5162-82-3|3-Chloro-4-methylbenzoic acid| Ambeed

CAS No. :	5162-82-3
Formula :	C₈H₇ClO₂
M.W :	170.59
SMILES Code :	O=C(O)C1=CC=C(C)C(Cl)=C1
MDL No. :	MFCD00045841
InChI Key :	SDKUOEOJAXGCLU-UHFFFAOYSA-N
Pubchem ID :	78840

Safety of [ 5162-82-3 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Computational Chemistry of [ 5162-82-3 ] Show Less

Physicochemical Properties

Num. heavy atoms	11
Num. arom. heavy atoms	6
Fraction Csp3	0.12
Num. rotatable bonds	1
Num. H-bond acceptors	2.0
Num. H-bond donors	1.0
Molar Refractivity	43.38
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	37.3 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.65
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	3.14
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.35
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	2.52
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	2.31
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	2.39

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-3.21
Solubility	0.104 mg/ml ; 0.000612 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-3.59
Solubility	0.0436 mg/ml ; 0.000255 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-2.77
Solubility	0.29 mg/ml ; 0.0017 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	Yes
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	No
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	No
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-5.11 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	1.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.56

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	0.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	1.25

Application In Synthesis of [ 5162-82-3 ]

* 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.

Downstream synthetic route of [ 5162-82-3 ]

[ 5162-82-3 ] Synthesis Path-Downstream 1~56

1
[ 5162-82-3 ]
[ 586-30-1 ]

References: [1]Chemische Berichte,1877,vol. 10,p. 1250.
Chemische Berichte,1878,vol. 11,p. 368.

2
[ 5162-82-3 ]
[ 1967-31-3 ]

References: [1]Zeitschrift fur Physikalische Chemie, Stoechiometrie und Verwandtschaftslehre,1929,vol. <A> 143,p. 18.

3
[ 95-72-7 ]
[ 5162-82-3 ]
[ 34633-69-7 ]

References: [1]Journal of the Indian Chemical Society,1935,vol. 12,p. 540.

4
[ 21423-81-4 ]
[ 5162-82-3 ]

References: [1]Archiv der Pharmazie,1998,vol. 331,p. 177 - 192.
[2]Journal fur praktische Chemie (Leipzig 1954),1889,vol. <2> 39,p. 496.
Justus Liebigs Annalen der Chemie,1891,vol. 265,p. 349.

5
[ 3411-03-8 ]
[ 5162-82-3 ]
[ 39652-32-9 ]

References: [1]Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences,1934,vol. 198,p. 1612.
Annales de Chimie (Cachan, France),1936,vol. <11> 5,p. 5,39, 40.
[2]Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences,1934,vol. 198,p. 1612.
Annales de Chimie (Cachan, France),1936,vol. <11> 5,p. 5,39, 40.

6
[ 2719-40-6 ]
[ 5162-82-3 ]

References: [1]Journal of the Chemical Society,1920,vol. 117,p. 525.

7
[ 99-94-5 ]
[ 5162-82-3 ]

Yield	Reaction Conditions	Operation in experiment
	With cetyltrimethylammonim bromide; chlorine; In water; at 60℃; for 8h;	Add in a glass reactor equipped with a thermometer, a stirring paddle and a condenser200 g of p-toluic acid and 800 ml of water, and 2 g of cetyltrimethylammonium bromide,After heating to 60 C, chlorine gas was introduced and the reaction was monitored using a chromatogram.When the product yield is greater than 98%, the reaction is stopped and the reaction is carried out for 8 hours.The reaction solution was added to a Buchner funnel, filtered, and washed with 1500 ml of water.The obtained filter cake was vacuum dried at 80 C to a constant weight.Quantitative analysis by liquid chromatography,A purity of 98% 3-chloro-4-methylbenzoic acid was obtained.The other 2% is p-toluic acid.

References: [1]Journal of Organic Chemistry USSR (English Translation),1981,vol. 17,p. 583 - 591.
Zhurnal Organicheskoi Khimii,1981,vol. 17,p. 673 - 681.
[2]Patent: FR835727,1938, .
[3]Organic Process Research and Development,1999,vol. 3,p. 196 - 200.
[4]Patent: CN109608325,2019,A .Location in patent: Paragraph 0066; 0067; 0068; 0069.

8
[ 4395-79-3 ]
[ 5162-82-3 ]

References: [1]Journal of the American Chemical Society,1951,vol. 73,p. 455.

9
[ 124-38-9 ]
[ 95-73-8 ]
[ 118-90-1 ]
[ 95-49-8 ]
[ 5162-82-3 ]
[ 7499-06-1 ]

References: [1]Tetrahedron,1988,vol. 44,p. 1631 - 1636.

10
[ 124-38-9 ]
[ 95-73-8 ]
[ 118-90-1 ]
[ 5162-82-3 ]
[ 7499-06-1 ]
[ 99-94-5 ]

References: [1]Tetrahedron,1988,vol. 44,p. 1631 - 1636.
[2]Tetrahedron,1988,vol. 44,p. 1631 - 1636.

11
[ 2458-12-0 ]
[ 5162-82-3 ]
[ 82998-57-0 ]

References: [1]Journal of Heterocyclic Chemistry,1986,vol. 23,p. 1333 - 1337.

12
[ 3411-03-8 ]
[ 5162-82-3 ]

References: [1]Tetrahedron Letters,1982,vol. 23,p. 3131 - 3134.

13
[ 104-87-0 ]
[ 5162-82-3 ]

References: [1]Tetrahedron Letters,1982,vol. 23,p. 3131 - 3134.
[2]Tetrahedron Letters,1982,vol. 23,p. 3131 - 3134.

14
[ 99-94-5 ]
[ 76-05-1 ]
[ 1642-81-5 ]
[ 100-21-0 ]
[ 5162-82-3 ]
[ 3006-96-0 ]
[ 619-66-9 ]
[ 78504-88-8 ]

References: [1]Journal of Organic Chemistry USSR (English Translation),1981,vol. 17,p. 583 - 591.
Zhurnal Organicheskoi Khimii,1981,vol. 17,p. 673 - 681.

15
[ 99-94-5 ]
[ 1642-81-5 ]
[ 5162-82-3 ]

References: [1]Journal of Organic Chemistry USSR (English Translation),1986,vol. 22,p. 24 - 32.
Zhurnal Organicheskoi Khimii,1986,vol. 22,p. 30 - 39.

16
[ 95-72-7 ]
[ 5162-82-3 ]

References: [1]Journal of Organic Chemistry,1967,vol. 32,p. 134 - 136.

17
[ 5162-82-3 ]
[ 21900-30-1 ]

References: [1]Bulletin des Societes Chimiques Belges,1968,vol. 77,p. 273 - 285.

18
[ 5162-82-3 ]
[ 108-95-2 ]
[ 209461-56-3 ]

Yield	Reaction Conditions	Operation in experiment
39.8%	With copper(l) iodide; copper; potassium carbonate; at 230℃; for 48h;	To a solution of 68 (15.0 g, 87.9 mmol), 69 (77.3 mL, 87.9 mmol),Cu-powder (2.79 g, 43.9 mmol), CuI (8.37 g, 43.9 mmol) and K2CO3(24.3 g, 175 mmol) were mixed in a steel vessel and stirred for 2 days at230 C. Progress of the reaction mixture was monitored by TLC andLCMS. The resulting mixture was diluted with EtOAc (250 mL), 1 NNaOH (500 mL) and stirred for 1 h at room temperature. The aqueouslayer was extracted with EtOAc (3 × 250 mL) and then acidified with1 N HCl solution (pH 2) and extracted with EtOAc (3 × 250 mL). Theorganic layer was washed with brine solution (1 × 250 mL), dried withanhydrous sodium sulphate and then concentrated under vacuo to give58 (8.0 g, 39.8%) as a white solid. 1H NMR (400 MHz; DMSO-d6): 12.96(s, 1H), 7.64 (d, 1H), 7.46-7.38 (m, 3H), 7.30 (s, 1H), 7.15 (t, 1H), 6.97(d, 2H), 2.27 (s, 3H).

References: [1]Bioorganic and medicinal chemistry,2020,vol. 28.
[2]Archiv der Pharmazie,1998,vol. 331,p. 177 - 192.

19
[ 7697-37-2 ]
[ 4395-79-3 ]
[ 5162-82-3 ]

References: [1]Chemische Berichte,1877,vol. 10,p. 1250.
Chemische Berichte,1878,vol. 11,p. 368.

20
[ 5162-82-3 ]
potash [ No CAS ]
[ 586-30-1 ]

References: [1]Chemische Berichte,1877,vol. 10,p. 1250.
Chemische Berichte,1878,vol. 11,p. 368.

22
2.2-dichloro-1-<i>p</i>-tolyl-ethanone-⁽¹⁾ [ No CAS ]
[ 5162-82-3 ]

References: [1]Roczniki Chemii,1930,vol. 10,p. 541,545.
Chemisches Zentralblatt,1930,vol. 101,p. 3273.

23
2-chloro-cymene [ No CAS ]
[ 5162-82-3 ]

References: [1]Chemische Berichte,1873,vol. 6,p. 1090.

24
[ 4974-59-8 ]
[ 7697-37-2 ]
[ 5162-82-3 ]

References: [1]Roczniki Chemii,1930,vol. 10,p. 541,545.
Chemisches Zentralblatt,1930,vol. 101,p. 3273.

25
[ 95-72-7 ]
cobalt palmitate [ No CAS ]
[ 5162-82-3 ]

References: [1]Patent: DE767366,1940, .
DRP/DRBP Org.Chem.,.

26
[ 90792-98-6 ]
hypobromite [ No CAS ]
[ 5162-82-3 ]

References: [1]Justus Liebigs Annalen der Chemie,1906,vol. 346,p. 281.

27
[ 95-72-7 ]
[ 7697-37-2 ]
[ 108-24-7 ]
SO₂ [ No CAS ]
[ 5162-82-3 ]
[ 34633-69-7 ]

References: [1]Journal of the Indian Chemical Society,1935,vol. 12,p. 540.

28
[ 7664-93-9 ]
[ 95-72-7 ]
[ 7697-37-2 ]
[ 5162-82-3 ]
[ 13711-22-3 ]
[ 34633-69-7 ]
[ 52415-01-7 ]

References: [1]Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences,1934,vol. 198,p. 100.
Annales de Chimie (Cachan, France),1936,vol. <11> 5,p. 5,30.

29
[ 2719-40-6 ]
permanganate [ No CAS ]
[ 5162-82-3 ]

References: [1]Journal of the Chemical Society,1920,vol. 117,p. 525.

30
[ 64-17-5 ]
[ 5162-82-3 ]
[ 99500-36-4 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 1421 - 1425.
[2]RSC Advances,2018,vol. 8,p. 6306 - 6314.

31
[ 5162-82-3 ]
[ 467442-07-5 ]

Yield	Reaction Conditions	Operation in experiment
	With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); In tetrachloromethane; at 80℃; for 3h;	Example 80A 4-Bromomethyl-3-chloro-benzoic acid A 50 mL round bottom flask was charged with <strong>[5162-82-3]3-chloro-4-methyl-benzoic acid</strong> (1 g, 5.9 mmol), NBS (1.043 g, 5.9 mmol), AIBN (97 mg, 0.59 mmol) and CCl4 (20 mL). The mixture was completed after refluxing at 80 C. for 3 hours, then quenched with water, diluted with CH2Cl2. The aqueous layer was extracted with CH2Cl2. The combined organic layer was washed with brine, dried over Na2SO4, concentrated to provide the crude mixtures. Then preparative reverse-phase HPLC was used to provide the pure title compound. 1H NMR (500 MHz, DMSO-d6) delta ppm 4.79(s, 2H), 7.75(d, 1H, J=7.93), 7.89(d, 1H, J=7.93), 7.94 (s, 1H), 13.35(s, br, 1H); MS (ESI) m/e 246.6 (M-H)+.

References: [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 2365 - 2371.
[2]Patent: US2005/209274,2005,A1 .Location in patent: Page/Page column 47.

32
[ 5162-82-3 ]
[ 865449-91-8 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 2365 - 2371.

33
[ 5162-82-3 ]
N-[1-(2-chloro-4-[(2-pyrrolidin-1-ylethyl)amino]carbonyl}benzyl)piperidin-4-yl]-7-fluoro-4-oxo-4H-chromene-2-carboxamide [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 2365 - 2371.

34
[ 5162-82-3 ]
[ 133486-61-0 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 1421 - 1425.
[2]Patent: US6348474,2002,B1 .

35
[ 5162-82-3 ]
[ 895519-99-0 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 1421 - 1425.

36
[ 5162-82-3 ]
[ 880874-02-2 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 1421 - 1425.

37
[ 5162-82-3 ]
3-chloro-4-(4-methylpiperazin-1-ylmethyl)benzoyl chloride dihydrochloride [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 1421 - 1425.

38
[ 5162-82-3 ]
3-chloro-4-(4-methylpiperazin-1-ylmethyl)-N-{4-methyl-3-[4-(pyridin-3-yl)pyrimidin-2-ylamino]phenyl}benzamide [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 1421 - 1425.

39
[ 5162-82-3 ]
[ 106269-39-0 ]