75279-55-9|2-Chloro-6-fluorophenylacetonitrile| Ambeed

CAS No. :	75279-55-9
Formula :	C₈H₅ClFN
M.W :	169.58
SMILES Code :	C1=C(C(=C(C=C1)Cl)CC#N)F
MDL No. :	MFCD00001900
InChI Key :	ZGSAFMIRVLOISC-UHFFFAOYSA-N
Pubchem ID :	123575

Safety of [ 75279-55-9 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302+H312+H332-H315-H319-H335
Precautionary Statements:	P261-P280-P305+P351+P338

Computational Chemistry of [ 75279-55-9 ] Show Less

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	0.0
Molar Refractivity	40.93
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.	1.83
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	2.31
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.97
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.	2.79
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	3.18
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.	-2.68
Solubility	0.351 mg/ml ; 0.00207 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.	-2.45
Solubility	0.605 mg/ml ; 0.00357 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	-3.78
Solubility	0.0283 mg/ml ; 0.000167 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.	-5.69 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	2.0
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)	1.59

Application In Synthesis of [ 75279-55-9 ]

* 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 [ 75279-55-9 ]

[ 75279-55-9 ] Synthesis Path-Downstream 1~55

1
[ 75279-55-9 ]
[ 149488-93-7 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In diethyl ether; water;	Example 116 N-(2-(2-fluoro-6-chloro)phenethyl)-N'-(2-thiazolyl)thiourea 2-Chloro-6-fluorophenylacetonitrile (2.5 g, 14.7 mmol) was dissolved in 30 ml diethyl ether. Lithium aluminium hydride (1.5 g) was added in small portions over a period of 10 minutes. The mixture was then heated to reflux for 15 minutes. After cooling to room temperature, 1.5 ml water, 1.5 ml aqueous sodium hydroxide, and 4 ml water was added slowly. The ether solution containing the product 2-chloro-6-fluorophenethylamine was decanted off and the solvent was removed in vacuo.

References: [1]Journal of Medicinal Chemistry,1995,vol. 38,p. 4929 - 4936.
[2]Patent: US5593993,1997,A .

2
[ 5941-55-9 ]
[ 75279-55-9 ]
Sodium; [3-cyano-4-fluoro-inden-(1Z)-ylidene]-ethoxy-methanolate [ No CAS ]

References: [1]Organic Letters,2004,vol. 6,p. 2357 - 2360.

3
[ 75279-55-9 ]
[ 185040-32-8 ]
6-(2-chloro-6-fluoro-phenyl)-8-methyl-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-one [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 1931 - 1935.

4
[ 1003-29-8 ]
[ 75279-55-9 ]
2-(2-chloro-6-fluoro-phenyl)-3-(1H-pyrrol-2-yl)-acrylonitrile [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 993 - 997.

5
[ 75279-55-9 ]
[ 74-88-4 ]
2,2-dimethyl-2(2-chloro-6-fluorophenyl)acetonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With lithium diisopropyl amide; In tetrahydrofuran;	N-(2,2-dimethyl-2-(2-chloro-6-fluoro)phenethyl)-N'-(2-thiazolyl)thiourea A solution of 2-chloro-6-fluorophenyl acetonitrile (1.69 g, 10 mmole) in dry THF (70 ml) was cooled to -60 C., and lithium diisopropylamide (5.25 ml, 10.5 mmole) was added. After 30 min, methyl iodide (0.68 ml, 11 ml) was added into the reaction mixture, and the reaction was slowly warmed to 0 C., and kept at 0 C. for 1 hr. Then it was cooled to -60 C. again, and more lithium diisopropylamide (6 ml, 12 mmole) was added. After 30 min, methyl iodide (1.87 ml, 30 mmole) was added. The reaction mixture was allowed to warm to room temperature and kept there for 2 hr after which it was poured into a sodium hydrogen carbonate solution, and extracted with chloroform. The organic phase was washed with water, dried, and the solvent was evaporated in vacuo. The product 2,2-dimethyl-2(2-chloro-6-fluorophenyl)acetonitrile (1.07 g) was isolated by silica gel column chromatography. 1 H-NMR (CDCl3) d: 7.25 (m, 2H, Ph), 7.03 (m, 1H, Ph), 1.98 (s, 3H, Me), 1.96 (s, 3H, Me).

References: [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 6836 - 6840.
[2]Patent: US5593993,1997,A .
[3]ACS Medicinal Chemistry Letters,2016,vol. 7,p. 1207 - 1212.

6
[ 75279-55-9 ]
6-(2-chloro-6-fluoro-phenyl)-2-methanesulfonyl-8-methyl-8H-pyrido[2,3-d]pyrimidin-7-one [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 1931 - 1935.

7
[ 75279-55-9 ]
6-(2-chloro-6-fluoro-phenyl)-8-methyl-2-phenylamino-8H-pyrido[2,3-d]pyrimidin-7-one [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 1931 - 1935.

8
[ 75279-55-9 ]
N-(2-(2-fluoro-6-chlorophenyl)ethyl)-N'-(2-thiazolyl)thiourea [ No CAS ]

References: [1]Journal of Medicinal Chemistry,1995,vol. 38,p. 4929 - 4936.

9
[ 75279-55-9 ]
[ 1663-67-8 ]
[ 872853-49-1 ]

References: [1]Patent: WO2006/358,2006,A1 .Location in patent: Page/Page column 67.

10
[ 80019-71-2 ]
[ 75279-55-9 ]
[ 114388-70-4 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; NaH; In water; N,N-dimethyl-formamide; toluene;	Step 1--Preparation of alpha-[2-(4-chlorophenyl)ethyl]-<strong>[75279-55-9]2-chloro-6-fluorophenylacetonitrile</strong> A 3 neck 200 ml round bottom flask was charged with 7.5 gms of 60% NaH (0.187 mole, 1.5 eq.), washed three times with 25 ml hexanes, in 60 ml of 2:1 toluene:DMF. To this was added 21.2 gms (0.125 mole, 1.0 eq.) of <strong>[75279-55-9]2-chloro-6-fluorophenylacetonitrile</strong> dropwise over 0.5 hour in 40 ml of 2:1 toluene:DMF. The reaction was stirred for 20 minutes at 10 C. then at room temperature for 1 hour after which 32.1 gms of 2-(4-chlorophenyl)ethyl methanesulfonate (0.137 mole, 1.1 eq.) in 60 ml of 2:1 toluene:DMF was added dropwise over 1 hour. Approximately 70 ml of 2:1 toluene:DMF was added to permit constant stirring and the reaction was stirred for an additional 3.5 hours after which gas liquid chromatography indicated the reaction was complete. Then 50 ml of water was added, followed by 10 ml of 10% HCl and 300 ml of ether. The ether was washed with 100 ml of water which was extracted twice with 50 ml of ether then washed with water. The combined ethers were dried and concentrated to give 40.0 gms of crude product which was distilled under reduced pressure. 26.6 gms (69.8%) of product resulted having a boiling point of 175-185 C. at 1 mm Hg. NMR (90 MHz): 2.2-2.9(m, 4H), 4.2-4.4(t, 1H) and 7.0-7.4(m, 7H).

References: [1]Patent: US5087635,1992,A .

11
[ 75279-55-9 ]
1-cyano-1-(4-nitrophenyl)-2-vinylcyclopropane [ No CAS ]
1-cyano-1-(6-chloro-2-fluorophenyl)-2-vinylcyclopropane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Similar results are obtained when the above reaction is repeated using substituted-phenylacetonitriles. For example, when 1,4-dichlorobutene-2 is reacted with <strong>[75279-55-9]6-chloro-2-fluorophenylacetonitrile</strong> or 4-nitrophenylacetonitrile in accordance with the above process 1-cyano-1-(6-chloro-2-fluorophenyl)-2-vinylcyclopropane and 1-cyano-1-(4-nitrophenyl)-2-vinylcyclopropane are respectively produced.

References: [1]Patent: US4399076,1983,A .

12
[ 40138-16-7 ]
[ 75279-55-9 ]
[ 1005346-91-7 ]

References: [1]Journal of Organic Chemistry,2008,vol. 73,p. 495 - 501.

13
[ 609-12-1 ]
[ 75279-55-9 ]
C₁₅H₁₉ClFNO₂ [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2008,vol. 51,p. 4641 - 4652.

14
[ 35657-96-6 ]
[ 75279-55-9 ]
C₁₆H₂₁ClFNO₂ [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2008,vol. 51,p. 4641 - 4652.

15
[ 75279-55-9 ]
[ 533-68-6 ]
C₁₄H₁₇ClFNO₂ [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2008,vol. 51,p. 4641 - 4652.

16
[ 609-12-1 ]
[ 75279-55-9 ]
[ 1044749-11-2 ]

References: [1]Russian Journal of Organic Chemistry,2010,vol. 46,p. 1691 - 1694.

17
[ 75279-55-9 ]
[ 1044749-16-7 ]

References: [1]Russian Journal of Organic Chemistry,2010,vol. 46,p. 1691 - 1694.

18
[ 75279-55-9 ]
[ 1044749-14-5 ]

References: [1]Russian Journal of Organic Chemistry,2010,vol. 46,p. 1691 - 1694.
[2]ChemMedChem,2011,vol. 6,p. 826 - 833.

19
[ 75279-55-9 ]
[ 1044749-15-6 ]

References: [1]Russian Journal of Organic Chemistry,2010,vol. 46,p. 1691 - 1694.
[2]ChemMedChem,2011,vol. 6,p. 826 - 833.

20
[ 75279-55-9 ]
[ 1242134-31-1 ]

References: [1]Russian Journal of Organic Chemistry,2010,vol. 46,p. 1691 - 1694.

21
[ 75279-55-9 ]
[ 1242134-33-3 ]

References: [1]Russian Journal of Organic Chemistry,2010,vol. 46,p. 1691 - 1694.

22
[ 75279-55-9 ]
[ 1262963-59-6 ]

References: [1]Russian Journal of Organic Chemistry,2010,vol. 46,p. 1691 - 1694.

23
[ 75279-55-9 ]
[ 1262963-60-9 ]

References: [1]Russian Journal of Organic Chemistry,2010,vol. 46,p. 1691 - 1694.

24
[ 75279-55-9 ]
[ 1262963-61-0 ]

References: [1]Russian Journal of Organic Chemistry,2010,vol. 46,p. 1691 - 1694.

25
[ 75279-55-9 ]
[ 41978-69-2 ]
[ 1044749-09-8 ]

References: [1]Russian Journal of Organic Chemistry,2010,vol. 46,p. 1691 - 1694.
[2]ChemMedChem,2011,vol. 6,p. 826 - 833.

26
[ 75279-55-9 ]
[ 533-68-6 ]
[ 1044749-10-1 ]

References: [1]Russian Journal of Organic Chemistry,2010,vol. 46,p. 1691 - 1694.
[2]ChemMedChem,2011,vol. 6,p. 826 - 833.

27
[ 75279-55-9 ]
[ 1307310-97-9 ]