.162 g,Triethylamine 0.42 mL, EDCI · HCl 0.230 g,5- (2,5-dimethylphenoxy) -dimethylpentan-1-amine, 0.235 g,Stirred at room temperature for 12 hours,10ml of methylene chloride was added to the reaction solution, washed with dilute hydrochloric acid, washed with saturated sodium bicarbonate, washed with saturated sodium chloride and dried over anhydrous magnesium sulfate. The title compound was 0.29 g, the yield was 71.6%.

Reference： [1]Current Patent Assignee: CHINA NATIONAL PHARMACEUTICAL GROUP CORPORATION - CN106478446, 2017, A Location in patent: Paragraph 0125; 0126; 0127

77
[ 86-48-6 ]
C₂₂H₁₄N₂O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With Vilsmeier reagent; hydrazine hydrate; triethylamine In acetonitrile at 20℃; for 8h;	General Procedure for One-pot Synthesis of Symmetrical 1,3,4-oxadiazoles 5a-k(Method B) General procedure: Hydrazine hydrate (0.3 mmol) was added to a solution of carboxylic acid (1.0 mmol),Vilsmeier reagent (1.0 mmol) and Et3N (2.0 mmol) in dry CH3CN (20 mL) at room temperature.After 2 hours Vilsmeier reagent (0.4 mmol) and Et3N (1.0 mmol) were addedand the mixture was stirred at room temperature for 8 hours. Saturated NaHCO3 (20 mL) was added and the mixture was extracted with EtOAc (3 £ 20 mL). The organic layerwas washed with brine (20 mL), dried (Na2SO4), filtered and the solvent was removedunder reduced pressure to give the crude products. The crude residues were purified bycrystallization from 95% ethanol. Spectral data for 5a-b, 5d, 5f-h and 5j have been previouslyreported,26-32 and were matched by the products of this work.

Reference： [1]Zarei, Maaroof; Rasooli, Fatemeh [Organic Preparations and Procedures International, 2017, vol. 49, # 4, p. 355 - 362]

78
[ 608-27-5 ]
[ 86-48-6 ]
N-(2,3-dichlorophenyl)-1-hydroxynaphthalene-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
59%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	General Procedure for Synthesis of N-(substituted phenyl)-1-hydroxynaphthalene-2-carboxamides 1-24 General procedure: 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 °C, using infrared flask-surface control of temperature, for 15 min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. All the studied compounds are presented in Table 1.

Reference： [1]Gonec, Tomas; Kos, Jiri; Pesko, Matus; Dohanosova, Jana; Oravec, Michal; Liptaj, Tibor; Kralova, Katarina; Jampilek, Josef [Molecules, 2017, vol. 22, # 10]

79
[ 554-00-7 ]
[ 86-48-6 ]
[ 68352-26-1 ]

Yield	Reaction Conditions	Operation in experiment
76%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	General Procedure for Synthesis of N-(substituted phenyl)-1-hydroxynaphthalene-2-carboxamides 1-24 General procedure: 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 °C, using infrared flask-surface control of temperature, for 15 min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. All the studied compounds are presented in Table 1.

Reference： [1]Gonec, Tomas; Kos, Jiri; Pesko, Matus; Dohanosova, Jana; Oravec, Michal; Liptaj, Tibor; Kralova, Katarina; Jampilek, Josef [Molecules, 2017, vol. 22, # 10]

80
[ 95-82-9 ]
[ 86-48-6 ]
N-(2,5-dichlorophenyl)-1-hydroxynaphthalene-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	General Procedure for Synthesis of N-(substituted phenyl)-1-hydroxynaphthalene-2-carboxamides 1-24 General procedure: 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 °C, using infrared flask-surface control of temperature, for 15 min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. All the studied compounds are presented in Table 1.

Reference： [1]Gonec, Tomas; Kos, Jiri; Pesko, Matus; Dohanosova, Jana; Oravec, Michal; Liptaj, Tibor; Kralova, Katarina; Jampilek, Josef [Molecules, 2017, vol. 22, # 10]

81
[ 608-31-1 ]
[ 86-48-6 ]
N-(2,6-dichlorophenyl)-1-hydroxynaphthalene-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
59%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	General Procedure for Synthesis of N-(substituted phenyl)-1-hydroxynaphthalene-2-carboxamides 1-24 General procedure: 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 °C, using infrared flask-surface control of temperature, for 15 min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. All the studied compounds are presented in Table 1.

Reference： [1]Gonec, Tomas; Kos, Jiri; Pesko, Matus; Dohanosova, Jana; Oravec, Michal; Liptaj, Tibor; Kralova, Katarina; Jampilek, Josef [Molecules, 2017, vol. 22, # 10]

82
[ 95-76-1 ]
[ 86-48-6 ]
N-(3,4-dichlorophenyl)-1-hydroxynaphthalene-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	General Procedure for Synthesis of N-(substituted phenyl)-1-hydroxynaphthalene-2-carboxamides 1-24 General procedure: 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 °C, using infrared flask-surface control of temperature, for 15 min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. All the studied compounds are presented in Table 1.

Reference： [1]Gonec, Tomas; Kos, Jiri; Pesko, Matus; Dohanosova, Jana; Oravec, Michal; Liptaj, Tibor; Kralova, Katarina; Jampilek, Josef [Molecules, 2017, vol. 22, # 10]

83
[ 626-43-7 ]
[ 86-48-6 ]
N-(3,5-dichlorophenyl)-1-hydroxynaphthalene-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With phosphorus trichloride; In chlorobenzene; at 130℃; for 0.25h;Microwave irradiation;	General procedure: 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 C, using infrared flask-surface control of temperature, for 15 min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. All the studied compounds are presented in Table 1.

Reference： [1]Molecules,2017,vol. 22

84
[ 636-30-6 ]
[ 86-48-6 ]
1-hydroxy-N-(2,4,5-trichlorophenyl)naphthalene-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	General Procedure for Synthesis of N-(substituted phenyl)-1-hydroxynaphthalene-2-carboxamides 1-24 General procedure: 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 °C, using infrared flask-surface control of temperature, for 15 min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. All the studied compounds are presented in Table 1.

Reference： [1]Gonec, Tomas; Kos, Jiri; Pesko, Matus; Dohanosova, Jana; Oravec, Michal; Liptaj, Tibor; Kralova, Katarina; Jampilek, Josef [Molecules, 2017, vol. 22, # 10]

85
[ 634-93-5 ]
[ 86-48-6 ]
[ 101883-71-0 ]

Yield	Reaction Conditions	Operation in experiment
75%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	General Procedure for Synthesis of N-(substituted phenyl)-1-hydroxynaphthalene-2-carboxamides 1-24 General procedure: 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 °C, using infrared flask-surface control of temperature, for 15 min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. All the studied compounds are presented in Table 1.

Reference： [1]Gonec, Tomas; Kos, Jiri; Pesko, Matus; Dohanosova, Jana; Oravec, Michal; Liptaj, Tibor; Kralova, Katarina; Jampilek, Josef [Molecules, 2017, vol. 22, # 10]

86
[ 634-91-3 ]
[ 86-48-6 ]
1-hydroxy-N-(3,4,5-trichlorophenyl)naphthalene-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	General Procedure for Synthesis of N-(substituted phenyl)-1-hydroxynaphthalene-2-carboxamides 1-24 General procedure: 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 °C, using infrared flask-surface control of temperature, for 15 min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. All the studied compounds are presented in Table 1.

Reference： [1]Gonec, Tomas; Kos, Jiri; Pesko, Matus; Dohanosova, Jana; Oravec, Michal; Liptaj, Tibor; Kralova, Katarina; Jampilek, Josef [Molecules, 2017, vol. 22, # 10]

87
[ 615-57-6 ]
[ 86-48-6 ]
N-(2,4-dibromophenyl)-1-hydroxynaphthalene-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	General Procedure for Synthesis of N-(substituted phenyl)-1-hydroxynaphthalene-2-carboxamides 1-24 General procedure: 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 °C, using infrared flask-surface control of temperature, for 15 min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. All the studied compounds are presented in Table 1.

Reference： [1]Gonec, Tomas; Kos, Jiri; Pesko, Matus; Dohanosova, Jana; Oravec, Michal; Liptaj, Tibor; Kralova, Katarina; Jampilek, Josef [Molecules, 2017, vol. 22, # 10]

88
[ 3638-73-1 ]
[ 86-48-6 ]
N-(2,5-dibromophenyl)-1-hydroxynaphthalene-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%	With phosphorus trichloride; In chlorobenzene; at 130℃; for 0.25h;Microwave irradiation;	General procedure: 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 C, using infrared flask-surface control of temperature, for 15 min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. All the studied compounds are presented in Table 1.

Reference： [1]Molecules,2017,vol. 22

89
[ 608-30-0 ]
[ 86-48-6 ]
N-(2,6-dibromophenyl)-1-hydroxynaphthalene-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	General Procedure for Synthesis of N-(substituted phenyl)-1-hydroxynaphthalene-2-carboxamides 1-24 General procedure: 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 °C, using infrared flask-surface control of temperature, for 15 min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. All the studied compounds are presented in Table 1.

Reference： [1]Gonec, Tomas; Kos, Jiri; Pesko, Matus; Dohanosova, Jana; Oravec, Michal; Liptaj, Tibor; Kralova, Katarina; Jampilek, Josef [Molecules, 2017, vol. 22, # 10]

90
[ 147-82-0 ]
[ 86-48-6 ]
1-hydroxy-N-(2,4,6-tribromophenyl)naphthalene-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	General Procedure for Synthesis of N-(substituted phenyl)-1-hydroxynaphthalene-2-carboxamides 1-24 General procedure: 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 °C, using infrared flask-surface control of temperature, for 15 min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. All the studied compounds are presented in Table 1.

Reference： [1]Gonec, Tomas; Kos, Jiri; Pesko, Matus; Dohanosova, Jana; Oravec, Michal; Liptaj, Tibor; Kralova, Katarina; Jampilek, Josef [Molecules, 2017, vol. 22, # 10]

91
[ 873-38-1 ]
[ 86-48-6 ]
N-(2-bromo-4-chlorophenyl)-1-hydroxynaphthalene-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69%	With phosphorus trichloride; In chlorobenzene; at 130℃; for 0.25h;Microwave irradiation;	General procedure: 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 C, using infrared flask-surface control of temperature, for 15 min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. All the studied compounds are presented in Table 1.

Reference： [1]Molecules,2017,vol. 22

92
[ 38762-41-3 ]
[ 86-48-6 ]
N-(4-bromo-2-chlorophenyl)-1-hydroxynaphthalene-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56%	With phosphorus trichloride; In chlorobenzene; at 130℃; for 0.25h;Microwave irradiation;	General procedure: 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 C, using infrared flask-surface control of temperature, for 15 min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. All the studied compounds are presented in Table 1.

Reference： [1]Molecules,2017,vol. 22

93
[ 60811-17-8 ]
[ 86-48-6 ]
N-(5-bromo-2-chlorophenyl)-1-hydroxynaphthalene-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
35%	With phosphorus trichloride; In chlorobenzene; at 130℃; for 0.25h;Microwave irradiation;	General procedure: 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 C, using infrared flask-surface control of temperature, for 15 min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. All the studied compounds are presented in Table 1.

Reference： [1]Molecules,2017,vol. 22

94
[ 21402-26-6 ]
[ 86-48-6 ]
N-(4-bromo-3-chlorophenyl)-1-hydroxynaphthalene-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
58%	With phosphorus trichloride In chlorobenzene at 130℃; for 0.25h; Microwave irradiation;	General Procedure for Synthesis of N-(substituted phenyl)-1-hydroxynaphthalene-2-carboxamides 1-24 General procedure: 1-Hydroxynaphthalene-2-carboxylic acid (5.3 mmol) and the corresponding substituted aniline (5.3 mmol) were suspended in 30 mL of dry chlorobenzene. Phosphorous trichloride (2.65 mmol) was added dropwise, and the reacting mixture was heated in the microwave reactor at maximal allowed power 500 W and 130 °C, using infrared flask-surface control of temperature, for 15 min. The solvent was evaporated under reduced pressure, the solid residue washed with 2 M HCl, and the crude product was recrystallized from aqueous ethanol. All the studied compounds are presented in Table 1.

Reference： [1]Gonec, Tomas; Kos, Jiri; Pesko, Matus; Dohanosova, Jana; Oravec, Michal; Liptaj, Tibor; Kralova, Katarina; Jampilek, Josef [Molecules, 2017, vol. 22, # 10]

95
[ 67-51-6 ]
[ 5743-04-4 ]
[ 86-48-6 ]
Cd(3,5-dimethylpyrazole)4(1-hydroxy-2-naphthoate)2 [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81.5%	In methanol at 20℃; for 2h;	3 2.2.2. Synthesis of Cd(Hdmpz)4(L2)2 (2) A solution of Cd(CH3COO)22H2O (0.027 g, 0.10 mmol) in 6 mLof MeOH was added to a MeOH solution (10 mL) containingHdmpz (0.019 g, 0.20 mmol) and 1-hydroxy-2-naphthoic acid(HL2) (0.0760 g, 0.4 mmol) under continuous stirring. The solutionwas stirred for about 2 h at room temperature, a smallamount of precipitate formed, then a few drops of conc. ammoniawere added until the precipitate dissolved completely. The clearsolution was filtered into a test tube and after several days colorlessblock crystals formed, which were filtered off, washed withMeOH and dried under vacuum to afford 0.071 g of the product.Yield: 81.5% (Based on Hdmpz). Elemental analysis performedon crystals exposed to the atmosphere: Anal. Calc. forC42H46CdN8O6 (871.27): C, 57.85; H, 5.28; N, 12.85. Found: C,57.77; H, 5.24; N, 12.79%. Infrared spectrum (KBr disc, cm-1):3340w, 3292w, 3037m, 2972m, 2864m, 1616s (mas(COO)),1481m, 1444m, 1416s (ms(COO)), 1272m, 1230m, 1183m,1139m, 1085m, 1041m, 997m, 949m, 896m, 848m, 792m,745m, 696m, 662m, 636m, 611m.

Reference： [1]Hu, Kaikai; Jin, Shouwen; Xie, Zuoran; Guo, Ming; Lin, Zhihao; Wang, Daqi [Polyhedron, 2018, vol. 139, p. 17 - 32]

96
[ 52-86-8 ]
[ 86-48-6 ]
C₂₁H₂₃ClFNO₂*C₁₁H₈O₃ [ No CAS ]

Reference： [1]Journal of Pharmaceutical Sciences,2018,vol. 107,p. 1870 - 1878

97
[ 379270-37-8 ]
[ 86-48-6 ]
tenofovir alafenamide bis-xinafoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In acetone; at 50℃;	Alternatively, 4 g of tenofovir alafenamide free base was dissolved in 40 mL acetone at 50 °C, filtered, charged with 3.16 g 1 -hydroxy -naphthoic acid (2 eq.) to form a solution. The solution was dried in a rotary evaporator at 50 °C to a foam, and redissolved in 40 mL IPAc(isopropyl acetate). The solution was seeded with crystals of tenofovir alafenamide bis- xinafoate, sonicated, and a thick slurry formed soon afterwards. The slurry was diluted with 16 mL IPAc, filtered, and dried in the vacuum oven at 50 °C for three days.

Reference： [1]Patent: WO2018/144390,2018,A1 .Location in patent: Paragraph 0326

98
5-(2,5-dimethylphenoxy)-2,2-dimethylpentan-1-amine [ No CAS ]
[ 86-48-6 ]
N-(5-(2,5-dimethylphenoxy)-2,2-dimethylpentyl)-1-hydroxy-2-naphthamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55.1%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃; for 12h;	2.1.12. N-(5-(2,5-dimethylphenoxy)-2,2-dimethylpentyl) benzamide (BI-9) General procedure: To a solution of benzoic acid (0.122 g) and 5-(2,5-dimethylphenoxy)-2,2-dimethylpentan-1-amine 4 (0.235 g) in DCM (15 mL) were added triethylamine (0.42 mL), HOBT (0.162 g), and EDCIHCl (0.230 g). The reaction mixture was stirred at room temperature for 12 h, and then washed with diluted HCl, saturated with NaHCO3 and brine, dried over MgSO4, filtrated, concentrated and the residue was purified by chromatography to afford compound BI-9. Yield 75.1%, mp: 111.5-111.7oC; 1H NMR (400 MHz, DMSO-d6) δ: 8.31 (t, J = 6.2 Hz, 1H), 7.84 (d, J = 7.1Hz, 2H), 7.49-7.45 (m, 3H), 6.97 (d, J = 7.5 Hz, 1H), 6.71 (s, 1H), 6.62 (d, J = 7.5 Hz, 1H), 3.90 (t, J = 6.4 Hz, 2H), 3.17 (d, J = 6.2 Hz, 2H), 2.24 (s, 3H), 2.07 (s, 3H), 1.81 - 1.64 (m, 2H), 1.45 - 1.30 (m, 2H), 0.91 (s, 6H); ESI-MS m/z: 338 [M-H] +. 340 [M+H] +.

Reference： [1]Nian, Siyun; Yu, Zhenpeng; Tan, Xiangduan; Gan, Xia; Huang, Mohan; Zhou, Yihuan; Wang, Guoping [Letters in drug design and discovery, 2018, vol. 15, # 9, p. 923 - 936]

99
[ 39994-75-7 ]
[ 86-48-6 ]
(2S,3R)-methyl 3-hydroxy-2-(1-hydroxy-2-naphthamido)butanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
48%	Stage #1: 1-hydroxy-2-naphthoic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 1h; Stage #2: L-threonine methyl ester hydrochloride With 4-methyl-morpholine In N,N-dimethyl-formamide at 20℃; for 24h; Sealed tube;	1.3.2 Synthesis of (2S,3R)-methyl 3-hydroxy-2-(1-hydroxy-2-naphthamido)butanoate 12 In a 50 mL round bottom flask charged with 1-hydroxy-2-naphthoic acid 10 (2 mmol, 376 mg), EDC.HCl (2.6 mmol, 498 mg), 1-HOBt.xH 2 O (2.4 mmol, 324 mg) was added DMF (10 mL). The mixture was stirred at room temperature for 1 hour and L-threonine methyl ester hydrochloride (2 mmol, 340 mg) dissolved in DMF (5 mL) and the N-methylmorpholine (3 mmol, 0.33 mL) were added. The flask was sealed and the reaction was stirred for 24 hours at room temperature. The content was transferred to a separation funnel and the extraction was proceed with aqueous saturated solution of NH 4 Cl (100mL) and EtOAc (3 x 30 mL). The combined organic phases were washed with water (2 x 100 mL) and brine (100 mL), dried over MgSO 4 , filtered off and volatiles were evaporated. The crude residue was purified by chromatography column eluting with hexanes/EtOAc (3:2). Yield: 48% m.p.: 116-119°C 1 H NMR: (300 MHz, CDCl 3 ): δ (ppm) 13.43 (s, 1H), 8.39 (d, J = 8.1 Hz, 1H), 7.72 (d, J = 8.1 Hz, 1H), 7.62-7.45 (m, 3H), 7.30-7.17(m, 2H), 4.86 (dd, J = 8.7 e 2.1 Hz, 1H), 4.50 (dq, J = 6.3 e 2.4 Hz, 1H), 3.81 (s, 3H), 3.10-2.60 (bs, 1H), 1.32 (d, J = 6.6 Hz, 3H). 13 C NMR: (75 MHz, CDCl 3 ): δ (ppm) 171.6, 171.2, 160.9, 136.6, 129.1, 127.4, 126.0, 125.6, 123.9, 121.2, 118.5, 106.4, 68.3, 57.2, 53.0, 20.2. IR: max (neat, cm -1 ) 3388, 2978, 2956, 1737, 1620, 1598, 1525, 1503, 1469, 1439, 1415, 1393, 1359, 1281, 1208, 1181, 1149, 1095, 1018, 996, 963, 910, 881, 868, 795, 765, 726,661. HRMS: (ESI) m/z, calcd for [C 16 H 17 NO 5 + H + ]: 304,1185; found: 304,1191.

Reference： [1]Reis, Joel S.; Fernandes, Arthur B.; Freitas-Dörr, Barbara C.; Bastos, Erick L.; Stefani, Hélio A. [Tetrahedron, 2018, vol. 74, # 48, p. 6866 - 6872]

100
[ 33640-67-4 ]
[ 86-48-6 ]
(2S,3R)-benzyl 3-hydroxy-2-(1-hydroxy-2-naphthamido)butanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
52%	With 4-methyl-morpholine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 2h; Sonication;	1.3.1 Synthesis of (2S,3R)-benzyl 3-hydroxy-2-(1-hydroxy-2-naphthamido)butanoate 11 A 50 mL round bottom flask was charged with 1-hydroxy-2-naphthoic acid 10 (2 mmol, 376 mg), EDC.HCl (2.6 mmol, 498 mg), 1-HOBt.xH 2 O (2.4 mmol, 324 mg), L-threonine benzyl ester (2 mmol, 418 mg), DCM (20 mL) and N-methylmorpholine (3 mmol, 0.33 mL). Ultrasound was irradiated by a probe (amplitude 21%, pulse 2s ON, 1s OFF) directly into reaction media for 2 hours at room temperature. The content was transferred to a separation funnel and the extraction was proceed with aqueous saturated solution of NH 4 Cl (40mL) and DCM (3 x 20 mL). The combined organic was washed wit brine (50 mL), dried over MgSO 4 , filtered off and volatiles were evaporated. The crude mixture was purified by chromatography column eluting with hexanes/EtOAc (3:2). The product was obtained as a viscous oil. Yield: 52% 1 H NMR: (300 MHz, CDCl 3 ): δ (ppm): 13.43 (s, 1H), 8.39 (d, J = 8.1 Hz, 1H), 7.72 (d, J = 8 Hz, 1H), 7.60-7.42 (m, 3H), 7.34 (s, 5H), 7.27-7.15 (m, 2H), 5.24 (d, J = 5.2 Hz, 2H), 4.89 (d, J = 8.2 Hz, 1H), 4.49 (m, 1H), 2.31 (s, 1H), 1.28 (d, J = 6.3 Hz, 3H). 13 C NMR: (75 MHz, CDCl 3 ): δ (ppm) 171.2, 170.9, 160.9, 136.6, 135.2, 129.1, 128.8, 128.6, 128.3, 127.4, 125.9, 125.6, 123.9, 121.2, 118.4, 106.4, 68.3, 67.7, 57.4, 20.3. IR: max (film, cm -1 ) 3394, 3037, 3067, 2981, 2933, 2854, 1737, 1529, 1287, 795. HRMS: (ESI) m/z, calcd for [C 22 H 20 NO 5 + H + ]: 380,1498; found: 380,1293.

Reference： [1]Reis, Joel S.; Fernandes, Arthur B.; Freitas-Dörr, Barbara C.; Bastos, Erick L.; Stefani, Hélio A. [Tetrahedron, 2018, vol. 74, # 48, p. 6866 - 6872]

101
iron(II) perchlorate hexahydrate [ No CAS ]
[ 136768-57-5 ]
[ 86-48-6 ]
[(N¹,N²-dimethyl-N¹,N²-bis(2-pyridylmethyl)ethane-1,2-diamine)Fe^II(1-hydroxy-2-naphthoate)](ClO₄) [ No CAS ]

Reference： [1]Dalton Transactions,2019,vol. 48,p. 16993 - 17004

102
(R)-N-(3-(5-fluoro-2-(2-fluoro-3-(methylsulfonyl)phenylamino)pyrimidin-4-yl)-1H-indol-7-yl)-3-methoxy-2-(4-methylpiperazin-1-yl)propanamide [ No CAS ]
[ 86-48-6 ]
(R)-N-(3-(5-fluoro-2-((2-fluoro-3-(methylsulfonyl)phenyl)amino)pyrimidin-4-yl)-1H-indol-7-yl)-3-methoxy-2-(4-methylpiperazin-1-yl)propanamide xinafoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	Stage #1: (R)-N-(3-(5-fluoro-2-(2-fluoro-3-(methylsulfonyl)phenylamino)pyrimidin-4-yl)-1H-indol-7-yl)-3-methoxy-2-(4-methylpiperazin-1-yl)propanamide In methanol; ethyl acetate at 65℃; Inert atmosphere; Stage #2: 1-hydroxy-2-naphthoic acid In methanol; ethyl acetate at 50℃; Inert atmosphere;	3.11 Step 11: (R)-N-(3-(5-fluoro-2-((2-fluoro-3-(methylsulfonyl)phenyl)amino)pyrimidiii-4-yl)-lH- mdol-7-yl)-3-methoxy-2-(4-methylpiperazin-l-yl)propanamide xinafoic acid salt (14) (R)-N-(3-(5-fluoro-2-((2-fluoro-3-(methylsulfonyl)phenyl)amino)pyrimidin-4-yl)-lH-indol-7- yl)-3-methoxy-2-(4-methylpiperazin-l-yl)propanamide (13) (345 g, 563.82 mmol) was charged to a inertized 10F reactor ethyl acetate (7 F, 20 vol) and methanol (1.4 F, 4 vol) was charged. The mixture was heated to 65 °C until all had dissolved. The solution was polish filtered hot through a celite filter. Crystallization occurred in the filtrate. The slurry filtrate was transferred back to the reactor and heated to 60°C until fully redissolved. 1 -hydroxyl- naphthoic acid (106 g, 563.82 mmol) was charged to a inertized 2F reactor. Methanol (0.7 F, 1.5 vol) and ethyl acetate (0.7 F, 1.5 vol) was charged and the mixture was heated to 50°C until all had dissolved. The solution was polish filtered and the filter was rinsed with EtOAc/MeOH (2: 1 , 150 ml). The resulting solution was added to the 10F reactor at 60°C giving a clear solution which was stirred for 10 min. The solution was seeded with crystalline material (7 g) from a previous batch. Crystallization initiates instantly. Solvent was distilled off at ambient pressure and 75°C jacket temperature with the aid of a nitrogen flow over the headspace until the reflux temperature was above 70°C. 5L distillate was collected and EtOAc (2L) was added to the reactor to compensate the volume loss. The reactor was slowly cooled to lO°C over lOh and kept at that temperature for 4h. The solid was filtered off and was washed via the reactor with ethyl acetate (2 L). The solid was dried under vacuum at 40°C. (R)-N-(3-(5-fluoro-2-((2-fluoro-3-(methylsulfonyl)phenyl)amino)pyrimidin-4-yl)-lH-indol-7- yl)-3-methoxy-2-(4-methylpiperazin-l-yl)propanamide xinafoic acid salt (14) (420 g, yield 95 %) was obtained as an off-white crystalline solid. Purity (NMR) 97.7% 1H NMR (400 MHz, DMSO) d 2.29 (s, 3H), 2.58 - 3.03 (m, 8H), 3.09 (s, 7H), 3.37 - 3.72 (m, 3H), 6.69 - 6.97 (m, 2H), 7.1 1 - 7.36 (m, 4H), 7.42 (s, 1H), 7.54 (t, 2H), 7.86 - 8.16 (m, 4H), 8.24 (s, 1H), 9.26 (s, 1H), 9.86 (s, 1H), 1 1.52 (s, 1H). 19F NMR (376 MHz, DMSO) d - 147.71 , -120.45. Melting point: l89°C (DSC, peak) HRMS (ESI+): [M+H]+ m/z calc’d for C28H31F2N7O4S 600.2204; Found 600.2199 (Parent)

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2020/16302, 2020, A1 Location in patent: Page/Page column 27; 37-38

103
[ 6973-09-7 ]
[ 86-48-6 ]
(E)-1-hydroxy-4-((4-methyl-3-sulfamoylphenyl)diazenyl)-2-naphthoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	Stage #1: 5-amino-2-methylbenzenesulfonamide With hydrogenchloride; sodium nitrite In water at -5℃; for 0.25h; Stage #2: 1-hydroxy-2-naphthoic acid With sodium hydroxide In water	4.1.1. General procedure for the synthesis of target compounds 9a-9x General procedure: The synthesis of the target compounds was achieved according topublished literature procedures with some modifications utilizing thefollowing two steps.37Step 1: Preparation of diazonium chloride solutions of aromaticamines: The aromatic amine-containing compound (0.20 g, 1.0 eq) was dissolved in a freshly prepared 40% solution of concentrated hydrochloricacid in de-ionized water (3 ml) then cooled down to -5 °C inice/sodium chloride path. To that was added dropwise an aqueous solutionof NaNO2 (1.2 eq, 2 M). Then the reaction mixture was keptstirring at the same temperature for 15 min to produce the diazoniumchloride solution which is required for the next step. The solution wasfreshly prepared prior to use.Step 2: Diazo coupling of the diazonium chloride solutions withsubstituted aromatic carbocyclic and heterocyclic compounds:Method A: The solution of diazonium chloride (prepared in step 1)was added dropwise to a solution of a substituted aromatic carbocyclicor heterocyclic compound (1.0 equiv.) in a saturated aqueous solutionof sodium acetate (3.0 ml) at -5 °C. Upon reaction completion, themixture was warmed to room temperature and the pH was adjusted to7. The solid was collected by filtration, washed with a minimumamount of deionized H2O, air dried and purified by silica gel columnchromatography eluting with 5% MeOH in DCM to give the desiredcompounds in good yields. Method B: In this method, similar procedure as in method A was used to synthesize the target compoundsexcept in method B sodium hydroxide was used as a base instead ofsodium acetate.

Reference： [1]Al-Oudat, Buthina A.; Al-Shar'i, Nizar A.; Bedi, Mel F.; Bryant-Friedrich, Amanda; Jaradat, Hana'a M.; Al‑Balas, Qosay A. [Bioorganic and medicinal chemistry, 2020, vol. 28, # 16]

104
[ 98-18-0 ]
[ 86-48-6 ]
(E)-1-hydroxy-4-((3-sulfamoylphenyl)diazenyl)-2-naphthoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	Stage #1: m-aminobenzenesulfonamide With hydrogenchloride; sodium nitrite In water at -5℃; for 0.25h; Stage #2: 1-hydroxy-2-naphthoic acid With sodium hydroxide In water	4.1.1. General procedure for the synthesis of target compounds 9a-9x General procedure: The synthesis of the target compounds was achieved according topublished literature procedures with some modifications utilizing thefollowing two steps.37Step 1: Preparation of diazonium chloride solutions of aromaticamines: The aromatic amine-containing compound (0.20 g, 1.0 eq) was dissolved in a freshly prepared 40% solution of concentrated hydrochloricacid in de-ionized water (3 ml) then cooled down to -5 °C inice/sodium chloride path. To that was added dropwise an aqueous solutionof NaNO2 (1.2 eq, 2 M). Then the reaction mixture was keptstirring at the same temperature for 15 min to produce the diazoniumchloride solution which is required for the next step. The solution wasfreshly prepared prior to use.Step 2: Diazo coupling of the diazonium chloride solutions withsubstituted aromatic carbocyclic and heterocyclic compounds:Method A: The solution of diazonium chloride (prepared in step 1)was added dropwise to a solution of a substituted aromatic carbocyclicor heterocyclic compound (1.0 equiv.) in a saturated aqueous solutionof sodium acetate (3.0 ml) at -5 °C. Upon reaction completion, themixture was warmed to room temperature and the pH was adjusted to7. The solid was collected by filtration, washed with a minimumamount of deionized H2O, air dried and purified by silica gel columnchromatography eluting with 5% MeOH in DCM to give the desiredcompounds in good yields. Method B: In this method, similar procedure as in method A was used to synthesize the target compoundsexcept in method B sodium hydroxide was used as a base instead ofsodium acetate.

Reference： [1]Al-Oudat, Buthina A.; Al-Shar'i, Nizar A.; Bedi, Mel F.; Bryant-Friedrich, Amanda; Jaradat, Hana'a M.; Al‑Balas, Qosay A. [Bioorganic and medicinal chemistry, 2020, vol. 28, # 16]

105
[ 91-21-4 ]
[ 86-48-6 ]
(3,4-dihydroisoquinolin-2(1H)-yl)(1-hydroxynaphthalen-2-yl)methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81.6%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃;	4.1.1 General procedure for the preparation of cinnamic acid hyrbids 4a-4p and 5a-5p) General procedure: The starting materials 1a-1q (1mmol) were dissolved in anhydrous dichloromethane (8mL), respectively. EDCI) (1.5mmol) and HOBt (1.5mmol) were added to the solution as condensating agent. Finally, the excessive amounts of 1,2,3,4-tetrahydroisoquinoline (a) and 4-benzylpiperidine (b) (1~2mmol) was added to the aforementioned solution, respectively. The reaction mixture was stirred under room temperature for 6~8h monitored by TLC. After reaction finished, the mixture was diluted with water and extracted with CH2Cl2. The organic phases were combined, washed with saturated aqueous NaHCO3 and brine, dried over Na2SO4, filtered, and evaporated in vacuo. The residue was purified by silica gel chromatography with dichloromethane/acetone=50:1 as eluent to give the target compounds 4a-4p and 5a-5p.

Reference： [1]Wang, Keren; Shi, Jian; Zhou, Yi; He, Ying; Mi, Jing; Yang, Jing; Liu, Shuang; Tang, Xiangcheng; Liu, Wenmin; Tan, Zhenghuai; Sang, Zhipei [Bioorganic Chemistry, 2021, vol. 112]

106
[ 31252-42-3 ]
[ 86-48-6 ]
(4-benzylpiperidin-1-yl)(1-hydroxynaphthalen-2-yl)methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74.4%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃;	4.1.1 General procedure for the preparation of cinnamic acid hyrbids 4a-4p and 5a-5p) General procedure: The starting materials 1a-1q (1mmol) were dissolved in anhydrous dichloromethane (8mL), respectively. EDCI) (1.5mmol) and HOBt (1.5mmol) were added to the solution as condensating agent. Finally, the excessive amounts of 1,2,3,4-tetrahydroisoquinoline (a) and 4-benzylpiperidine (b) (1~2mmol) was added to the aforementioned solution, respectively. The reaction mixture was stirred under room temperature for 6~8h monitored by TLC. After reaction finished, the mixture was diluted with water and extracted with CH2Cl2. The organic phases were combined, washed with saturated aqueous NaHCO3 and brine, dried over Na2SO4, filtered, and evaporated in vacuo. The residue was purified by silica gel chromatography with dichloromethane/acetone=50:1 as eluent to give the target compounds 4a-4p and 5a-5p.

Reference： [1]Wang, Keren; Shi, Jian; Zhou, Yi; He, Ying; Mi, Jing; Yang, Jing; Liu, Shuang; Tang, Xiangcheng; Liu, Wenmin; Tan, Zhenghuai; Sang, Zhipei [Bioorganic Chemistry, 2021, vol. 112]

107
(1′S,2S,3S)-1-(1′-phenylethyl)-2-phenyl-3-aminoazetidine [ No CAS ]
[ 86-48-6 ]
1-hydroxy-N-((2S,3S)-2-phenyl-1-((S)-1-phenylethyl)azetidin-3-yl)-2-naphthamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	Stage #1: 1-hydroxy-2-naphthoic acid With 1,1'-carbonyldiimidazole In tetrahydrofuran at 20℃; for 4h; Stage #2: (1′S,2S,3S)-1-(1′-phenylethyl)-2-phenyl-3-aminoazetidine In tetrahydrofuran	General Procedure for the Synthesis of amide 3 General procedure: Acid 2 (2.2mmol), CDI (2.2mmol) was stirred in THF (10mL) for 4h at room temperature. To this solution 3-amino-2-phenyl-azetidine 1 (2 mmol) was added. After being stirred overnight, the mixture was washed with water (10 mL), saturated NaHCO3 (10 mL), and dried over Na2SO4. The solvent was removed under reduced pressure. The residue was purified by gradient column chromatography on silica gel with PE/EA (10:1-5:1) as eluent to give amide 3.

Reference： [1]Mao, Baiyi; Zhang, Zhanbin; Zhou, Xin [Molecules, 2021, vol. 26, # 4]

108
[ 1003-29-8 ]
[ 5329-29-3 ]
[ 86-48-6 ]
C₁₁H₇O₃^(1-)*C₁₆H₁₈N₉⁽¹⁺⁾ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	Stage #1: 1-hydroxy-2-naphthoic acid With sodium hydroxide In ethanol; water Stage #2: triaminoguanidine hydrochloride In ethanol; water for 0.0833333h; Stage #3: 2-pyrrole aldehyde In ethanol; water at 80℃; for 6h;	Compound (3). Compound 3 was also synthesized according to asimilar procedure as that of compounds 1 and 2. Herein, the sodium saltof 1-hydroxy-2-naphthoic acid was prepared in-situ by the reaction ofsodium hydroxide (0.028 g) with 1-hydroxy-2-naphthoic acid (0.134 g,0.713 mmol) in a separate flask. Pyrrole-2-carboxaldehyde (0.210 g,2.21 mmol) in ethanol was slowly added dropwise to the mixture of thesodium salt of 1-hydroxy-2-naphthoic acid and triaminoguanidiniumchloride. The resulting mixture was allowed to reflux at 80 C for 6 h.After a few days, orange-colored needle-type single crystals were obtainedfrom the reaction mixture. Yield: 73%, Mp. 148-150 C.

Reference： [1]Anitha, Ottoor; Kaminsky, Werner; Mathivanan, Moorthy; Murugesapandian, Balasubramanian; Tharmalingam, Balamurugan [Journal of Solid State Chemistry, 2022, vol. 305]

109
[ 121-57-3 ]
[ 86-48-6 ]
C₁₇H₁₂N₂O₆S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	Stage #1: 4-aminobenzene sulfonic acid With hydrogenchloride In lithium hydroxide monohydrate; N,N-dimethyl-formamide at 20℃; for 0.25h; Stage #2: With NaNO₂ In lithium hydroxide monohydrate; N,N-dimethyl-formamide at 4℃; for 0.5h; Stage #3: 1-hydroxy-2-naphthoic acid With anhydrous sodium carbonate In lithium hydroxide monohydrate; N,N-dimethyl-formamide at 4℃; for 2h;	1 The synthetic route is as follows: 1.1. After dissolving p-aminobenzenesulfonic acid (1.73g, 10.0mmol) in 2mL of DMF,Add 3 mL of HCl (1 mol/L) solution, stir at room temperature for 15 min,Add 10% NaNO2 dropwise until the potassium iodide paper turns blue,Then continue to stir at 4°C for 30 min to obtain A liquid.1.2. Weigh 1-hydroxy-2-naphthoic acid (1.88 g, 10.0 mmol) into saturated 3 mL Na2CO3 solution, and cool to 4°C to obtain B solution.1.3. Slowly add solution A to solution B, adjust the pH to 8-9, stir at 4 °C for 2 h to obtain a red precipitate; finally, adjust the pH of the solution to 3.0 with hydrochloric acid, continue stirring at 4 °C for 30 min, and filter under reduced pressure , a red residue was obtained, which was dried at 37°C to obtain a crude sample.1.4. Purify the crude sample by recrystallization, and dissolve 3.2 g of the crude sample in methanol. After completely dissolving, let it stand overnight at room temperature, a red precipitate can be precipitated, filter with filter paper, rinse with petroleum ether 2-3 times, and dry at 50°C to obtain a red precipitate (2.4g),That is hapten AOI, yield: 75.0%.The amount of p-aminobenzenesulfonic acid in step 1.1 was adjusted to 0.173 g (1.0 mmol), the amount of 1-hydroxy-2-naphthoic acid was 0.188 g (1.0 mmol), and the yield was 81.5%.

Reference： [1]Current Patent Assignee: JIANGNAN UNIVERSITY - CN113754568, 2021, A Location in patent: Paragraph 0046-0053

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	86-48-6	MDL No. :	MFCD00003960
Formula :	C₁₁H₈O₃	Boiling Point :	-
Linear Structure Formula :	C₁₀H₆(COOH)(OH)	InChI Key :	SJJCQDRGABAVBB-UHFFFAOYSA-N
M.W :	188.18	Pubchem ID :	6844
Synonyms :

Num. heavy atoms :	14
Num. arom. heavy atoms :	10
Fraction Csp3 :	0.0
Num. rotatable bonds :	1
Num. H-bond acceptors :	3.0
Num. H-bond donors :	2.0
Molar Refractivity :	52.93
TPSA :	57.53 Å²

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.59 cm/s

Log Po/w (iLOGP) :	1.59
Log Po/w (XLOGP3) :	2.61
Log Po/w (WLOGP) :	2.24
Log Po/w (MLOGP) :	2.02
Log Po/w (SILICOS-IT) :	1.84
Consensus Log Po/w :	2.06

[ CAS No. 86-48-6 ] {[proInfo.proName]}

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Physicochemical Properties

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Lipophilicity

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Water Solubility

Medicinal Chemistry

Safety of [ 86-48-6 ]

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[ 86-48-6 ] Synthesis Path-Downstream 1~109

Technical Information

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.56

Log S (ESOL) :	-3.11
Solubility :	0.145 mg/ml ; 0.00077 mol/l
Class :	Soluble
Log S (Ali) :	-3.47
Solubility :	0.0641 mg/ml ; 0.000341 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.87
Solubility :	0.252 mg/ml ; 0.00134 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.01

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

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P378
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P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
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