425379-16-4|2-Bromo-3-fluorobenzonitrile| Ambeed

CAS No. :	425379-16-4
Formula :	C₇H₃BrFN
M.W :	200.01
SMILES Code :	N#CC1=CC=CC(F)=C1Br
MDL No. :	MFCD07368773
InChI Key :	DBECKESJFGWYFN-UHFFFAOYSA-N
Pubchem ID :	2783393

Safety of [ 425379-16-4 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302
Precautionary Statements:	P280-P305+P351+P338

Computational Chemistry of [ 425379-16-4 ] Show Less

Physicochemical Properties

Num. heavy atoms	10
Num. arom. heavy atoms	6
Fraction Csp3	0.0
Num. rotatable bonds	0
Num. H-bond acceptors	2.0
Num. H-bond donors	0.0
Molar Refractivity	38.81
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	23.79 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.84
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	2.43
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.88
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.	2.63
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	2.9
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	2.54

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-3.05
Solubility	0.176 mg/ml ; 0.000881 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.	-2.57
Solubility	0.535 mg/ml ; 0.00268 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	-3.62
Solubility	0.0481 mg/ml ; 0.00024 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	Yes
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.	-5.79 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.	0.55

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)	1.7

Application In Synthesis of [ 425379-16-4 ]

* 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 [ 425379-16-4 ]

[ 425379-16-4 ] Synthesis Path-Downstream 1~55

1
[ 425378-68-3 ]
[ 425379-16-4 ]
[ 425379-17-5 ]

Yield	Reaction Conditions	Operation in experiment
		2-Bromo-3-fluorobenzonitrile (2.50 g, 12.5 mmol) was coupled to 2-(2-fluoro-5-nitrophenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane as described in Example 1 to give 6,2'-difluoro-5'-nitrobiphenyl-2-carbonitrile as a black solid: 1H NMR (360 MHz, CDCl3) delta 7.40-7.44 (1H, m), 7.47-7.52 (1H, m), 7.59-7.67 (2H, m), 8.37-8.44 (2H, m).

References: [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 35 - 38.
[2]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 1582 - 1585.
[3]Journal of Medicinal Chemistry,2006,vol. 49,p. 1235 - 1238.
[4]Patent: US2003/55060,2003,A1 .

2
[ 115661-37-5 ]
[ 425379-16-4 ]

Yield	Reaction Conditions	Operation in experiment
53%		To a solution of 2-amino-3-fluorobenzonitrile (17.07 g, 0.125 mol) in 1,4-dioxane (20 ml) was added 48% aqueous hydrobromic acid (200 ml) and the solution was cooled to 0C before adding dropwise a solution of sodium nitrite (9.95 g, 0.144 mol) in water (22 ml) over 35 min so that the temperature did not rise above 3C. The resulting mixture was stirred at 2-3C for 2 h then poured onto a cooled (5C) solution of copper (I) bromide (26.98 g, 0.188 mol) in 48% hydrobromic acid (100 ml). The mixture was stirred for 10 min then heated to 50C over 1 h. The mixture was cooled to ambient temperature, diluted with water (11) and extracted with diethyl ether (2 x 500 ml). The combined organic extracts were washed with 1 M aqueous Na2SO3 (500 ml), then saturated aqueous NH4C1 (200 ml), dried (MgSO4), and evaporated to give a brown oil/solid. Purification by chromatography (silica gel, 10% EtOAc/isohexane) and trituration of a mixed fraction with isohexane afforded 13.22 g (53%) of 2-bromo-3- fluorobenzonitrile as a pale yellow solid : 1H NMR (360 MHz, CDCl3) 5 7.62-7. 68 (1H, m), 7.74-7. 85 (1H, ddd, J 9, 9,1), 7.74-7. 85 (1H, ddd, J 8, 1, 1).
		2-Amino-3-fluorobenzonitrile (9.8 g, 71.9 mmol) was bromo-deaminated as described in Example 1 to afford 2-bromo-3-fluorobenzonitrile as a pale brown solid: 1H NMR (360 MHz, CDCl3) delta 7.62-7.68 (1H, m), 7.74-7.85 (1H, ddd, J 9, 9, 1 Hz), 7.74-7.85 (1H, ddd, J 8, 1, 1 Hz).

References: [1]Patent: WO2003/93272,2003,A1 .Location in patent: Page/Page column 36-37.
[2]Journal of Medicinal Chemistry,2006,vol. 49,p. 1235 - 1238.
[3]Patent: US2003/55060,2003,A1 .

3
[ 21524-39-0 ]
[ 425379-16-4 ]

References: [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 1235 - 1238.

4
[ 425379-16-4 ]
[ 425379-21-1 ]

References: [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 1235 - 1238.
[2]Journal of Organic Chemistry,2005,vol. 70,p. 5938 - 5945.
[3]Patent: WO2011/11712,2011,A1 .

5
[ 425379-16-4 ]
TPA₀₂₃B [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 1235 - 1238.
[2]Journal of Organic Chemistry,2005,vol. 70,p. 5938 - 5945.
[3]Journal of Organic Chemistry,2005,vol. 70,p. 5938 - 5945.
[4]Journal of Organic Chemistry,2005,vol. 70,p. 5938 - 5945.

6
[ 425379-16-4 ]
[ 425379-18-6 ]

References: [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 1235 - 1238.

7
[ 425379-16-4 ]
[ 488799-60-6 ]

References: [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 1235 - 1238.

8
[ 425379-16-4 ]
3',5'-dibromo-6,2'-difluoro-biphenyl-2-carbonitrile [ No CAS ]

References: [1]Journal of Organic Chemistry,2005,vol. 70,p. 5938 - 5945.

10
[ 731817-89-3 ]
[ 425379-16-4 ]
[ 731817-94-0 ]