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Structure of 886497-81-0

Chemical Structure| 886497-81-0

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Product Details of [ 886497-81-0 ]

CAS No. :886497-81-0
Formula : C8H4F4O2
M.W : 208.11
SMILES Code : FC1=C(C=O)C=C(OC(F)(F)F)C=C1
MDL No. :MFCD04115886
InChI Key :FMDGCHMPSCBYFX-UHFFFAOYSA-N
Pubchem ID :2783324

Safety of [ 886497-81-0 ]

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

Computational Chemistry of [ 886497-81-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 6
Fraction Csp3 0.12
Num. rotatable bonds 3
Num. H-bond acceptors 6.0
Num. H-bond donors 0.0
Molar Refractivity 38.47
TPSA ?

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

26.3 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.92
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

3.25
Log Po/w (WLOGP)?

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

4.22
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.

2.01
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

2.99
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.88

Water Solubility

Log S (ESOL):?

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

-3.3
Solubility 0.105 mg/ml ; 0.000505 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.

-3.48
Solubility 0.0695 mg/ml ; 0.000334 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

-3.26
Solubility 0.115 mg/ml ; 0.000552 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.

-5.26 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

0.0
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

1.0 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)

1.6

Application In Synthesis of [ 886497-81-0 ]

* 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.

  • Downstream synthetic route of [ 886497-81-0 ]

[ 886497-81-0 ] Synthesis Path-Downstream   1~13

  • 1
  • [ 886497-81-0 ]
  • [ 890132-95-3 ]
YieldReaction ConditionsOperation in experiment
88% With hydroxylamine hydrochloride; sodium acetate; In ethanol; for 2h;Heating / reflux; b) E-2-Fluoro-5-trifluoromethoxy-benzaldehyde oxime A solution of <strong>[886497-81-0]2-fluoro-5-trifluoromethoxy-benzaldehyde</strong> (9.78 g, 47 mmol) in ethanol (50 ml) was treated with hydroxylamine HCl (3.59 g, 52 mmol) and sodium acetate (4.27 g, 52 mmol). The mixture was refluxed for 2 h, the solvent was evaporated and the residue stirred with water (50 ml). The precipitate was filtered, dried and chromatographed (SiO2, heptanes:Ethyl acetate=100:0 to 80:2) and afforded the title compound (9.21 g, 88%) as a white solid. MS: m/e=223.0 [M]+.
  • 2
  • [ 352-67-0 ]
  • [ 68-12-2 ]
  • [ 886497-81-0 ]
YieldReaction ConditionsOperation in experiment
53% EXAMPLE 49 3-Trifluoromethoxy-10-methyl-9H-imidazo[1,5-a][1,2,4]triazolo[1,5-d][1,4]benzodiazepine; a) 2-Fluoro-5-trifluoromethoxy-benzaldehyde; A solution of 1-fluoro-4-trifluoromethoxy-benzene (21.0 g, 117 mmol) in THF (233 ml) was cooled to <-70 C. Tert.-butyllithium (86 ml of a 1.5 molar solution in pentane, 129 mmol) was added at such a rate that temperature was kept <-70 C. Stirring in the dry ice bath was continued for 15 min, then DMF (11.6 ml, 150 mmol) was added dropwise keeping temperature <-70 C. After 30 min the reaction mixture was allowed to reach rt, quenched with saturated NH4Cl solution and extracted with ether. The organic phase was washed with brine, concentrated and chromatographed (SiO2, heptane:ethyl acetate=100:0 to 80:2). The title compound (11.0 g, 53%) was obtained as a light yellow oil. 1H-NMR (300 MHz, DMSO): delta=7.60 (t, J=9.2 Hz, 1H), 7.75-7.85 (m, 2H), 10.20 (s, 1H).
  • 3
  • [ 109-04-6 ]
  • [ 886497-81-0 ]
  • 2-[(2-fluoro-5-trifluoromethoxyphenyl)(1-methylpiperidin-4-yloxy)methyl]pyridine [ No CAS ]
  • 4
  • [ 109-04-6 ]
  • [ 886497-81-0 ]
  • (2-fluoro-5-trifluoromethoxyphenyl)pyridin-2-ylmethanol [ No CAS ]
YieldReaction ConditionsOperation in experiment
1B [0232] To a solution of 2-bromopyridine (380 mg) in anhydrous tetrahydrofuran (3 mL) is slowly added a 1M solution of isopropylmagnesium bromide in tetrahydrofuran (2.64 mL) at room temperature. After stirring for 2 hours, <strong>[886497-81-0]2-fluoro-5-(trifluoromethoxy)benzaldehyde</strong> (0.50 mL) is added and the reaction mixture stirred for 2 hours. After hydrolysis with water and 3N hydrochloric acid, the mixture is washed with diethyl ether, basified with concentrated sodium hydroxide and extracted with ethyl acetate twice. The pooled organic extracts are dried over magnesium sulfate and concentrated under reduced pressure. The residue is purified by chromatography over silica gel (heptane/ethyl acetate 2/1) to afford (2-fluoro-5-trifluoromethoxyphenyl)pyridin-2-ylmethanol as an orange oil.
  • 5
  • [ 886497-81-0 ]
  • [ 2365-48-2 ]
  • methyl 5-trifluoromethoxybenzo[b]thiophene-2-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
1.38 g With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 2h; 12279] A mixture of 3.00 g of 2-fluoro-3-trifluoromethoxy- benzaldehyde, 1.33 g of methyl thioglycolate, 2.66 g ofpotassium carbonate, and 10 ml of N,N-dimethylformamide was stirred for 2 hours at 80 C. After the reaction mixture was cooled to room temperature, water was added thereto, and extraction was performed three times by using ethyl acetate. The collected organic layer was washed with water and saturated saline, dried over magnesium sulfate, and then concentrated under reduced pressure, thereby obtaining 1.38 g of methyl 5-trifluoromethoxybenzo[b]thiophene-2-carboxylate (hereinafier, described as a ?compound 98 of the present invention?).12280] Compound 98 of the Present Invention 12281] ?H-NMR(CDC13) oe: 8.05 (s, 1H), 7.87 (d, 1H, J=8.8Hz), 7.73 (d, 1H, J=1 .0Hz), 7.34 (dq, 1H, J=8.8, 1.0Hz), 3.96(s, 3H).
1.38 g With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 2h; A mixture of 3.00 g of <strong>[886497-81-0]2-fluoro-5-trifluoromethoxybenzaldehyde</strong>, 1.33 g of methyl thioglycolate, 2.66 g of potassiumcarbonate, and 10 ml of N,N-dimethylformamide was stirred for 2 hours at 80C. After the reaction mixture wascooled to room temperature, water was added thereto, and extraction was performed three times by using ethyl acetate.The collected organic layer was washed with water and saturated saline, dried over magnesium sulfate, and thenconcentrated under reduced pressure, thereby obtaining 1.38 g of methyl 5-trifluoromethoxybenzo[b]thiophene-2-carboxylate.
  • 6
  • [ 886497-81-0 ]
  • [ 885279-13-0 ]
  • 7
  • [ 886497-81-0 ]
  • [ 716-06-3 ]
  • N-(2-fluoro-5-(trifluoromethoxy)benzyl)-2-(5-methoxy-1-methyl-1H-indol-3-yl)ethan-1-amine [ No CAS ]
  • 8
  • [ 886497-81-0 ]
  • [ 716-06-3 ]
  • C20H18F4N2O2 [ No CAS ]
  • 9
  • [ 886497-81-0 ]
  • (R)-5-(2-amino-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-N-(1-(2-fluoro-5-(trifluoromethoxy)phenyl)ethyl-2,2,2-d3)-2,6-dimethylnicotinamide [ No CAS ]
  • 10
  • [ 886497-81-0 ]
  • (S)-N-((R)-1-(2-fluoro-5-(trifluoromethoxy)phenyl)ethyl-2,2,2-d3)-2-methylpropane-2-sulfinamide [ No CAS ]
  • 11
  • [ 886497-81-0 ]
  • (R)-1-(2-fluoro-5-(trifluoromethoxy)phenyl)ethan-2,2,2-d3-1-amine hydrochloride [ No CAS ]
  • 12
  • [ 886497-81-0 ]
  • (S)-N-((R)-1-(2-fluoro-5-(trifluoromethoxy)phenyl)ethyl)-2-methylpropane-2-sulfinamide [ No CAS ]
  • 13
  • [ 886497-81-0 ]
  • [ 343338-28-3 ]
  • (S,E)-N-(2-fluoro-5-(trifluoromethoxy)benzylidene)-2-methylpropane-2-sulfinamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
91% With titanium(IV)isopropoxide; In tetrahydrofuran; at 20℃; for 72h; Titanium(IV) isopropoxide (5.69 mL, 19.22 mmol) was added to a THF (20 mL) solution of <strong>[886497-81-0]2-fluoro-5-(trifluoromethoxy)benzaldehyde</strong> (2.0 g, 9.61 mmol) and (S)-(10 )-2-methyl-2-propanesulfinamide (1.165 g, 9.61 mmol) at ft and stirred for 72 h. Thereaction mixture was quenched by adding brine (10 mL) and hexanes (10 mL) at 0 C.The mixture was filtered through a pad of celite, and the pad was rinsed with ethyl acetate(2 x 10 mL). The combined organic solutions were dried over sodium sulfate, filtered andconcentrated under reduced pressure to give crude product which was purified on a silicagel column with Hexanes/EtOAc (100/0 to 50/50) to give (S,E)-N-(2-fluoro-5-(trifluoromethoxy)benzylidene)-2-methylpropane-2-sulfinamide (2.827 g, 8.73 mmol, 91%yield).MS ESI m/z 312.0 (M+H)
 

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