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Chemical Structure| 699-92-3 Chemical Structure| 699-92-3
Chemical Structure| 699-92-3

3'-Fluoro-2'-hydroxyacetophenone

CAS No.: 699-92-3

4.5 *For Research Use Only !

Cat. No.: A261976 Purity: 97%

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Product Details of [ 699-92-3 ]

CAS No. :699-92-3
Formula : C8H7FO2
M.W : 154.14
SMILES Code : CC(=O)C1=C(O)C(F)=CC=C1
MDL No. :MFCD09055140
InChI Key :WXTHZWWWCICGAN-UHFFFAOYSA-N
Pubchem ID :10773176

Safety of [ 699-92-3 ]

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

Calculated chemistry of [ 699-92-3 ] 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 3.0
Num. H-bond donors 1.0
Molar Refractivity 38.62
TPSA ?

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

37.3 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.64
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

1.9
Log Po/w (WLOGP)?

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

2.15
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.

1.55
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

2.09
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.87

Water Solubility

Log S (ESOL):?

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

-2.33
Solubility 0.72 mg/ml ; 0.00467 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.

-2.31
Solubility 0.762 mg/ml ; 0.00494 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

-2.42
Solubility 0.583 mg/ml ; 0.00378 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

No
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.

-5.89 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)

1.17

Application In Synthesis [ 699-92-3 ]

* 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 [ 699-92-3 ]

[ 699-92-3 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 699-92-3 ]
  • [ 363-52-0 ]
YieldReaction ConditionsOperation in experiment
To a 3-fluoro-2-hydroxyacetophenone (5, 100 g, 0.648 moles) was add 1N aq. NaOH solution (1.25 Lit., 1.5 equiv.) in a drop-wise manner at 25oC for 30 min. Exotherm upto 40oC was observed. The reaction mixture was further stirred at 40?45oC for 1 h and then cooled to 25°C. 3percent Aq. H2O2 solution was added drop-wise (1.5 Lit., 1.6equiv.) for the period of 1 h, where exotherm upto 50?55°C was observed. The reaction mixtures was further stirred at 25°C for 3 h and then cooled to 10oC. Conc. hydrochloric acid (90 ml) was added with vigorous stirring to bring the pH upto 1.5?2.0 and continued the stirring for 30 min. The reaction mixture was then extracted with tert-butyl methyl ether (1x700 ml, 3x300 ml) and the combined organic layer was evaporated upto 75 percent recovery of MTBE. To the obtained residual organic layer, K2CO3 (294.8 g, 3.3equiv.) and TBAB (20.8 g, 0.064 mol) was added. The reaction mixture was stirred vigorously and diethyl sulfate (328.8 g, 3.3 equiv.) was added drop-wise over 45 min. The mixture was refluxed for 3 h (monitored by GC) and then distilled the MTBE. After cooling the reaction mixture to 40oC, water was added (330 ml) and again heated at 70oC for 2 h for hydrolysis of excess diethyl sulfate (monitored by GC). The reaction mixture was cooled to room temperature and organic layer was separated. The aqueous layer was extracted by tert-butyl methyl ether (2x200 ml). The combined organic layer was evaporated under vacuum to furnish liquid residue of 2 (109.3 g). This residue was subjected for the treatment of sodium borohydride (0.7 g) in 220 ml methanol at rt for 30 min to reduce the respective alkylated acetophenones 4 and 5. The organic layer was concentrated under vacuum and then resulting residue was distilled under vacuum using Micro-Liquid divider. The pure fraction of 2 (62.9 g, 52.6 percent yield, GC purity 99.25 percent) was isolated at 95?99oC and 9 ? 10 mbar. 1HNMR (CDCl3, 300 MHz) delta: 6.97-6.89 (m, 1H, ArH), 6.74-6.65 (m, 2H, ArH), 4.10 (m, 4H, CH2), 1.44 (t, 3H, CH3), 1.37 (t, 3H, CH3). Observed LCMS (M+23) 207.00.
 

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