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Chemical Structure| 330-93-8 Chemical Structure| 330-93-8

Structure of 330-93-8

Chemical Structure| 330-93-8

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Product Details of [ 330-93-8 ]

CAS No. :330-93-8
Formula : C12H8F2O
M.W : 206.19
SMILES Code : FC1=CC=C(OC2=CC=C(F)C=C2)C=C1
MDL No. :MFCD00013552
InChI Key :UUKHFGSOCZLVJO-UHFFFAOYSA-N
Pubchem ID :67615

Safety of [ 330-93-8 ]

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

Computational Chemistry of [ 330-93-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 15
Num. arom. heavy atoms 12
Fraction Csp3 0.0
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 52.87
TPSA ?

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

9.23 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.76
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

2.92
Log Po/w (WLOGP)?

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

4.6
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.

4.15
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

3.86
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.66

Water Solubility

Log S (ESOL):?

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

-3.42
Solubility 0.0788 mg/ml ; 0.000382 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.

-2.78
Solubility 0.346 mg/ml ; 0.00168 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

-5.22
Solubility 0.00125 mg/ml ; 0.00000604 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

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

Yes
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.

-5.48 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)

1.72

Application In Synthesis of [ 330-93-8 ]

* 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 [ 330-93-8 ]

[ 330-93-8 ] Synthesis Path-Downstream   1~20

  • 1
  • [ 330-93-8 ]
  • [ 26619-97-6 ]
YieldReaction ConditionsOperation in experiment
...presented by the following formula (4) which can respectively correspond to the formula (1) can be obtained. (D) Fluorine substituted aromatic compound represented by the formula (4) corresponding to the hydroxy compound wherein X1 is a substituent of the group (a) in the formula(1): ... 4-trifluoromethoxy-4'-fluorodiphenylsulfide, 4-trichloromethoxy-4'-fluorodiphenylsulfide, 2,2'-difluorodiphenylether, 2,3'-difluorodiphenylether, 2,4'-difluorodiphenylether, 3,3'-difluorodiphenylether, 3,4'-difluorodiphenylether, 4,4'-difluorodiphenylether, 4-methyl-4'-fluorodiphenylether, 4-methoxy-4'-fluorodiphenylether, 4-phenyl-4'-fluorodiphenylether, 4-nitro-4'-fluorodiphenylether, 4-cyano-4'-fluorodiphenylether, 4-chloro-4'-fluorodiphenylether, ...
  • 4
  • [ 460-00-4 ]
  • potassium-<4-fluoro-phenolate> [ No CAS ]
  • [ 330-93-8 ]
  • 5
  • [ 371-41-5 ]
  • [ 330-93-8 ]
  • 7
  • [ 330-93-8 ]
  • [ 28051-36-7 ]
  • 8
  • [ 330-93-8 ]
  • 2,8-difluoro-10-oxo-10<i>H</i>-10λ5-phenoxaphosphin-10-ol; piperidine salt [ No CAS ]
  • 9
  • [ 330-93-8 ]
  • [ 26619-98-7 ]
  • 10
  • [ 330-93-8 ]
  • [ 26749-29-1 ]
  • 11
  • [ 330-93-8 ]
  • [ 26723-78-4 ]
  • 12
  • [ 330-93-8 ]
  • [ 4492-47-1 ]
  • ethereal HCl [ No CAS ]
  • (+/-) cis-1-Amino-2-[4-(4-fluorophenoxy)phenoxymethyl]cyclopentane hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
In diethyl ether; acetic acid; dimethyl sulfoxide; EXAMPLE 9 (+-) cis-1-Amino-2-[4-(4-fluorophenoxy)phenoxymethyl]cyclopentane hydrochloride A solution of (+-) cis-1-amino-2-hydroxymethylcyclopentane (0.46 g, 4.0 mol) in dry dimethyl sulfoxide (12 ml), was treated with sodium hydride (0.144 g of an 80% dispersion in oil; 4.8 mmol). After stirring for 3 h at room temperature under argon a solution of <strong>[330-93-8]bis-(4-fluorophenyl)-ether</strong> (1.65g, 8.0 mmol) in dimethyl sulfoxide (2 ml) was added. The mixture was heated to 60 C. and held at this temperature for 19 h. The reaction was quenched at ice temperature with glacial acetic acid (0.27 ml, 4.8 mmol) and then worked up as described in Example 5. Purification by chromatography on silica gel eluding with 0-5% ethanol in diethyl ether afforded an oil. The product was extracted into diethyl ether-hexane, and insoluble impurities were discarded. Treatment with ethereal HCl produced the hydrochloride salt which was crystallized to give the title compound as a white solid (0.56 g) m.p. 170-171 C. (from methanol/diethyl ether). 1 H Nmr (DMSO-d6) delta: 1.50-2.10 (6H, m), 2.47 (1H, m), 3.63 (1H, m), 3.97 (1H, m), 4.12 (1H, m), 6.96 (6H, m), 7.18 (2H, m), 8.18 (3H, br s)
  • 13
  • [ 352-34-1 ]
  • [bis(1,10-phenanthroline)Cu][bis(p-fluorophenoxide)Cu] [ No CAS ]
  • [ 330-93-8 ]
  • 14
  • [ 330-93-8 ]
  • [ 71-43-2 ]
  • [ 108-95-2 ]
YieldReaction ConditionsOperation in experiment
With lithium aluminium tetrahydride; cobalt acetylacetonate; sodium t-butanolate; In toluene; at 140℃; for 24h;Inert atmosphere; Sealed tube; General procedure: To a dried 40mL tube equipped with a magnetic stirrer, 0.2mmol of substrate, 0.5mmol of LiAlH4, 0.03mmol of Co(acac)2, 0.5mmol of t-BuONa, and 2 or 1.5mL of toluene were added under nitrogen atmosphere. The reaction tube was sealed and placed in a constant-temperature oil bath set at 140C to perform the reaction for 24h (note: the pressure tube was required because the pressure of the reaction system was more than the standard atmospheric pressure). Once the reaction time was reached, the mixture was cooled to room temperature. The mixture was then acidified to pH5-6 with 2M hydrochloric acid. GC analysis of the mixture provided the GC yields of the products (note: in order to minimize the analysis error, the mixture after the reaction was not purified or concentrated). The reductive cleavage products were identified by GC-MS data. Some products were purified by column chromatography, and identified by 1H-NMR.
  • 16
  • [ 371-41-5 ]
  • [ 352-34-1 ]
  • [ 330-93-8 ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate; In N,N-dimethyl-formamide; at 150℃; for 24h; Chemical compound4-fluorophenol (2mmol)With the compound 4-fluoroiodobenzene (6mmol)Dissolve in N, N-dimethylformamide (20mL) solution,After adding sodium carbonate, it was stirred at 150 C for 24h.The formed compound was extracted with ethyl acetate and washed with saturated brine to obtain compound 1a
  • 17
  • [ 123-75-1 ]
  • [ 330-93-8 ]
  • [ 31708-14-2 ]
  • [ 4096-21-3 ]
  • 18
  • [ 330-93-8 ]
  • [ 1821-36-9 ]
  • [ 71-43-2 ]
YieldReaction ConditionsOperation in experiment
48% With ammonium hydroxide; sodium tetrahydroborate; 10 wt% Pd(OH)2 on carbon; In 5,5-dimethyl-1,3-cyclohexadiene; at 150℃; for 36h;Inert atmosphere; Put a moderate stirrer in a dry reaction tube (20 ml), add palladium hydroxide / carbon (20 mol%),NaBH4 (2 times equivalent), then the reaction tube is evacuated, filled with argon, repeated three times, dissolved in an argon atmosphereA solution of <strong>[330-93-8]bis(4-fluorophenyl)ether</strong> (0.2 mmol) and aqueous ammonia (1 mmol) in xylene was slowly added to the reaction tube with a syringe, which was reversed.The tube should be placed in a 150 C oil bath and heated and stirred. After 36 hours, the reaction was stopped and the reaction tube was taken out of the oil bath.It was naturally cooled to room temperature, diluted with ethyl acetate, and then the reaction liquid was filtered with celite, and the yield of the filtrate was determined by gas phase detection.62%. The filtrate was concentrated and separated by an activated thin layer chromatography chromatography plate (eluent: n-hexane/ethyl acetate = 30/1).The final product 3a is obtained after separation. Product 3a (yield: 48%)
  • 19
  • [ 732306-64-8 ]
  • [ 330-93-8 ]
References: [1],.
  • 20
  • [ 330-93-8 ]
  • [ 86-74-8 ]
  • bis(4-(9H-carbazol-9-yl)phenyl) ether [ No CAS ]
YieldReaction ConditionsOperation in experiment
40% In N,N-dimethyl-formamide; at 60℃; for 36h; Compound 1a (2mmol) and carbazole(12mmol) dissolved in N, N-dimethylformamide (30mL) solution, in 1,Stir at 60 C for 36h. The precipitate formed is separated by vacuum suction filtration,It was washed with saturated saline and recrystallized in acetone to obtain compound 3.
 

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