[ CAS No. 25026-64-6 ] {[proInfo.proName]}

Name: 25026-64-6|3-Chloro-5-fluorobenzoic acid|95%
Brand: Ambeed
SKU: A175779
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Quality Control of [ 25026-64-6 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 25026-64-6 ]

Product Details of [ 25026-64-6 ]

CAS No. :	25026-64-6	MDL No. :	MFCD00973904
Formula :	C₇H₄ClFO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	QFMRANWPGGSNHS-UHFFFAOYSA-N
M.W :	174.56	Pubchem ID :	2734840
Synonyms :

Calculated chemistry of [ 25026-64-6 ]

Physicochemical Properties

Num. heavy atoms :	11
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.0
Num. rotatable bonds :	1
Num. H-bond acceptors :	3.0
Num. H-bond donors :	1.0
Molar Refractivity :	38.37
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) :	-5.61 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.49
Log Po/w (XLOGP3) :	2.47
Log Po/w (WLOGP) :	2.6
Log Po/w (MLOGP) :	2.63
Log Po/w (SILICOS-IT) :	2.28
Consensus Log Po/w :	2.29

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.82
Solubility :	0.267 mg/ml ; 0.00153 mol/l
Class :	Soluble
Log S (Ali) :	-2.9
Solubility :	0.221 mg/ml ; 0.00127 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.66
Solubility :	0.379 mg/ml ; 0.00217 mol/l
Class :	Soluble

Medicinal Chemistry

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

Safety of [ 25026-64-6 ]

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 [ 25026-64-6 ]

* 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 [ 25026-64-6 ]

[ 25026-64-6 ] Synthesis Path-Downstream 1~43

1
[ 191337-05-0 ]
[ 25026-64-6 ]
3-chloro-N-{4-((7-chloroquinolin-4-yl)amino)cyclohexyl}-5-fluorobenzamide trifluoroacetic acid salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 1-hydroxy-7-aza-benzotriazole; In dichloromethane; ISOPROPYLAMIDE; for 2h;	A mixture of Example 23A (15 mg, 0.055 mmol), <strong>[25026-64-6]3-chloro-5-fluorobenzoic acid</strong> (14 mg, 0.083 mmol), solid supported dicyclohexanecarbodiimide(0.110 mmol), 1-hydroxy-7-azabenzotriazole (11.3 mg, 0.094 mmol) 2.5 ml dimethylacetamide/dichloromethane (2/3) was shaken for 2 hours, and filtered. The filtrate was the concentrated and the residue was purified by HPLC to provide the desired compound as its trifluoroacetic acid salt. MS (ESI(+)Q1MS m/z 432 (M+H)+; 1H NMR (300 MHz, DMSO) delta ppm 8.84 (d, 1H), 8.71 (d, 1H), 8.56 (d, 1H), 8.35 (d, 1H), 7.95 (d, 1H), 7.83 (m, 1H), 7.81 (dd, 1H), 7.69 (m, 1H), 7.65 (dt, 1H), 7.00 (d, 1H), 3.99 (m, 2H), 1.98-2.03 (m, 4H), 1.73-1.83 (m, 4H).

Reference： [1]Patent: US2003/229119,2003,A1 .Location in patent: Page 62

Yield	Reaction Conditions	Operation in experiment
15.14g (85%)		3-Chloro-5-fluorobenzoic Acid A mixture of 1-bromo-3-chloro-5-fluorobenzene (25.0 g, 120 mmol), zinc cyanide (8.45 g, 72 mmol) zinc (dust, 235 mg, 3.6 mmol), [1,1'Bis(diphenylphosphino)ferrocene] dichloropalladium(II), complex with dichloromethane (1:1) (1.5 g, 1.8 mmol) in N,N-dimethylformamide (70 ml) was heated at reflux for 1 hour. After cooling the reaction was diluted with ethyl acetate and extracted with water and brine. Silica gel chromatography afforded 15.9g (85%) 3-chloro-5-fluorobenzonitrile. The intermediate nitrile was treated with a solution of sodium hydroxide (100 mL of 10 N solution, 1 mol) in 100 mL water and heated at reflux for 2 hours. After this time the solution was cooled and acidified with concentrated hydrochloric acid. Extraction with dichloromethane and evaporation of the solvent, afforded 15.14g (85%) of 3-chloro-5-fluorobenzoic acid.

3
[ 79-37-8 ]
[ 25026-64-6 ]
[ 886496-62-4 ]

Yield	Reaction Conditions	Operation in experiment
	N,N-dimethyl-formamide; In dichloromethane;	3-Chloro-5-fluorobenzoic acid (400 mg, 2.3 mmol) was treated with a solution of oxalyl chloride (4.6 mL of 2.5 M in dichloromethane, 11.5 mmol) and a catalytic amount of N,N-dimethylformamide. The reaction was stirred at ambient temperature for 2.5 hours. The excess oxalyl chloride was removed in vacuo to afford 3-chloro-5-fluorobenzoyl chloride.

Reference： [1]Patent: US2003/55085,2003,A1

4
[ 327056-55-3 ]
[ 79-37-8 ]
[ 25026-64-6 ]
[ 453566-59-1 ]

Yield	Reaction Conditions	Operation in experiment
	In dichloromethane; N,N-dimethyl-formamide;	3-(5-Chloropyrid-2-yl)-5-(3-chloro-5-fluorophenyl)-1,2,4-oxadiazole Using the general procedure for the preparation of acid chlorides, 3-chloro-5-fluorobenzoyl chloride is prepared from <strong>[25026-64-6]3-chloro-5-fluorobenzoic acid</strong> using a solution of oxalyl chloride in dichloromethane and a catalytic amount of N,N-dimethylformamide. Treatment of the intermediate acid chloride in dichloromethane with 1 equivalent of 5-chloropyrid-2-ylamidoxime followed by heating in N,N-dimethylformamide overnight at 110 C. affords crude product. Standard work up and purification by one or more methods, including silica gel chromatography, recystallization, and trituration, affords purified 3-(5-chloropyrid-2-yl)-5-(3-chloro-5-fluorophenyl)-1,2,4-oxadiazole.

Reference： [1]Patent: US2003/55085,2003,A1

5
[ 79-37-8 ]
[ 25026-64-6 ]
[ 453565-48-5 ]
[ 453566-66-0 ]

Yield	Reaction Conditions	Operation in experiment
	In dichloromethane; N,N-dimethyl-formamide;	3-(5-Cyanopyrid-2-yl)-5-(3-fluoro-5-chlorophenyl)-1,2,4-oxadiazole Using the general procedure for the preparation of acid chlorides, 3-chloro-5-fluorobenzoyl chloride is prepared from <strong>[25026-64-6]3-chloro-5-fluorobenzoic acid</strong> using a solution of oxalyl chloride in dichloromethane and a catalytic amount of N,N-dimethylformamide. Treatment of the intermediate acid chloride in dichloromethane with 1 equivalent of 5-cyanopyrid-2-ylamidoxime followed by heating in N,N-dimethylformamide overnight at 110 C. affords crude product. Standard work up and purification by one or more methods, including silica gel chromatography, recystallization, and trituration, affords purified 3-(5-cyanopyrid-2-yl)-5-(3-chloro-5-fluorophenyl)-1,2,4-oxadiazole.

Reference： [1]Patent: US2003/55085,2003,A1

6
[ 79-37-8 ]
[ 25026-64-6 ]
[ 327056-58-6 ]
[ 453566-63-7 ]

Yield	Reaction Conditions	Operation in experiment
	In dichloromethane; N,N-dimethyl-formamide;	3-(5-Fluoropyrid-2-yl)-5-(3-fluoro-5-chlorophenyl)-1,2,4-oxadiazole Using the general procedure for the preparation of acid chlorides, 3-chloro-5-fluorobenzoyl chloride is prepared from <strong>[25026-64-6]3-chloro-5-fluorobenzoic acid</strong> using a solution of oxalyl chloride in dichloromethane and a catalytic amount of N,N-dimethylformamide. Treatment of the intermediate acid chloride in dichloromethane with 1 equivalent of 5-fluoropyrid-2-ylamidoxime followed by heating in N,N-dimethylformamide overnight at 110 C. affords crude product. Standard work up and purification by one or more methods, including silica gel chromatography, recystallization, and trituration, affords purified 3-(5-fluororopyrid-2-yl)-5-(3-chloro-5-fluorophenyl)-1,2,4-oxadiazole.

Reference： [1]Patent: US2003/55085,2003,A1

7
[ 25026-64-6 ]
[ 327056-75-7 ]

Yield	Reaction Conditions	Operation in experiment
13.6g (92%)	With thionyl chloride; In methanol;	3-Fluoro-5-cyanobenzoic Acid 3-Chloro-5-fluorobenzoic acid (13.74g, 78.7 mmol) was treated with 50 ml thionyl chloride and heated at reflux for 2 hours. The excess thionyl chloride was removed in vacuo and the residue treated with 100 ml dry methanol to afford 13.6g (92%) of methyl 3-chloro-5-fluorobenzoate.

Reference： [1]Patent: US2003/55085,2003,A1

8
[ 25026-64-6 ]
[ 75-65-0 ]
[ 940054-42-2 ]

Yield	Reaction Conditions	Operation in experiment
81%	With diphenyl phosphoryl azide; N-ethyl-N,N-diisopropylamine; In toluene; for 16h;Heating / reflux;	Stage 1: (3-chloro-5-fluorophenyl)-carbamic acid tert-butyl ester A solution of <strong>[25026-64-6]3-chloro-5-fluorobenzoic acid</strong> (2.44 g, 14.0 mmol), diisopropylethylamine (2.8 ml, 2.20 g, 17 mmol) and azidophoshoric acid diphenyl ester (3.7 ml, 4.70 g, 17 mmol) in toluene (10 ml) and tert-butanol (10 ml) was heated under reflux for 16 h. The reaction mixture was then concentrated in vacuo. The residue was taken up in water (20 ml) and the mixture was extracted with ethyl acetate/cyclohexane 1:4 (4*10 ml). The combined organic phases were washed with sodium chloride solution, dried with magnesium sulfate and concentrated. The crude product (4.1 g) was purified by flash chromatography with ethyl acetate/cyclohexane (1:6). Yield: 2.79 g (81%), white solid. Melting point: 55-58 C.

Reference： [1]Patent: US2008/293749,2008,A1 .Location in patent: Page/Page column 11

9
[ 25026-64-6 ]
[ 768-35-4 ]
[ 1214352-53-0 ]

Yield	Reaction Conditions	Operation in experiment
100%		Step 1. 3',5-Difluoro-[1,1'-biphenyl]-3-carboxylic acidA 2 dram vial was charged with (3-fluorophenyl)boronic acid (168 mg, 1.2 mmol), <strong>[25026-64-6]3-chloro-5-fluorobenzoic acid</strong> (175 mg, 1.0 mmol), potassium carbonate (345 mg, 2.5 mmol), palladium acetate (1.1 mg, 0.005 mmol) and 2-dicyclohexylphosphino-2,6-dimethoxy-3-sulfonato-1,1'-biphenyl hydrate sodium salt (5 mg, 0.01 mmol). The vial was fitted with a septum cap, degassed water (1.5 mL) was added and the mixture was purged with nitrogen and stirred at room temperature. After stirring for 4 d, the mixture was diluted with water (30 mL), acidified to pH 4 with 1.0 N aqueous HCl and extracted with EtOAc (3×25 mL). The combined extracts were dried (Na2SO4), filtered and concentrated in vacuo to afford 235 mg (quant.) of 3',5-difluoro-[1,1'-biphenyl]-3-carboxylic acid which was used without further purification.

Reference： [1]Patent: US2011/184055,2011,A1 .Location in patent: Page/Page column 8

10
[ 25026-64-6 ]
[ 1357920-41-2 ]
[ 1357920-49-0 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 6523 - 6540

11
[ 25026-64-6 ]
[ 107-31-3 ]
3-chloro-5-fluoro-4-formylbenzoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
51.2%		To a solution of <strong>[25026-64-6]3-chloro-5-fluorobenzoic acid</strong> (28.6 mmol, 5000 mg) in 2- methyltetrahydrofuran (100 ml_) N1 ,N1 ,N2,N2-tetramethylethane-1 ,2-diamine (63.0 mmol, 9.51 ml), was added at room temperature. The resulting solution was cooled at -785C. Afterward, butyllithium (68.7 mmol, 27.5 ml) was added drop- wise, during which the temperature of the mixture remained at less than -655C. The mixture was then stirred at -785C for 1 .5 h. Anhydrous methyl formate (60.2 mmol, 3.71 ml) was added dropwise at a rate that allowed the temperature to be maintained at less than -655C. The resulting solution was allowed to warm at room temperature and then maintained at room temperature while being stirred for 18 h. The reaction was then cooled to 05C, and excess base was quenched with 1 M HCI aqueous solution (40 ml_). The phases were then separated, and the aqueous layer was extracted 3 times with EtAcO. The combined organic phases were washed with brine, dried over anhydrous MgS04, filtered, and concentrated under vacuum. The residue was dissolved in EtAcO (8 ml_) at reflux, and cooled to room temperature. Hexanes (10 ml_) were then added, and the resulting mixture was further cooled to 05C. The solid was collected by filtration, rinsed with hexanes, and dried under vacuum. (2970 mg, yield: 51 .2%). LC-MS: tR = 0.63 [M+H]" = 201 (method 6) 1 H NMR (300 MHz, DMSO-d6) delta 10.32 (1 H, s) 8.47 (1 H, brs), 7.96-769 (2H, m).

Reference： [1]Patent: WO2013/149997,2013,A1 .Location in patent: Page/Page column 248; 149

12
[ 25026-64-6 ]
5-((10H-phenothiazin-10-yl)methyl)-4-amino-4H-1,2,4-triazole-3-thiol [ No CAS ]
10-((6-(3-chloro-5-fluorophenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-3-yl)methyl)-10H-phenothiazine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With trichlorophosphate;Reflux;	General procedure: An equimolar mixture of compound 5 (10 mmol) andaromatic acids 6 (10 mmol) in phosphorus oxychloride (10mL) was refluxed for 46 h. The reaction mixture wascooled to room temperature and then gradually poured on tocrushed ice with stirring. The mixture was allowed to standovernight and the solid which separated out was filtered,treated with dilute sodium hydroxide solution and washedthoroughly with cold water.

Reference： [1]Letters in drug design and discovery,2013,vol. 10,p. 977 - 983

13
[ 25026-64-6 ]
2-(5-fluoropyridin-2-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine [ No CAS ]
(3-chloro-5-fluorophenyl)[2-(5-fluoropyridine-2-yl)-6,7-dihydropyrazolo[1,5-a]pyrazin-5(4H)-yl]methanone [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 3866 - 3869

14
[ 25026-64-6 ]
2-(5-fluoropyridine-2-yl)-4,5,6,7-tetrahydro[1,3]oxazolo[4,5-c]pyridine [ No CAS ]
(3-chloro-5-fluorophenyl)[2-(5-fluoropyridine-2-yl)-6,7-dihydro[1,3]oxazolo[4,5-c]pyridine-5(4H)-yl]methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.2 g	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20℃; for 16h;	The DMF (20 mL) solution of the manufacture working example 1-3 (0.88g) <strong>[25026-64-6]3-chloro-5-fluorobenzoic acid</strong> (0.72g), an EDC hydrochloride (1.15g), and a HOBt monohydrate (0.81g) in addition, it stirred at the room temperature for 16 hours. Water was added to the reaction mixture and ethyl acetate extracted twice. After the saturated sodium chloride solution's having washed the doubled organic layer and drying with magnesium sulfate, decompression distilling off of the solvent was carried out. Silica gel column chromatography (NH silica gel, hexane / ethyl acetate =3/1-1/2) refined residue, and it obtained the title compound (1.20g) as a solid.

Reference： [1]Patent: JP2016/11257,2016,A .Location in patent: Paragraph 0093-0094

15
[ 25026-64-6 ]
C₁₅H₂₀N₂O₂ [ No CAS ]
benzyl 1-(3-chloro-5-fluorobenzamido)-6-azaspiro[2.5]octane-6-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 12h;	To a solution of the crude product from Step F (500mg) in DCM (15 mL) was added EDCI (522 mg, 2.7 mmol), HOBT (366 mg, 2.7 mmol), DIPEA (464 mg, 3.6 mmol) and <strong>[25026-64-6]3-chloro-5-fluorobenzoic acid</strong> (470 mg, 2.7 mmol). The reaction mixture was stirred at rt for 12 h, then diluted with DCM (100 mL), washed successively with sat. aq. NH4C1 solution, sat. aq. NaHCO3, water and brine and concentrated. The residue was purified by silica gel chromatography (hexanes / EtOAc = 2:1) to afford the product benzyl (R)-1-(3- chloro-5 -fluorobenzamido)-6-azaspiro[2.5] octane-6-carboxyl ate or benzyl (S)-i -(3 -chloro-5 - fluorobenzamido)-6-azaspiro[2.5]octane-6-carboxylate as a yellow oil (600 mg, 80% yield). Mass Spectrum (ESI) m/z = 417 (M+1).

Reference： [1]Patent: WO2017/83867,2017,A1 .Location in patent: Paragraph 00396

16
[ 25026-64-6 ]
[ 940054-45-5 ]

Reference： [1]Patent: US2008/293749,2008,A1

17
[ 25026-64-6 ]
[ 940054-46-6 ]

Reference： [1]Patent: US2008/293749,2008,A1

18
[ 25026-64-6 ]
[ 940054-44-4 ]

Reference： [1]Patent: US2008/293749,2008,A1

19
[ 25026-64-6 ]
[ 940054-48-8 ]

Reference： [1]Patent: US2008/293749,2008,A1

20
[ 25026-64-6 ]
[ 940054-43-3 ]