2-Bromo-4-fluoro-5-methylbenzoic acid

Cat.NO.:A1475881 Purity:99+%

Product Details of [ 1003709-39-4 ]

CAS No. :	1003709-39-4
Formula :	C₈H₆BrFO₂
M.W :	233.03
SMILES Code :	O=C(O)C1=CC(C)=C(F)C=C1Br
MDL No. :	MFCD09263434
InChI Key :	UVSGTNJGIMPLAM-UHFFFAOYSA-N
Pubchem ID :	45073546

Safety of [ 1003709-39-4 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Computational Chemistry of [ 1003709-39-4 ] Show Less

Physicochemical Properties

Num. heavy atoms	12
Num. arom. heavy atoms	6
Fraction Csp3	0.12
Num. rotatable bonds	1
Num. H-bond acceptors	3.0
Num. H-bond donors	1.0
Molar Refractivity	46.03
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.	1.61
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	2.6
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	3.02
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.	3.09
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	2.77
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	2.62

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-3.23
Solubility	0.138 mg/ml ; 0.000593 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.	-3.03
Solubility	0.216 mg/ml ; 0.000928 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	-3.3
Solubility	0.118 mg/ml ; 0.000505 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.	-5.88 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	0.0
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)	1.56

Application In Synthesis of [ 1003709-39-4 ]

* 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.

Downstream synthetic route of [ 1003709-39-4 ]

[ 1003709-39-4 ] Synthesis Path-Downstream 1~6

1
[ 1003709-39-4 ]
[ 1610472-28-0 ]

References: [1]Patent: WO2014/76104,2014,A1 .

2
[ 1003709-39-4 ]
[ 1610472-53-1 ]

Yield	Reaction Conditions	Operation in experiment
74%	With N-Bromosuccinimide; dibenzoyl peroxide; In acetonitrile; for 4.0h;Reflux;	A mixture of 2-bromo-4-fluoro-5-methyl-benzoic acid (0.5 g, 2.14 mmol), N-bromosuccinimide (381 mg, 2.15 mmol) and benzoyl peroxide (10 mg, 0.04 mmol) in CH3CN (10 mL) was heated at reflux for 4 h. The reaction mixture was cooled to 0 C and 5% aqueous Na2S203 was added. The CH3CN was evaporated and the residue was extracted with EtOAc (3 x 100 mL). The combined organic phases were dried (Na2S04), filtered, and evaporated. The residue was purified by chromatography (silica gel, 2-20% EtOAc/hexane) to give 2-bromo-5-bromomethyl- 4-fluoro-benzoic acid (500 mg, 74%). MS calcd. for C8H6Br2F02 [(M-H) ] 309, obsd. 308.6.

References: [1]Patent: WO2014/76104,2014,A1 .Location in patent: Page/Page column 76-77.

3
[ 1003709-39-4 ]
[ 1610472-54-2 ]

References: [1]Patent: WO2014/76104,2014,A1 .

4
[ 1003709-39-4 ]
[ 1610472-55-3 ]

References: [1]Patent: WO2014/76104,2014,A1 .

5
[ 1003709-39-4 ]
[ 1610472-56-4 ]

References: [1]Patent: WO2014/76104,2014,A1 .

6
[ 916792-17-1 ]
[ 1003709-39-4 ]

Yield	Reaction Conditions	Operation in experiment
93%	With sodium chlorite; potassium dihydrogenphosphate; aminosulfonic acid; In 1,4-dioxane; water; at 20.0℃;	A mixture of 2-bromo-4-fluoro-5-methyl-benzaldehyde (available from 3B Scientific Corporation, 1840 Industrial Drive, Suite 160, LibertyviUe, IL 60048, USA; 1.0 g, 4.61 mmol), sulfamic acid (2.68 g, 27.65 mmol), sodium chlorite (539 mg, 6 mmol) and KH2P04 (7.52 g, 55.3 mmol) in 50% aqueous dioxane (96 mL) was stirred at room temperature overnight. The reaction mixture was concentrated, and water (20 mL) was added. The resulting mixture was extracted with EtOAc (3 x 250 mL). The combined organic layers were dried (Na2S04), filtered, and evaporated to give 2-bromo-4-fluoro-5-methyl-benzoic acid (1.0 g, 93%) as an off-white solid. MS calcd. for C8H7BrF02 [(M-H) ] 231, obsd. 231.0.

References: [1]Patent: WO2014/76104,2014,A1 .Location in patent: Page/Page column 76.

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2-Bromo-4-fluoro-5-methylbenzoic acid

Product Details of [ 1003709-39-4 ]

Safety of [ 1003709-39-4 ]

Computational Chemistry of [ 1003709-39-4 ] Show Less

Physicochemical Properties

Lipophilicity

Water Solubility

Pharmacokinetics

Druglikeness

Medicinal Chemistry

Application In Synthesis of [ 1003709-39-4 ]

[ 1003709-39-4 ] Synthesis Path-Downstream 1~6

Details

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3-Amino-4-bromobenzene-1-sulfonamide

2-Bromo-5-fluoro-4-methylbenzoic acid

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