[ CAS No. 4864-01-1 ] {[proInfo.proName]}

Name: 4864-01-1|2-Methoxy-5-(trifluoromethyl)benzoic acid|97%
Brand: Ambeed
SKU: A362194
Price: 5.0 USD
Availability: InStock
Rating: 91 (40 reviews)

,{[proInfo.pro_purity]}

Cat. No.: {[proInfo.prAm]}

DV 2D 3D

3d Animation Molecule Structure of 4864-01-1

Structure of 4864-01-1 * Storage: {[proInfo.prStorage]}

Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

For Research Only 110K+ Compounds Competitive Price 1-2 Day Shipping

Quality Control of [ 4864-01-1 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 4864-01-1 ]

SDS Specification

Alternatived Products of [ 4864-01-1 ]

Product Details of [ 4864-01-1 ]

CAS No. :	4864-01-1	MDL No. :	MFCD01862091
Formula :	C₉H₇F₃O₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	NAKZCKOHULJEID-UHFFFAOYSA-N
M.W :	220.15	Pubchem ID :	13585909
Synonyms :

Calculated chemistry of [ 4864-01-1 ]

Physicochemical Properties

Num. heavy atoms :	15
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.22
Num. rotatable bonds :	3
Num. H-bond acceptors :	6.0
Num. H-bond donors :	1.0
Molar Refractivity :	44.9
TPSA :	46.53 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.89 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.56
Log Po/w (XLOGP3) :	2.47
Log Po/w (WLOGP) :	3.56
Log Po/w (MLOGP) :	2.36
Log Po/w (SILICOS-IT) :	2.29
Consensus Log Po/w :	2.45

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.86
Solubility :	0.305 mg/ml ; 0.00138 mol/l
Class :	Soluble
Log S (Ali) :	-3.09
Solubility :	0.178 mg/ml ; 0.00081 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.79
Solubility :	0.355 mg/ml ; 0.00161 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.62

Safety of [ 4864-01-1 ]

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 [ 4864-01-1 ]

* 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 [ 4864-01-1 ]
Downstream synthetic route of [ 4864-01-1 ]

[ 4864-01-1 ] Synthesis Path-Upstream 1~5

1
[ 124-38-9 ]
[ 402-52-8 ]
[ 4864-01-1 ]

Reference： [1] Patent: WO2011/25982, 2011, A2, . Location in patent: Page/Page column 145

2
[ 124-38-9 ]
[ 402-10-8 ]
[ 1068-55-9 ]
[ 4864-01-1 ]
[ 79-31-2 ]

Reference： [1] Patent: US2007/88070, 2007, A1, . Location in patent: Page/Page column 17

3
[ 328-87-0 ]
[ 4864-01-1 ]

Reference： [1] Patent: US3953595, 1976, A,

4
[ 402-45-9 ]
[ 4864-01-1 ]

Reference： [1] Patent: WO2011/25982, 2011, A2,

5
[ 4864-01-1 ]
[ 79427-88-6 ]

Reference： [1] Patent: WO2011/38572, 2011, A1, . Location in patent: Page/Page column 82
[2] Patent: WO2015/8230, 2015, A1, . Location in patent: Page/Page column 192

[ 4864-01-1 ] Synthesis Path-Downstream 1~56

1
[ 4864-01-1 ]
[ 64507-07-9 ]

Yield	Reaction Conditions	Operation in experiment
	With thionyl chloride; for 2h;Heating / reflux;	Example 38B 2-methoxy-5-(trifluoromethyl)benzoyl chloride A solution of the <strong>[4864-01-1]2-methoxy-5-(trifluoromethyl)benzoic acid</strong> (0.68 g, 3.1 mmol) in thionyl chloride (10 mL) was warmed to reflux and was allowed to stir for 2 h. The mixture was cooled to ambient temperature, concentrated under reduced pressure and diluted with 10 mL toluene. This material was again concentrated under reduced pressure and was again diluted with 10 mL toluene. This concentration and dilution was repeated for an additional time and the crude acid chloride was carried on.
	With thionyl chloride; for 2h;Heating / reflux;	Step B Ethyl 3-[2-methoxy-5-(trifluoromethyl)phenyl]-3-oxopropanoate. <strong>[4864-01-1]2-Methoxy-5-(trifluoromethyl)benzoic acid</strong> (2.11 g) was refluxed in thionyl chloride (5 mL) for 2 hr, the excess reagent was evaporated off and vacuum dried to constant weight. This residue was dissolved in dry ethyl acetate (20 mL) and added slowly to a suspension which was prepared by mixing potassium ethyl malonate (1.85 g, 12 mMol), MgCl2 (1.26 g, 14 mmol), and triethylamine (5.6 mL, 40 mmol) in dry ethyl acetate (30 mL) at 45 C. for 12 hr. The resulting mixture was stirred at room temperature overnight, then washed with 2N HCl, brine, and dried over Na2SO4. Flash column chromatography eluding with a gradient 0 to 10% ethyl acetate:hexane (1% HOAc) to give the title compound as a colorless oil. 1H-NMR (500 MHz, CDCl3) delta:1.22 (t, 3H); 3.96 (s, 3H); 3.97 (s, 2H); 4.18 (q, 2H); 7.07 (d, 1H); 7.75 (d, 1H); 8.16 (s, 1H); This compound in CDCl3 also exists in the enol form in a ratio of 1:8 enol:keto form.
	With thionyl chloride; for 2h;Reflux;	General procedure: A solution of 24 (1.0 equiv.) in SOCl2 (40.5 equiv.) was heated under reflux for 2 hours. After cooling, the reaction mixture was concentrated under vacuum. Crude residue was diluted in DCM and cooled at 0C. The appropriate amine (1.2 equiv.) and Et3N (2.0 equiv.) were added and the resulting mixture was stirred at rt overnight. The solution was washed successively with a solution of HCl 2N, a saturated solution of NaHCO3 and brine, dried over Na2SO4 and concentrated under vacuum. The resulting solid was then purified by column chromatography on silica gel using the appropriate heptanes:EtOAc mixture.

With thionyl chloride; In toluene; for 2h;Reflux;

Example 1B 2-methoxy-5-(trifluoromethyl)benzoyl chloride A solution of <strong>[4864-01-1]2-methoxy-5-(trifluoromethyl)benzoic acid</strong> (0.68 g, 3.1 mmol) in thionyl chloride (10 mL) was warmed to reflux and was allowed to stir for 2 h. The mixture was cooled to ambient temperature, concentrated under reduced pressure and diluted with 10 mL of toluene. This material was again concentrated under reduced pressure and was again diluted with 10 mL of toluene. This concentration and dilution was repeated for an additional time and the crude acid chloride was carried on to the next step.

Reference： [1]Journal of Medicinal Chemistry,1998,vol. 41,p. 2939 - 2945
[2]Patent: US2008/242654,2008,A1 .Location in patent: Page/Page column 41
[3]Patent: US2007/88070,2007,A1 .Location in patent: Page/Page column 17
[4]Chemistry and biodiversity,2012,vol. 9,p. 2618 - 2634
[5]Organometallics,2017,vol. 36,p. 1810 - 1821
[6]Journal of Organic Chemistry,2018,vol. 83,p. 9929 - 9938
[7]European Journal of Medicinal Chemistry,2019,vol. 177,p. 269 - 290
[8]Patent: US2009/247500,2009,A1 .Location in patent: Page/Page column 21

2
[ 4864-01-1 ]
[ 98482-39-4 ]
2-Methoxy-N-((2R,6S,9aS)-6-methyl-octahydro-quinolizin-2-yl)-5-trifluoromethyl-benzamide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,1999,vol. 9,p. 2177 - 2180

4
[ 4864-01-1 ]
2-Hydroxy-N-((2S,6R,9aR)-6-methyl-octahydro-quinolizin-2-yl)-5-trifluoromethyl-benzamide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,1999,vol. 9,p. 2177 - 2180

5
[ 4864-01-1 ]
N-(3,4-Dichloro-phenyl)-2-hydroxy-5-trifluoromethyl-benzamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1998,vol. 41,p. 2939 - 2945

6
[ 4864-01-1 ]
N-(3,4-Dichloro-phenyl)-2-methoxy-5-trifluoromethyl-benzamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1998,vol. 41,p. 2939 - 2945

7
[ 4864-01-1 ]
N-{5-Chloro-4-[(4-chloro-phenyl)-cyano-methyl]-2-methyl-phenyl}-2-hydroxy-5-trifluoromethyl-benzamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1998,vol. 41,p. 2939 - 2945

8
[ 4864-01-1 ]
N-{5-Chloro-4-[(4-chloro-phenyl)-cyano-methyl]-2-methyl-phenyl}-2-methoxy-5-trifluoromethyl-benzamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1998,vol. 41,p. 2939 - 2945

9
[ 328-87-0 ]
[ 4864-01-1 ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 28 2-Methoxy-5-trifluoromethylbenzoic Acid Starting with 4-chloro-3-cyanobenzotrifluoride and sodium methoxide and following the procedure of Example 4, the above product is prepared, m.p. 105-106.5 C. Netherlands Application 6,507,712 (C.A., 64, 12606g) reports a melting point of 103-105 C. for this compound. In a similar manner are prepared 2-methoxy-3-trifluoromethylbenzoic acid and 3-trifluoromethyl-4-methoxybenzoic acid.

Reference： [1]Patent: US3953595,1976,A

10
[ 1075243-02-5 ]
[ 4864-01-1 ]
[ 1075243-41-2 ]

Yield	Reaction Conditions	Operation in experiment
63%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In tetrahydrofuran; at 60℃; for 12h;	Example 127; N-r(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-2-methoxy-5-(trifluoromethyl)benzamide; To a solution of Example HOB (1.0 g, 4.7 mmol) in THF (50 mL) were added 2- methoxy-5-(trifluoromethyl)benzoic acid (1.1 g, 5.2 mmol, JRD Fluorochemicals Ltd), N-(3- dimethylaminopropyl)-N-ethylcarbodimide hydrochloride (1.0 g, 5.2 mmol, Aldrich), 1- hydroxybenzotriazole (0.8 g, 5.2 mmol, Aldrich) and triethylamine (2.0 mL, 14.3 mmol, Aldrich). The mixture was stirred at 60 0C for 12 hr. The reaction mixture was then cooled to room temperature, diluted with 1 M aqueous NaHCO3 (50 mL) and extracted with ethyl acetate (2 X 50 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated. The residue was purified by column chromatography using an AnalogixIntellifiash280 (SiO2, 0-50% ethyl acetate in hexanes) to afford 1.23 g (63%) of the title compound. 1H NMR (300 MHz, DMSO-d6) delta ppm 0.93 (t, J=7.3 Hz, 3 H), 1.17 - 1.45 (m, 2 H), 1.62 (s, 9 H), 1.64 - 1.73 (m, 2 H), 2.64 - 2.80 (m, 2 H), 3.88 (s, 3 H), 7.30 (d, J=8.7 Hz, 1 H), 7.80 (dd, J=8.3, 2.8 Hz, 1 H), 8.08 (d, J=2.4 Hz, 1 H), 8.64 (s, 1 H); MS (ESI+) mZz 415 (M+H)+; Anal. Calculated C20H25F3N2O2S: C, 57.95; H, 6.08; N, 6.76. Found: C, 57.82; H, 5.92; N, 7.07.
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In tetrahydrofuran; at 60℃; for 12h;	Example 127; N-r(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene1-2-methoxy-5-(trifluoromethyl)benzamide; To a solution of Example HOB (1.0 g, 4.7 mmol) in THF (50 mL) were added 2- methoxy-5-(trifluoromethyl)benzoic acid (1.1 g, 5.2 mmol, JRD Fluorochemicals Ltd), N-(3- dimethylaminopropyl)-N-ethylcarbodimide hydrochloride (1.0 g, 5.2 mmol, Aldrich), 1- hydroxybenzotriazole (0.8 g, 5.2 mmol, Aldrich) and triethylamine (2.0 mL, 14.3 mmol,Aldrich). The mixture was stirred at 60 0C for 12 hr. The reaction mixture was then cooled to room temperature, diluted with 1 M aqueous NaHCO3 (50 mL) and extracted with ethyl acetate (2 X 50 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated. The residue was purified by column chromatography using an Analogix <n="107"/>Intelliflash280 (SiO2, 0-50% ethyl acetate in hexanes) to afford 1.23 g (63%) of the title compound. 1H NMR (300 MHz, DMSO-d6) delta ppm 0.93 (t, J=7.3 Hz, 3 H), 1.17 - 1.45 (m, 2 H), 1.62 (s, 9 H), 1.64 - 1.73 (m, 2 H), 2.64 - 2.80 (m, 2 H), 3.88 (s, 3 H), 7.30 (d, J=8.7 Hz, 1 H), 7.80 (dd, J=8.3, 2.8 Hz, 1 H), 8.08 (d, J=2.4 Hz, 1 H), 8.64 (s, 1 H); MS (ESI+) m/z 415 (M+H)+; Anal. Calculated C20H25F3N2O2S: C, 57.95; H, 6.08; N, 6.76. Found: C, 57.82; H, 5.92; N, 7.07.

Reference： [1]Patent: WO2010/54024,2010,A2 .Location in patent: Page/Page column 121
[2]Patent: WO2008/130953,2008,A2 .Location in patent: Page/Page column 105-106

11
[ 1140917-42-5 ]
[ 4864-01-1 ]
[ 1140918-36-0 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In tetrahydrofuran; at 60℃;	Example 66B N-[(2Z)-5-tert-butyl-3-[(2R)-tetrahydrofuran-2-ylmethyl]-1,3-oxazol-2(3H)-ylidene]-2-methoxy-5-(trifluoromethyl)benzamide To a solution of Example 66A (100 mg, 0.45 mmol) in tetrahydrofuran (4 mL) was added N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (85.0 mg, 0.45 mmol), 1-hydroxybenzotriazole (68.3 mg, 0.45 mmol), triethylamine (93 muL, 0.67 mmol) and <strong>[4864-01-1]2-methoxy-5-trifluoromethylbenzoic acid</strong> (Alfa) (98.0 mg, 0.45 mmol). The mixture was stirred at 60 C. overnight, cooled to room temperature, diluted with ethyl acetate, washed with 1 M aqueous NaHCO3, dried (MgSO4), filtered and concentrated. The residue was purified by column chromatography using an Analogix Intelliflash280 (SiO2, 0-50% ethyl acetate in hexanes) to provide the title product. MS (ESI+) m/z 428 (M+H)+; 1H NMR (300 MHz, CDCl3) delta ppm 1.15-1.19 (m, 1H), 1.20 (s, 9H), 1.61-1.72 (m, 1H), 1.83-1.96 (m, 2H), 2.02-2.15 (m, 1H), 3.68 (dd, J=14.3, 7.1 Hz, 1H), 3.75-3.87 (m, 2H), 3.89 (s, 3H), 4.02-4.12 (m, 1H), 4.14-4.25 (m, 1H), 6.53 (s, 1H), 6.97 (d, J=8.7 Hz, 1H), 7.58 (dd, J=8.7, 2.4 Hz, 1H), 8.06 (d, J=2.0 Hz, 1H).
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In tetrahydrofuran; at 60℃;	Example 66B; N-[(2Z)-5-tert-butyl-3-[(2R)-tetrahydrofuran-2-ylmethyl]-1,3-oxazol-2(3H)-ylidene]-2-methoxy-5-(trifluoromethyl)benzamide; To a solution of Example 66A (100 mg, 0.45 mmol) in tetrahydrofuran (4 mL) was added N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (85.0 mg, 0.45 mmol), 1-hydroxybenzotriazole (68.3 mg, 0.45 mmol), triethylamine (93 muL, 0.67 mmol) and <strong>[4864-01-1]2-methoxy-5-trifluoromethylbenzoic acid</strong> (Alfa) (98.0 mg, 0.45 mmol). The mixture was stirred at 60 C. overnight, cooled to room temperature, diluted with ethyl acetate, washed with 1 M aqueous NaHCO3, dried (MgSO4), filtered and concentrated. The residue was purified by column chromatography using an Analogix Intelliflash280 (SiO2, 0-50% ethyl acetate in hexanes) to provide the title product. MS (ESI+) m/z 428 (M+H)+; 1H NMR (300 MHz, CDCl3) delta ppm 1.15-1.19 (m, 1H), 1.20 (s, 9H), 1.61-1.72 (m, 1H), 1.83-1.96 (m, 2H), 2.02-2.15 (m, 1H), 3.68 (dd, J=14.3, 7.1 Hz, 1H), 3.75-3.87 (m, 2H), 3.89 (s, 3H), 4.02-4.12 (m, 1H), 4.14-4.25 (m, 1H), 6.53 (s, 1H), 6.97 (d, J=8.7 Hz, 1H), 7.58 (dd, J=8.7, 2.4 Hz, 1H), 8.06 (d, J=2.0 Hz, 1H).

Reference： [1]Patent: US2009/105306,2009,A1 .Location in patent: Page/Page column 44
[2]Patent: US2010/249129,2010,A1 .Location in patent: Page/Page column 46-47

12
[ 1140918-22-4 ]
[ 4864-01-1 ]
[ 1140918-23-5 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In tetrahydrofuran; at 60℃; for 16h;	Example 63D N-(3-tert-butyl-1-((tetrahydro-2H-pyran-2-yl)methyl)-1H-pyrazol-5-yl)-2-methoxy-5-(trifluoromethyl)benzamide To a solution of Example 63C (0.73 g, 3.1 mmol) in tetrahydrofuran (20 mL) were added <strong>[4864-01-1]2-methoxy-5-(trifluoromethyl)benzoic acid</strong> (0.68 g, 3.1 mmol, JRD Fluorochemicals), 1-hydroxybenzotriazole (0.47 g, 3.1 mmol, Aldrich), N-(3-dimethylaminopropyl)-N-ethylcarbodimide hydrochloride (0.59 g, 3.1 mmol) and triethylamine (1.3 mL, 9.2 mmol). After stirring at 60 C. for 16 h, the reaction mixture was cooled and quenched with saturated NaHCO3 (20 mL). The aqueous layer was extracted with ethyl acetate (3*20 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography using an Analogix Intelliflash280 (SiO2, 0-50% ethyl acetate in hexanes) to provide 0.2 g of the title compound. MS (ESI+) m/z 440 (M+H)+.
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In tetrahydrofuran; at 60℃; for 16h;	Example 63D; N-(3-tert-butyl-1-((tetrahydro-2H-pyran-2-yl)methyl)-1H-pyrazol-5-yl)-2-methoxy-5-(trifluoromethyl)benzamide; To a solution of Example 63C (0.73 g, 3.1 mmol) in tetrahydrofuran (20 mL) were added <strong>[4864-01-1]2-methoxy-5-(trifluoromethyl)benzoic acid</strong> (0.68 g, 3.1 mmol, JRD Fluorochemicals), 1-hydroxybenzotriazole (0.47 g, 3.1 mmol, Aldrich), N-(3-dimethylaminopropyl)-N-ethylcarbodimide hydrochloride (0.59 g, 3.1 mmol) and triethylamine (1.3 mL, 9.2 mmol). After stirring at 60 C. for 16 hours, the reaction mixture was cooled and quenched with saturated NaHCO3 (20 mL). The aqueous layer was extracted with ethyl acetate (3×20 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography using an Analogix Intelliflash280 (SiO2, 0-50% ethyl acetate in hexanes) to provide 0.2 g of the title compound. MS (ESI+) m/z 440 (M+H)+.

Reference： [1]Patent: US2009/105306,2009,A1 .Location in patent: Page/Page column 42
[2]Patent: US2010/249129,2010,A1 .Location in patent: Page/Page column 45

13
[ 124-38-9 ]
[ 402-10-8 ]
[ 1068-55-9 ]
[ 4864-01-1 ]
[ 79-31-2 ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 1; Step A 2-Methoxy-5-(trifluoromethyl)benzoic acid. A solution of 2-bromo-1-methoxy-4-(trifluoromethyl)-benzene (3 g, 11.2 mmol) in THF (5 mL) was added to a mixture of LiCl (0.5 g, 12 mmol) and isopropylmagnesium chloride (2 M in ether, 12 mL, 24 mmol) in THF (10 mL). After 15 h at room temperature the mixture was cooled to -78 C., and quenched with Dry Ice. The resulting mixture was allowed to warm up to room temperature and diluted with ethyl acetate, washed with 2N HCl. The ethyl acetate layer was then extracted with 5% K2CO3 three times. The combined base extracts was acidified and extracted with DCM twice. The DCM layer was then washed with brine, dried over Na2SO4. Evaporation of solvent yielded the title compound contaminated with isobutyric acid. 1H-NMR (500 MHz, CDCl3) delta: 4.12 (s, 3H); 7.16 (d, 1H); 7.81 (d, 1H); 8.41 (s, 1H).

Reference： [1]Patent: US2007/88070,2007,A1 .Location in patent: Page/Page column 17

14
[ 4864-01-1 ]
[ 74-88-4 ]
[ 1268463-99-5 ]