[ CAS No. 2612-02-4 ] {[proInfo.proName]}

Name: 2612-02-4|2-Hydroxy-5-methoxybenzoic acid|98%
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Quality Control of [ 2612-02-4 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 2612-02-4 ]

Product Details of [ 2612-02-4 ]

CAS No. :	2612-02-4	MDL No. :	MFCD00002459
Formula :	C₈H₈O₄	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	IZZIWIAOVZOBLF-UHFFFAOYSA-N
M.W :	168.15	Pubchem ID :	75787
Synonyms :	5-MeOSA	Chemical Name :	2-Hydroxy-5-methoxybenzoic acid

Calculated chemistry of [ 2612-02-4 ]

Physicochemical Properties

Num. heavy atoms :	12
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.12
Num. rotatable bonds :	2
Num. H-bond acceptors :	4.0
Num. H-bond donors :	2.0
Molar Refractivity :	41.92
TPSA :	66.76 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.86 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.06
Log Po/w (XLOGP3) :	2.07
Log Po/w (WLOGP) :	1.1
Log Po/w (MLOGP) :	0.74
Log Po/w (SILICOS-IT) :	0.73
Consensus Log Po/w :	1.14

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.42
Solubility :	0.633 mg/ml ; 0.00376 mol/l
Class :	Soluble
Log S (Ali) :	-3.1
Solubility :	0.133 mg/ml ; 0.000792 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-1.32
Solubility :	8.1 mg/ml ; 0.0482 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.43

Safety of [ 2612-02-4 ]

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:

Application In Synthesis of [ 2612-02-4 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Upstream synthesis route of [ 2612-02-4 ]
Downstream synthetic route of [ 2612-02-4 ]

[ 2612-02-4 ] Synthesis Path-Upstream 1~31

1
[ 490-79-9 ]
[ 77-78-1 ]
[ 2150-46-1 ]
[ 2785-98-0 ]
[ 2612-02-4 ]
[ 2905-82-0 ]

Reference： [1] Justus Liebigs Annalen der Chemie, 1905, vol. 340, p. 219

2
[ 586-38-9 ]
[ 121-34-6 ]
[ 877-22-5 ]
[ 2612-02-4 ]
[ 99-06-9 ]

Reference： [1] Canadian Journal of Chemistry, 2001, vol. 79, # 4, p. 394 - 404

3
[ 586-38-9 ]
[ 2612-02-4 ]

Reference： [1] Journal of the American Chemical Society, 2009, vol. 131, # 41, p. 14654 - 14655
[2] Synlett, 2016, vol. 27, # 2, p. 277 - 281

4
[ 2785-98-0 ]
[ 2612-02-4 ]

Reference： [1] Synthesis, 2000, # 2, p. 243 - 246

5
[ 124-38-9 ]
[ 150-76-5 ]
[ 61227-25-6 ]
[ 2612-02-4 ]

Reference： [1] Journal of the American Chemical Society, 1985, vol. 107, # 8, p. 2571 - 2573
[2] Journal of the American Chemical Society, 1985, vol. 107, # 8, p. 2571 - 2573

6
[ 22921-68-2 ]
[ 2612-02-4 ]

Reference： [1] Patent: US7335791, 2008, B1, . Location in patent: Page/Page column 20-21

7
[ 6280-89-3 ]
[ 2612-02-4 ]

Reference： [1] Synthetic Communications, 2003, vol. 33, # 10, p. 1783 - 1787
[2] Chemische Berichte, 1905, vol. 38, p. 2121
[3] Chemische Berichte, 1905, vol. 38, p. 2121

8
[ 298-14-6 ]
[ 150-76-5 ]
[ 2612-02-4 ]

Reference： [1] RSC Advances, 2014, vol. 4, # 19, p. 9673 - 9679

9
[ 56-23-5 ]
[ 150-76-5 ]
[ 2612-02-4 ]

Reference： [1] Journal of the American Chemical Society, 1950, vol. 72, p. 2301
[2] Yakugaku Zasshi, 1951, vol. 71, p. 961[3] Chem.Abstr., 1952, p. 8058

10
[ 124-38-9 ]
[ 1200-06-2 ]
[ 2612-02-4 ]

Reference： [1] Patent: US2816137, 1954, ,

11
[ 150-76-5 ]
[ 2612-02-4 ]

Reference： [1] Synthesis, 1984, vol. NO. 9, p. 758 - 760
[2] Angewandte Chemie - International Edition, 2015, vol. 54, # 7, p. 2255 - 2259[3] Angew. Chem., 2015, vol. 127, # 7, p. 2283 - 2287,5

12
[ 150-19-6 ]
[ 2612-02-4 ]

Reference： [1] Synthesis, 1984, vol. NO. 9, p. 758 - 760

13
[ 71917-43-6 ]
[ 2612-02-4 ]

Reference： [1] Synthesis, 1984, vol. NO. 9, p. 758 - 760

14
[ 1315577-29-7 ]
[ 2612-02-4 ]

Reference： [1] Angewandte Chemie - International Edition, 2015, vol. 54, # 7, p. 2255 - 2259[2] Angew. Chem., 2015, vol. 127, # 7, p. 2283 - 2287,5

15
[ 186581-53-3 ]
[ 490-79-9 ]
[ 2612-02-4 ]

Reference： [1] Biochemical Journal, 1933, vol. 27, p. 629

16
[ 95646-23-4 ]
[ 2612-02-4 ]

Reference： [1] Synthesis, 1984, vol. NO. 9, p. 758 - 760

17
[ 490-79-9 ]
[ 77-78-1 ]
[ 2612-02-4 ]

Reference： [1] Justus Liebigs Annalen der Chemie, 1905, vol. 340, p. 219
[2] Journal of the Chemical Society, 1948, p. 2220

18
[ 62536-85-0 ]
[ 2612-02-4 ]

Reference： [1] Chemische Berichte, 1881, vol. 14, p. 1986

19
[ 490-79-9 ]
[ 74-88-4 ]
[ 2612-02-4 ]

Reference： [1] Monatshefte fuer Chemie, 1895, vol. 16, p. 921 Anm.

20
[ 672-13-9 ]
[ 2612-02-4 ]

Reference： [1] Chemische Berichte, 1881, vol. 14, p. 1986

21
[ 56-23-5 ]
[ 150-76-5 ]
[ 2612-02-4 ]
[ 30070-60-1 ]

Reference： [1] Yakugaku Zasshi, 1951, vol. 71, p. 961[2] Chem.Abstr., 1952, p. 8058

22
[ 490-79-9 ]
[ 77-78-1 ]
[ 2785-98-0 ]
[ 2612-02-4 ]

Reference： [1] Justus Liebigs Annalen der Chemie, 1905, vol. 340, p. 219

23
[ 490-79-9 ]
[ 77-78-1 ]
[ 2612-02-4 ]
[ 2905-82-0 ]

Reference： [1] Justus Liebigs Annalen der Chemie, 1905, vol. 340, p. 219

24
[ 586-38-9 ]
[ 121-34-6 ]
[ 877-22-5 ]
[ 2612-02-4 ]
[ 99-06-9 ]

Reference： [1] Canadian Journal of Chemistry, 2001, vol. 79, # 4, p. 394 - 404

25
[ 490-79-9 ]
[ 77-78-1 ]
[ 2150-46-1 ]
[ 2785-98-0 ]
[ 2612-02-4 ]
[ 2905-82-0 ]

Reference： [1] Justus Liebigs Annalen der Chemie, 1905, vol. 340, p. 219

26
[ 2612-02-4 ]
[ 74-88-4 ]
[ 2905-82-0 ]

Yield	Reaction Conditions	Operation in experiment
82.8%	With sodium hydrogencarbonate In DMF (N,N-dimethyl-formamide) at 80℃; for 3 h;	To a solution of 2-hydroxy-5-methoxybenzoic acid (6.0 g, 35.68 mmol) in dimethylformamide (80 ml) were added sodium hydrogen carbonate (3.15 g, 37.46 mmol) and methyl iodide (2.33 ml, 37.46 mmol), and the mixture was stirred at 80° C. for 3 hours. After an ice water was added to the reaction, the mixture was extracted with ether, and the extract was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was removed in vacuo to give A1 (5.38 g, 82.8percent) as brown oil.

Reference： [1] Patent: US2004/242615, 2004, A1, . Location in patent: Page/Page column 13
[2] ChemMedChem, 2016, vol. 11, # 1, p. 108 - 118
[3] Bioorganic and Medicinal Chemistry, 2006, vol. 14, # 2, p. 334 - 343
[4] Organic Letters, 2018, vol. 20, # 5, p. 1316 - 1319

27
[ 67-56-1 ]
[ 2612-02-4 ]
[ 2905-82-0 ]

Reference： [1] Dalton Transactions, 2015, vol. 45, # 2, p. 479 - 483
[2] Australian Journal of Chemistry, 2008, vol. 61, # 7, p. 484 - 499
[3] Organic Letters, 2011, vol. 13, # 24, p. 6524 - 6527
[4] Journal of the Chemical Society, 1948, p. 2220
[5] Justus Liebigs Annalen der Chemie, 1905, vol. 340, p. 219
[6] Journal of Medicinal Chemistry, 1992, vol. 35, # 2, p. 310 - 319
[7] Chemical and Pharmaceutical Bulletin, 2007, vol. 55, # 4, p. 613 - 624
[8] Chemistry - A European Journal, 2012, vol. 18, # 16, p. 4859 - 4865
[9] Organic and Biomolecular Chemistry, 2018, vol. 16, # 11, p. 1837 - 1842

28
[ 2612-02-4 ]
[ 2905-82-0 ]

Reference： [1] Patent: US4604390, 1986, A,

29
[ 490-79-9 ]
[ 77-78-1 ]
[ 2612-02-4 ]
[ 2905-82-0 ]

Reference： [1] Justus Liebigs Annalen der Chemie, 1905, vol. 340, p. 219

30
[ 490-79-9 ]
[ 77-78-1 ]
[ 2150-46-1 ]
[ 2785-98-0 ]
[ 2612-02-4 ]
[ 2905-82-0 ]

Reference： [1] Justus Liebigs Annalen der Chemie, 1905, vol. 340, p. 219

31
[ 2612-02-4 ]
[ 86455-98-3 ]

Reference： [1] Journal of Medicinal Chemistry, 1983, vol. 26, # 9, p. 1240 - 1246

[ 2612-02-4 ] Synthesis Path-Downstream 1~88

1
[ 67-56-1 ]
[ 2612-02-4 ]
[ 2905-82-0 ]

Yield	Reaction Conditions	Operation in experiment
96%	With sulfuric acid for 18h; Reflux; Inert atmosphere;
94%	With thionyl chloride Heating;
90%	With sulfuric acid for 24h; Reflux; Inert atmosphere;

	With sulfuric acid
	With hydrogenchloride
	With hydrogenchloride Heating;
	With thionyl chloride Heating;
	With sulfuric acid Inert atmosphere; Reflux;
0.42 g	With sulfuric acid for 18h; Reflux;
	With sulfuric acid for 24h; Reflux;
	With sulfuric acid at 80℃;	General procedure for the preparation of compounds 2 (2a as a model). General procedure: To a solution of 1a (5 mmol) in CH3OH (25 mL) concentrated sulfuric acid was added dropwise (10 drops). After stirring under reflux for 12 h, the reaction mixture was concentrated under reduced pressure, diluted with water, and extracted with ethyl acetate. The organic layer was washed with saturated aqueous NaHCO3 solution and brine, dried over Na2SO4, and concentrated under reduced pressure. The crude mixture was purified by flash chromatography (petroleum ether/ethyl acetate = 5:1) to afford 2a.
	With hydrogenchloride for 2h; Reflux;	4.1. Synthesis of aryl esters 1b, 1c. Typical procedure General procedure: According to the procedure reported by Paquette [20], HCl 37%(1 mL) was carefully added to a solution of the corresponding benzoic acid derivative (15.6 mmol) in MeOH (20 mL). The reaction mixture was refluxed for 2 h. MeOH was removed under reduced pressure, and the reaction mixture was extracted with CPME(3.0 mL 3). The volatiles were removed under reduced pressure togive the methyl ester 1b or 1c without further purification.
	With thionyl chloride at 0 - 20℃; for 15h; Inert atmosphere;

Reference： [1]Carrillo-Arcos, Ulises A.; Rojas-Ocampo, Jonathan; Porcel, Susana [Dalton Transactions, 2015, vol. 45, # 2, p. 479 - 483]
[2]Moloney, Gerard P.; Angus, James A.; Robertson, Alan D.; Stoermer, Martin J.; Robinson, Michael; Lay, Lucy; Wright, Christine E.; McRae, Ken; Christopoulos, Arthur [Australian Journal of Chemistry, 2008, vol. 61, # 7, p. 484 - 499]
[3]Petrovic, Denis; Brueckner, Reinhard [Organic Letters, 2011, vol. 13, # 24, p. 6524 - 6527]
[4]Chaudhury et al. [Journal of the Chemical Society, 1948, p. 2220]
[5]Graebe; Martz [Justus Liebigs Annalen der Chemie, 1905, vol. 340, p. 219]
[6]Robertson, David W.; Lacefield, William B.; Bloomquist, William; Pfeifer, William; Simon, Richard L.; Cohen, Marlene L. [Journal of Medicinal Chemistry, 1992, vol. 35, # 2, p. 310 - 319]
[7]Sugiyama, Hideyuki; Yoshida, Masato; Mori, Kouji; Kawamoto, Tomohiro; Sogabe, Satoshi; Takagi, Terufumi; Oki, Hideyuki; Tanaka, Toshimasa; Kimura, Hiroyuki; Ikeura, Yoshinori [Chemical and Pharmaceutical Bulletin, 2007, vol. 55, # 4, p. 613 - 624]
[8]Shen, Zengming; Ni, Zhenjie; Mo, Song; Wang, Jing; Zhu, Yamin [Chemistry - A European Journal, 2012, vol. 18, # 16, p. 4859 - 4865]
[9]Carrillo-Arcos, Ulises A.; Porcel, Susana [Organic and Biomolecular Chemistry, 2018, vol. 16, # 11, p. 1837 - 1842]
[10]Jesumoroti, Omobolanle J.; Faridoon; Mnkandhla, Dumisani; Isaacs, Michelle; Hoppe, Heinrich C.; Klein, Rosalyn [MedChemComm, 2019, vol. 10, # 1, p. 80 - 88]
[11]Hu, Xiaojing; Lai, Huimin; Zhao, Fangfei; Hu, Shuyu; Sun, Qianqian; Fang, Lizhen [Acta Chimica Slovenica, 2019, vol. 66, # 3, p. 745 - 750]
[12]Quivelli, Andrea F.; D'Addato, Giovanna; Vitale, Paola; García-Álvarez, Joaquín; Perna, Filippo M.; Capriati, Vito [Tetrahedron, 2021, vol. 81]
[13]Takahashi, Hiroto; Nagashima, Yuki; Tanaka, Ken [European Journal of Organic Chemistry, 2021, vol. 2021, # 12, p. 1891 - 1895]

2
[ 108-73-6 ]
[ 2612-02-4 ]
[ 491-64-5 ]

Yield	Reaction Conditions	Operation in experiment
76.2%	With zinc(II) chloride; trichlorophosphate at 75℃; Microwave irradiation;	1 5.2.3. Synthesis of 1,3-dihydroxyxanthones (2a ~ i) General procedure: The synthesis refers to a procedure described in the literature [43]. To a 50-mL flask 8mL phosphorus oxychloride (POCl3) and anhydrous zinc chloride (6.8g, 0.05mol) were added. The suspension was stirred at 70°C until ZnCl2 was completely dissolved into phosphorus oxychloride. The mixture was then cooled down to room temperature (r.t.). Afterwards, salicylic acids (1a-i) (l.0mmol) and 1,3,5-trihydroxybenzene (1.1mmol) were added, respectively, and the mixture was heated with microwave reactor with a programmed procedure of 75°C for 30min, where the power was 200W. Then the mixture was cooled down to r. t. and pulled into ice water stirring for 20min. The mixed solution was filtered, washed with cold water. The solid residues were collected and purified by flash column liquid chromatography.
	With zinc(II) chloride; trichlorophosphate
	With Eaton′s Reagent at 80℃; for 3h;	6.1.1. Synthesis of substituted 1,3-dihydroxy-9H-xanthen-9-ones (32) General procedure: To a mixture of commercially available phloroglucinol (1.2 equiv) and an appropriate substituted salicylic acid (1 equiv), 20 mL of Eaton's reagent (P2O5-CH3SO3H) was added slowly. The mixture was stirred for 3 h at 80 °C, cooled to rt, and poured onto ice. After vigorous stirring at rt for 2 h, a brown solid was precipitated. The solid was collected by filtration, washed with water (pH ∼ 6), and dried at 60 °C. In most instances, this intermediate 1,3-dihydroxy-9H-xanthen-9-one was used without further purification.

	With Eaton′s Reagent at 80℃; for 2h;	1,3,8-Trihydroxy-9H-xanthen-9-one (3). General procedure: 2,6-dihydroxybenzoic acid (5.0 g, 32.4 mmol) andphloroglucinol (4.09 g, 32.4 mmol) were added to Eaton’s reagent (20 mL) and heated on an 80 °Coil bath for 2 h. After cooling to r.t., the dark-brown solution was transferred slowly to crushedice while being vigorously stirred. The mixture was filtered and the filter cake was washed withwater, dried, and purified by flash column chromatography to afford xanthone 3 as a yellow solid(2.3 g, yield: 29%).
	With Eaton′s Reagent Reflux;

Reference： [1]Liu, Jie; Zhang, Cao; Wang, Huailing; Zhang, Lei; Jiang, Zhenlei; Zhang, Jianrun; Liu, Zhijun; Chen, Heru [European Journal of Medicinal Chemistry, 2018, vol. 151, p. 158 - 172]
[2]Grover et al. [Journal of the Chemical Society, 1955, p. 3982,3984]
[3]Location in patent: experimental part Zhou, Ting; Shi, Qian; Chen, Chin-Ho; Huang, Li; Ho, Phong; Morris-Natschke, Susan L.; Lee, Kuo-Hsiung [European Journal of Medicinal Chemistry, 2012, vol. 47, # 1, p. 86 - 96]
[4]Wang, Penghui; Jiang, Lulu; Cao, Yang; Ye, Deyong; Zhou, Lu [Molecules, 2018, vol. 23, # 6]
[5]Ye, Gao-Jie; Lan, Tian; Huang, Zhi-Xin; Cheng, Xiao-Ning; Cai, Chao-Yun; Ding, Sen-Miao; Xie, Min-Li; Wang, Bo [European Journal of Medicinal Chemistry, 2019, vol. 177, p. 362 - 373]

3
[ 6280-89-3 ]
[ 2612-02-4 ]

Reference： [1]Synthetic Communications,2003,vol. 33,p. 1783 - 1787
[2]Chemische Berichte,1905,vol. 38,p. 2121
[3]Chemische Berichte,1905,vol. 38,p. 2121

4
[ 490-79-9 ]
furan-2,3,5(4H)-trione pyridine (1:1) [ No CAS ]
[ 77-78-1 ]
[ 2150-46-1 ]
[ 2785-98-0 ]
[ 2612-02-4 ]
[ 2905-82-0 ]

Reference： [1]Justus Liebigs Annalen der Chemie,1905,vol. 340,p. 219

5
[ 490-79-9 ]
[ 77-78-1 ]
[ 2785-98-0 ]
[ 2612-02-4 ]

Reference： [1]Justus Liebigs Annalen der Chemie,1905,vol. 340,p. 219

6
[ 2612-02-4 ]
[ 15198-09-1 ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; thionyl chloride In Petroleum ether
	With phosphorus trichloride In chlorobenzene for 0.25h; Heating;
	With thionyl chloride; N,N-dimethyl-formamide In n-heptane at 60℃;

	With thionyl chloride In dichloromethane at 40℃; for 1h;
	With thionyl chloride at 75℃;
	With thionyl chloride; N,N-dimethyl-formamide In dichloromethane for 2h; Electric arc;	1 5 g of 5-methoxysalicylic acid (5.95 mmol)Dissolved in 30ml of anhydrous dichloromethane,2.14 g (10.7 mmol) of thionyl chloride,1 drop of N, N-dimethylformamide,After warming to reflux for 2h,Cool to room temperature,Spin dry to remove the solvent,Dissolved in anhydrous methylene chloride,Was added dropwise to 1.85 g (17.80 mmol) of triethylamine,And benzylamine 0.76 g (7.14 mmol)In anhydrous dichloromethane.After the addition was complete and stirred at room temperature 5min,Spin dried crude,Purification by column chromatography of the purified white solid1.27 g of N-benzyl-2-hydroxy-5-methoxybenzamide,Yield 83%.
	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.

Reference： [1]Amakasu,T.; Sato,K. [Bulletin of the Chemical Society of Japan, 1967, vol. 40, p. 1428 - 1432]
[2]Coburn; Batista; Evans; Genco [Journal of Medicinal Chemistry, 1981, vol. 24, # 10, p. 1245 - 1249]
[3]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]
[4]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]
[5]Sha, Shao; Han, Hong-Wei; Gao, Fei; Liu, Tian-Bao; Li, Zhen; Xu, Chi; Zhong, Wei-Qing; Zhu, Hai-Liang [MedChemComm, 2015, vol. 6, # 11, p. 2029 - 2035]
[6]Current Patent Assignee: CHINA PHARMACEUTICAL UNIVERSITY - CN107176932, 2017, A Location in patent: Paragraph 0030; 0031
[7]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]

7
[ 2612-02-4 ]
[ 33184-48-4 ]
[ 86456-23-7 ]

Reference： [1]Journal of Medicinal Chemistry,1983,vol. 26,p. 1240 - 1246

8
[ 124-38-9 ]
[ 150-76-5 ]
[ 61227-25-6 ]
[ 2612-02-4 ]

Yield	Reaction Conditions	Operation in experiment
46%	With tert.-butyl lithium In pentane Ambient temperature;
46%	With tert.-butyl lithium In pentane Ambient temperature;

Reference： [1]Posner, Gary H.; Canella, Karen A. [Journal of the American Chemical Society, 1985, vol. 107, # 8, p. 2571 - 2573]
[2]Posner, Gary H.; Canella, Karen A. [Journal of the American Chemical Society, 1985, vol. 107, # 8, p. 2571 - 2573]

9
[ 2612-02-4 ]
[ 137-07-5 ]
[ 30612-17-0 ]

Yield	Reaction Conditions	Operation in experiment
83%	With phosphorus trichloride In toluene for 4h; Heating;

Reference： [1]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]

10
[ 2612-02-4 ]
[ 5307-05-1 ]

Reference： [1]Chemical and pharmaceutical bulletin,1979,vol. 27,p. 816 - 820

11
[ 37595-74-7 ]
[ 2612-02-4 ]
[ 171016-61-8 ]

Yield	Reaction Conditions	Operation in experiment
71%	With sodium hydride In tetrahydrofuran

Reference： [1]Kraus, George A.; Liu, Peng [Tetrahedron Letters, 1995, vol. 36, # 42, p. 7595 - 7598]

12
[ 2612-02-4 ]
[ 23356-96-9 ]
[ 171016-57-2 ]

Yield	Reaction Conditions	Operation in experiment
90%	With benzotriazol-1-ol; dicyclohexyl-carbodiimide In tetrahydrofuran at 0℃;

Reference： [1]Kraus, George A.; Liu, Peng [Tetrahedron Letters, 1995, vol. 36, # 42, p. 7595 - 7598]

13
[ 2612-02-4 ]
[ 41951-76-2 ]

Yield	Reaction Conditions	Operation in experiment
85%	With lithium aluminium tetrahydride
78%	With sodium bis(2-methoxyethoxy)aluminium dihydride In diethyl ether for 0.666667h; Reflux;	4-Hydroxy-3-(hydroxymethyl)anisole (8) A solution of 2-hydroxy-5-methoxybenzoic acid (7) (849.5mg, 5.0mmol) in ether (5mL) was placed in a reaction flask and added slowly with Red-Al (6.0mmol) while being heated at reflux for 40min. After the reaction was complete, the mixture was quenched by adding water (2mL) and HCl (1.0M, 2mL). The mixture was extracted with ethyl acetate (20mL×5) and the combined organic layer was collected, washed with saturated NaCl, dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified in a silica gel column (hexanes/ethyl acetate, 1.5:1) and then recrystallized from dichloromethane to afford a white solid 8 (610.0mg, 78%) (mp 75-76°C). The 1 H NMR is in complete accord with the literature values.26 IR (KBr plate) 3440, 3185, 1513, 1443, 1219, 1164, 1039, 1001, 864, 818, 759, 702cm-1; 13C NMR (100MHz, CDCl3) δ 153.1, 149.6, 125.7, 117.0, 114.3, 113.6, 64.2, 55.8; MS (EI, 75eV) m/z (rel intensity) 154 (M+, 32), 152 (2), 136 (100), 121 (4), 110 (5), 108 (45), 93 (7), 78 (25), 65 (29), 53 (8); HRMS (EI) calcd for C8H10O3 154.0630, found 154.0636. Anal. Calcd for C8H10O3: C, 62.33%; H, 6.54%. Found: C, 62.19%; H, 6.61%.
	With lithium aluminium tetrahydride

	With lithium aluminium tetrahydride Yield given;
	With lithium aluminium tetrahydride In diethyl ether Yield given;
	With boron trifluoride-tetrahydrofuran complex In tetrahydrofuran at 0 - 60℃; for 3.5h;
	Stage #1: 5-methoxysalicylic acid With borane-THF In tetrahydrofuran at 60℃; for 3h; Stage #2: With hydrogenchloride In tetrahydrofuran at 0℃; for 0.5h;	63 To a cooled (O0C) solution of 5-methoxysalicylic acid (11.95 g) in THF (150 mL) was added IM borane tetrahydrofuran complex in THF (200 mL) , and the mixture was heated at 600C for 3 hr. The mixture was cooled with an ice-bath, quenched by the addition of IN HCl (200 mL) , stirred for 0.5 hr, salted out by the addition of NaCl, and extracted with ethyl acetate. The extract was dried over MgSO4 and concentrated, and the residue was chromatographed on silica gel using n-hexane/ethyl acetate as an eluent to give the title compound as colorless crystals (3.00 g) . 1H-NMR (300 MHz, CDCl3) δ: 2.10 - 2.30 (br, IH), 3.75 (s, 3H), 4.83 (s, 2H), 6.62 (d, J = 3.0 Hz, IH), 6.77 - 6.81 (m, 3H) .

Reference： [1]Meier, Chris; De Clercq, Eric; Balzarini, Jan [European Journal of Organic Chemistry, 1998, # 5, p. 837 - 846]
[2]Chen, Yu-Jen; Wang, Hui-Ling; Villarante, Nelson R.; Chuang, Gary Jing; Liao, Chun-Chen [Tetrahedron, 2013, vol. 69, # 46, p. 9591 - 9599]
[3]Meier, Chris [Angewandte Chemie, 1996, vol. 108, # 1, p. 77 - 79]
[4]Meier, Chris; Lorey, Martina; De Clercq, Eric; Balzarini, Jan [Nucleosides and Nucleotides, 1997, vol. 16, # 7-9, p. 1303 - 1306]
[5]Lorey, Martina; Meier, Chris; De Clercq, Eric; Balzarini, Jan [Nucleosides and Nucleotides, 1997, vol. 16, # 7-9, p. 1307 - 1310]
[6]Johnsson, Richard; Mani, Katrin; Cheng, Fang; Ellervik, Ulf [Journal of Organic Chemistry, 2006, vol. 71, # 9, p. 3444 - 3451]
[7]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - WO2007/77961, 2007, A2 Location in patent: Page/Page column 324-325

14
[ 2612-02-4 ]
[ 3410-94-4 ]

Yield	Reaction Conditions	Operation in experiment
88%	With nitric acid; acetic acid In water at 15℃; for 1h;
50%	With nitric acid In acetic acid at 10 - 15℃; for 1h;
50%	With nitric acid In acetic acid at 10℃; for 2h;

Reference： [1]Dantas De Araujo, Aline; Christensen, Caspar; Buchardt, Jens; Kent, Stephen B. H.; Alewood, Paul F. [Chemistry - A European Journal, 2011, vol. 17, # 50, p. 13983 - 13986]
[2]Cotelle, Philippe; Catteau, Jeanpierre [Synthetic Communications, 1996, vol. 26, # 22, p. 4105 - 4112]
[3]Bréhu, Laetitia; Fernandes, Anne-Cécile; Lavergne, Olivier [Tetrahedron Letters, 2005, vol. 46, # 9, p. 1437 - 1440]

15
[ 2612-02-4 ]
[ 132020-40-7 ]

Yield	Reaction Conditions	Operation in experiment
86%	With bromine; sodium acetate; acetic acid
86%	With bromine; sodium acetate In acetic acid

Reference： [1]Churcher; Hallett; Magnus [Journal of the American Chemical Society, 1998, vol. 120, # 14, p. 3518 - 3519]
[2]Churcher, Ian; Hallett, David; Magnus, Philip [Journal of the American Chemical Society, 1998, vol. 120, # 40, p. 10350 - 10358]

16
[ 2785-98-0 ]
[ 2612-02-4 ]

Reference： [1]Synthesis,2000,p. 243 - 246

17
[ 124-38-9 ]
[ 1200-06-2 ]
[ 2612-02-4 ]

Reference： [1]Patent: US2816137,1954,

18
[ 110-89-4 ]
[ 6280-89-3 ]
[ 7732-18-5 ]
copper [ No CAS ]
[ 2612-02-4 ]

Reference： [1]Chemische Berichte,1905,vol. 38,p. 2121

19
[ 6280-89-3 ]
[ 7732-18-5 ]
[ 124-40-3 ]
copper [ No CAS ]
[ 2612-02-4 ]

Reference： [1]Chemische Berichte,1905,vol. 38,p. 2121

20
[ 2612-02-4 ]
[ 100-39-0 ]
[ 54625-34-2 ]

Yield	Reaction Conditions	Operation in experiment
71.8%	With potassium carbonate In acetone at 55℃; for 16h; Inert atmosphere;	2.1 2-Chlorobenzyl 5-bromo-2-(2-chlorobenzyloxy)benzoate(10a) General procedure: To a suspension of 5-bromo-2-hydroxybenzoic acid (400 mg, 1.843 mmol) and potassiumcarbonate (509 mg, 3.69 mmol) in acetone (50 mL) under nitrogen at 20 °C was added 1-(bromomethyl)-2-chlorobenzene (833 mg, 4.05 mmol) dropwise. The mixture was stirred at55 °C for 16 hours. The organic phase was evaporated and the residue was dissolved in water (25mL), extracted with ethyl acetate (30*3 mL). The organic layer was concentrated to give the titlecompound 10a (520 mg, 60.5 % yield) as a light yellow solid.
	With potassium carbonate In N,N-dimethyl-formamide at 0 - 20℃; for 21.5h;
	With potassium carbonate In acetone for 12h; Reflux;	6 Potassium carbonate (690 mg, 5.00 mmol) was added to a stirred solution of 2-hydroxy- 5-(methyloxy)benzoic acid (336 mg, 2.00 mmol) in acetone (20 ml) followed by the addition of ((bromomethyl)benzene (854 mg, 5.00 mmol). The mixture was refluxed for 12 h and then cooled to room temperature. The mixture was filtered and the filtrate was concentrated to a yellow solid. Flash chromatography over silica gel eluttng with 1 : 10 ethyl acetate: petroleum ether yielded the title compound as a pure, white powder. 500 mg.MS (electrospray): m/z [ +H]+ = 349

With sodium hydroxide In N,N,N,N,N,N-hexamethylphosphoric triamide; water

3 (6-Methoxy-4-Oxo-4H-1-Benzopyran-2-ylamino)Oxamic Acid, Ethyl Ester EXAMPLE 3 (6-Methoxy-4-Oxo-4H-1-Benzopyran-2-ylamino)Oxamic Acid, Ethyl Ester A solution of 5-methoxysalicylic acid (33.6 g., 0.2 mol) in 300 ml. of hexamethylphosphorustriamide is treated successively with 16 g. of sodium hydroxide in 40 ml. of water and 68.4 g. (0.4 mol) of benzyl bromide. The resulting solution is stirred 14 hours at room temperature, poured into water and extracted with diethyl ether. The ether solution is dried and evaporated to a yellow oil which solidified on standing. Recrystallization from benzenehexane gives the desired 2-benzyloxy-5-methoxy benzoic acid benzyl ester.

Reference： [1]Ding, Xiao; Dai, Xuedong; Long, Kai; Peng, Cheng; Andreotti, Daniele; Bamborough, Paul; Eatherton, Andrew J.; Edge, Colin; Jandu, Karamjit S.; Nichols, Paula L.; Philps, Oliver J.; Stasi, Luigi Piero; Wan, Zehong; Xiang, Jia-Ning; Dong, Kelly; Dossang, Pamela; Ho, Ming-Hsun; Li, Yi; Mensah, Lucy; Guan, Xiaoming; Reith, Alastair D.; Ren, Feng [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 17, p. 4034 - 4038]
[2]Yokokawa, Fumiaki; Izumi, Kentaro; Omata, Junko; Shioiri, Takayuki [Tetrahedron, 2000, vol. 56, # 19, p. 3027 - 3034]
[3]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2011/38572, 2011, A1 Location in patent: Page/Page column 51
[4]Current Patent Assignee: PFIZER INC - US3937719, 1976, A

21
[ 2612-02-4 ]
[ 75-36-5 ]
[ 17336-15-1 ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine at 0 - 25℃; for 0.5h;
	With triethylamine In dichloromethane at 0 - 20℃;	1 EXAMPLE 1; Compound Preparation; [0044] Preparation of Compound 1; [0045] 5-methoxysalicylic acid (30.0 g, 0.1786 mol) and methylene chloride (350 ml) were placed in a 1 L round bottomed flask fitted with argon purge and magnetic stir bar. The resulting tan reaction mixture was cooled to 0° C. in an ice water bath. Triethylamine (39.68 g, 0.3929 mol) was added in one portion, followed by dropwise addition of acetyl chloride (15.42 g, 0.1964 mol) over a period of thirty-five minutes. The reaction mixture was allowed to come to room temperature overnight and then 350 mL of methylene chloride was added. The mixture was washed with two 300 ml portions of 0.5 HCl, and then with two 300 ml portions of water. At this point it was noted that a tan solid had precipitated. This solid was isolated by filtration, recrystallized from methylene chloride and dried in vacuo. 26.24 g of 5-methoxyacetylsalicylic acid was isolated.
	With triethylamine In dichloromethane

Reference： [1]Shi, Guo-Qiang [Tetrahedron Letters, 2000, vol. 41, # 14, p. 2295 - 2298]
[2]Current Patent Assignee: NOVO NORDISK A/S - US2003/216589, 2003, A1 Location in patent: Page/Page column 5
[3]Jeankumar, Variam Ullas; Chandran, Manoj; Samala, Ganesh; Alvala, Mallika; Koushik, Pulla Venkat; Yogeeswari, Perumal; Salina, Elena G.; Sriram, Dharmarajan [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 24, p. 7414 - 7417]

22
[ 2612-02-4 ]
[ 108-42-9 ]
[ 521272-43-5 ]

Yield	Reaction Conditions	Operation in experiment
77%	With phosphorus trichloride In dibutyl ether at 140℃; for 4h;
	With phosphorus trichloride In chlorobenzene for 3h; Heating;
	With phosphorus trichloride In toluene at 120℃;

Reference： [1]Liechti, Christoph; Sequin, Urs; Bold, Guido; Furet, Pascal; Meyer, Thomas; Traxler, Peter [European Journal of Medicinal Chemistry, 2004, vol. 39, # 1, p. 11 - 26]
[2]Waisser, Karel; Bures, Otakar; Holy, Pavel; Kunes, Jiri; Oswald, Radek; Jiraskova, Lucie; Pour, Milan; Klimesova, Vera; Kubicova, Lenka; Kaustova, Jarmila [Archiv der Pharmazie, 2003, vol. 336, # 1, p. 53 - 71]
[3]Baugh, Simon D.P.; Pabba, Praveen K.; Barbosa, Joseph; Coulter, Eric; Desai, Urvi; Gay, Jason P.; Gopinathan, Suma; Han, Qiang; Hari, Rajee; Kimball, S. David; Nguyen, Huy V.; Ni, Chi-You; Powell, David R.; Smith, Arian; Terranova, Kristen M.; Wilson, Alan; Yu, Xuan-Chuan; Lombardo, Victoria K. [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 18, p. 3836 - 3839]

23
[ 2612-02-4 ]
[ 104-86-9 ]
N-(4-chlorobenzyl)-2-hydroxy-5-methoxybenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%	With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate In dichloromethane; N,N-dimethyl-formamide at 0 - 20℃; for 6h;	Procedure 1 General procedure: In a 100 mL flask equipped with magnetic stirring, the organic acid (1.35 mmol, 200 mg) was dissolved in dimethylformamide (DMF, 2.7 mL) and trimethylamine (0.14 mL, 1.35 mmol). The solution was cooled in an ice bath (0 °C). Then, 4-chlorobenzylamine (1.35 mmol) was added. Soon after a 1.35 mmol solution of BOP in CH2Cl2 (10 mL) was added to the flask. The reaction was stirred at 0 °C for 30 min, and then for an additional period, at room temperature for 2 h. After the reaction, the CH2Cl2 was removed under reduced pressure and the solution was poured into a separatory funnel containing water (10 mL) and EtOAc (10 mL). The product was extracted with EtOAc (3 × 10 mL). The organic phase was washed sequentially with 1 N HCl, water, 1 M NaHCO3 and water (10 mL of each); dried with Na2SO4, filtered and concentrated in a rotavapor. The amide was purified by gel chromatography on a silica gel column using as the mobile phase an EtOAc:Hex mixture gradient of increasing polarity.
50%	With phosphorus trichloride In chlorobenzene for 3h; Heating;
	With phosphorus trichloride In chlorobenzene Reflux;

Reference： [1]Montes, Ricardo Carneiro; Perez, Ana Luiza A. L.; Medeiros, Cássio Ilan S.; De Araújo, Marianna Oliveira; Lima, Edeltrudes De Oliveira; Scotti, Marcus Tullius; De Sousa, Damião Pergentino [Molecules, 2016, vol. 21, # 12]
[2]Waisser, Karel; Perina, Milan; Klimesova, Vera; Kaustova, Jarmila [Collection of Czechoslovak Chemical Communications, 2003, vol. 68, # 7, p. 1275 - 1294]
[3]Kralova, Katarina; Perina, Milan; Waisser, Karel; Jampilek, Josef [Medicinal Chemistry, 2015, vol. 11, # 2, p. 156 - 164]

24
[ 2612-02-4 ]
[ 100-39-0 ]
[ 53985-53-8 ]

Yield	Reaction Conditions	Operation in experiment
63%	With potassium carbonate In N,N-dimethyl-formamide at 0 - 20℃;

Reference： [1]Davies, James R.; Kane, Peter D.; Moody, Christopher J. [Tetrahedron, 2004, vol. 60, # 18, p. 3967 - 3977]

25
[ 2612-02-4 ]
[ 74-88-4 ]
[ 2905-82-0 ]

Yield	Reaction Conditions	Operation in experiment
82.8%	With sodium hydrogencarbonate In DMF (N,N-dimethyl-formamide) at 80℃; for 3h;	4 Reference 4 Methyl 2-hydroxy-5-methoxybenzoate (compound A1) To a solution of 2-hydroxy-5-methoxybenzoic acid (6.0 g, 35.68 mmol) in dimethylformamide (80 ml) were added sodium hydrogen carbonate (3.15 g, 37.46 mmol) and methyl iodide (2.33 ml, 37.46 mmol), and the mixture was stirred at 80° C. for 3 hours. After an ice water was added to the reaction, the mixture was extracted with ether, and the extract was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was removed in vacuo to give A1 (5.38 g, 82.8%) as brown oil.
46%	Stage #1: 5-methoxysalicylic acid With caesium carbonate In N,N-dimethyl-formamide at 0℃; for 0.166667h; Stage #2: methyl iodide In N,N-dimethyl-formamide at 0 - 20℃; for 0.5h;
	With caesium carbonate In N,N-dimethyl-formamide for 1.5h;

With caesium carbonate In N,N-dimethyl-formamide at 20℃; for 2h; Inert atmosphere;

Reference： [1]Current Patent Assignee: SHIONOGI & CO., LTD. - US2004/242615, 2004, A1 Location in patent: Page/Page column 13
[2]Cantore, Mariangela; Benadiba, Marcel; Elsinga, Philip H.; Kwizera, Chantal; Dierckx, Rudi A. J. O.; Colabufo, Nicola Antonio; Luurtsema, Gert [ChemMedChem, 2016, vol. 11, # 1, p. 108 - 118]
[3]Anderson, Marc O.; Sherrill, John; Madrid, Peter B.; Liou, Ally P.; Weisman, Jennifer L.; DeRisi, Joseph L.; Guy, R. Kiplin [Bioorganic and Medicinal Chemistry, 2006, vol. 14, # 2, p. 334 - 343]
[4]Morack, Tobias; Metternich, Jan B.; Gilmour, Ryan [Organic Letters, 2018, vol. 20, # 5, p. 1316 - 1319]

26
[ 22921-68-2 ]
[ 2612-02-4 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 2-bromo-5-methoxy-benzoic acid With sodium carbonate In water at 50 - 75℃; Stage #2: With water at 80℃; for 4h; Stage #3: With hydrogenchloride In water at 20℃;	21; 22 Under nitrogen, 2 mmol of the halogen-substituted benzoic acid indicated in Table 6 was stirred with a solution of 3 mmol Na2CO3 at 50-75° C. until all of the halogen-substituted benzoic acid was dissolved. Subsequently, 0.02 mmol CuSO4 and 0.04 mmol rac-trans-N,N'-dimethylcyclohexane-1,2-diamine (Ligand F) dissolved in 1 mL deionized water were added and the reaction mixture was heated at 80-100° C. for 4 h. After cooling to ambient temperature the reaction mixtures were carefully acidified with 35% aqueous HCl.In isolation method A, the products were extracted from the aqueous layer twice with ethyl acetate, the ethyl acetate fractions were combined and the crude reaction product was isolated by evaporation of ethyl acetate under vacuum. In isolation method B, the products were isolated by filtration, washed with water and dried under vacuum. The crude reaction product was analyzed by 1H NMR (d6-dmso). The results are summarized in Table 6. TABLE 6 Examples 8~23 Starting material Halogenated Benzoic Acid Isolation CONV SEL Example Benzoic Acid Product T (° C.) Method (%) (%) 8 2,5-dibromo- 2-hydroxy-5- 80 B >99 >99 bromo- 9 2-bromo-5-nitro- 2-hydroxy-5- 80 B >99 >99 nitro- 10 2-bromo-5-nitro- 2-hydroxy-5- 100 A >99 >99 nitro- 11 2-bromo-5-methyl- 2-hydroxy-5- 80 B >99 >99 methyl- 12 2-bromo-5-methyl- 2-hydroxy-5- 100 A >99 >99 methyl- 13 4-bromo- 4-hydroxy- 100 A >99 >99 14 4-chloro- 4-hydroxy- 80 B >99 >99 15 2,4-dichloro- 2-hydroxy-4- 100 A 70 >99 chloro- 16 2,5-dichloro- 2,5-dihydroxy- 80 B 93 >99 17 2-chloro-5-nitro- 2-hydroxy-5- 100 A 74 >99 nitro- 18 2-chloro-3,5-dinitro- 2-hydroxy-3,5- 100 A >99 >99 dinitro- 19 2-chloro-3,5-dinitro- 2-hydroxy-3,5- 80 B >99 >99 dinitro- 20 2-chloro-5-methyl- 2-hydroxy-5- 100 A >99 >99 methyl- 21 2-bromo-5- 2-hydroxy-5- 100 A >99 >99 methoxy- methoxy- 22 2-bromo-5- 2-hydroxy-5- 80 B >99 >99 methoxy- methoxy- 23 2-chloro-5-bromo- 2-hydroxy-5- 80 B 73 >99 bromo-

Reference： [1]Current Patent Assignee: DUPONT DE NEMOURS INC - US7335791, 2008, B1 Location in patent: Page/Page column 20-21

27
[ 2612-02-4 ]
2-hydroxy-N,5-dimethoxy-N-methylbenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	Stage #1: N,O-dimethylhydroxylamine*hydrochloride With triethylamine In N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: 5-methoxysalicylic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 15h;	35 Reference Example 35 Reference Example 35 To a mixture of N,O-dimethylhydroxylamine hydrochloride (6.38 g) and N,N-dimethylformamide (100 ml) was added triethylamine (6.62 g), and the mixture was stirred at room temperature for 30 min. 5-Methoxysalicylic acid (10.00 g), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (12.54 g) and 1-hydroxybenzotriazole (10.02 g) were added to the reaction mixture, and the mixture was stirred at room temperature for 15 hr. Ethyl acetate was added to the reaction mixture, and the mixture was washed with water and aqueous potassium carbonate solution, dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography, eluted with ethyl acetate-hexane (1:4→1:1, v/v) to give 2-hydroxy-N,5-dimethoxy-N-methylbenzamide (9.73 g, yield 77%) as a colorless oil. 1H-NMR (300 MHz, CDCl3) δ:3.41 (3 H, s), 3.66 (3 H, s), 3.76 (3 H, s), 6.92 (1 H, d, J=9.0 Hz), 7.01 (1 H, dd, J=3.0, 9.0 Hz), 7.51 (1 H, d, J=3.0 Hz), 10.59 (1 H, s).

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - EP1911738, 2008, A1 Location in patent: Page/Page column 42

28
[ 108-86-1 ]
[ 2612-02-4 ]
[ 936716-83-5 ]
[ 14770-96-8 ]

Yield	Reaction Conditions	Operation in experiment
1: 63% 2: 14%	Stage #1: bromobenzene With magnesium In diethyl ether for 1h; Heating; Stage #2: 5-methoxysalicylic acid In diethyl ether at 20℃; Further stages.;

Reference： [1]Pengfei, Wang; Huayou, Hu; Yun, Wang [Organic Letters, 2007, vol. 9, # 8, p. 1533 - 1535]

29
[ 2612-02-4 ]
[ 345924-12-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: Cs₂CO₃ / dimethylformamide / 1.5 h 2: Et₃N / CH₂Cl₂ / -78 - 20 °C
	Multi-step reaction with 2 steps 1: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C / Inert atmosphere 2: triethylamine / dichloromethane / 12 h / -78 - 20 °C / Inert atmosphere
	Multi-step reaction with 2 steps 1: thionyl chloride / 15 h / 0 - 20 °C / Inert atmosphere 2: triethylamine / dichloromethane / 20 h / 0 - 20 °C / Inert atmosphere

Reference： [1]Anderson, Marc O.; Sherrill, John; Madrid, Peter B.; Liou, Ally P.; Weisman, Jennifer L.; DeRisi, Joseph L.; Guy, R. Kiplin [Bioorganic and Medicinal Chemistry, 2006, vol. 14, # 2, p. 334 - 343]
[2]Morack, Tobias; Metternich, Jan B.; Gilmour, Ryan [Organic Letters, 2018, vol. 20, # 5, p. 1316 - 1319]
[3]Takahashi, Hiroto; Nagashima, Yuki; Tanaka, Ken [European Journal of Organic Chemistry, 2021, vol. 2021, # 12, p. 1891 - 1895]

30
[ 2612-02-4 ]
[ 284469-98-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: 63 percent / K₂CO₃ / dimethylformamide / 0 - 20 °C 2.1: Et₃N; ethyl chloroformate / tetrahydrofuran / 0.25 h / 0 °C 2.2: 89 percent / aq. NH₃ / tetrahydrofuran / 0.25 h 3.1: 26 percent / Rh₂(OAc)4 / 1,2-dichloro-ethane / Heating 4.1: 23 percent / triphenylphosphine; iodine; triethylamine / CH₂Cl₂ / 16 h
	Multi-step reaction with 5 steps 1: K₂CO₃ / dimethylformamide / 21.5 h / 0 - 20 °C 2: 2.15 g / aq. NaOH / methanol / 1 h / 20 °C 3: 98 percent / DEPC; Et₃N / dimethylformamide / 12 h / 0 - 20 °C 4: Dess-Martin periodinane / CH₂Cl₂ / 1 h / 20 °C 5: 146 mg / PPh₃; Et₃N; Cl₃CCCl₃ / CH₂Cl₂ / 0.5 h / -10 °C

Reference： [1]Davies, James R.; Kane, Peter D.; Moody, Christopher J. [Tetrahedron, 2004, vol. 60, # 18, p. 3967 - 3977]
[2]Yokokawa, Fumiaki; Izumi, Kentaro; Omata, Junko; Shioiri, Takayuki [Tetrahedron, 2000, vol. 56, # 19, p. 3027 - 3034]

31
[ 2612-02-4 ]
[ 58138-72-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 18 N H₂SO₄ 2: (COCl)2; DMF / ethyl acetate
	Multi-step reaction with 2 steps 1: pyridine / 10 h / 20 °C 2: SOCl₂; urea / toluene / 3 h / 100 - 110 °C
	Multi-step reaction with 2 steps 1: pyridine / 0.5 h / 0 - 25 °C 2: (COCl)2 / CH₂Cl₂ / 1 h / 25 °C / Heating

Multi-step reaction with 2 steps 1: triethylamine / dichloromethane 2: oxalyl dichloride / dichloromethane; N,N-dimethyl-formamide

Reference： [1]Spencer, Jeffrey R; McGee, Danny; Allen, Darin; Katz, Bradley A; Luong, Christine; Sendzik, Martin; Squires, Neil; Mackman, Richard L [Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 15, p. 2023 - 2026]
[2]Jung; Min; Park [Synthetic Communications, 2001, vol. 31, # 12, p. 1837 - 1845]
[3]Shi, Guo-Qiang [Tetrahedron Letters, 2000, vol. 41, # 14, p. 2295 - 2298]
[4]Jeankumar, Variam Ullas; Chandran, Manoj; Samala, Ganesh; Alvala, Mallika; Koushik, Pulla Venkat; Yogeeswari, Perumal; Salina, Elena G.; Sriram, Dharmarajan [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 24, p. 7414 - 7417]

32
[ 2612-02-4 ]
[ 86455-98-3 ]

Reference： [1]Journal of Medicinal Chemistry,1983,vol. 26,p. 1240 - 1246

33
sodium-5-methoxysalicylate [ No CAS ]
[ 2612-02-4 ]

Yield	Reaction Conditions	Operation in experiment
	With sulfuric acid In water for 2h;	11 Example 11 In a 200 ml four-necked flask were placed 49.53 g (0.240 mol) of 4-tert-octylphenol, 2.05 g (0.018 mol) of DMi and 40 g of xylene, and the solution was heated until reflux begun. Afterward, azeotropic dehydration was carried out, while 4.41 g (0:054 mol) of a 49 wt % aqueous NaOH solution was added dropwise over 5 hours. Next, 20 g of xylene was added dropwise, and the solution was allowed to mature under the reflux for 2 hours. It was confirmed that a stoichiometric amount of water was distilled. The reaction solution was put in a 300 ml autoclave, heated up to 130° C., and then allowed to absorb a carbon dioxide gas at 6 kg/cm2G, followed by maturation at the same temperature for 5 hours. In this case, a conversion was 86.7%/NaOH. The reaction solution was slowly cooled to 70° C., and then crystallized at 70° C. for 2 hours. The reaction solution was filtered at the same temperature, and then washed three times with 20 g of xylene to obtain wet sodium 5-tert-octylsalicylate. According to analysis, the recovery yield of sodium 5-tert-octylsalicylate was 85.3%/NaOH, and any DMi was not detected. It was confirmed that DMi was completely recovered in a filtrate and a wash liquid in the steps of the heating, the filtration and the washing. The wet product was dissolved in 54 g of water at 60° C., and an extraction operation was carried out twice with 18 g of xylene to obtain an aqueous layer. Xylene dissolved in this aqueous layer was distilled off under reduced pressure, and the aqueous layer was added dropwise to 49 g of a 6% sulfuric acid solution over 2 hours to crystallize. The resulting precipitate was filtered, and then washed 3 times with 12 g of water. Next, wet 5-tert-octylsalicylic acid was taken out, and then dried to obtain 11.52 g of 5 tert-octylsalicylic acid. In this case, a purity was 99.9% or more and a total recovery yield in terms of pure product from the raw material was 85.2%/NaOH.

Reference： [1]Current Patent Assignee: MITSUI CHEMICALS,INC. - US6392090, 2002, B1 Location in patent: Page column 11,12

34
6-(2,5-dimethyl-1H-pyrrol-1-yl)-4-methyl-2-pyridinebutanamide [ No CAS ]
[ 2612-02-4 ]
[ 254979-36-7 ]

Yield	Reaction Conditions	Operation in experiment
47%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 25℃;	8.2 8.2) N-{4[6-(2,5-Dimethyl-1H-pyrrol-1-yl)-4-methyl-2-pyridinyl]butyl}-2-hydroxy-5-methoxy Benzamide: 0.515 g (2 mmoles) of intermediate 8.1, 0.3 ml of triethylamine, 0.27 g (2 mmoles) of hydroxybenzotriazole and 0.383 g (2 mmoles) of 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride are added successively to a solution of 0.336 g (2 mmoles) of 2-hydroxy-5-methoxy-benzoic acid in 20 ml of dichloromethane. After having agitated the reaction mixture overnight at 25 C., the whole is diluted with 40 ml of water and agitation is maintained for another 10 minutes. The product is finally extracted with twice 50 ml of dichloromethane. The organic solution is dried over sodium sulphate, filtered and concentrated under vacuum. The evaporation residue is purified on a silica column (eluant ethyl acetate/heptane: 7/3) in order to produce a yellow oil with a yield of 47%. NMR 1H (DMSO d6, 400 MHz, ?): 1.56 (m, 2H, CH2); 1.71 (m, 2H, CH2); 2.00 (s, 6H, 2CH3 pyrrole); 2.34 (s, 3H, CH3 pyridine); 2.73 (m, 2H, CH2); 3.30 (m, 2H, CH2); 3.71 (s, 3H, OCH3); 5.75 (s, 2H, pyrrole); 6.80-7.38 (m, 5H, arom.); 8.83 (broad t, 1H), CONH, J=5.44 Hz); 12.20 (broad s, 1H, arom. OH).

Reference： [1]Current Patent Assignee: IPSEN SA - US6727239, 2004, B1 Location in patent: Page column 26

35
[ 2612-02-4 ]
[ 50343-02-7 ]

Yield	Reaction Conditions	Operation in experiment
35%	With bromine In chloroform at 0 - 20℃; for 5h;	8 3-BROMO-2-HYDROXY-5-METHOXY-BENZALDEHYDE (25) To a cooled 0° C. solution of methyl 4-methoxysalicylate (30 g, 200 mmol) in chloroform (500 ml) was added bromine (32 g, 200 mmol) and the reaction was stirred at room temperature for 5 hr. The reaction then was washed with 10% sodium sulfite, dried, and concentrated to give a solid. The solid was triturated with hexane and filtered to give 25 as a yellow solid (14 g, 35%): Mp=107-110° C.

Reference： [1]Current Patent Assignee: PFIZER INC - US2006/4087, 2006, A1 Location in patent: Page/Page column 15; 21

36
[ 2612-02-4 ]
[ 100-39-0 ]
benzyl 2-hydroxy-5-methoxybenzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	In NaH; N,N-dimethyl-formamide	3 Benzyl 2-hydroxy-5-methoxybenzoate Benzyl 2-hydroxy-5-methoxybenzoate To 2-hydroxy 5-methoxybenzoic acid (5.0 g, 30 mmol) in DMF (30 mL) in an ice bath was added 60% NaH (1.32 g, 33 mmol). The reaction mixture was stirred for 15 minutes before warming to room temperature and stirring for 1 hour. Benzyl bromide (3.6 mL, 30 mmol) was added, and the reaction mixture was stirred overnight. The reaction mixture was poured into water (100 mL) and extracted with 25% ethyl acetate/hexanes. The combined organics were washed with water and brine, dried over sodium sulfate and concentrated to a yellow oil. Purification by column chromatography (SiO2, 5% ethyl acetate/hexanes) afforded an oil (5.8 g, 75%). 1H NMR (300 MHz, CDCl3) δ10.35 (s, 1H), 7.38 (m, 6H), 7.09 (dd, 1H, J=3.1, 9.0 Hz), 6.93 (d, 1H, J=9.0 Hz), 5.40 (s, 2H), 3.77 (s, 3H). MS calcd for C15 H15O4 [M+H]+259.097, found 259.090.
	With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 2h;
	With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 2h;

Reference： [1]Current Patent Assignee: NEO GENESIS PHARMACEUTICALS - US2002/77491, 2002, A1
[2]Rackham, Mark D.; Yu, Zhiyong; Brannigan, James A.; Heal, William P.; Paape, Daniel; Barker, K. Victoria; Wilkinson, Anthony J.; Smith, Deborah F.; Leatherbarrow, Robin J.; Tate, Edward W. [MedChemComm, 2015, vol. 6, # 10, p. 1761 - 1766]
[3]Yu, Zhiyong; Brannigan, James A.; Rangachari, Kaveri; Heal, William P.; Wilkinson, Anthony J.; Holder, Anthony A.; Leatherbarrow, Robin J.; Tate, Edward W. [MedChemComm, 2015, vol. 6, # 10, p. 1767 - 1772]

37
[ 6138-90-5 ]
[ 2612-02-4 ]
2-geranyloxy-5-methoxybenzoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sulfuric acid; sodium hydrogencarbonate In ethanol; water	7 Synthesis of 2-geranyloxy-5-methoxybenzoic acid Reference Example 7 Synthesis of 2-geranyloxy-5-methoxybenzoic acid To a solution of 2-hydroxy-5-methoxybenzoic acid (8.40 g) in ethanol (100 ml) was added sulfuric acid (5 ml) and then the mixture was refluxed with heating for 3 hours. After the reaction, the reaction mixture was concentrated and then water (100 ml) and sodium hydrogencarbonate were added thereto. The mixture was extracted with chloroform and the extract was purified by silica gel column chromatography (hexane:ethyl acetate), thereby yielding ethyl 2-hydroxy-5-methoxybenzoate. In a manner identical to Reference Example 1, from the resulting compound (9.10 g) and geranylbromide(10.86 g), 7.34 g(48%) of 2-geranyloxy-5-methoxybenzoic acid was obtained.
	With sulfuric acid; sodium hydrogencarbonate In ethanol; water	R.7 Synthesis of 2-geranyloxy-5-methoxybenzoic acid Reference Example 7 Synthesis of 2-geranyloxy-5-methoxybenzoic acid To a solution of 2-hydroxy-5-methoxybenzoic acid (8.40 g) in ethanol (100 ml) was added sulfuric acid (5 ml) and then the mixture was refluxed with heating for 3 hours. After the reaction, the reaction mixture was concentrated and then water(100 ml) and sodium hydrogencarbonate were added thereto. The mixture was extracted with chloroform and the extract was purified by silica gel column chromatography (hexane: ethyl acetate), thereby yielding ethyl 2-hydroxy-5-methoxybenzoate. In a manner identical to Reference Example 1, from the resulting compound (9.10 g) and geranylbromide(10.86 g), 7.34 g(48%) of 2-geranyloxy-5-methoxybenzoic acid was obtained.

Reference： [1]Current Patent Assignee: SHISEIDO COMPANY LIMITED - US6001880, 1999, A
[2]Current Patent Assignee: SHISEIDO COMPANY LIMITED - US5814634, 1998, A

38
[ 638-31-3 ]
[ 2612-02-4 ]
[ 197584-85-3 ]

Yield	Reaction Conditions	Operation in experiment
55%	With hydrogenchloride; sodium hydrogencarbonate; 1,1'-carbonyldiimidazole In dichloromethane; water	8 Preparation of (R,S)-7-Methoxy-3a-methyl-2,3-dihydro-1H-pyrrolo [2,1-b][1,3]benzoxazine-9-one (Compound VIII; per generic formula: R1 =OCH3, R2 =H, R3 =CH3 and n =2) STR13 EXAMPLE 8 Preparation of (R,S)-7-Methoxy-3a-methyl-2,3-dihydro-1H-pyrrolo [2,1-b][1,3]benzoxazine-9-one (Compound VIII; per generic formula: R1 =OCH3, R2 =H, R3 =CH3 and n =2) STR13 The synthesis of this compound was performed by activating 5-methoxysalicylic acid and combining it with 2-pyrroline. Specifically, 5-methoxysalicylic acid (1.21 g, 7.20 mmol) was suspended in 12 mL CH2 Cl2, and carbonyldiimidazole (1.19 g) was added with stirring. After 3.5 hours, 2-pyrroline (0.71 mL) was added, and the solution was allowed to stand for 5 days. UV spectra in water and Na2 CO3 revealed no free phenol. The solution was then diluted with diethyl ether and washed three times with small volumes of 0.5N HCl, then three times with 5% NaHCO3, and then dried over Na2 SO4 /K2 CO3. After being filtered through MgSO4, the solution was concentrated to an orange oil and purified by silica gel chromatography to yield 0.916 g (55% yield) of product as a yellow oil that solidified upon standing. 1 H NMR: δ 7.405 (1H, d, J=3.15 Hz); 6.99 (1H, q, J=8.86 and 3.12 Hz); 6.85 (1H, d, J=8.84 Hz); 3.85 (1H, dr, J=11.89 and 8.14 Hz); 3.82 (3H, s); 3.60-3.66 (1H, m); 2.34-2.42 (1H, m); 2.24-2.30 (1H, m); 2.05--2.13 (1H, m); 1.89-1.99 (1H, m); and 1.498 ppm (3H, s). This confirmed the structure as that of (R,S)-7-methoxy-3a-methyl-2,3-dihydro-1H-pyrrolo[2,1-b][1,3]benzoxazine-9-one.

Reference： [1]Current Patent Assignee: UNIVERSITY OF CALIFORNIA - US5736543, 1998, A

39
[ 2612-02-4 ]
[ 2905-82-0 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; potassium carbonate In methanol; ethyl acetate	25 2-Hydroxy-5-methoxybenzoic acid, methyl ester EXAMPLE 25 2-Hydroxy-5-methoxybenzoic acid, methyl ester A mixture of 73 g of 5-methoxysalicylic acid, and 95 ml of concentrated hydrochloric acid in 700 ml of methanol was heated under reflux for 48 hours. Potassium carbonate (10 g) was added, and the mixture concentrated to an oily residue which was dissolved in 250 ml of ethyl acetate. This solution was washed with two 100 ml portions of 10% sodium bicarbonate solution, then dried over anhydrous sodium sulfate. Evaporation of solvent afforded the title compound as an amber oil.

Reference： [1]Current Patent Assignee: PFIZER INC - US4604390, 1986, A

40
[ 2612-02-4 ]
5-methoxy-2-phenylbenzofuran-7-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
45%		20.1 EXAMPLE 20 (1) 15 g of 2-hydroxy-5-methoxybenzoic acid is treated in the same manner as described in Example 1-(1) to (3) to give 10.8 g of 5-methoxy-2-phenylbenzofuran-7-carboxylic acid. yield: 45%. M.p. 185°-187° C.
		1 Preparation 1 2-hydroxy-5-methoxybenzoic acid (15 g) is treated in the same manner as described in Paragraph (1) to (3), whereby 5-methoxy-2-phenylbenzofuran-7-carboxylic acid (10.8 g) is obtained. m.p. 185°-187° C.

Reference： [1]Current Patent Assignee: COMMONWEALTH SCIENTIFIC AND INDUSTRIAL RESEARCH ORGANISATION; MITSUBISHI CHEMICAL HOLDINGS CORPORATION - US4829067, 1989, A
[2]Current Patent Assignee: MITSUBISHI CHEMICAL HOLDINGS CORPORATION - US4882340, 1989, A

41
[ 2612-02-4 ]
[ 328-74-5 ]
N-(3,5-bis(trifluoromethyl)phenyl)-2-hydroxy-5-methoxybenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56.8%		79 Example 79 Example 79 N-[3,5-Bis(trifluoromethyl)phenyl]-2-hydroxy-5-methoxybenzamide (Comopund No. 77). Using 5-methoxysalicylic acid and 3,5-bis(trifluoromethyl)aniline as the raw materials, the same operation as the example 16 gave the title compound. Yield: 56.8%. 1H-NMR(DMSO-d6): δ 3.77(3H, s), 6.97(1H, d, J=9.0Hz), 7.10(1H, dd, J=9.0 3.0Hz), 7.43(1H, d, J=3.0Hz), 7.84(1H, s), 8.47(2H, s), 10.84(1H, s), 10.91(1H, s).
52%	With pyridine; phosphorus trichloride In toluene Inert atmosphere; Reflux;	N-(3,5-Bis(trifluoromethyl)phenyl)-5-chloro-2-hydroxybenzamide (2a).^S-1 General Procedure A. General procedure: Phosphorus trichloride (0.13ml, 1.5mmol) was added to a stirred solution of 3,5-bis(trifluoromethyl)aniline (0.47ml, 3mmol), a catalytic amount of pyridine and 5-chloro salicylic acid (621.3mg, 3.6mmol) in anhydrous toluene (10ml) in in a Radley’s Carousel reaction tube under an argon atmosphere. After the reaction mixture was refluxed for overnight, it was cooled to room temperature and aq. sodium bicarbonate was added dropwise until PH=6 - 7. After extracting with ethyl acetate, the organic layers was dried, dried (MgSO4) and concentrated in vacuo. After chromatography (EA-Hex, 1:10) of the crude product, and followed by recrystalization from EtOAc/hexane provided 2a as a white solid (320mg, 28%).
16%	With phosphorus trichloride In toluene Inert atmosphere; Reflux;

	With pyridine; phosphorus trichloride In toluene for 12h; Inert atmosphere; Reflux;	10 4.1.1 Procedure A General procedure: The salicylic acid (1.2 equiv) was added to a mixture of toluene (0.3 M), aniline (1.0 equiv), phosphorus trichloride (1.1 equiv), and pyridine (0.05 equiv) in a Radley’s Carousel reaction tube (modified from Itai et al.20). The mixture was refluxed under nitrogen for 12 h then cooled to room temperature. Aqueous sodium bicarbonate was added dropwise to attain pH 6-7. The resultant mixture was extracted with EtOAc. The organic extracts were combined, dried (MgSO4), and concentrated under vacuum. After chromatography (1:10 EtOAc:Hex) compounds were recrystallized (EtOAc/Hex).
	With phosphorus trichloride In 5,5-dimethyl-1,3-cyclohexadiene for 5h; Reflux;

Reference： [1]Current Patent Assignee: INSTITUTE OF MEDICINAL MOLECULAR DESIGN INC - EP1352650, 2003, A1
[2]Kang, Sunghyun; Min, Hye-Jin; Kang, Min-Seo; Jung, Myung-Geun; Kim, Semi [Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 6, p. 1748 - 1751]
[3]Barker, William T.; Basak, Akash K.; Hendricks, Tyler A.; Jania, Leigh A.; Koller, Beverly H.; Marrujo, Santiana A.; Melander, Christian; Melander, Roberta J.; Nemeth, Ansley M.; O'Connor, Patrick M.; Sullivan, Ashley E.; Weig, Alexander W. [ChemMedChem, 2019]
[4]Lee, Ill-Young; Gruber, Todd D.; Samuels, Amanda; Yun, Minhan; Nam, Bora; Kang, Minseo; Crowley, Kathryn; Winterroth, Benjamin; Boshoff, Helena I.; Barry III, Clifton E. [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 1, p. 114 - 126]
[5]Tian, Maoqun; Abdelrahman, Aliaa; Baqi, Younis; Fuentes, Eduardo; Azazna, Djamil; Spanier, Claudia; Densborn, Sabrina; Hinz, Sonja; Schmid, Ralf; Müller, Christa E. [Journal of Medicinal Chemistry, 2020, vol. 63, # 11, p. 6164 - 6178]

42
[ 2612-02-4 ]
[ 75-03-6 ]
[ 22775-40-2 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile	254.1 Synthesis of 3-{(2S,4S)-4-[4-(5-methoxy-3-benz[d]isoxazolyl)-1-piperazinyl]-2-pyrrolidinylcarbonyl}-1,3,-thiazolidine trihydrochloride (1) 5-Methoxysalicylic acid (41 g) was dissolved in acetonitrile (500 mL), and ethyl iodide (20 mL) and DBU (38 mL) were added thereto. The mixture was refluxed for 6 hr. The reaction mixture was concentrated under reduced pressure, and 1 mol/L hydrochloric acid was added to the residue. 'The mixture was extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogencarbonate solution and brine, dried and concentrated under reduced pressure to give a mixture (44 g) containing ethyl 5-methoxysalicylate as a brown oil.

Reference： [1]Current Patent Assignee: MITSUBISHI CHEMICAL HOLDINGS CORPORATION - EP1308439, 2003, A1

43
[ 2612-02-4 ]
[ 121-50-6 ]
N-[2-Chloro-5-(trifluoromethyl)phenyl]-2-hydroxy-5-methoxybenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56.4%		133 Example 133 Example 133 N-[2-Chloro-5-(trifluoromethyl)phenyl]-2-hydroxy-5-methoxybenzamide (Comopund No. 133). Using 5-methoxysalicylic acid and 2-chloro-5-(trifluoromethyl)aniline as the raw materials, the same operation as the example 16 gave the title compound. Yield: 56.4%. 1H-NMR(DMSO-d6): δ 3.77(3H, s), 6.91(1H, d, J=9.0Hz), 7.07(1H, dd, J=8.7, 3.0Hz), 7.20(1H, t, J=1.8Hz), 7.52-7.54(3H, m), 10.33(1H, s), 11.44(1H, s).

Reference： [1]Current Patent Assignee: INSTITUTE OF MEDICINAL MOLECULAR DESIGN INC - EP1352650, 2003, A1

44
[ 64-17-5 ]
[ 2612-02-4 ]
[ 22775-40-2 ]

Yield	Reaction Conditions	Operation in experiment
	With sulfuric acid for 48h; Heating;
	With sulfuric acid at 80℃;
	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.

	With sulfuric acid for 5h; Reflux;	- General synthetic procedure for the preparation of hydrazides R¹-CO-NHNH₂ General procedure: To a solution of the acid R1-CO2H in EtOH was added concentrated H2SO4 (2 equiv.) and the reaction mixture was refluxed for 5 h. After cooling to room temperature, water was added and the solution was neutralized with Na2CO3. The aqueous phase was extracted twice with EtOAc. The organic phases were combined, dried over MgSO4, filtered and evaporated under vacuum to yield the ethyl ester, which was used without necessity of purification.
	With sulfuric acid for 5h; Reflux;	- General synthetic procedure for the preparation of hydrazides R1-CO-NHNH2 General procedure: To a solution of the acid R1-CO2H in EtOH was added concentrated H2SO4 (2 equiv.) and thereaction mixture was refluxed for 5h. After cooling to room temperature, water was added andthe solution was neutralized with Na2CO3. The aqueous phase was extracted twice with EtOAc.The organic phases were combined, dried over MgSO4, filtered and evaporated under vacuumto yield the ethyl ester, which was used without necessity of purification. The ester was then solubilized in EtOH and treated with hydrazine, hydrate (5 equiv.). Themixture was refluxed overnight and solvents were evaporated. Diethyl ether was added and the formed precipitate was filtered and washed with the same solvent to yield the expectedhydrazide compound as a powder.

Reference： [1]Hadj-esfandiari, Narges; Navidpour, Latifeh; Shadnia, Hooman; Amini, Mohsen; Samadi, Nasrin; Faramarzi, Mohammad Ali; Shafiee, Abbas [Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 22, p. 6354 - 6363]
[2]Begam, Hasina Mamataj; Jana, Ranjan; Manna, Kartic; Samanta, Krishanu [Organic Letters, 2020, vol. 22, # 19, p. 7443 - 7449]
[3]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]
[4]Gavara, Laurent; Legru, Alice; Verdirosa, Federica; Sevaille, Laurent; Nauton, Lionel; Corsica, Giuseppina; Mercuri, Paola Sandra; Sannio, Filomena; Feller, Georges; Coulon, Rémi; De Luca, Filomena; Cerboni, Giulia; Tanfoni, Silvia; Chelini, Giulia; Galleni, Moreno; Docquier, Jean-Denis; Hernandez, Jean-François [Bioorganic Chemistry, 2021, vol. 113]
[5]Legru, Alice; Verdirosa, Federica; Hernandez, Jean-François; Tassone, Giusy; Sannio, Filomena; Benvenuti, Manuela; Conde, Pierre-Alexis; Bossis, Guillaume; Thomas, Caitlyn A.; Crowder, Michael W.; Dillenberger, Melissa; Becker, Katja; Pozzi, Cecilia; Mangani, Stefano; Docquier, Jean-Denis; Gavara, Laurent [European Journal of Medicinal Chemistry, 2021, vol. 226]

45
[ 671207-19-5 ]
[ 2612-02-4 ]
[ 671204-60-7 ]

Yield	Reaction Conditions	Operation in experiment
32%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In tetrahydrofuran at 20℃;

Reference： [1]Location in patent: experimental part Sato, Ippei; Morihira, Koichiro; Inami, Hiroshi; Kubota, Hirokazu; Morokata, Tatsuaki; Suzuki, Keiko; Ohno, Kazuki; Iura, Yosuke; Nitta, Aiko; Imaoka, Takayuki; Takahashi, Toshiya; Takeuchi, Makoto; Ohta, Mitsuaki; Tsukamoto, Shin-ichi [Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 16, p. 5989 - 6002]

46
[ 586-38-9 ]
[ 2612-02-4 ]

Yield	Reaction Conditions	Operation in experiment
73%	With oxygen; potassium acetate; palladium diacetate; p-benzoquinone In N,N-dimethyl acetamide at 115℃; for 15h;
72%	With tert.-butylhydroperoxide; (2S,3S)-N-acetyl-2-amino-3-methylpentanoic acid; potassium acetate; palladium diacetate; p-benzoquinone In 1,2-dimethoxyethane; water at 100℃;
	With oxygen; potassium acetate; palladium diacetate; p-benzoquinone In N,N-dimethyl acetamide at 115℃; for 15h; Schlenk technique; regioselective reaction;	(21) Synthesis of para-Hydroxylated Arenes General procedure: A 50 mL Schlenk-type tube (with a Teflon high-pressure valveand side arm) was charged with m-toluic acid (68.0 mg, 0.50mmol), benzoquinone (54.0 mg, 0.50 mmol), KOAc (98.0 mg,1.00 mmol), Pd(OAc)2 (11.2 mg, 0.050 mmol), and N,N-dimethylacetamide(1.5 mL). The reaction tube was evacuated and backfilledwith O2 (3×, ballon). After the reaction mixture wasstirred at 115 °C for 15 h, it was allowed to cool down to r.t. Thereaction mixture was diluted with EtOAc (10 mL) and then filteredthrough a pad of Celite. The filtrate was concentrated invacuo to yield crude 2-hydroxylbenzoic acid. A mixture of thecrude product, Cu2O (3.6 mg, 0.025 mmol), and 1,10-phenanthroline(9.0 mg, 0.050 mmol) in a solution of NMP (1.5 mL) andquinoline (0.5 mL) was heated under an atmosphere of N2 at220 °C for 12 h. The reaction mixture was quenched by additionof 0.2 M aq HCl (10 mL), diluted with EtOAc (10 mL), and thenfiltered through a pad of Celite. The filtrate was washed withbrine (10 mL), dried over Na2SO4, and concentrated in vacuo.The residue was purified by silica gel preparative TLC to give pcresol.

Reference： [1]Zhang, Yang-Hui; Yu, Jin-Quan [Journal of the American Chemical Society, 2009, vol. 131, # 41, p. 14654 - 14655]
[2]Luo, Feihua; He, Shuhua; Gou, Quan; Chen, Jinyang; Zhang, mingzhong [Tetrahedron Letters, 2021, vol. 84]
[3]Pan, Shulei; Zhou, Bo; Zhang, Yanghui; Shao, Changdong; Shi, Guangfa [Synlett, 2016, vol. 27, # 2, p. 277 - 281]

47
[ 2612-02-4 ]
[ 33513-42-7 ]
2-hydroxy-5-methoxy-N,N-dimethylbenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With phosphorus pentoxide at 160℃; for 48h;

Reference： [1]Location in patent: experimental part Mavel, Sylvie; Meheux, Nathalie; Guilloteau, Denis; Emond, Patrick [Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 1, p. 236 - 241]

48
[ 2612-02-4 ]
[ 74-88-4 ]
[ 2150-40-5 ]

Yield	Reaction Conditions	Operation in experiment
87%	Stage #1: 5-methoxysalicylic acid With potassium carbonate In N,N-dimethyl-formamide at 0℃; for 0.166667h; Stage #2: methyl iodide In N,N-dimethyl-formamide at 0 - 20℃; for 6h;	2. Experimental procedure for the preparation of methyl 2,5-dimethoxybenzoate (2) To a stirred solution of 2-hydroxy-5-methoxybenzoic acid (59.5 mmol, 10.0 g) in DMF, K2CO3 (178.5 mmol, 24.6 g) was added at 0 °C and stirred for 10 min. Then MeI (238.0 mmol, 15.3 mL) was added at 0 °C. The reaction mixture was stirred at room temperature for 6 h. TLC analysis (30% EA/ petether) showed completion of the reaction. The RM was quenched with water, extracted with EtOAc thrice. The combined organic layer was dried over Na2SO4 and concentrated in vacuum to give the compound 2 (10.1 g, 87%) as light brown liquid. 1H NMR (400 MHz, CDCl3): δ 7.33 (d, 1H, J = 3.2 Hz), 7.03 (dd, 1H, J = 3.2 Hz), 6.92 (d, 1H , J = 8.8 Hz), 3.89 (s, 3H), 3.86 (s, 3H), 3.79 (s, 3H); LC-MS m/z 197.2 (M+H+); Purity: 98.38%.
	With potassium carbonate In acetone at 20℃; Reflux; Darkness;

Reference： [1]Aitha, Anjaiah; Yennam, Satyanarayana; Behera, Manoranjan; Anireddy, Jaya Shree [Tetrahedron Letters, 2016, vol. 57, # 13, p. 1507 - 1510]
[2]Location in patent: experimental part Jiang, Qian-Qian; Darhkijav, Burenkhangai; Liu, Hao; Wang, Fang; Li, Zhao; Jiang, Yun-Bao [Chemistry - An Asian Journal, 2010, vol. 5, # 3, p. 543 - 549]

49
[ 2612-02-4 ]
[ 1381883-25-5 ]
[ 1402058-22-3 ]

Yield	Reaction Conditions	Operation in experiment
79%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane Reflux;	(5-(4-(Benzyloxy)phenyl)-3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazol -1-yl)(2-hydroxy-5-methoxyphenyl)methanone (13) General procedure: A stirred solution of pyrazoline derivatives 5-8 (1.0 mmol, 1 equiv) in CH2Cl2 (10 mL) was treated with equimolar quantities of substituted salicylic acid; EDC.HCl (1.2 mmol, 1.2 equiv) and HOBt (1.2 mmol, 1.2 equiv) were added. The mixture was refluxed overnight. The product was collected by filtration, and the crude residue was purified by recrystallization from ethanol. After completion of the reaction, if the solid was not formed, the mixture was evaporated under reduced pressure to give a residue. The residue was purified by silica gel chromatography (PE/EtOAc=4:1) to afford pure compounds.

Reference： [1]Li, Qing-Shan; Zhang, Yan-Bin; Dong, Jing-Jun; Zhou, Wen-Ping; Yang, Yang; Zhu, Hai-Liang; Lv, Xian-Hai [Bioorganic and medicinal chemistry letters, 2012, vol. 22, # 21, p. 6596 - 6601,6]

50
[ 2612-02-4 ]
[ 76973-45-0 ]
[ 1402058-32-5 ]

Yield	Reaction Conditions	Operation in experiment
69%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane Reflux;	3,5-Bis(4-methoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl)(2-hydroxy-5-methoxyphenyl)methanone (18) General procedure: A stirred solution of pyrazoline derivatives 5-8 (1.0 mmol, 1 equiv) in CH2Cl2 (10 mL) was treated with equimolar quantities of substituted salicylic acid; EDC.HCl (1.2 mmol, 1.2 equiv) and HOBt (1.2 mmol, 1.2 equiv) were added. The mixture was refluxed overnight. The product was collected by filtration, and the crude residue was purified by recrystallization from ethanol. After completion of the reaction, if the solid was not formed, the mixture was evaporated under reduced pressure to give a residue. The residue was purified by silica gel chromatography (PE/EtOAc=4:1) to afford pure compounds.

51
[ 2612-02-4 ]
[ 75745-48-1 ]
[ 1402058-54-1 ]

Yield	Reaction Conditions	Operation in experiment
87%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane Reflux;	(5-(4-Chlorophenyl)-3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl) (2-hydroxy-5-methoxyphenyl)methanone (28) General procedure: A stirred solution of pyrazoline derivatives 5-8 (1.0 mmol, 1 equiv) in CH2Cl2 (10 mL) was treated with equimolar quantities of substituted salicylic acid; EDC.HCl (1.2 mmol, 1.2 equiv) and HOBt (1.2 mmol, 1.2 equiv) were added. The mixture was refluxed overnight. The product was collected by filtration, and the crude residue was purified by recrystallization from ethanol. After completion of the reaction, if the solid was not formed, the mixture was evaporated under reduced pressure to give a residue. The residue was purified by silica gel chromatography (PE/EtOAc=4:1) to afford pure compounds.

52
[ 2612-02-4 ]
[ 202827-81-4 ]
[ 1402058-42-7 ]

Yield	Reaction Conditions	Operation in experiment
64%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane Reflux;	(5-(4-Bromophenyl)-3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazol-1yl) (2-hydroxy-5-methoxyphenyl)methanone (23) General procedure: A stirred solution of pyrazoline derivatives 5-8 (1.0 mmol, 1 equiv) in CH2Cl2 (10 mL) was treated with equimolar quantities of substituted salicylic acid; EDC.HCl (1.2 mmol, 1.2 equiv) and HOBt (1.2 mmol, 1.2 equiv) were added. The mixture was refluxed overnight. The product was collected by filtration, and the crude residue was purified by recrystallization from ethanol. After completion of the reaction, if the solid was not formed, the mixture was evaporated under reduced pressure to give a residue. The residue was purified by silica gel chromatography (PE/EtOAc=4:1) to afford pure compounds.

53
[ 2612-02-4 ]
[ 108-46-3 ]
[ 5042-05-7 ]
[ 1605285-02-6 ]

Yield	Reaction Conditions	Operation in experiment
1: 70% 2: 20%	With phosphotungstic acid for 0.0666667h; Microwave irradiation; Green chemistry; regioselective reaction;	General Procedure for the Preparation of Xanthone and Thioxanthone Derivatives General procedure: To a mixture of phenols derivatives (1 mmol) and salicylic acid/ thiosalicilic acid derivatives (1 mmol) were added heteropoly acid (0.05 mmol). The homogenized mixture was placed in vessel microwave and was irradiated in the microwave oven within 4 min. The reaction mixture was allowed to cool, poured into ethyl acetate and extracted with a sat. aq solution of NaHCO3 (3*15 ml). The organic layer was dried over Na2SO4 and evaporated in vacuum to give an impure residue. Chromatography of the crude products was performed on a column of silica gel eluted with n-hexane/EtOAc, to give pure crystalline products. The products were characterized by comparison of their NMR, IR, MS. The spectral data is given below.

Reference： [1]Nasseri, Mohammad A.; Alizadeh, Somayyeh; Zakerinasb, Batol; Beni, Alireza Salimi [Letters in Organic Chemistry, 2014, vol. 11, # 5, p. 338 - 344]

54
[ 504-15-4 ]
[ 2612-02-4 ]
[ 108012-07-3 ]
1,8-dihydroxy-5-methoxy-3-methyl-9H-xanthen-9-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1: 65% 2: 25%	With phosphotungstic acid for 0.0666667h; Microwave irradiation; Green chemistry; regioselective reaction;	General Procedure for the Preparation of Xanthone and Thioxanthone Derivatives General procedure: To a mixture of phenols derivatives (1 mmol) and salicylic acid/ thiosalicilic acid derivatives (1 mmol) were added heteropoly acid (0.05 mmol). The homogenized mixture was placed in vessel microwave and was irradiated in the microwave oven within 4 min. The reaction mixture was allowed to cool, poured into ethyl acetate and extracted with a sat. aq solution of NaHCO3 (3*15 ml). The organic layer was dried over Na2SO4 and evaporated in vacuum to give an impure residue. Chromatography of the crude products was performed on a column of silica gel eluted with n-hexane/EtOAc, to give pure crystalline products. The products were characterized by comparison of their NMR, IR, MS. The spectral data is given below.

Reference： [1]Nasseri, Mohammad A.; Alizadeh, Somayyeh; Zakerinasb, Batol; Beni, Alireza Salimi [Letters in Organic Chemistry, 2014, vol. 11, # 5, p. 338 - 344]

55
[ 75-09-2 ]
[ 2612-02-4 ]
[ 1591954-13-0 ]

Yield	Reaction Conditions	Operation in experiment
95%	With potassium phosphate tribasic trihydrate In N,N-dimethyl-formamide at 100℃; for 6h; Green chemistry;

Reference： [1]Lin, Feng; Song, Qiuling; Gao, Yuyu; Cui, Xiuling [RSC Advances, 2014, vol. 4, # 38, p. 19856 - 19860]

56
[ 75-34-3 ]
[ 2612-02-4 ]
[ 1591954-32-3 ]

Yield	Reaction Conditions	Operation in experiment
51%	With potassium phosphate tribasic trihydrate In N,N-dimethyl-formamide at 130℃; for 10h; Green chemistry;

Reference： [1]Lin, Feng; Song, Qiuling; Gao, Yuyu; Cui, Xiuling [RSC Advances, 2014, vol. 4, # 38, p. 19856 - 19860]

57
[ 2612-02-4 ]
[ 5468-37-1 ]
2-hydroxy-5-methoxy-N-(2-oxo-2-phenyl-ethyl)-benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	Stage #1: 5-methoxysalicylic acid With thionyl chloride; N,N-dimethyl-formamide In dichloromethane for 3h; Reflux; Stage #2: 2-aminoacetophenone hydrochloride With sodium hydrogencarbonate In dichloromethane; water at 20℃; for 2h; Cooling with ice;

Reference： [1]Xu, Wei; Nachtsheim, Boris J. [Organic Letters, 2015, vol. 17, # 6, p. 1585 - 1588]

58
[ 2612-02-4 ]
[ 3883-94-1 ]
2-hydroxy-5-methoxy-N-[2-(4-methoxy-phenyl)-2-oxo-ethyl]-benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%	Stage #1: 5-methoxysalicylic acid With thionyl chloride; N,N-dimethyl-formamide In dichloromethane for 3h; Reflux; Stage #2: 2-amino-4'-methoxyacetophenone hydrochloride With sodium hydrogencarbonate In dichloromethane; water at 20℃; for 2h; Cooling with ice;

Reference： [1]Xu, Wei; Nachtsheim, Boris J. [Organic Letters, 2015, vol. 17, # 6, p. 1585 - 1588]

59
[ 2612-02-4 ]
[ 1416767-53-7 ]
6,6-dibenzyl-2-methoxy-6,7,8,9-tetrahydro-5aH,11H-pyrido[2,1-b][1,3] benzoxazin-11-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; N-ethyl-N,N-diisopropylamine In toluene at 90℃; for 20h;	General procedure for the DIA reaction General procedure: To a solution of imine (1 mmol) and acid (1.2 mmol) in drytoluene (10 mL) was added sequentially DIPEA (1.85 mmol) andthen T3P (1.5 mmol, 50% in THF). The resulting solution was heatedat 90°C or 120°C in a sealable tube for the specified time, before cooling to RT and pouring into satd aq NaHCO3 (20 mL). The aqueous layer was extracted with DCM (330 mL), concentrated in vacuo and purified by column chromatography.

Reference： [1]Kitsiou, Christiana; Unsworth, William P.; Coulthard, Graeme; Taylor, Richard J.K. [Tetrahedron, 2014, vol. 70, # 40, p. 7172 - 7180]

60
[ 2612-02-4 ]
[ 150-76-5 ]

Yield	Reaction Conditions	Operation in experiment
	With quinoline; copper(I) oxide; 1,10-Phenanthroline In 1-methyl-pyrrolidin-2-one at 220℃; for 12h; Schlenk technique; Inert atmosphere;	(21) Synthesis of para-Hydroxylated Arenes General procedure: A 50 mL Schlenk-type tube (with a Teflon high-pressure valveand side arm) was charged with m-toluic acid (68.0 mg, 0.50mmol), benzoquinone (54.0 mg, 0.50 mmol), KOAc (98.0 mg,1.00 mmol), Pd(OAc)2 (11.2 mg, 0.050 mmol), and N,N-dimethylacetamide(1.5 mL). The reaction tube was evacuated and backfilledwith O2 (3×, ballon). After the reaction mixture wasstirred at 115 °C for 15 h, it was allowed to cool down to r.t. Thereaction mixture was diluted with EtOAc (10 mL) and then filteredthrough a pad of Celite. The filtrate was concentrated invacuo to yield crude 2-hydroxylbenzoic acid. A mixture of thecrude product, Cu2O (3.6 mg, 0.025 mmol), and 1,10-phenanthroline(9.0 mg, 0.050 mmol) in a solution of NMP (1.5 mL) andquinoline (0.5 mL) was heated under an atmosphere of N2 at220 °C for 12 h. The reaction mixture was quenched by additionof 0.2 M aq HCl (10 mL), diluted with EtOAc (10 mL), and thenfiltered through a pad of Celite. The filtrate was washed withbrine (10 mL), dried over Na2SO4, and concentrated in vacuo.The residue was purified by silica gel preparative TLC to give pcresol.1H NMR (400 MHz, CDCl3): δ = 7.05 (d, J = 8.3 Hz, 2 H),6.75 (d, J = 8.3 Hz, 2 H), 4.95 (br, 1 H), 2.29 (s, 3 H). 13C NMR (100MHz, CDCl3): δ = 153.18, 130.03, 129.92, 115.06, 20.43. HRMS(ESI-TOF): m/z calcd for C7H9O+: 109.0648 [M + H]+; found:109.0657.

Reference： [1]Pan, Shulei; Zhou, Bo; Zhang, Yanghui; Shao, Changdong; Shi, Guangfa [Synlett, 2016, vol. 27, # 2, p. 277 - 281]

61
[ 2612-02-4 ]
4-(1,3-benzothiazol-2-yl)benzohydrazide [ No CAS ]
2-(5-(4-(benzo[d]thiazol-2-yl)phenyl)-1,3,4-oxadiazol-2-yl)-4-methoxyphenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85.1%	With trichlorophosphate at 120℃;

Reference： [1]Taha, Muhammad; Ismail, Nor Hadiani; Imran, Syahrul; Selvaraj, Manikandan; Rahim, Fazal [RSC Advances, 2016, vol. 6, # 4, p. 3003 - 3012]

62
[ 108-86-1 ]
[ 2612-02-4 ]
[ 936716-83-5 ]

Yield	Reaction Conditions	Operation in experiment
58%	Stage #1: bromobenzene With magnesium In diethyl ether for 2.2h; Inert atmosphere; Reflux; Stage #2: 5-methoxysalicylic acid In diethyl ether at 20℃; Inert atmosphere;	3.c Synthesis of 2-(hydroxydiphenylmethyl)-4-methoxyphenol Synthesis of 2-(hydroxydiphenylmethyl)-4-methoxyphenol A solution of bromobenzene (23.55 g, 150 mmol) in ether (70 mL) was added dropwise during 1.2 h to a suspension of magnesium turnings (4.37 g, 180 mmol) in ether (5 mL). The reaction mixture was heated under reflux for 1 h. After cooling to room temperature, 5-methoxysalicylic acid (3.03 g, 18 mmol) in ether (70 mL) was added dropwise during 45 min, and the reaction mixture was left stirring at room temperature overnight. The reaction mixture was decanted and cooled on an ice -bath, before HCl (10%) was added. Extraction with ether (2x), washing with water (2x) and drying (Na2S04) afforded the crude product. Filtration and washing with cold ethyl acetate and re-crystallizing the filtrate finally gave 3.17 g (58%) of the target compound. 1H-NMR: 7.60 (s, 1 H), 7.35-7.28 (m, 6 H), 7.23-7.18 (m, 4 H), 6.79 (d, 1 H), 6.74 (dd, 1 H), 6.10 (d, 1 H), 3.86 (s, 1 H), 3.58 (s, 3 H). 13C-NMR: 152.14, 149.73, 144.73, 131.17, 128.17, 127.92, 127.73, 117.89, 116.57, 113.78, 84.11, 55.58.
46%	Stage #1: bromobenzene With iodine; magnesium In diethyl ether for 1h; Reflux; Inert atmosphere; Stage #2: 5-methoxysalicylic acid In diethyl ether at 20℃; Inert atmosphere;

Reference： [1]Current Patent Assignee: Firmenich International SA - WO2016/116420, 2016, A1 Location in patent: Page/Page column 26
[2]Trachsel, Alain; Buchs, Barbara; Herrmann, Andreas [Photochemical and Photobiological Sciences, 2016, vol. 15, # 9, p. 1183 - 1203]

63
[ 4383-22-6 ]
[ 2612-02-4 ]
C₁₈H₁₉NO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; Inert atmosphere;	General procedure for peptidic coupling of anthranilic and salicylic acid derivatives : General procedure: In a round bottom flask, 1.0 equiv. of allyl benzylamine was placed in DCM (C = 0.067mol/L) under argon. Then 1.2 equiv. of the desired tosyl/boc anthranilic acid or salicylic acid were added, followed successively by 1.2 equiv. of EDC.HCl and 1.2 equiv. of HOBt. The clear solution was stirred at room temperature or reflux until starting material was totally consumed (monitored by TLC). The reaction mixture was then quenched with water. The aqueous layer was extracted with DCM (3 times). The combined organic phases were then dried with MgSO4, filtrated and the solvent was removed under vacuum. The crude residue was purified by silica gel flash chromatography using pentane/Et2O as eluent (9:1 to 1:1).

Reference： [1]Manick, Anne-Doriane; Berhal, Farouk; Prestat, Guillaume [Synthesis, 2016, vol. 48, # 21, p. 3719 - 3729]

64
[ 42974-19-6 ]
[ 2612-02-4 ]
2-(5-(benzofuran-2-yl)-1,3,4-oxadiazol-2-yl)-4-methoxyphenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With trichlorophosphate Reflux;	4.2. General procedure for the synthesis of compounds 1-20 General procedure: A mixture of 6-nitrobenzofuran-2-carbohydrazide (0.5 mmol)and various aromatic acid (0.5 mmol) in POCl3 (5 ml) was refluxedfor 6-10 h. The mixture was cooled and poured onto crushed ice. Itwas neutralized with NaHCO3 solution and the resulting solid massprecipitated out was filtered, dried, and crystallized.

Reference： [1]Taha, Muhammad; Ismail, Nor Hadiani; Imran, Syahrul; Wadood, Abdul; Rahim, Fazal; Saad, Syed Muhammad; Khan, Khalid Mohammed; Nasir, Abdul [Bioorganic Chemistry, 2016, vol. 66, p. 117 - 123]

65
iron(II) perchlorate hexahydrate [ No CAS ]
potassium hydridotris(3,5-diphenylpyrazol-1-yl)borate [ No CAS ]
[ 2612-02-4 ]
(hydrotris(3,5-diphenylpyrazole-1-yl)borate)FeII(5-methoxysalicylate) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%	With triethylamine In methanol at 20℃; for 4h;

Reference： [1]Rahaman, Rubina; Chakraborty, Biswarup; Paine, Tapan Kanti [Angewandte Chemie - International Edition, 2016, vol. 55, # 44, p. 13838 - 13842][Angew. Chem., 2016, vol. 128, p. 14042 - 14046]

66
[ 2612-02-4 ]
C₁₂H₁₂N₂O [ No CAS ]
2-hydroxy-5-methoxy-N-(6-oxo-5-(m-tolyl)-1,6-dihydropyridin-3-yl) benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 5-methoxysalicylic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 0.166667h; Stage #2: C₁₂H₁₂N₂O With triethylamine In dimethyl sulfoxide at 100℃;	4.1.4 General procedure for preparation of compounds 8a-8z General procedure: To the mixture solution of 2-hydroxybenzoic acid (141mg, 1.02mmol) in DMF(10mL)were added with EDC (254mg, 1.32mmol) and HOBt (179mg, 1.32mmol). After the reaction mixture was stirred at room temperature for 10min, 5-amino-3-(4-methoxyphenyl)pyridin-2(1H)-one (7a, 220mg, 1.02mmol) and triethylamine (514mg, 5.09mmol) were added slowly, which was stirred under 100°C overnight. Upon completion of the reaction, the reaction mixture was treated with water (60mL) and extracted with ethyl acetate (40mL×3). The organic layer was washed with salt solution (40mL), dried over anhydrous sodium sulfate, and then the solvent was removed under vacuum. The residue was chromatographed on silica gel using DCM and methanol. Pure fractions were collected and concentrated, giving the desired compounds 8a-8z in good yield.

Reference： [1]Jia, Haiyong; Song, Yang; Yu, Ji; Zhan, Peng; Rai, Diwakar; Liang, Xiaohong; Ma, Chunhong; Liu, Xinyong [European Journal of Medicinal Chemistry, 2017, vol. 136, p. 144 - 153]

67
[ 2612-02-4 ]
C₁₃H₁₄N₂O₂ [ No CAS ]
N-(5-(4-ethoxyphenyl)-6-oxo-1,6-dihydropyridin-3-yl)-2-hydroxy-5-methoxybenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 5-methoxysalicylic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 0.166667h; Stage #2: C₁₃H₁₄N₂O₂ With triethylamine In dimethyl sulfoxide at 100℃;	4.1.4 General procedure for preparation of compounds 8a-8z General procedure: To the mixture solution of 2-hydroxybenzoic acid (141mg, 1.02mmol) in DMF(10mL)were added with EDC (254mg, 1.32mmol) and HOBt (179mg, 1.32mmol). After the reaction mixture was stirred at room temperature for 10min, 5-amino-3-(4-methoxyphenyl)pyridin-2(1H)-one (7a, 220mg, 1.02mmol) and triethylamine (514mg, 5.09mmol) were added slowly, which was stirred under 100°C overnight. Upon completion of the reaction, the reaction mixture was treated with water (60mL) and extracted with ethyl acetate (40mL×3). The organic layer was washed with salt solution (40mL), dried over anhydrous sodium sulfate, and then the solvent was removed under vacuum. The residue was chromatographed on silica gel using DCM and methanol. Pure fractions were collected and concentrated, giving the desired compounds 8a-8z in good yield.

Reference： [1]Jia, Haiyong; Song, Yang; Yu, Ji; Zhan, Peng; Rai, Diwakar; Liang, Xiaohong; Ma, Chunhong; Liu, Xinyong [European Journal of Medicinal Chemistry, 2017, vol. 136, p. 144 - 153]

68
[ 462-08-8 ]
[ 2612-02-4 ]
C₁₃H₁₂N₂O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide	4 Procedures for Preparation of Intermediates 12 General procedure: To a solution of 5-bromo-2-hydroxybenzoic acid (2 g, 9.22 mmol) in DMF (15 mL) was addedDIPEA (3.22 mL, 18.43 mmol), 3-aminopyridine (1.128 g, 11.98 mmol), HOBT (1.694 g, 11.06mmol) and EDC (3.53 g, 18.43mmol). The reaction was stirred overnight, water was added andthe solid was filtered to give the title compound 12 (346 mg, 12% yield).

69
[ 51-17-2 ]
[ 2612-02-4 ]
2-methoxy-12H-benzo[e]benzo[4,5]imidazo[2,1-b][1,3]oxazine-12-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62%	With pyridine; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; copper(I) bromide In para-xylene at 120℃; for 36h; Schlenk technique; Green chemistry;	17 Example 17, Prepartion of 2-Methoxy-12H-benzo[e]benzo[4,5]imidazo[2,1-b][1,3]oxazine-12-one (Compound III-16) CuBr 6 mg (0.04 mmol), TEMPO 5 mg (0.03 mmol), compounded in a 25 mL Schlenk reaction tubeBenzimidazole 47 mg (0.4 mmol),5-methoxysalicylic acid 34 mg (0.2 mmol), p-xylene (0.5 mL), and then pyridine 33 μL (0.4 mmol) were added and the temperature was controlled at 120°C. The reaction was stirred and refluxed for 36 hours.Cool to room temperature, transfer all to a 25 mL flask, spin off the solvent on a rotary evaporator, add an appropriate amount of silica gel, spin dry, and then use a 300-400 mesh silica gel column. The developing solvent used is petroleum ether:ethyl acetate=16: 1 to 6:1, namely compound III-16 33mg, yield 62%; white solid

Reference： [1]Current Patent Assignee: SOUTHWEST UNIVERSITY - CN107955020, 2018, A Location in patent: Paragraph 0084; 0085; 0086

70
[ 2612-02-4 ]
4-(bis(5-chloro-1H-indol-3-yl)methyl)benzohydrazide [ No CAS ]
2-(5-(4-(bis(5-chloro-1H-indol-3-yl)methyl)phenyl)-1,3,4-oxadiazol-2-yl)-4-methoxyphenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With trichlorophosphate	8 General procedure for the synthesis of bis-indole linked 1,3,4-oxadiazole derivatives (7-31) General procedure: A mixture of 4-(bis(5-chloro-1H-indol-3-yl)methyl)benzohydrazide (II) (0.5mmol) and various aromatic acid (0.5mmol) in POCl3 (5mL) was refluxed for 4-6h. The mixture was cooled and poured onto crushed ice. It was neutralized with NaHCO3 solution and the resulting solid mass precipitated out was filtered, dried, and crystallized in methanol.

Reference： [1]Taha, Muhammad; Rashid, Umer; Imran, Syahrul; Ali, Muhammad [Bioorganic and Medicinal Chemistry, 2018, vol. 26, # 12, p. 3654 - 3663]

71
[ 2612-02-4 ]
[ 2136-75-6 ]
[ 1252024-59-1 ]

Yield	Reaction Conditions	Operation in experiment
	In toluene at 60℃; for 8h; Inert atmosphere;	General procedures for the preparation of 15a-h. General procedure: A mixture of a corresponding aldehyde (1.0 mmol) with(Triphenylphosphoranylidene)acetaldehyde (365 mg, 1.2 mmol) in anhydrous toluene(2.0 mL) was stirred at 60° C under nitrogen for 8 h. The crude product was directlypurified by flash chromatography on silica gel column to provide the compounds 15ah(55-79%).

Reference： [1]Lu, Shan; Obianom, Obinna N.; Ai, Yong [Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 17, p. 2869 - 2874]

72
[ 58-08-2 ]
[ 2612-02-4 ]
[ 142-71-2 ]
[Cu(5-methoxysalicylate)₂(H₂O)₂]*2(caffeine) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In water at 20℃;	2.4.3. Compound 4 Light-blue crystals were obtained water - ethanol mixture solvent in ratio 1:1. Caffeine (0.5mmol) was added to aqua solution of copper acetate (0.5mmol). Appropriate 5-methoxysalicylic acid (1mmol) was added to reaction mixture under stiring. After few hours stirring the solution was left for crystallization. The crystals were separated after two weeks which were dried at laboratory temperature and were suitable for X-ray structure determination. [Cu(5-MeOSal)2(H2O)2]·2caf (4) Anal Calc: C, 46.74; H, 4.65; N, 13.64. Found: C, 46.81; H, 4.69; N, 13.14%. IR (ATR, cm-1): 3221(w), 3129(w), 3114 (w), 1691(s), 1644(s), 1601(m), 1549(m), 1502(m), 1457(m), 1421(s), 1391(m), 1368(m), 1300(m), 1238(m), 1205(mw), 1023(ms), 979(mw), 743(s), 605(ms), 449(m). UV-Vis (solid phase, λ/nm): 642.

Reference： [1]Puchoňová, Miroslava; Matejová, Simona; Švorec, Jozef; Mazúr, Milan; Jorík, Vladimír; Moncoľ, Ján; Valigura, Dušan [Inorganica Chimica Acta, 2019, vol. 486, p. 324 - 331]

73
[ 2612-02-4 ]
bis(tert-butoxycarbonylmethyl)-Lys-bis(tert-butoxycarbonylmethyl)-Lys(Dde)-O-2-chloro trityl resin [ No CAS ]
C₂₈H₄₀N₄O₁₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85 mg	Stage #1: bis(tert-butoxycarbonylmethyl)-Lys-bis(tert-butoxycarbonylmethyl)-Lys(Dde)-O-2-chloro trityl resin With N-ethyl-N,N-diisopropylamine; hydrazine In N,N-dimethyl-formamide at 20℃; for 0.166667h; Stage #2: 5-methoxysalicylic acid With benzotriazol-1-ol; diisopropyl-carbodiimide In N,N-dimethyl-formamide at 20℃; Stage #3: With chlorotriisopropylsilane; trifluoroacetic acid In water at 20℃; for 3h;	1-4; 4 Compound 1c and 700 ml of 2% hydrazine in DMF were placed in an 800 ml reaction vessel and reacted at room temperature for 5 minutes. The reaction solution was removed by filtration, and the synthesized resin was washed with 500 ml of DMF. Then, 700 ml of 10% DIPEA in DMF was added thereto and reacted at room temperature for 5 minutes. The reaction solution was removed by filtration, and the synthesized resin was sequentially washed with 500 ml each of DCM, MeOH, DCM and DMF. And dried in vacuo to obtain 30 g of compound 1d (tert-butoxycarbonylmethyl) 2-Lys (tert-butoxycarbonylmethyl) 2-Lys (NH2) -O-2-chloro trityl resin in 99% yield. To a reaction vessel of 10 ml, 1d (460 mg, 1 equivalent) 5-Methoxysalicylic acid (269 mg, 8 eq.), DIC (248 ul, 8 eq.) And HOBt (216 mg, 8 eq.) Were dissolved in 5 ml of DMF and reacted at room temperature for 2 hours. The reaction solution was removed by filtration, and the synthesized resin was sequentially washed with 5 ml each of DCM, MeOH and DCM. After vacuum drying, 5 ml of cleavage cocktail (trifluoroacetic acid: triisopropylsilane: DW = 95: 2.5: 2.5) was added and reacted at room temperature for 3 hours. The reaction solution was collected by filtration, and 45 ml of diethyl ether was added thereto to precipitate the product. The solid product was collected using a centrifuge and washed twice with 45 ml of diethyl ether. The obtained solid product was purified by Prep-HPLC (column C18, 10um, 250mm X 22mm) and then lyophilized to obtain 85mg of compound 4 (molecular weight measured by LC Mass: 656.64) in 65% yield.

Reference： [1]Current Patent Assignee: INCOSPHARM CORP - KR2018/117869, 2018, A Location in patent: Paragraph 0106-0108; 0122-0124

74
[ 2612-02-4 ]
4-(6-chlorobenzo[d]thiazol-2-yl)benzo hydrazide [ No CAS ]
2-(5-(4-(6-chlorobenzo[d]thiazol-2-yl)phenyl)-1,3,4-oxadiazol-2-yl)-4-methoxyphenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With trichlorophosphate Reflux;	10 2.2. General procedure General procedure: Methyl 4-formylbenzoate (41 mmol) and sodium metabisulfite(41 mmol) was mixed in methanol and refluxed for 6 h at room temperatureto give us sodium hydroxy (4-(methoxycarbonyl)phenyl) methanesulfonate intermediate (I). Then reaction mixture was poured intoice water and the solid product was filtered. The progress of reactioncompletion was checked by TLC. Compound (I) was then reacted with2-amino-5-chlorobenzothiol in DMF (40 mL) and refluxed for 12 h togive us methyl 4-(6-chlorobenzo[d]thiazol-2-yl) benzoate (II) whichwas further mixed with hydrazine hydrate in methanol to form 4-(6-chlorobenzo[d]thiazol-2-yl)benzo hydrazide (III). Compound (III) wasthen reacted with different substituted aromatic carboxylic acids inPOCl3 to give us the desired benzothiazole based oxadiazole derivatives1-23 in good yields. The synthetic compounds were fully characterizedby spectroscopy methods including 1H NMR, 13C NMR, HREI-MS.

Reference： [1]Gollapalli, Mohammed; Taha, Muhammad; Javid, Muhammad Tariq; Almandil, Noor Barak; Rahim, Fazal; Wadood, Abdul; Mosaddik, Ashik; Ibrahim, Mohamed; Alqahtani, Mohammed A.; Bamarouf, Yasser A. [Bioorganic Chemistry, 2019, vol. 85, p. 33 - 48]

75
[ 2612-02-4 ]
[ 2905-83-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: sulfuric acid / 24 h / Reflux 2: hydrazine / 80 - 90 °C
	Multi-step reaction with 2 steps 1: sulfuric acid / Reflux 2: hydrazine hydrate / neat (no solvent) / 120 °C / Sealed tube
	Multi-step reaction with 2 steps 1: sulfuric acid / 5 h / Reflux 2: hydrazine hydrate / ethanol / 100 °C / Sealed tube

Multi-step reaction with 2 steps 1: sulfuric acid / 5 h / Reflux 2: hydrazine hydrate / ethanol / 100 °C / Sealed tube

Reference： [1]Jesumoroti, Omobolanle J.; Faridoon; Mnkandhla, Dumisani; Isaacs, Michelle; Hoppe, Heinrich C.; Klein, Rosalyn [MedChemComm, 2019, vol. 10, # 1, p. 80 - 88]
[2]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]
[3]Gavara, Laurent; Legru, Alice; Verdirosa, Federica; Sevaille, Laurent; Nauton, Lionel; Corsica, Giuseppina; Mercuri, Paola Sandra; Sannio, Filomena; Feller, Georges; Coulon, Rémi; De Luca, Filomena; Cerboni, Giulia; Tanfoni, Silvia; Chelini, Giulia; Galleni, Moreno; Docquier, Jean-Denis; Hernandez, Jean-François [Bioorganic Chemistry, 2021, vol. 113]
[4]Legru, Alice; Verdirosa, Federica; Hernandez, Jean-François; Tassone, Giusy; Sannio, Filomena; Benvenuti, Manuela; Conde, Pierre-Alexis; Bossis, Guillaume; Thomas, Caitlyn A.; Crowder, Michael W.; Dillenberger, Melissa; Becker, Katja; Pozzi, Cecilia; Mangani, Stefano; Docquier, Jean-Denis; Gavara, Laurent [European Journal of Medicinal Chemistry, 2021, vol. 226]

76
[ 2612-02-4 ]
[ 33640-67-4 ]
(2S,3R)-benzyl 3-hydroxy-2-(2-hydroxy-5-methoxybenzamido)butanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 4-methyl-morpholine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 25℃; for 6h; Sonication;	2.2.1. General procedure for the synthesis of (2S,3R)-benzyl 3-hydroxy-2-(2-hydroxybenzamido)butanoate derivates (3a-d) General procedure: 2-hydroxybenzoic acid derivatives (1a-d) (1 mmol, 1 equiv) and benzyl threonine (1 mmol, 1 equiv), EDC·HCl (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (1.3 mmol, 1.3 equiv), 1-HOBt (1-hydroxybenzotriazole)(1.2 mmol, 1.2 equiv), N-methylmorpholine(1.5 mmol, 1.5 equiv) were dissolved in 5 mL of CH2Cl2. The reaction mixture was stirred for the required time at room temperature in ultrasonic bath. The completion of the reaction was monitored by thin layer chromatography (TLC). Then the reaction mixture was diluted with ethyl acetate and washed with saturated solution of NH4Cl(3×20 mL), the organic phase was collected, dried over MgSO4, filteredand the solvent was removed under vacuum. The crude residue was purified by flash chromatography on silica gel (eluting with ethyl acetate/hexane 3:7).2.2.2. (2S,3R)-benzyl 3-hydroxy-2-(2-hydroxybenzamido)butanoate (3a)

Reference： [1]Santos, Fabiano S.; Zanotto, Gabriel M.; Argomedo, Luis M.Z.; Darbem, Mariana P.; Gonçalves, Paulo F.B.; Stefani, Helio A.; Rodembusch, Fabiano S. [Dyes and Pigments, 2019, vol. 165, p. 372 - 382]

77
2-(1H-indol-2-yl)acetohydrazide [ No CAS ]
[ 2612-02-4 ]
2-(5-((1H-indol-2-yl)methyl)-1,3,4-oxadiazol-2-yl)-4-methoxyphenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With trichlorophosphate	3.4. General Procedure Indole Based 2,5-Disubstituted-1,3,4-Oxadiazoles (1-22) General procedure: A combination of methyl 2-(1H-indol-2-yl) acetohydrazide (0.3 mmol) and several aromatic acid(0.33 mmol) in POCl3 (7 mL) was reacted for 4-6 h. The mixture left for cooling once confirmed reactioncompletion by TLC then poured into cold water. The reaction mixture was treated with NaHCO3solution and the subsequent solid formed was filtered, dried, and crystallized in ethanolic solution [39].

Reference： [1]Anouar, El Hassane; Moustapha, Moustapha Eid; Taha, Muhammad; Geesi, Mohammed H.; Farag, Zeinab R.; Rahim, Fazal; Almandil, Noor Barak; Farooq, Rai Khalid; Nawaz, Muhammad; Mosaddik, Ashik [Molecules, 2019, vol. 24, # 5]

78
[ 41951-76-2 ]
[ 2612-02-4 ]

Yield	Reaction Conditions	Operation in experiment
96%	With sodium hypochlorite; water at 25℃; for 0.5h;
93%	With oxygen In acetonitrile at 20℃; for 8h;	2.8. General procedure for the one-pot preparation of carboxylicacid through oxidation of alcohols using Fe3O4(at)SiO2(at)Im[Cl]Mn(III)complex nanocomposite in the presence of molecular O2 General procedure: In a 10mL round bottom flask equipped with O2 purging,alcohol (10.0 mmol) and the catalyst (20 mg, 0.25 mol % Mn) wereadded to 3mL dry acetonitrile. Oxygen with flow rate of 120 mL/minwas purged to the mixture during the reaction and the reactionwas stirred at room temperature. Reaction progress was monitoredby GC. After completion of the reaction, the purge system wasremoved and the catalyst 9 was filter off by an external magnet. Theresultant mixture was washed with diethyl ether to remove ofalcohol residues. The aqueous layer was acidified with HCl (3N),then extracted with ethyl acetate. The organic layer was dried overMg2SO4, the solutionwas filtered and the desire carboxylic acidwasobtained after remove of solvent under reduced pressure. All carboxylicacids were identified by comparison of their NMR spectrawith the literature data.

Reference： [1]Hamah-Ameen, Baram Ahmed; Kazemnejadi, Milad; Mahmoudi, Boshra; Rostami, Amin [Green Chemistry, 2020, vol. 22, # 19, p. 6600 - 6613]
[2]Kazemnejadi, Milad; Alavi, Seyyedeh Ameneh; Rezazadeh, Zinat; Nasseri, Mohammad Ali; Allahresani, Ali; Esmaeilpour, Mohsen [Journal of Molecular Structure, 2019, vol. 1186, p. 230 - 249]

79
[ 51-17-2 ]
[ 2612-02-4 ]
[ 142-71-2 ]
[Cu(5-methoxylsalicylate)₂(benzimidazole)₂] [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73.9%	Stage #1: benzoimidazole; copper diacetate In water Stage #2: 5-methoxysalicylic acid In water	Complex 5 The nitrogen donor ligand benzimidazole (1mmol, 0.118g) was mixed in a water solution of copper acetate (0.5mmol, 5ml, 0.1M). After a few minutes 5-methoxysalicylic acid (1mmol, 0.168g) was added to the reaction mixture which was stirred at laboratory temperature until the reaction finished. The precipitates were filtered off, washed with a small amount of appropriate solvent and dried in air at ambient temperature. The clear mother liquid solutions were left to crystallize at laboratory temperature. The purple-violet powder sample was characterized by available methods and by powder diffraction analysis. The same product was found in water solvent as well as in 27 water-acetonitrile mixture. [Cu(5-MeOsal)2(bzim)2], Yield: 73.90%, 0.235g. Anal. Calc: C, 56.82; H, 4.13; N, 8.84. Found: C, 56.64; H, 4.02; N, 8.80. IR (ATR/cm-1): 3313(w), 3119(w), 2999(w),1561(ms), 1482(m), 1446(m), 1386(s), 1232(s), 983(m), 742(s) 598 (ms), 301(m), 238(m). UV-Vis (λ/nm):548.

Reference： [1]Matejová, Simona; Puchoňová, Miroslava; Mazúr, Milan; Valigura, Dušan; Rohlíček, Jan; Jorík, Vladimír; Moncoľ, Ján [Polyhedron, 2019, vol. 170, p. 86 - 94]

80
[ 2612-02-4 ]
[ 39581-55-0 ]

Reference： [1]Acta Chimica Slovenica,2019,vol. 66,p. 745 - 750

81
iron(II) perchlorate hexahydrate [ No CAS ]
[ 2612-02-4 ]
[ 136768-57-5 ]
[(N¹,N²-dimethyl-N¹,N²-bis(2-pyridylmethyl)ethane-1,2-diamine)Fe^II(5-methoxysalicylate)](ClO₄) [ No CAS ]

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

82
[ 2612-02-4 ]
5-methoxysalicylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tetra(n-butyl)ammonium hydroxide In acetonitrile

Reference： [1]Hammarström, Leif; Meyer, Gerald J.; Swords, Wesley B. [Chemical Science, 2020, vol. 11, # 13, p. 3460 - 3473]

83
[ 2612-02-4 ]
[ 85272-31-7 ]
C₁₆H₂₄O₄Si [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With 2,6-dimethylpyridine In acetonitrile at 0 - 22℃; for 16h; Inert atmosphere;	General Experimental Procedure A. General procedure: To a mixture of salicylic acid (1.00 eq) in acetonitrile (1.0 M solution) at 0 C was added 2,6-lutidine (4.00 eq) followed by the dropwise addition of di-tert-butylsilyl bis(trifluoromethansulfonate) (2.00 eq). The reaction was warmed to room temperature and allowed to stir overnight (16 h). The reaction was poured into H2O, extracted with EtOAc, and washed with brine. The combined organic layers were dried over anhydrous Na2SO4, filtered, concentrated in vacuo, and the resulting residue was purified by medium pressure flash chromatography (Silicycle SiliaSep Si column, 25 g, 1.0% EtOAc:hexanes, 25 mL/min detected at 254 nm) to afford the desired di-tert-butylsilylenes.

Reference： [1]Pongdee, Gabriel J.; Bell, Kathryn G.; Prestwood, Peri R.; Pongdee, Rongson [Tetrahedron Letters, 2020, vol. 61, # 48]

84
[ 2612-02-4 ]
(S)-N-(5-amino-1-(5-(naphthalen-2-yl)-1H-imidazol-2-yl)pentyl)thiazole-5-carboxamide [ No CAS ]
(S)-N-(5-(2-hydroxy-5-methoxybenzamido)-1-(5-(naphthalen-2-yl)-1H-imidazol-2-yl)pentyl)thiazole-5-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
12%	With N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 16h;

Reference： [1]Liu, Jian; Yu, Younong; Kelly, Joseph; Sha, Deyou; Alhassan, Abdul-Basit; Yu, Wensheng; Maletic, Milana M.; Duffy, Joseph L.; Klein, Daniel J.; Holloway, M. Katharine; Carroll, Steve; Howell, Bonnie J.; Barnard, Richard J. O.; Wolkenberg, Scott; Kozlowski, Joseph A. [ACS Medicinal Chemistry Letters, 2020, vol. 11, # 12, p. 2476 - 2483]

85
[ 2612-02-4 ]
[ 121-87-9 ]
3-chloro-4-[(2-hydroxy-5-methoxybenzene)amido]-N,N-dioxoanilinium [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With phosphorus trichloride In 5,5-dimethyl-1,3-cyclohexadiene for 4h; Reflux;	a) General procedure: The5-chloro-2-methoxybenzoic acid (0.1 g, 0.536 mmol) and 2-chloro-4-nitroaniline (0.092 g, 0.536 mmol) were suspended in dry Xylene (2.68 mL). After heating to reflux, Phosphorus trichloride (0.019 mL, 0.214 mmol) was added and the reaction mixture stirred under reflux for four hours. The reaction mixture was then cooled to RT and an equal volume of water was added. The mixtutre was stirred for 30 min and then pH was adjusted to >8 by adding sat. NaHCO3. The resultant mixture was then filtered and washed with Hexanes to get the dry solid. DMSO (5 mL) was added and the compound was dissolved via heating. On cooling, the pure compound crashed out. It was then filtered, washed with hexanes and dried to provide 5-chloro-N-(2-chloro-4-nitrophenyl)-2-methoxybenzamide (.125 g, 0.366 mmol, 68 % yield) as the pure product.

Reference： [1]Shamim, Khalida; Xu, Miao; Hu, Xin; Lee, Emily M; Lu, Xiao; Huang, Ruili; Shah, Pranav; Xu, Xin; Chen, Catherine Z.; Shen, Min; Guo, Hui; Chen, Lu; Itkin, Zina; Eastman, Richard T.; Shinn, Paul; Klumpp-Thomas, Carleen; Michael, Sam; Simeonov, Anton; Lo, Donald C.; Ming, Guo-li; Song, Hongjun; Tang, Hengli; Zheng, Wei; Huang, Wenwei [Bioorganic and Medicinal Chemistry Letters, 2021, vol. 40]

86
[ 2612-02-4 ]
[ 65-45-2 ]
2-(2-hydroxy-5-methoxyphenyl)-4H-benzo[e][1,3]oxazin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; thionyl chloride In 5,5-dimethyl-1,3-cyclohexadiene at 140℃; for 18h;	2.2. General procedure for the synthesis of 3,5-disubstituted phenyl-1,2,4-triazole (compounds 1-10) General procedure: Substituted o-hydroxybenzoic acid (1 eq, 10 mmol) and o-hydroxybenzamide (1.1 eq, 11 mmol) were added to 20 mL of xylene, anhydrouspyridine (catalytic amount) was added, and thionyl chloride (2 eq, 20.6mmol) in xylene was added dropwise over 2 h. Afterwards, the mixturewas stirred at 140 C for 16 h. The solvent was distilled off underreduced pressure, and the residue was recrystallized with ethanol toyield the intermediates. The intermediates (1 eq, 2 mmol) and hydrazinehydrate (2.05 eq, 4.1 mmol) were added to 10 mL of absolute ethanol,and the mixture was refluxed for 2 h. When the reaction was complete,the formed precipitate was collected by filtration and washed with EtOHand water. The target compounds were recrystallized in ethanol.2.2.1.

Reference： [1]Shi, Jinguo; Wang, Yang; Chen, Jianwen; Lao, Yaoqiang; Huang, Ping; Liao, Liping; Jiang, Caibao; Li, Xinhua; Wen, Jin; Zhou, Shujia; Zhang, Jingxia [Neurochemistry International, 2021, vol. 148]

87
[ 100-97-0 ]
[ 2612-02-4 ]
3-formyl-2-hydroxy-5-methoxybenzoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	Stage #1: hexamethylenetetramine; 5-methoxysalicylic acid With trifluoroacetic acid for 18h; Reflux; Stage #2: With hydrogenchloride; water at 20℃; for 24h;	1.1.11 3-Formyl-2-hydroxy-5-methoxybenzoic acid. Hexamethylenetetramine (40.019 g, 0.285 mol) was added to the mixture of 2-hydroxy-5-methoxybenzoic acid (24.0 g, 0.143 mol) in trifluoroacetic acid (190.0 mL). The reaction was refluxed for 18 h. After completion, the reaction was cooled down to ambient temperature and a solution of 2M hydrochloric acid (700 mL) was added to the mixture which was stirred at ambient temperature for 24 h. The precipitate was filtered, washed with water (500 mL) and dried in the vacuum oven to give 3-formyl-2-hydroxy-5-methoxybenzoic acid as a pale yellow solid (21.30 g, 0.11 mol, 77.0%) UPLC-MS (acidic method, 2 min): rt = 0.69 min; m/z = 195.1 [M-H]-, peak area >98% 1H NMR (400 MHz, DMSO-d6) δ 10.36 (s, 1H), 7.62 (d, J = 3.4 Hz, 1H), 7.44 (d, J = 3.4 Hz, 1H), 3.78 (s, 3H).

Reference： [1]Current Patent Assignee: VIFOR PHARMA LTD - EP3878837, 2021, A1 Location in patent: Paragraph 0255; 0256

88
[ 61-54-1 ]
[ 2612-02-4 ]
N-(2-(1H-indol-3-yl)ethyl)-2-hydroxy-5-methoxybenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃; for 2h; Inert atmosphere;	4.3 General procedure for the preparation of compound L1-L22 General procedure: A mixture of salicylic acid derivatives (1.0mmol, 1.0eq), tryptamine derivatives (1.0mmol, 1.0eq), 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCIHCl, 1.2mmol, 1.2eq), 1-Hydroxybenzotriazole (HOBt, 1.1mmol, 1.1eq), triethylamine (Et3N, 2.0mmol, 2.0eq) and dichloromethane (DCM, 2.0mL) were stirred at room temperature for 2h under argon condition. After completion of the reaction detected by thin layer chromatography (TLC), the reaction liquid was removed by rotary evaporation under reduced pressure. Then the resulting residue was purified by silica gel flash column chromatography to afford the desired product as a solid (68-93%).

Reference： [1]Bai, Yinliang; Liu, Dan; Zhang, Honghua; Wang, Yuying; Wang, Degui; Cai, Hongbin; Wen, Huaixiu; Yuan, Guoqiang; An, Hui; Wang, Yali; Shi, Tao; Wang, Zhen [Bioorganic Chemistry, 2021, vol. 115]

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P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 2612-02-4 ] {[proInfo.proName]}

Quality Control of [ 2612-02-4 ]

Related Doc. of [ 2612-02-4 ]

Product Details of [ 2612-02-4 ]

Calculated chemistry of [ 2612-02-4 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 2612-02-4 ]

Application In Synthesis of [ 2612-02-4 ]

[ 2612-02-4 ] Synthesis Path-Upstream 1~31

[ 2612-02-4 ] Synthesis Path-Downstream 1~88

Related Functional Groups of [ 2612-02-4 ]

Aryls

Ethers

Carboxylic Acids

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 2612-02-4 ]