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Chemical Structure| 703-67-3 Chemical Structure| 703-67-3

Structure of 703-67-3

Chemical Structure| 703-67-3

6-Fluoro-1-tetralone

CAS No.: 703-67-3

4.5 *For Research Use Only !

Cat. No.: A124542 Purity: 97%

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Product Details of [ 703-67-3 ]

CAS No. :703-67-3
Formula : C10H9FO
M.W : 164.18
SMILES Code : O=C1CCCC2=C1C=CC(F)=C2
MDL No. :MFCD09031370
Boiling Point : No data available
InChI Key :NJYZZEHPEKDFEK-UHFFFAOYSA-N
Pubchem ID :14915116

Safety of [ 703-67-3 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335-H412
Precautionary Statements:P261-P273-P305+P351+P338

Computational Chemistry of [ 703-67-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.3
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 44.25
TPSA ?

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

17.07 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.99
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

2.12
Log Po/w (WLOGP)?

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

2.76
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.

2.42
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

3.42
Consensus Log Po/w?

Consensus Log Po/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.

-2.56
Solubility 0.449 mg/ml ; 0.00273 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.

-2.11
Solubility 1.28 mg/ml ; 0.00777 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

-3.67
Solubility 0.0355 mg/ml ; 0.000216 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.

-5.8 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)

1.76

Application In Synthesis of [ 703-67-3 ]

* 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 [ 703-67-3 ]

[ 703-67-3 ] Synthesis Path-Downstream   1~36

  • 1
  • [ 703-67-3 ]
  • [ 1895-39-2 ]
  • [ 63082-44-0 ]
  • 4
  • [ 703-67-3 ]
  • 6-fluoro-1-tetralone-2-oxime [ No CAS ]
  • 5
  • [ 70631-88-8 ]
  • [ 703-67-3 ]
YieldReaction ConditionsOperation in experiment
100% With PPA; at 110℃; for 2h; 6-Fluoro-3, 4-dihydro-2H-naphthalen-1-one Heat a mixture of 4- (3-fluoro-phenyl)-butyric acid (1.92 g, 10.5 mmol) and polyphosphoric acid (2 g) at 110°C under nitrogen for two hours. After cooling to room temperature, quench with water, dilute with ether, wash with saturated aqueous sodium bicarbonate (2x), dry over anhydrous sodium sulfate, and concentrate to obtain the title compound (1.51 g, 87percent). NMR (400 MHz, CDCl3) : 8 2.16 (m, 2H), 2. 64 (t, 2H), 2.97 (t, 2H), 6.92 (dd, 1H), 6.99 (dt, 1H), 8. 04 (dd, 1H).
53.97% With methanesulfonic acid; phosphorus pentoxide; A solution of methanesulfonic acid (75 mL) and P2O5 was stirred at 85 ° C for 15 minutes, at which point most of the P2Os had dissolved. An additional 15 mL of methanesulfonic acid was added dropwise, and the mixture was stirred at 85 ° C for 2 hours. The reaction mixture was poiured into 500 mL of water and extracted twice with 400 mL of EtOAc. The combined organic layers were washed with saturated NaHCO3, water, and saturated brine, and then dried over MgSO4. The solvent was removed under reduced pressure to give an oil that was eluted through silica gel using hexanes/EtOAc (9:1). Removal of solvent under reduced pressure yielded 6.06 g, 36.91 mmol, 53.97percent) of 6-fluoro-3,4-dihydro-2H-naphthalen-l-one as a yellow oil. MS: 165 (M+H)+.
53.97% With methanesulfonic acid; phosphorus pentoxide; at 85℃; for 2.25h; Step 36-Fluoro-3,4-dihydro-2H-naphthalen-l-one A solution of methanesulfonic acid (75 mL) and P2Os was stirred at 85 ° C for 15 minutes, at which point most of the P2Os had dissolved. An additional 15 mL of methanesulfonic acid was added dropwise, and the mixture was stirred at 85 ° C for 2 hours. The reaction mixture was poiured into 500 mL of water and extracted twice with 400 mL of EtOAc. The combined organic layers were washed with saturated NaHCO3, water, and saturated brine, and then dried over MgSO4. The solvent was removed under reduced pressure to give an oil that was eluted through silica gel using hexanes/EtOAc (9:1). Removal of solvent under reduced pressure yielded 6.06 g, 36.91 mmol, 53.97percent) of 6-fluoro-3,4-dihydro-2H-naphthalen~l-one as a yellow oil. MS: 165 (M+H)+.
53.97% With methanesulfonic acid; phosphorus pentoxide; Step 3 6-Fluoro-3,4-dihydro-2H-naphthalen-1-one A solution of methanesulfonic acid (75 mL) and P2O5 was stirred at 85° C. for 15 minutes, at which point most of the P2O5 had dissolved. An additional 15 mL of methanesulfonic acid was added dropwise, and the mixture was stirred at 85° C. for 2 hours. The reaction mixture was poured into 500 mL of water and extracted twice with 400 mL of EtOAc. The combined organic layers were washed with saturated NaHCO3, water, and saturated brine, and then dried over MgSO4. The solvent was removed under reduced pressure to give an oil that was eluted through silica gel using hexanes/EtOAc (9:1). Removal of solvent under reduced pressure yielded 6.06 g, 36.91 mmol, 53.97percent) of 6-fluoro-3,4-dihydro-2H-naphthalen-1-one as a yellow oil. MS: 165 (M+H)+.
53.97% With methanesulfonic acid; phosphorus pentoxide; at 85℃; for 2h; Step 36-Fluoro-3,4-dihvdro-2H-naphthalen- 1 -oneA solution of methanesulfonic acid (75 mL) and P2O5 was stirred at 85 ° C for 15 minutes, at which point most of the P2O5 had dissolved. An additional 15 mL of methanesulfonic acid was added dropwise, and the mixture was stirred at 85 ° C for 2 hours. The reaction mixture was poiured into 500 mL of water and extracted twice with 400 mL of EtOAc. The combined organic layers were washed with saturated NaHCpsi3, water, and saturated brine, and then dried over MgSO4. The solvent was removed under reduced pressure to give an oil that was eluted through silica gel using hexanes/EtOAc (9:1). Removal of <n="44"/>solvent under reduced pressure yielded 6.06 g, 36.91 mmol, 53.97percent) of 6-fluoro-3,4- dihydro-2H-naphthalen-l-one as a yellow oil. MS: 165 (M+H)+.
With sulfuric acid; at 40 - 60℃; for 3h; Step 3 6-Fluoro-3,4-dihydro-2H-naphthalen-1-one Crude 4-(3-fluorophenyl)butyric acid (8.83 kg) was added to concentrated sulfuric acid (30 kg) in a chemical reactor at a rate such that the pot temperature stayed between 40° C. and 60° C. (jacket heating was not necessary). The reaction was stirred at 45° C. for 3 hours and reaction completion was confirmed by LC. The reaction mixture was cooled and quenched with water (16 L), and then extracted with 35percent THF in methylene chloride (25.8 kg). The organic layer was separated and washed with water (16 L), saturated aqueous NaHCO3 (16.9 kg) and then a mixture of water (16.1-kg)/brine (4.7-kg). The organic later was concentrated under vacuum and re-stripped with the aid of hexane to remove water and afford 6-fluoro-3,4-dihydro-2H-naphthalen-1-one as an oil (5.88 kg): MS (M+1)=165; H1 NMR (300 MHz): delta ppm (CDCl3): 2.14 (2H, m, J=6.03, 5.75 Hz), 2.64 (2H, dd, J=6.03, 5.75 Hz); 2.94 (2H, t, J=6.03), 6.9-7.0 (2H,m, J=2.26,2.64, 6.03 Hz), 8.02-8.07 (1H, dd, J=6.03).
Step-h product (9 g, 0.049 mol) was dissolved in benzene (90 mL) and thionyl chloride (10.8 mL, 0.148 mol) was added to it followed by two drops of DMF. The reaction mixture was refluxed for two hours. After that solvent was removed under reduced pressure and water was removed by forming azeotrope with benzene. The residue was dissolved in dichloromethane (50 mL) and added to the suspension of aluminium chloride (26.37 g, 0.198 mol) in dichloromethane (100 mL) under nitrogen atmosphere at -10 0C. After 30 minutes total consumption of starting material occurred and the reaction mixture was poured into the ice and it was extracted with 30percent ethyl acetate in hexane (3 x 100 mL). The combined organic layer was dried over magnesium sulphate and concentrated under reduced pressure. . The crude compound was purified by column chromatography using 5percent ethyl acetate in hexane as eluent to afford 7 g pure compound
With PPA; In water; Step C 6-Fluoro-3,4-dihydro-2H-naphthalene-1-one A mixture of 4-(3-fluorophenyl)butanoic acid (10 g) and polyphosphoric acid (100 g) was heated to 70° C. with stirring for 2 h. The reaction mixture was cooled and water was carefully added (400 cm3). The aqueous mixture was extracted with diethyl ether (3*75 cm3) and the combined extracts were washed sequentially with aqueous potassium hydroxide solution (1 M, 75 cm3), water (75 cm3) and saturated aqueous sodium chloride solution (75 cm3). The combined organic extracts were dried (Na2SO4), and the solvent was distilled off under reduced pressure. The crude product (6.58 g) was purified by column chromatography [silica, eluding with petroleum ether (b. p. 40-60° C.)-ethyl acetate (20:1)] to afford the title compound (6.36 g).

  • 6
  • [ 703-67-3 ]
  • [ 74-88-4 ]
  • [ 149455-96-9 ]
  • 8
  • [ 703-67-3 ]
  • [ 53842-01-6 ]
YieldReaction ConditionsOperation in experiment
162 mg (0.92 mmol,11%) With hydrogen azide; sulfuric acid; In chloroform; water; Step A: 7-fluoro-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one Sodium azide 1.1 g (16.92 mmol) was added to a mixture of 6.0 mL of chloroform and 1.1 mL of water at 0° C. Concentrated sulfuric acid (0.44 mL) was added dropwise and the mixture stirred at 0° C. for two hours then filtered. The chloroform layer containing hydrazoic acid was added to a solution of 1.3 g (7.92 mmol) of <strong>[703-67-3]6-fluoro-1-tetralone</strong> (prepared by the method of Allinger and Jones, J. Org. Chem., 27, 70-76 (1962)) in 4.8 mL of chloroform. Additional sulfuric acid (2.16 mL) was added dropwise with stirring while maintaining the temperature below 40° C. The mixture was stirred at 40° C. for two hours then at room temperature for 16 hours. The mixture was transferred to a separatory funnel and the layers were separated. The aqueous layer was added to ice; the resulting precipitate was extracted with methylene chloride (5*). The combined extracts were washed with brine, dried over magnesium sulfate and filtered through a silica plug. Solvents were removed under vacuum to afford 162 mg (0.92 mmol,11percent) of the product. 1 H NMR (300 MHz, CDCl3): 2.21 (m,2H), 2.32 (t,7 Hz,2H), 2.77 (t,7 Hz,2H), 6.93 (m,3H), 7.8 (br s,1H). FAB-MS: calculated for C10 H10 FNO 179; found 180 (M+H,100percent).
  • 9
  • [ 703-67-3 ]
  • [ 86517-04-6 ]
  • 1-(4-chloro-butyl)-6-fluoro-1,2,3,4-tetrahydro-naphthalen-1-ol [ No CAS ]
  • 10
  • [ 703-67-3 ]
  • [ 278605-08-6 ]
  • 1-(5-chloro-pentyl)-6-fluoro-1,2,3,4-tetrahydro-naphthalen-1-ol [ No CAS ]
  • 11
  • [ 37595-74-7 ]
  • [ 703-67-3 ]
  • [ 556107-58-5 ]
  • 12
  • [ 703-67-3 ]
  • [ 1779-49-3 ]
  • 6-fluoro-1-methylene-1,2,3,4-tetrahydro-naphthalene [ No CAS ]
  • 13
  • [ 703-67-3 ]
  • 3,3,3-trifluoro-2-(6-fluoro-1,2,3,4-tetrahydro-naphthalen-1-ylmethyl)-2-hydroxy-<i>N</i>-(4-methyl-1-oxo-1<i>H</i>-benzo[<i>d</i>][1,2]oxazin-6-yl)-propionamide [ No CAS ]
  • 14
  • [ 703-67-3 ]
  • 3,3,3-trifluoro-2-(6-fluoro-3,4-dihydro-naphthalen-1-ylmethyl)-2-hydroxy-<i>N</i>-(4-methyl-1-oxo-1<i>H</i>-benzo[<i>d</i>][1,2]oxazin-6-yl)-propionamide [ No CAS ]
  • 15
  • [ 703-67-3 ]
  • [ 556107-61-0 ]
  • 16
  • [ 703-67-3 ]
  • [ 117922-86-8 ]
  • 17
  • [ 703-67-3 ]
  • [ 489439-76-1 ]
  • 18
  • [ 703-67-3 ]
  • [ 489439-75-0 ]
  • 19
  • [ 703-67-3 ]
  • [ 489439-72-7 ]
  • 20
  • [ 703-67-3 ]
  • [ 439082-36-7 ]
  • 21
  • [ 703-67-3 ]
  • [ 489439-73-8 ]
  • 22
  • [ 703-67-3 ]
  • (S)-4-(6-Fluoro-naphthalen-1-yl)-2-methyl-piperazine-1-carboxylic acid benzyl ester [ No CAS ]
  • 23
  • [ 703-67-3 ]
  • (R)-4-(6-Fluoro-naphthalen-1-yl)-2-methyl-piperazine-1-carboxylic acid benzyl ester [ No CAS ]
  • 24
  • [ 703-67-3 ]
  • (S)-4-(7-Fluoro-naphthalen-1-yl)-2-methyl-piperazine-1-carboxylic acid benzyl ester [ No CAS ]
  • 25
  • [ 703-67-3 ]
  • (R)-4-(7-Fluoro-naphthalen-1-yl)-2-methyl-piperazine-1-carboxylic acid benzyl ester [ No CAS ]
  • 26
  • [ 703-67-3 ]
  • 4-(6-fluoro-naphthalen-1-yl)-piperazine-1-carboxylic acid benzyl ester [ No CAS ]
  • 27
  • [ 703-67-3 ]
  • 4-(6-fluoro-naphthalen-1-yl)-2,2-dimethyl-piperazine-1-carboxylic acid benzyl ester [ No CAS ]
  • 28
  • [ 703-67-3 ]
  • 1-[2-(2-fluoro-4,7-dihydro-5<i>H</i>-thieno[2,3-<i>c</i>]pyran-7-yl)-ethyl]-4-(6-fluoro-naphthalen-1-yl)-2-methyl-piperazine [ No CAS ]
  • 29
  • [ 703-67-3 ]
  • 7-{2-[4-(6-fluoro-naphthalen-1-yl)-2-methyl-piperazin-1-yl]-ethyl}-4,7-dihydro-5<i>H</i>-thieno[2,3-<i>c</i>]pyran-2-carboxylic acid amide [ No CAS ]
  • 30
  • [ 703-67-3 ]
  • 7-{2-[4-(6-fluoro-naphthalen-1-yl)-2-methyl-piperazin-1-yl]-ethyl}-4,7-dihydro-5<i>H</i>-thieno[2,3-<i>c</i>]pyran-2-carboxylic acid amide [ No CAS ]
  • 31
  • [ 703-67-3 ]
  • 7-{2-[4-(7-fluoro-naphthalen-1-yl)-2-methyl-piperazin-1-yl]-ethyl}-4,7-dihydro-5<i>H</i>-thieno[2,3-<i>c</i>]pyran-2-carboxylic acid amide [ No CAS ]
  • 32
  • [ 703-67-3 ]
  • 7-{2-[4-(7-fluoro-naphthalen-1-yl)-2-methyl-piperazin-1-yl]-ethyl}-4,7-dihydro-5<i>H</i>-thieno[2,3-<i>c</i>]pyran-2-carboxylic acid amide [ No CAS ]
  • 33
  • [ 703-67-3 ]
  • 4-{2-[4-(6-fluoro-naphthalen-1-yl)-2-methyl-piperazin-1-yl]-ethyl}-6,7-dihydro-4<i>H</i>-thieno[3,2-<i>c</i>]pyran-2-carboxylic acid amide [ No CAS ]
  • 34
  • [ 703-67-3 ]
  • 7-{2-[4-(6-fluoro-naphthalen-1-yl)-piperazin-1-yl]-ethyl}-4,7-dihydro-5<i>H</i>-thieno[2,3-<i>c</i>]pyran-2-carboxylic acid amide [ No CAS ]
  • 35
  • [ 703-67-3 ]
  • 7-{2-[4-(6-fluoro-naphthalen-1-yl)-2-methyl-piperazin-1-yl]-ethyl}-4,7-dihydro-5<i>H</i>-thieno[2,3-<i>c</i>]pyran-3-carboxylic acid amide [ No CAS ]
  • 36
  • [ 703-67-3 ]
  • 7-{2-[4-(6-fluoro-naphthalen-1-yl)-2-methyl-piperazin-1-yl]-ethyl}-4,7-dihydro-5<i>H</i>-thieno[2,3-<i>c</i>]pyran-2-sulfonic acid amide [ No CAS ]
 

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