[ CAS No. 5162-82-3 ] {[proInfo.proName]}

Name: 5162-82-3|3-Chloro-4-methylbenzoic acid|97%
Brand: Ambeed
SKU: A219410
Price: 5.0 USD
Availability: InStock
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3d Animation Molecule Structure of 5162-82-3

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Quality Control of [ 5162-82-3 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 5162-82-3 ]

SDS Specification

Alternatived Products of [ 5162-82-3 ]

Product Details of [ 5162-82-3 ]

CAS No. :	5162-82-3	MDL No. :	MFCD00045841
Formula :	C₈H₇ClO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	SDKUOEOJAXGCLU-UHFFFAOYSA-N
M.W :	170.59	Pubchem ID :	78840
Synonyms :

Calculated chemistry of [ 5162-82-3 ]

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 :	37.3 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.11 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.65
Log Po/w (XLOGP3) :	3.14
Log Po/w (WLOGP) :	2.35
Log Po/w (MLOGP) :	2.52
Log Po/w (SILICOS-IT) :	2.31
Consensus Log Po/w :	2.39

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.21
Solubility :	0.104 mg/ml ; 0.000612 mol/l
Class :	Soluble
Log S (Ali) :	-3.59
Solubility :	0.0436 mg/ml ; 0.000255 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.77
Solubility :	0.29 mg/ml ; 0.0017 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.25

Safety of [ 5162-82-3 ]

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 [ 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.

Upstream synthesis route of [ 5162-82-3 ]
Downstream synthetic route of [ 5162-82-3 ]

[ 5162-82-3 ] Synthesis Path-Upstream 1~32

1
[ 99-94-5 ]
[ 1642-81-5 ]
[ 5162-82-3 ]

Reference： [1] Journal of Organic Chemistry USSR (English Translation), 1986, vol. 22, p. 24 - 32[2] Zhurnal Organicheskoi Khimii, 1986, vol. 22, # 1, p. 30 - 39

2
[ 99-94-5 ]
[ 76-05-1 ]
[ 1642-81-5 ]
[ 100-21-0 ]
[ 5162-82-3 ]
[ 3006-96-0 ]
[ 619-66-9 ]
[ 78504-88-8 ]

Reference： [1] Journal of Organic Chemistry USSR (English Translation), 1981, vol. 17, # 4, p. 583 - 591[2] Zhurnal Organicheskoi Khimii, 1981, vol. 17, # 4, p. 673 - 681

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

Reference： [1] Journal of Organic Chemistry USSR (English Translation), 1981, vol. 17, # 4, p. 583 - 591[2] Zhurnal Organicheskoi Khimii, 1981, vol. 17, # 4, p. 673 - 681
[3] Patent: FR835727, 1938, ,
[4] Organic Process Research and Development, 1999, vol. 3, # 3, p. 196 - 200

4
[ 124-38-9 ]
[ 95-73-8 ]
[ 118-90-1 ]
[ 5162-82-3 ]
[ 7499-06-1 ]
[ 99-94-5 ]

Reference： [1] Tetrahedron, 1988, vol. 44, # 6, p. 1631 - 1636
[2] Tetrahedron, 1988, vol. 44, # 6, p. 1631 - 1636

5
[ 104-87-0 ]
[ 5162-82-3 ]

Reference： [1] Tetrahedron Letters, 1982, vol. 23, # 31, p. 3131 - 3134
[2] Tetrahedron Letters, 1982, vol. 23, # 31, p. 3131 - 3134

6
[ 21423-81-4 ]
[ 5162-82-3 ]

Reference： [1] Archiv der Pharmazie, 1998, vol. 331, # 5, p. 177 - 192
[2] Journal fuer Praktische Chemie (Leipzig), 1889, vol. <2> 39, p. 496[3] Justus Liebigs Annalen der Chemie, 1891, vol. 265, p. 349

7
[ 3411-03-8 ]
[ 5162-82-3 ]

Reference： [1] Tetrahedron Letters, 1982, vol. 23, # 31, p. 3131 - 3134

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

Reference： [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 ]

Reference： [1] Tetrahedron, 1988, vol. 44, # 6, p. 1631 - 1636

10
[ 3411-03-8 ]
[ 5162-82-3 ]
[ 39652-32-9 ]

Reference： [1] Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences, 1934, vol. 198, p. 1612[2] Annales de Chimie (Cachan, France), 1936, vol. <11> 5, p. 5,39, 40
[3] Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences, 1934, vol. 198, p. 1612[4] Annales de Chimie (Cachan, France), 1936, vol. <11> 5, p. 5,39, 40

11
[ 99-94-5 ]
[ 1642-81-5 ]
[ 5162-82-3 ]

Reference： [1] Journal of Organic Chemistry USSR (English Translation), 1986, vol. 22, p. 24 - 32[2] Zhurnal Organicheskoi Khimii, 1986, vol. 22, # 1, p. 30 - 39

12
[ 95-72-7 ]
[ 5162-82-3 ]

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

13
[ 2719-40-6 ]
[ 5162-82-3 ]

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

14
[ 2458-12-0 ]
[ 5162-82-3 ]
[ 82998-57-0 ]

Reference： [1] Journal of Heterocyclic Chemistry, 1986, vol. 23, # 5, p. 1333 - 1337

15
[ 95-74-9 ]
[ 5162-82-3 ]

Reference： [1] Journal fuer Praktische Chemie (Leipzig), 1889, vol. <2> 39, p. 496[2] Justus Liebigs Annalen der Chemie, 1891, vol. 265, p. 349

16
[ 95-72-7 ]
[ 5162-82-3 ]
[ 34633-69-7 ]

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

17
[ 99-94-5 ]
[ 76-05-1 ]
[ 1642-81-5 ]
[ 100-21-0 ]
[ 5162-82-3 ]
[ 3006-96-0 ]
[ 619-66-9 ]
[ 78504-88-8 ]

Reference： [1] Journal of Organic Chemistry USSR (English Translation), 1981, vol. 17, # 4, p. 583 - 591[2] Zhurnal Organicheskoi Khimii, 1981, vol. 17, # 4, p. 673 - 681

18
[ 7664-93-9 ]
[ 95-72-7 ]
[ 7697-37-2 ]
[ 5162-82-3 ]
[ 13711-22-3 ]
[ 34633-69-7 ]
[ 52415-01-7 ]

Reference： [1] Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences, 1934, vol. 198, p. 100[2] Annales de Chimie (Cachan, France), 1936, vol. <11> 5, p. 5,30

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

Reference： [1] Chemische Berichte, 1877, vol. 10, p. 1250[2] Chemische Berichte, 1878, vol. 11, p. 368

20
[ 4974-59-8 ]
[ 7697-37-2 ]
[ 5162-82-3 ]

Reference： [1] Roczniki Chemii, 1930, vol. 10, p. 541,545[2] Chem. Zentralbl., 1930, vol. 101, # II, p. 3273

21
[ 124-38-9 ]
[ 95-73-8 ]
[ 118-90-1 ]
[ 5162-82-3 ]
[ 7499-06-1 ]
[ 99-94-5 ]

Reference： [1] Tetrahedron, 1988, vol. 44, # 6, p. 1631 - 1636
[2] Tetrahedron, 1988, vol. 44, # 6, p. 1631 - 1636

22
[ 124-38-9 ]
[ 95-73-8 ]
[ 118-90-1 ]
[ 95-49-8 ]
[ 5162-82-3 ]
[ 7499-06-1 ]

Reference： [1] Tetrahedron, 1988, vol. 44, # 6, p. 1631 - 1636

23
[ 7647-01-0 ]
[ 7722-64-7 ]
[ 5162-82-3 ]
[ 1967-31-3 ]

Reference： [1] Inorganic Chemistry, 2013, vol. 52, # 22, p. 12878 - 12880

24
[ 5162-82-3 ]
[ 1967-31-3 ]

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

25
[ 5162-82-3 ]
[ 3411-03-8 ]

Reference： [1] Patent: US6348474, 2002, B1,

26
[ 5162-82-3 ]
[ 39652-34-1 ]

Reference： [1] Justus Liebigs Annalen der Chemie, 1891, vol. 265, p. 361

27
[ 2458-12-0 ]
[ 5162-82-3 ]
[ 82998-57-0 ]

Reference： [1] Journal of Heterocyclic Chemistry, 1986, vol. 23, # 5, p. 1333 - 1337

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

Reference： [1] Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences, 1934, vol. 198, p. 100[2] Annales de Chimie (Cachan, France), 1936, vol. <11> 5, p. 5,30

29
[ 95-72-7 ]
[ 5162-82-3 ]
[ 34633-69-7 ]

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

30
[ 7664-93-9 ]
[ 7697-37-2 ]
[ 5162-82-3 ]
[ 13711-22-3 ]
[ 34633-69-7 ]
[ 52415-01-7 ]

Reference： [1] Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences, 1934, vol. 198, p. 100[2] Annales de Chimie (Cachan, France), 1936, vol. <11> 5, p. 5,30

31
[ 5162-82-3 ]
[ 55737-77-4 ]

Reference： [1] ChemMedChem, 2012, vol. 7, # 9, p. 1551 - 1566

32
[ 5162-82-3 ]
[ 74733-30-5 ]

Reference： [1] Patent: WO2017/156165, 2017, A1,

[ 5162-82-3 ] Synthesis Path-Downstream 1~88

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

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

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

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

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

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

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

Reference： [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 ]

Reference： [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 ]

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

7
[ 124-38-9 ]
[ 95-73-8 ]
[ 118-90-1 ]
[ 95-49-8 ]
[ 5162-82-3 ]
[ 7499-06-1 ]

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

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

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

9
[ 2458-12-0 ]
[ 5162-82-3 ]
[ 82998-57-0 ]

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

10
[ 3411-03-8 ]
[ 5162-82-3 ]

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

11
[ 104-87-0 ]
[ 5162-82-3 ]

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

12
[ 99-94-5 ]
[ 76-05-1 ]
[ 1642-81-5 ]
[ 100-21-0 ]
[ 5162-82-3 ]
[ 3006-96-0 ]
[ 619-66-9 ]
[ 78504-88-8 ]

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

13
[ 99-94-5 ]
[ 1642-81-5 ]
[ 5162-82-3 ]

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

14
[ 95-72-7 ]
[ 5162-82-3 ]

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

15
[ 5162-82-3 ]
[ 21900-30-1 ]

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

16
[ 64-17-5 ]
[ 5162-82-3 ]
[ 99500-36-4 ]

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

17
[ 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)+.

Reference： [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

18
[ 5162-82-3 ]
[ 865449-91-8 ]

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

19
[ 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 ]

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

20
[ 5162-82-3 ]
[ 133486-61-0 ]

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

21
[ 5162-82-3 ]
[ 895519-99-0 ]

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

22
[ 5162-82-3 ]
[ 880874-02-2 ]

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

23
[ 5162-82-3 ]
3-chloro-4-(4-methylpiperazin-1-ylmethyl)benzoyl chloride dihydrochloride [ No CAS ]

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

24
[ 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 ]

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

25
[ 5162-82-3 ]
[ 106269-39-0 ]

Reference： [1]Archiv der Pharmazie,1998,vol. 331,p. 177 - 192

26
[ 5162-82-3 ]
[ 209461-37-0 ]

Reference： [1]Archiv der Pharmazie,1998,vol. 331,p. 177 - 192

27
[ 5162-82-3 ]
[ 25539-20-2 ]

Reference： [1]Archiv der Pharmazie,1998,vol. 331,p. 177 - 192

28
[ 5162-82-3 ]
[ 134560-28-4 ]

Reference： [1]Archiv der Pharmazie,1998,vol. 331,p. 177 - 192

29
[ 5162-82-3 ]
9-Oxo-9H-xanthene-3-carboxylic acid amide [ No CAS ]

Reference： [1]Archiv der Pharmazie,1998,vol. 331,p. 177 - 192

30
[ 5162-82-3 ]
[ 209461-33-6 ]

Reference： [1]Archiv der Pharmazie,1998,vol. 331,p. 177 - 192

31
[ 5162-82-3 ]
2,7-Dinitro-9-oxo-9H-xanthene-3-carboxylic acid methyl ester [ No CAS ]

Reference： [1]Archiv der Pharmazie,1998,vol. 331,p. 177 - 192

32
[ 5162-82-3 ]
[ 21460-88-8 ]

Reference： [1]Justus Liebigs Annalen der Chemie,1891,vol. 265,p. 359

33
[ 5162-82-3 ]
[ 39652-34-1 ]

Reference： [1]Justus Liebigs Annalen der Chemie,1891,vol. 265,p. 361

34
[ 5162-82-3 ]
[ 637347-67-2 ]

Reference： [1]Justus Liebigs Annalen der Chemie,1891,vol. 265,p. 359

35
[ 95-74-9 ]
[ 5162-82-3 ]

Reference： [1]Journal fur praktische Chemie (Leipzig 1954),1889,vol. <2> 39,p. 496
Justus Liebigs Annalen der Chemie,1891,vol. 265,p. 349

36
[ 5162-82-3 ]
3-Chlor-4,4'-dimethyl-benzophenon [ No CAS ]

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

37
[ 74-96-4 ]
[ 5162-82-3 ]
[ 99500-36-4 ]

Yield	Reaction Conditions	Operation in experiment
		In the same manner as in Preparation Example 74-2, the objective compound (28.7 g) was obtained as a pale-yellow oil from <strong>[5162-82-3]3-chloro-4-methylbenzoic acid</strong> (28.7 g). 1H-NMR(CDCl3): 1.39(3H, t, J=6 Hz), 2.43(3H, s), 4.38(2H, q, J=6 Hz), 7.29(1H, d, J=8 Hz), 7.83(1H, d, J=8 Hz), 8.02(1H, s)

Reference： [1]Patent: US6348474,2002,B1 .Location in patent: Page column 141

38
[ 5162-82-3 ]
[ 39652-32-9 ]

Yield	Reaction Conditions	Operation in experiment
85%	With borane-THF; In tetrahydrofuran; at 0 - 20℃;	A. (3-chloro-4-methylphenyl methanol [00667] To a solution of 4-chloro-2-methylbenzoic acid (800 mg, 4.69 mmol) in THF (8 that was cooled at 0 C, BH3 THF (14 mL, 1M in THF) was added into the solution drop wise. The mixture was then stirred at r.t. overnight. Add methanol to the system at 0C slowly until no gas released. Remove the solvent and the residue was extracted with ethylacetate, concentrated the organic phase to give 894 mg of the title compound (85%). 1H NMR (400 MHz, CDC13): delta 2.36 (3H, s), 4.63 (2H, s), 7.13-7.22 (2H, m), 7.35 (1H, s).
	With borane-THF; In tetrahydrofuran; at 0 - 35℃; for 16h;Inert atmosphere;	To a solution of <strong>[5162-82-3]3-chloro-4-methylbenzoic acid</strong> (1.50 g) in THF (29 mL) was added dropwise borane-THF complex (1M THF solution, 17.6 mL) over 10 min under argon atmosphere at 0 C., and the reaction mixture was stirred at room temperature for 16 hr. The reaction was quenched with methanol at 0 C., and the mixture was stirred at room temperature for 1 hr. The organic solvent was evaporated under reduced pressure, and the residue was partitioned between water and ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and filtered through a pad of silica gel and NH silica gel. The filtrate was concentrated under reduced pressure to give crude (3-chloro-4-methylphenyl)methanol (1.39 g).
		In the same manner as in Preparation Example 74-4, the objective compound (23.0 g) was obtained as a colorless oil from <strong>[5162-82-3]3-chloro-4-methylbenzoic acid</strong> (25.0 g). 1H-NMR(CDCl3): 2.36(3H, s), 4.65(2H, s), 7.14(1H, d, J=8 Hz), 7.23(1H, d, J=8 Hz), 7.36(1H, S)

Reference： [1]Patent: WO2014/89364,2014,A1 .Location in patent: Paragraph 00666; 00667
[2]Patent: US2017/283406,2017,A1 .Location in patent: Paragraph 0771
[3]Patent: US6348474,2002,B1 .Location in patent: Page column 140

39
[ 161249-59-8 ]
[ 5162-82-3 ]
[ 1236942-43-0 ]

Yield	Reaction Conditions	Operation in experiment
	sulfuric acid;	EXAMPLE 57 (E)-3-[2-n-Butyl-1-[2-chloro-4(1H-tetrazol-5-yl)phenyl]methyl}-1H-imidazol-5-yl]-2-benzyl-2-propenoic Acid The procedure of Example 42 is followed using t-butyl 4-bromomethyl-3-chlorobenzoate (prepared from <strong>[5162-82-3]3-chloro-4-methylbenzoic acid</strong> by esterification with 2-methylpropene in the presence of concentrated sulfuric acid, followed by bromination with N-bromosuccinimide) in place of ethyl 4-bromomethyl-3-chlorobenzoate to give ethyl (E)-3-[2-n-butyl-1-[2-chloro-4-(carbo-t-butoxy)phenyl]-methyl}-1H-imidazol-5-yl]-2-benzyl-2-propenoate. The t-butyl ester is removed with trifluoroacetic acid.

Reference： [1]Patent: US5312828,1994,A

40
[ 5162-82-3 ]
[ 21900-30-1 ]
[ 109-89-7 ]
[ 97712-32-8 ]

Yield	Reaction Conditions	Operation in experiment
	In tetrahydrofuran; N-methyl-acetamide; thionyl chloride; water; ethyl acetate;	EXAMPLE 1 Preparation of 3-chloro-N,N-diethyl-p-toluamide STR47 A mixture of 32.2 g (0.19 mol) of <strong>[5162-82-3]3-chloro-4-methylbenzoic acid</strong> in 100 mL of thionyl chloride is treated with 2 drops of dimethylformamide and heated on a steam bath for one hour. The clear amber solution is evaporated in vacuo several times with anhydrous toluene to give a clear amber oily residue. After dilution to a volume of 125 mL with anhydrous tetrahydrofuran, the 3-chloro-4-methyl-benzoyl chloride is added dropwise to a stirred solution of 43.3 mL (0.418 mol) of diethylamine in 300 mL anhydrous tetrahydrofuran under N2 at -5 C. The reaction mixture is allowed to come to room temperature over a 72 hour period then is treated with 300 mL water. The phases are separated; the aqueous phase is extracted with a total of 300 mL ethyl acetate. All organic phases are combined, washed with 300 mL of a saturated sodium chloride solution, dried over magnesium sulfate and concentrated in vacuo to give 40.0 g of a clear dark red oil. The infrared and proton nmr spectra are consistent with the desired structure. Gas-liquid chromatography analysis gives a purity of 96%.
	In tetrahydrofuran; N-methyl-acetamide; thionyl chloride; water; ethyl acetate;	EXAMPLE 1 Preparation of 3-chloro-N,N-diethyl-p-toluamide STR12 A mixture of 32.2 g (0.19 mol) of <strong>[5162-82-3]3-chloro-4-methylbenzoic acid</strong> in 100 mL of thionyl chloride is treated with 2 drops of dimethylformamide and heated on a steam bath for one hour. The clear amber solution is evaporated in vacuo several times with anhydrous toluene to give a clear amber oily residue. After dilution to a volume of 125 mL with anhydrous tetrahydrofuran, the 3-chloro-4-methyl-benzoyl chloride is added dropwise to a stirred solution of 43.3 mL (0.418 mol) of diethylamine in 300 mL anhydrous tetrahydrofuran under N2 at -5 C. The reaction mixture is allowed to come to room temperature over a 72 hour period then is treated with 300 mL water. The phases are separated; the aqueous phase is extracted with a total of 300 mL ethyl acetate. All organic phases are combined, washed with 300 ml of a saturated sodium chloride solution, dried over magnesium sulfate and concentrated in vacuo to give 40.0 g of a clear dark red oil. The infrared and proton nmr spectra are consistent with the desired structure. Gas-liquid chromatography analysis gives a purity of 96%.

Reference： [1]Patent: US4608079,1986,A
[2]Patent: US4554013,1985,A

41
[ 626-23-3 ]
[ 5162-82-3 ]
[ 21900-30-1 ]
[ 27922-74-3 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In C6; thionyl chloride; benzene;	Preparation of 3-chloro,4-methyl-N,N-di-sec.butyl-benzamide Into a 150 ml flask, provided with a reflux condenser, were placed 17.1 g of <strong>[5162-82-3]3-chloro-4-methyl-benzoic acid</strong> (prepared according to French Pat. No. 835,727) and 55.5 g of SOCl2 and the whole was heated to reflux until complete dissolution. The boiling was continued for another 30 minutes. The excess in SOCl2 was then removed under vacuum and the residue was subjected to fractional distillation at a pressure of 0.2 mm Hg. The fraction passing over at 95C was then collected. 17.9 g of the chloride of 3-chloro,4-methylbenzoic acid were obtained. To these 17.9 g of the chloride of 3-chloro,4-methylbenzoic acid, dissolved in 60 ml of anhydrous benzene, were added 12.9 g of di-sec.butylamine dissolved in 15 ml of anhydrous C6 H 6 and 12.3 g of triethylamine. The whole was then boiled to reflux temperature for 1 hour and was then left to cool down to room temperature. The reaction mass was then concentrated to dryness under reduced pressure. The residue was washed with acidulated H2 O, with H2 O and extracted with ethyl ether. The etheral extract was dried on anhydrous Na 2 SO4, filtered, and the solvent was then removed by reduced pressure. The oily residue was fractionally distilled at a pressure of 0.05 mm Hg. The fraction which passed over at 143-144C was collected. Thereby were obtained 26.5 g of 3-chloro,4-methyl-N,N-di-sec.butyl-benzamide. The analysis gave: calculated C = 68.19%, found C = 64.93%; calculated H = 8.55%, found H = 8.83%.

Reference： [1]Patent: US3982931,1976,A

42
[ 5192-03-0 ]
[ 5162-82-3 ]
[ 930790-88-8 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; for 2h;	Step 1 A mixture of 5-aminoindole (1.32 g, 10 mmol), 1-hydroxybenzotriazole (1.49 g, 11 mmol), and 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride (2.11 g, 11 mmol) was dissolved in N,N-dimethylformamide (30 mL). To this was added <strong>[5162-82-3]3-chloro-4-methylbenzoic acid</strong> (1.71 g, 10 mmol) and the reaction mixture was stirred for 2 hours until the reaction was complete. The mixture was then partitioned between water and dichloromethane solution. The organic layer was separated and the aqueous layer was extracted with dichloromethane several times. The combined extracts were washed with water and brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified via Biotage Horizon (FlasH 40 M, silica, gradient from 0% ethyl acetate/hexane to 70% ethyl acetate/hexane) to give 3-chloro-N-(1H-indol-5-yl)-4-methylbenzamide as a light tan solid. MS (ESI) m/z 284.9 ([M+H]+).

Reference： [1]Patent: US2007/72897,2007,A1 .Location in patent: Page/Page column 69-70

43
[ 1004135-64-1 ]
[ 5162-82-3 ]
[ 1072875-26-3 ]

Yield	Reaction Conditions	Operation in experiment
	With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; triethylamine; In 1-methyl-pyrrolidin-2-one; at 20℃;	Example 27; Preparation of 3-chloro-N-{2-[3-(3-chloro-2-methyl-phenyl)-4-oxo-imidazolidin-1-yl]-2-oxo-ethyl}-N-(2-methoxy-ethyl)-4-methyl-benzamide; In a 4 mL vial was taken 100 mg of 3-(3-chloro-2-methyl-phenyl)-1-[2-(2-methoxy-ethylamino)-acetyl]-imidazolidin-4-one (0.31 mmol, 1.00 eq), 52 mg of <strong>[5162-82-3]3-chloro-4-methylbenzoic acid</strong> (0.31 mmol, 1.00 eq), 163 mg BOP (0.37 mmol, 1.20 eq), 171 uL (1.23 mmol, 4.00 eq), and 1.5 mL NMP. The mixture was stirred overnight at room temperature and the crude product was purified by reversed phase HPLC (acetonitrile -H2O with 0.1% TFA as the eluent) to yield 3-chloro-N-{2-[3-(3-chloro-2-methyl-phenyl)-4-oxo-imidazolidin-1-yl]-2-oxo-ethyl}-N-(2-methoxy-ethyl)-4-methyl-benzamide. MS (ES) M+H expected=478.0, found=478.1.

Reference： [1]Patent: US2008/269280,2008,A1 .Location in patent: Page/Page column 26

44
[ 75-77-4 ]
[ 5162-82-3 ]
[ 56525-63-4 ]

Yield	Reaction Conditions	Operation in experiment
	In methanol; at 20℃;	Chloro-trimethyl-silane (6.0 mL, 46.9 mmol) was added to a stirring solution of 3-chloro- 4-methyl-benzoic acid (2.0 g, 11.7 mmol) in methanol (40 mL). After stirring at RT overnight the solvent was removed in vacuo to give the title compound, which was used in the following step without further purification. GC/MS (m/z): 184

Reference： [1]Patent: WO2009/36996,2009,A2 .Location in patent: Page/Page column 97

45
[ 5162-82-3 ]
[ 1907-33-1 ]
[ 479234-38-3 ]

Yield	Reaction Conditions	Operation in experiment
79%		Thionyl chloride (11 ml, 150 mmol) was added to a suspension of <strong>[5162-82-3]3-chloro-4-methylbenzoic acid</strong> (5.12 g, 30 mmol) in toluene (25 ml) and the mixture was heated at reflux for 2 h. The solvent was removed in vacuo and the residue was azeotroped with toluene three times, then dissolved in anhydrous THF (40 ml) and cooled to 0C. Lithium tert-butoxide (2.4 g, 30 mmol) was added and the mixture was stirred at room temperature for 3 days. Water (5 ml) was added and the solvent was removed in vacuo. The residue was dissolved in ethyl acetate. The solution was washed with 0.3M KHSO4, sat. NaHCO3 and brine, dried over Na2SO4 and concentrated in vacuo to give a pale yellow gum identified as tert-butyl 3-chloro-4-methylbenzoate (5.4 g, 79%).

Reference： [1]Patent: EP1449844,2004,A1 .Location in patent: Page 19

46
[ 515135-62-3 ]
[ 5162-82-3 ]
[ 765-30-0 ]
[ 515135-27-0 ]

Reference： [1]Journal of Medicinal Chemistry,2009,vol. 52,p. 6257 - 6269

47
[ 5162-82-3 ]
[ 515135-60-1 ]

Reference： [1]Journal of Medicinal Chemistry,2009,vol. 52,p. 6257 - 6269

48
[ 5162-82-3 ]
[ 765-30-0 ]
[ 909219-17-6 ]
[ 515135-59-8 ]

Reference： [1]Journal of Medicinal Chemistry,2009,vol. 52,p. 6257 - 6269

49
[ 444287-40-5 ]
[ 5162-82-3 ]
[ 927671-89-4 ]

Yield	Reaction Conditions	Operation in experiment
79%		5.133 3-CHLORO-N-[2-(2,6-DIOXO-PIPERIDIN-3-YL)-1,3-DI-2,3-DIHYDRO-1H-ISOINDOL-4-YLMETHYL]-4-METHYL-BENZAMIDE To a stirred suspension of 4-aminomethyl-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride (0.7 g, 2.2 mmol) in CH3CN (60 ml), was added 1,8-diazabicyclo[5.4.0]undec-7-ene (0.8 g, 5.4 mmol). After stirring for 10 minutes, 1-hydroxybenzenetriazole (0.35 g, 2.6 mmol) and <strong>[5162-82-3]3-chloro-4-methyl-benzoic acid</strong> (0.4 g, 2.4 mmol) were added. To the reaction mixture, was then added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.62 g, 3.2 mmol), and the mixture was stirred at room temperature overnight. The reaction mixture was then concentrated in vacuo, and the residue was stirred in H2O (50 mL). A suspension formed and after filtration the solid was reslurried in acetone (20 mL). The suspension was filtered to afford 3-chloro-N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-4-methyl-benzamide as a white solid (0.75 g, 79%): mp, 249-251 C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, 40/60 (CH3CN/H2O): tR=6.8 min. (97%); 1H NMR (DMSO-d6): delta 2.06-2.11 (m, 1H), 2.39 (s, 3H), 2.53-2.64 (m, 2H), 2.85-2.96 (m, 1H), 4.94(d, J=5.8 Hz, 2H), 5.15-5.20 (dd, J=5, 12 Hz, 1H), 7.47-7.97 (m, 6H), 7.82-7.89 (m, 3H), 9.22 (t, J=6 Hz, 1H), 11.15 (s, 1H). 13C NMR (DMSO-d6) delta: 19.55, 21.97, 30.92, 38.36, 48.86, 121.89, 126.07, 127.15, 127.60, 131.22, 131.52, 133.11, 133.33, 134.80, 139.06, 139.10, 165.13, 166.94, 167.50, 169.81, 172.74. Anal Calcd for C22H18ClN3O5: C, 60.08; H, 4.12; N, 9.55; Cl, 8.06. Found: C, 59.69; H, 4.15; N, 9.60; Cl, 8.08.

Reference： [1]Patent: US2007/49618,2007,A1 .Location in patent: Page/Page column 121

50
[ 67-56-1 ]
[ 5162-82-3 ]
[ 56525-63-4 ]

Yield	Reaction Conditions	Operation in experiment
98%	With sulfuric acid; at 60℃; for 48h;	Concentrated sulfuric acid (4.00 mL, 73.3 mmol) was added to a solution of 3-chloro-4- methylbenzoic acid (1, 25.0 g, 147 mmol) in methanol (200 mL) and the reaction mix- ture was allowed to stir at 60 C for 2 days. The solution was cooled to room temperature, sodium hydrogencarbonate (6.80 g, 80.0 mmol) was added, and the mixture was evaporated under reduced pressure. The residue was partitioned between ethyl acetate (300 mL) and water (250 mL). The organic layer was separated; washed with 0.5 M aqueous solution of sodium hydroxide (2 x 250 mL), 0.5 M aqueous solution of hydro- chloric acid (200 mL) and brine (150 mL); dried over anhydrous sodium sulfate and evaporated in vacuo to give methyl 3-chloro-4-methylbenzoate (2) as orange oil. Yield : 27.0 g (98%). RF (Si02, dichlormethane/methanol 95: 5) : 0.80. JH NMR spectrum (300 MHz, CDCI3, deltaEta) : 8.00 (d, J = 1.65 Hz, 1 H); 7.80 (dd, J = 7.9 and 1.5 Hz, 1 H); 7.28 (d, J = 8.1 Hz, 1 H); 3.90 (s, 3 H); 2.42 (s, 3 H).
96%	With thionyl chloride; at 0 - 20℃; for 120h;	To a solution of3- chloro-4-methylbenzoic acid (20 g, 117 mmol) in MeOH (200 mL) was added drop wise thionyl chloride (25.6 mL, 352 mmol) at 0C with stirring. The mixture was stirred at room temperature for 5 days. The reaction was concentrated. The residue was dissolved in EA (500 mL), washed with 10% Na2C03 (250 mLx2), water (250 mL) and brine (250 mL), dried over Na2S04, filtered and concentrated to afford product as a yellow solid (20. 8 g, 96%).
	With thionyl chloride; at 100℃; for 16h;	To a solution of <strong>[5162-82-3]3-chloro-4-methyl-benzoic acid</strong> (20.0 g, 117 mmol) in methanol (200 mL) was added thionyl chloride (65.6 g, 551 mmol). The mixture was heated to 100 C and stirred at 100 C for 16 hours. On completion, the mixture was concentrated in vacuo to give a residue. The residue was purified with silica gel chromatography (petroleum ethenethyl acetate = 80: 1) to give the title compound. 1H NMR (400MHz, CDCh) delta = 8.01 (s, 1H), 7.83 (d, J = 8.0 Hz, 1H), 7.30 (d, J= 8.0 Hz, 1H), 3.91 (s, 3H), 2.43 (s, 3H).

Reference： [1]Patent: WO2019/92125,2019,A1 .Location in patent: Page/Page column 124; 125
[2]Patent: WO2011/99978,2011,A1 .Location in patent: Page/Page column 42
[3]Patent: WO2017/156165,2017,A1 .Location in patent: Paragraph 00525-00527

51
[ 5162-82-3 ]
[ 1331832-72-4 ]