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Structure of 162427-79-4

Chemical Structure| 162427-79-4

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Product Details of [ 162427-79-4 ]

CAS No. :162427-79-4
Formula : C8H9FO
M.W : 140.15
SMILES Code : C[C@@H](O)C1=CC=CC=C1F
MDL No. :MFCD03092991
InChI Key :SXFYVXSOEBCFLV-ZCFIWIBFSA-N
Pubchem ID :2779054

Safety of [ 162427-79-4 ]

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

Computational Chemistry of [ 162427-79-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.25
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 37.33
TPSA ?

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

20.23 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

1.54
Log Po/w (WLOGP)?

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

1.97
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.

2.3
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

2.25
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.01

Water Solubility

Log S (ESOL):?

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

-2.06
Solubility 1.23 mg/ml ; 0.00877 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.

-1.57
Solubility 3.74 mg/ml ; 0.0267 mol/l
Class?

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

Very 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

-2.51
Solubility 0.433 mg/ml ; 0.00309 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.

-6.06 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)

1.44

Application In Synthesis of [ 162427-79-4 ]

* 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 [ 162427-79-4 ]

[ 162427-79-4 ] Synthesis Path-Downstream   1~10

  • 1
  • [ 445-27-2 ]
  • [ 171032-87-4 ]
  • [ 162427-79-4 ]
YieldReaction ConditionsOperation in experiment
100% With RuBr2[(S,S)-2,4-bis(diphenylphosphino)pentane](2-picolylamine); potassium tert-butylate; hydrogen; In ethanol; at 40℃; under 7600.51 Torr; for 19h;Inert atmosphere; Autoclave; General procedure: In an autoclave, 1.32 mg of RuBr2[(S,S)-xylskewphos] (3,5-Me2pica) (1.29×10-3 mmol, S/C=10000) and 5.79 mg of potassium tert-butoxide (5.16×10-2 mmol) are placed, and replaced with argon gas. Under argon gas flow, 1.5 mL of acetophenone (12.9 mmol) and 2.9 mL of ethanol was added while measuring by a syringe, pressurized with hydrogen to 10 atm, stirred at 40 C. for 19 hours, then the reduction of the hydrogen pressure was confirmed and phenylethanol was obtained at 100% yield. The optical purity was 88.0% ee as measured by GC (CP-Chirasil-DEX CB (0.25 mml. D×25 m, DF=0.25 mum, from VARIAN), constant at 110 C., pressure: 102.0 kPa, column flow: 1.18 mL/min, vaporizing chamber temperature: 250 C., detector temperature: 275 C., the retention time of each enantiomer was: (R): 11.7 min, (S): 12.4 min), and (S) isomer has predominantly been generated.The reaction was carried out in similar way as Working Example 1 except that the complex was changed to RuBr2 [(S,S)-xylskewphos](pica), and the reaction solvent and substrate were changed as indicated in the Table below. The results are summarized in the Table below, which also describes the results from Comparative Example 1. Analysis conditions indicated in the Table is the same as the Table provided from Working Examples ito 6. From the results, it is clear that RuBr2[(S,S)-xylskewphos] (3,5-Me2pica) has a better enantioselectivity as compared to RuBr2[(S,S)-xyl- skewphos] (pica) complex.
With (S,S)-DPENDS; C36H24Cl2O18P2RuS6(6-)*6Na(1+); hydrogen; potassium hydroxide; In water; at 30℃; under 37503.8 Torr; for 3h;Autoclave; General procedure: To a 60 mL stainless autoclave with a glass liner and magnetic stirrer were added PEG-400, H2O, RuCl2(TPPTS)2, (S,S)-DPENDS, KOH, and reactant. Hydrogen was introduced to the desired pressure after the reaction mixture had been purged with H2 five times. The products were extracted by n-hexane and analyzed by GC-960 with a FID detector and beta-DEX120 capillary column (30 m × 0.25 mm, 0.25 mum film) at 115 C. The enantiomeric excess (ee value) was calculated from the equation: ee (%) = 100 × (R - S)/(R + S).
With dodecacarbonyl-triangulo-triruthenium; (S,S)-N-{1,2-diphenyl-2-[(pyridin-2-ylmethyl)amino]ethyl}-4-methylbenzenesulfonamide; In isopropyl alcohol; at 80℃; for 48h;Inert atmosphere; Schlenk technique; General procedure: A mixture of catalyst (2 mol%) and Ru3 (CO)12 (0.67 mol%) in IPA (10 cm3) was stirred at 80 C under an inert atmosphere in a schlenk tube for 30 min. To this solution, ketone (1 mmol) was added and the resulting mixture was stirred at 80 Cfor 48 h. The reaction mixture was filtered through a short column of silica using (EtOAc:hexane 1:1), a small amount of the filtrate was dilluted in EtOAc and then injected on the GC to determine the conversion and enantiomeric excess.
With formic acid; (S,S)-RuCl(eta6-CH3C6H4CH2CH2CH2CH2NHCH(C6H5)CH(C6H5)NSO2Ts); C32H35ClN2O2RuS; triethylamine; at 60℃; for 5h;Schlenk technique;Catalytic behavior; General procedure: As Examples 20 to 35, hydrogen transfer reactions to ketones shown in Tables 1, 2, and 3 below were conducted by the same operation as in Examples 16 and 18. In these reactions, the catalyst ratios (S/C) were as shown in the tables, the reaction temperature was 60 C., and a formic acid-triethylamine (5:2) azeotrope was used as a hydrogen source in such an amount that the concentration of the substrate was 2 mol/L. The conversions and the optical purities were determined by analyzing the reaction liquids by GC after predetermined periods.; In addition, as Comparative Examples, results of reactions in which RuCl ((S,S)-Tsdpen) (mesitylene) was used in the same manner are also shown in each table. Note that, in these tables, conv. represents the conversion of the ketone substrate, selec. represents the selectivity for the target product, % ee represents the optical purity, and S/C represents a value represented by the number of moles of the ketone substrate/the number of moles of the catalyst.
With dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; C26H29N4O3S(1+)*Cl(1-); sodium formate; In water; at 20℃; for 5h;Catalytic behavior; General procedure: To a solution of ligand 5d (2.1 mg, 0.004 mmol) in water (1 mL) was added [Cp*RhCl2]2 (1.2 mg, 0.002 mmol), HCO2Na (41 mg, 3.0 mmol), and ketone (2.0 mmol). The reaction mixture was stirred at room temperature for the time as indicated in Tables 1 and 2 . The reaction mixture was extracted by ethyl ether. The conversion was determined by 1H NMR analysis of the crude product. After concentration, the crude product was purified by chromatography on silica gel to give the pure product.
With dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; C26H29N4O3S(1+)*Cl(1-); sodium formate; In water; at 20℃; for 5h;Green chemistry; General procedure: To a solution of ligand 5d (2.1 mg, 0.004 mmol) in water (1 mL) was added [Cp*RhCl2]2 (1.2 mg, 0.002 mmol), HCO2Na (41 mg, 3.0 mmol), and ketone (2.0 mmol). The reaction mixture was stirred at room temperature for the time as indicated in Tables 1 and 2. The reaction mixture was extracted by ethyl ether. The conversion was determined by 1H NMR analysis of the crude product. After concentration, the crude product was purified by chromatography on silica gel to give the pure product.
General procedure: In a schlenk tube, BH3·SMe2(0.55 mmol, 275 L) was added inthe solution of IL 5 (28 mg, 10 mol%) dissolved in THF (1 mL), undernitrogen atmosphere. The homogenous mixture was stirred andheated at 70C for 30 min. Later, a solution of ketone (0.5 mmolin THF (0.5 mL)) was added within 30 min. After the addition wascompleted, the solvent was evaporated under vacuum. An aqueoussolution of 1M HCl (5 mL) was added and the product was extractedwith DCM. The solvent was dried on anhydrous sodium sulfateand evaporated under reduced pressure. Crude residue was furtherpurified by column chromatography on silica gel using hexane-ethyl acetate as eluent. Enantiomeric excesses of all alcohols weredetermined by HPLC analysis using Chiralcel OD-H/AD-H chiralcolumn, isopropanol-n-hexane as mobile phase and HPLC condi-tions are given in SI.
With (2R)-2-[benzyl([6-({benzyl[(1R)-2-[(diphenylphosphanyl)oxy]-1-phenylethyl]amino}methyl)pyridin-2-yl]methyl})amino]-2-phenylethyl diphenylphosphinite bis(dichloro-eta6-p-cymeneruthenium(II)); isopropyl alcohol; potassium hydroxide; at 82℃; for 0.5h;Inert atmosphere; Schlenk technique;Catalytic behavior; General procedure: Typical procedure for the catalytic hydrogen-transfer reaction: a solution of the Ru(II)-complexes 17-24 (0.005 mmol), KOH (0.025mmol) and the corresponding ketone (0.5 mmol) in degassed 2-propanol (5 mL) was refluxed until the reaction was completed. Periodically samples taken from the reaction medium were passed through acetone silica gel column and conversion rates were observed in gas chromatography, which were calculated based on unreacted ketone.
With [(1S,2S)-N-(p-toluensulfonyl)-1,2-diphenylethanediamine](p-cymene)ruthenium (I); sodium formate; In methanol; water; at 50℃; for 12h;Green chemistry; 0.5 mmol of 1-(2-fluorophenyl)ethanol was added to the test tube, 1.5 mmol of dipropylene glycol dimethyl ether was added to the oxygen balloon, and the reaction was completed at 120 C for 12 hours until the reaction was completed, and sodium formate was added to the reaction system, 2.5 mmol. Then add 0.0025 mmol of catalyst B, add 4 mL of methanol:water (3:1), replace with nitrogen three times, react at 50 C for 12 h, wash with water after the reaction, extract the aqueous phase with ethyl acetate three times, and concentrate the organic phase to dry Column chromatography (petroleum ether: ethyl acetate = 10:1) gave (S)-1-(2-fluorophenyl)ethanol (61.6 mg), yield 88%, ee value 86%. HPLC separation conditions: chiral column OD-H column, mobile phase: n-hexane / isopropanol = 98: 2 (volume ratio), flow rate: 1.0 ml / min, wavelength: 254 nm, temperature, 25 C, t1 = 11.82min, t2=12.72min;
With glucose dehydrogenase; D-glucose; NAD; acetophenone reductase from Geotrichum candidum NBRC 4597 (Trp288Ala mutant); In aq. buffer; at 30℃; for 14h;pH 7.2;Enzymatic reaction;Kinetics; General procedure: Reductions were performed in 50 mL of 100 mM HEPES-NaOH buffer (pH 7.2) consisting of1.4 mM NAD+, 0.23-0.39 mmol of 2a-13a, cofactor regeneration reagent written in Table S1, and purified GcAPRD with the amount written in Table S1. Reactions were done for 14 h at 30C with a rotational speed of 130 rpm. The product was extracted with diethyl ether, dried over MgSO4, and evaporated under reduced pressure. Silica gel column chromatography (hexane:ethyl acetate 4:1) were performed to give the corresponding chiral alcohols 2b-13b.

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  • 3
  • [ 445-26-1 ]
  • [ 171032-87-4 ]
  • [ 162427-79-4 ]
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  • [ 75-24-1 ]
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  • [ 162427-79-4 ]
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  • [ 544-97-8 ]
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  • [ 162427-79-4 ]
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  • [ 162427-79-4 ]
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  • [ 162427-79-4 ]
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  • [ 445-27-2 ]
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  • [ 162427-79-4 ]
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  • [ 445-26-1 ]
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  • 10
  • [ 1796-63-0 ]
  • (R)-O-acetyl-1-(2'-fluorophenyl)ethanol [ No CAS ]
  • C10H11FO2 [ No CAS ]
  • [ 171032-87-4 ]
  • [ 162427-79-4 ]
 

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