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Chemical Structure| 401-81-0 Chemical Structure| 401-81-0

Structure of 401-81-0

Chemical Structure| 401-81-0

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CAS No.: 401-81-0

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Product Details of [ 401-81-0 ]

CAS No. :401-81-0
Formula : C7H4F3I
M.W : 272.01
SMILES Code : FC(C1=CC(I)=CC=C1)(F)F
MDL No. :MFCD00001049
InChI Key :IGISPMBUGPHLBY-UHFFFAOYSA-N
Pubchem ID :67868

Safety of [ 401-81-0 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H227-H315-H319-H335
Precautionary Statements:P210-P261-P264-P271-P280-P302+P352-P304+P340-P305+P351+P338-P312-P370+P378-P362+P364-P403+P233-P501

Computational Chemistry of [ 401-81-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.14
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 44.16
TPSA ?

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

0.0 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.24
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

3.6
Log Po/w (WLOGP)?

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

4.46
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.

4.25
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

3.8
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.67

Water Solubility

Log S (ESOL):?

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

-4.13
Solubility 0.0201 mg/ml ; 0.0000738 mol/l
Class?

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

Moderately soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-3.29
Solubility 0.14 mg/ml ; 0.000517 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

-4.23
Solubility 0.0159 mg/ml ; 0.0000585 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

Low
BBB permeant?

BBB permeation: according to the yolk of the BOILED-Egg

No
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

Yes
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.

-5.4 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

1.0
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

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)

1.64

Application In Synthesis of [ 401-81-0 ]

* 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 [ 401-81-0 ]

[ 401-81-0 ] Synthesis Path-Downstream   1~15

  • 1
  • [ 401-81-0 ]
  • [ 67-64-1 ]
  • [ 21906-39-8 ]
  • 2
  • [ 201230-82-2 ]
  • [ 401-81-0 ]
  • [ 241813-23-0 ]
  • [ 37993-76-3 ]
  • 3-phenyl-4-(3-trifluoromethylphenyl)isoquinoline [ No CAS ]
  • 3-phenyl-4-(3-trifluoromethylbenzoyl)isoquinoline [ No CAS ]
  • 3
  • [ 401-81-0 ]
  • [ 25015-63-8 ]
  • [ 325142-82-3 ]
  • 4
  • [ 401-81-0 ]
  • [ 292638-85-8 ]
  • [ 87087-35-2 ]
YieldReaction ConditionsOperation in experiment
98% With bifunctional palladated rasta resin; In N,N-dimethyl-formamide; at 100℃; for 20h;Green chemistry; General procedure: Catalyst 2c (prepared according Ref. 26b, 133 mg, 6.2 equiv of Pd) was added to a solution of aryl iodide (0.20 mmol, 1.0 m equiv), alkene (0.40 mmol, 2.0 equiv) in DMF (2 mL). The reaction mixture was heated at 100 C for 20 h. After cooling to rt, compound 2c was filtered off under vacuum using a 0.2 μm membrane. The mixture of solvents was concentrated under vacuum to afford pure 3a-j after drying under vacuum (0.1 mbar). The catalyst 2c was then regenerated by reaction with NBu3 (0.16 mL, 0.66 mmol, 3.3 equiv) in DMF at rt for 3 h. Compound 2c was then filtered under vacuum, washed with Et2O (2 mL), and dried under vacuum.
95% With triethylamine; In N,N-dimethyl-formamide; toluene; at 100℃; for 20h; General procedure: Catalyst 1 (prepared according Ref.15a, 7.1 mg,0.05 mequiv of Pd) was added to a solution of aryl iodide (4 mmol,1.0 equiv), methyl acrylate (0.72 mL, 8 mmol, 2.0 equiv), Et3N (0.67 mL,4.8 mmol, 1.2 equiv) in a mixture of toluene (6.7 mL), DMF (3.3 mL) and H2O(0.1 mL). The reaction mixture was heated at 100 C for 20 h. After coolingto rt, 1 was filtered off under vacuum. The mixture of solvents wasconcentrated under vacuum and the residue was purified by flashchromatographyon silica gel to afford pure alkenes after drying under,vacuum (0.1 mbar).
  • 6
  • [ 401-81-0 ]
  • [ 1626-24-0 ]
  • [ 366-04-1 ]
  • [ 580-82-5 ]
  • 7
  • [ 19745-07-4 ]
  • [ 401-81-0 ]
  • [ 1233493-46-3 ]
  • 8
  • [ 401-81-0 ]
  • [ 73183-34-3 ]
  • [ 325142-82-3 ]
YieldReaction ConditionsOperation in experiment
81% With pyridine; cesium fluoride; In dimethyl sulfoxide; at 105℃; for 2h;Inert atmosphere; Schlenk technique; General procedure: An oven-dried Schlenk tube, containing a Teflon-coated magnetic stir bar was charged with CsF (228 mg, 1.5 mmol, 3 equiv) and bispinacolatodiboron (254 mg, 1 mmol, 2 equiv). Under an argon atmosphere, freshly distilled DMSO (0.4 mL), the appropriate aryl iodide (0.5mmol), and pyridine (0.4 to 1 equiv) were added successively. The reaction mixture was heated to 105 C and stirred for 2 h under argon.
59%Chromat. With copper(II) ferrite; potassium tert-butylate; In N,N-dimethyl-formamide; at 20℃; for 12h;Green chemistry; General procedure: 4-Iodoanisole (0.813 mmol, 200 mg), bis(pinacolato)diboron (1.219 mmol, 309 mg) were dissolved in 3 mL of dmf followed by copper ferrite nanoparticles (5mol% with respect to 4-iodoanisole) and potassiumtert-butoxide (1.219 mmol, 137 mg) were added to a 10 mLcapped vial and stirred at RT for time indicated. After stirring, the mixture was diluted with diethyl ether and filtered through celite bed. The filtrate was extracted with water (3 times) and the organic phase was dried over anhydrous MgSO4. The crude product was subjected to analyze by GC-MS. The conversion yield is accurately measured based on the consumption of 4-iodoanisole and the side product formed due to protodeiodination.
  • 9
  • [ 401-81-0 ]
  • [ 172732-52-4 ]
  • 3'-(trifluoromethyl)-[1,1'-biphenyl]-2-carbonitrile [ No CAS ]
  • 10
  • [ 401-81-0 ]
  • [ 172732-52-4 ]
  • 3-(trifluoromethyl)-9H-fluoren-9-one [ No CAS ]
  • 11
  • [ 401-81-0 ]
  • [ 38136-70-8 ]
  • [ 1454306-35-4 ]
  • 12
  • [ 563-83-7 ]
  • [ 401-81-0 ]
  • [ 1939-27-1 ]
YieldReaction ConditionsOperation in experiment
60% With cobalt(II) oxalate dihydrate; caesium carbonate; N,N`-dimethylethylenediamine; In water; at 130℃; for 24h;Green chemistry; General procedure: A mixture of cobalt(II) oxalate dihydrate(Sigma-Aldrich, 0.294 mmol), Cs2CO3 (2.94 mmol), pyrrolidinoneor aliphatic amide (1.47 mmol), DMEDA (0.588 mmol),distilled H2O (0.3 mL) and aryl halide (2.205 mmol) were addedto an 8.0-mL reaction vial fitted with a Teflon-sealed screw cap.The reaction mixture was stirred under air in a closed system at120 C and 130 C, respectively for 24 h. The heterogeneousmixture was subsequently cooled to r.t. and diluted withCH2Cl2. The combined organic extracts were dried over anhydNa2SO4, filtered and the solvent was removed under reducedpressure. The crude product was loaded into the column usingminimal amounts of CH2Cl2 and was purified by silica gel column chromatography to afford the N-arylated product. Theidentity and purity of products were confirmed by 1H NMR and13C NMR spectroscopic analysis.
  • 13
  • [ 401-81-0 ]
  • [ 78782-17-9 ]
  • [ 325142-82-3 ]
  • 14
  • [ 401-81-0 ]
  • [ 57090-88-7 ]
  • 1-(3-(trifluoromethyl)phenyl)-1H-imidazole-4-carbonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
With copper(l) iodide; (R,R)-N,N'-dimethyl-1,2-diaminocyclohexane; caesium carbonate; In N,N-dimethyl-formamide; at 100℃; for 2h; General procedure: A solution of <strong>[57090-88-7]4-cyano-1H-imidazole</strong> (1000 mg, 10.74 mmol), 4-iodo -2-(trifluoromethyl)pyridine (3800 mg,14 mmol), (1R,2R)-N1,N2-dimethyl cyclohexane -1,2-diamine (150 mg, 1.07 mmol), CuI (200 mg, 1.07 mmol) and Cs2CO3 (7000 mg, 21.5 mmol) in 20 mL anhydrous DMF was stirred at 100 oC for 2 hours. The reaction mixture was cooled to room temperature and poured into 200 mL water. The mixture was extracted with ethyl acetate (80 mL*3). The organic layer were combined, washed by brine, dried by Na2SO4 and evaporated. The crude product was purified by silica flash column to afford compound 2 as white solid(1.5 g, 59percent yield).
  • 15
  • [ 401-81-0 ]
  • [ 50413-30-4 ]
  • [ 1359967-66-0 ]
 

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