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Chemical Structure| 114897-91-5 Chemical Structure| 114897-91-5

Structure of 114897-91-5

Chemical Structure| 114897-91-5

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Product Details of [ 114897-91-5 ]

CAS No. :114897-91-5
Formula : C8H5BrFN
M.W : 214.03
SMILES Code : N#CCC1=CC=C(Br)C=C1F
MDL No. :MFCD07368653
InChI Key :QLASQEZPJFNZQC-UHFFFAOYSA-N
Pubchem ID :7172308

Safety of [ 114897-91-5 ]

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

Computational Chemistry of [ 114897-91-5 ] 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 43.62
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

23.79 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

1.97
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

2.37
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

3.07
Log Po/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.

2.94
Log Po/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

3.22
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.71

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-3.0
Solubility 0.215 mg/ml ; 0.00101 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.

-2.51
Solubility 0.661 mg/ml ; 0.00309 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

-4.03
Solubility 0.0202 mg/ml ; 0.0000942 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately 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.

-5.92 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)

1.45

Application In Synthesis of [ 114897-91-5 ]

* 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 [ 114897-91-5 ]

[ 114897-91-5 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 64-17-5 ]
  • [ 114897-91-5 ]
  • [ 924312-09-4 ]
YieldReaction ConditionsOperation in experiment
70% (2) Production of ethyl (4-bromo-2-fluorophenyl)acetate: Hydrochloric acid (10 mL) was added to an ethanol solution (20 mL) of (4-bromo-2-fluorophenyl)acetonitrile (2.11 g, 9.86 mmol), and heated under reflux for 15 hours. Next, with cooling with ice, aqueous saturated sodium hydrogencarbonate solution was gradually added to the reaction liquid for neutralization. After extracted with ethyl acetate, the obtained organic layer was washed with saturated saline, then dried with anhydrous sodium sulfate, and filtered. The obtained filtrate was concentrated under reduced pressure, then the residue was purified by silica gel column chromatography (hexane:ethyl acetate = 10:0 to 9:1) to obtain the entitled compound (1.81 g, 70 %). 1H-NMR (400 MHz, DMSO-d6, δ ppm): 1.26 (3H, t, J=7.2 Hz), 3.62 (2H, s), 4.17 (2H, q, J=7.2 Hz), 7.12-7.18 (1H, m), 7.23-7.28 (2H, m).
  • 2
  • [ 114897-91-5 ]
  • [ 107-04-0 ]
  • [ 872422-15-6 ]
YieldReaction ConditionsOperation in experiment
70% Step 1. 1-(4-Bromo-2-fluorophenyl)cyclopropanecarboxylic acid Sodium hydroxide, 50% aqueous solution (5.71 mL, 0.149 mol), was added to a mixture of (4-bromo-2-fluorophenyl)acetonitrile (3.16 g, 0.0145 mol), benzyltriethylammonium chloride (0.26 g, 0.0011 mol), and 1-bromo-2-chloro-ethane (2.51 mL, 0.0302 mol) at 50 C. for 10 h. The mixture was poured into ice-water (50 mL) and was extracted with ethyl ether (2*50 mL). The combined organic phase was washed with brine (30 mL), dried over MgSO4, filtered, and concentrated under reduced pressure to give 2.88 g of brown solid. 1H-NMR confirmed that desired nitrile intermediate was isolated. To the resulting residue was added 50% NaOH aqueous solution (3.8 mL) and ethylene glycol (20 mL) and the solution was heated to 100 C. and stirred overnight. The reaction mixture was poured into 50 mL of water and washed with ether (2*50 mL). The aqueous layer was cooled with an ice bath and then acidified by the slow addition of 6 N HCl. to pH=2. The product was extracted with EtOAc (2*100 mL), dried over MgSO4 and concentrated to give 1.634 g. (70%) of the desired product. 1H NMR confirmed that the desired product was isolated.
To a stirred mixture of the (4-bromo-2-fluorophenyl)acetonitrile (12.53 g, 0.05854 mol), benzyltriethylammonium chloride (0.9 g, 0.004 mol), and l-bromo-2-chloro-ethane (9.70 mL, 0.117 mol) was added dropwise sodium hydroxide, 50% aqueous solution (21.00 mL, 0.5484 mol) at 50 C. After stirring for 16 h, the reaction mixture was diluted with water, 1,2-ethanediol (65.00 mL, 1.166 mol), and sodium hydroxide, 50% aqueous solution (5 mL). The resulting mixture was heated at 100C for 16 h. The reaction mixture was extracted with diethyl ether and the aqueous layer was acidified to pH~2 and the product precipitated out and was collected by filtration and used in the subsequent reaction without further purification.
  • 3
  • [ 114897-91-5 ]
  • [ 872422-15-6 ]
 

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