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Chemical Structure| 321-38-0 Chemical Structure| 321-38-0

Structure of 1-Fluoronaphthalene
CAS No.: 321-38-0

Chemical Structure| 321-38-0

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Product Details of [ 321-38-0 ]

CAS No. :321-38-0
Formula : C10H7F
M.W : 146.16
SMILES Code : FC1=CC=CC2=C1C=CC=C2
MDL No. :MFCD00003873
InChI Key :CWLKTJOTWITYSI-UHFFFAOYSA-N
Pubchem ID :9450

Safety of [ 321-38-0 ]

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

Computational Chemistry of [ 321-38-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 10
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 1.0
Num. H-bond donors 0.0
Molar Refractivity 43.91
TPSA ?

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

0.0 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.12
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

3.03
Log Po/w (WLOGP)?

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

3.4
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.

3.76
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

3.44
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.15

Water Solubility

Log S (ESOL):?

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

-3.33
Solubility 0.0687 mg/ml ; 0.00047 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.

-2.7
Solubility 0.295 mg/ml ; 0.00202 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

-4.33
Solubility 0.00684 mg/ml ; 0.0000468 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

Low
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.

-5.04 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)

1.0

Application In Synthesis of [ 321-38-0 ]

* 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 [ 321-38-0 ]
  • Downstream synthetic route of [ 321-38-0 ]

[ 321-38-0 ] Synthesis Path-Upstream   1~6

  • 1
  • [ 321-38-0 ]
  • [ 438-32-4 ]
References: [1] Justus Liebigs Annalen der Chemie, 1931, vol. 487, p. 270,282.
[2] Bulletin des Societes Chimiques Belges, 1966, vol. 75, p. 577 - 581.
[3] Journal of Organic Chemistry, 2011, vol. 76, # 19, p. 7975 - 7984.
  • 2
  • [ 321-38-0 ]
  • [ 144-62-7 ]
  • [ 132335-49-0 ]
  • [ 132335-47-8 ]
YieldReaction ConditionsOperation in experiment
75.6%
Stage #1: With sodium hydride In N,N-dimethyl acetamide at 70℃; for 0.333333 h;
Stage #2: at 110℃; for 1 h;
DX-A 03 (2.0 g, 0.011 mol)Was dissolved in dimethylacetamide (100 mL)A solution of 60percent sodium hydride (463 mg, 0.012 mol)Dropwise.The resulting mixture was heated at 70 ° C. for 20 minutes.1-Fluoronaphthalene (1.27 mL, 0.012 mol)Was added dropwise to this mixed solution,And heated at 110 ° C. for 60 minutes.The reaction mixture was diluted with water,And extracted twice with diethyl ether.The extracts are combined,Wash with water,Then washed with saturated sodium chloride solution,It was dried over anhydrous sodium sulfate,After concentration under reduced pressure,To obtain an oily compound (DX-A 04, 3.28 g, 75.6percent).
References: [1] Patent: JP2016/172704, 2016, A, . Location in patent: Paragraph 0027; 0053.
  • 3
  • [ 321-38-0 ]
  • [ 144-62-7 ]
  • [ 132335-44-5 ]
  • [ 132335-47-8 ]
References: [1] Organic Process Research and Development, 2009, vol. 13, # 5, p. 854 - 856.
[2] Patent: WO2009/87463, 2009, A2, . Location in patent: Page/Page column 7-8.
  • 4
  • [ 13636-02-7 ]
  • [ 321-38-0 ]
  • [ 144-62-7 ]
  • [ 132335-47-8 ]
References: [1] Patent: WO2011/33366, 2011, A2, . Location in patent: Page/Page column 23.
  • 5
  • [ 321-38-0 ]
  • [ 132335-47-8 ]
YieldReaction ConditionsOperation in experiment
80 % With oxalic acid In ISOPROPYLAMIDE; water; (S)-3-dimethylamino-1-(2-thienyl)propan-1-ol; ethyl acetate; mineral oil Example 4
Synthesis of (S)-N,N-dimethyl-3-(1-naphthalenyloxy)-3-(2-thienyl)propanamine oxalate
In 50 ml of dimethylacetamide 0.5 g of sodium hydride (suspension in mineral oil) is suspended.
Suspension is stirred and in few portions 2 g of (s)-3-(dimethylamino)-1-(thienyl)-propan-1-ol is added.
After the addition is completed the suspension is warmed up to 70°C. 1.27 ml of 1-fluoronaphthalene is added and the reaction mixture is heated to 110°C.
At this temperature the solution is stirred for another three hours.
Then the reaction solution is dissolved with 300 ml of water and extracted twice with 100 ml ether.
Combined ether phases are rinsed with water, dried with sodium sulphate end evaporated to dryness.
Obtained oil is dissolved in 50 ml ethyl acetate and 0.9 g of oxalic acid is added.
The suspension is further stirred for one hour, filtered off the product and washed with ethyl acetate.
The product is dried to obtain 3.5 g (80 percent) of (S)-N,N-dimethyl-3-(1-naphthalenyloxy)-3-(2-thienyl)propanamine oxalate.
References: [1] Patent: EP2133072, 2009, A1, .
  • 6
  • [ 321-38-0 ]
  • [ 132335-44-5 ]
  • [ 132335-47-8 ]
References: [1] Tetrahedron Letters, 1990, vol. 31, # 45, p. 7101 - 7104.
 

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