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Chemical Structure| 312-94-7 Chemical Structure| 312-94-7

Structure of 312-94-7

Chemical Structure| 312-94-7

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Product Details of [ 312-94-7 ]

CAS No. :312-94-7
Formula : C8H4ClF3O
M.W : 208.57
SMILES Code : O=C(Cl)C1=CC=CC=C1C(F)(F)F
MDL No. :MFCD00000667
InChI Key :MXIUWSYTQJLIKE-UHFFFAOYSA-N
Pubchem ID :67561

Safety of [ 312-94-7 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H314
Precautionary Statements:P280-P305+P351+P338-P310
Class:8
UN#:3265
Packing Group:

Computational Chemistry of [ 312-94-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 6
Fraction Csp3 0.12
Num. rotatable bonds 2
Num. H-bond acceptors 4.0
Num. H-bond donors 0.0
Molar Refractivity 41.63
TPSA ?

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

17.07 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.2
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

2.31
Log Po/w (WLOGP)?

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

4.24
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.

3.08
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

3.36
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.04

Water Solubility

Log S (ESOL):?

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

-2.8
Solubility 0.332 mg/ml ; 0.00159 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 1.03 mg/ml ; 0.00493 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

-3.85
Solubility 0.0291 mg/ml ; 0.00014 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.

-5.93 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

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)

1.4

Application In Synthesis of [ 312-94-7 ]

* 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 [ 312-94-7 ]

[ 312-94-7 ] Synthesis Path-Downstream   1~6

  • 1
  • [ 36725-28-7 ]
  • [ 312-94-7 ]
  • <i>N</i>-[4-(4-methyl-6-oxo-1,4,5,6-tetrahydro-pyridazin-3-yl)-phenyl]-2-trifluoromethyl-benzamide [ No CAS ]
  • 2
  • [ 79902-31-1 ]
  • [ 2456-81-7 ]
  • [ 312-94-7 ]
  • [ 124879-80-7 ]
YieldReaction ConditionsOperation in experiment
With lithium bromide; In pyridine; ethyl acetate; (a) Preparation of 6(R)-[2-[8(S)-(2-trifluoromethyl-benzoyloxy)-2(S),6(R) dimethyl 1,2,6,7,8,8a(R)-hexahydronaphthyl-1(S)]ethyl]-4(R)-tert-butyl -dimethylsilyloxy-3,4,5,6-tetrahydro-2H-pyran-2-one (2a) Anhydrous LiBr (0.51 g, 0.006 mol) was added to a solution of 2-trifluoromethylbenzoyl chloride (0.63 g, 0.003 mol) in pyridine (6 ml). After stirring at room temperature for 20 minutes followed by heating for about 5 minutes at 80° C. the mixture was allowed to cool to room temperature. <strong>[2456-81-7]4-Pyrrolidinopyridine</strong> (0.06 g) was added followed by 6(R)-[2-[8(S)-hydroxy-2(S),6(R)-dimethyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1(S)]ethyl]-4(R)-tert butyldimethylsilyloxy-3,4,5,6-tetrahydro-2H -pyran-2-one. (0.62 g, 0.0014 mol). The mixture was heated at 90° C. for 15 hours. After cooling to room temperature, the reaction mixture was poured into diethyl ether and water. The ether phase washed with H2 O (3x), dilute HCl, H2 O, saturated aqueous NaHC3, and saturated brine. After filtration the ether solution was evaporated to dryness. The yellow oil was chromatographed on silica gel (230-400 mesh) employing 20percent ethyl acetate/hexanes as a developing solvent. The colorless oil isolated gave a single spot by TLC with Rf =0.36 using 20percent ether/hexane. The 1 H NMR spectrum was consistent with the desired structure.
  • 3
  • [ 639068-43-2 ]
  • [ 312-94-7 ]
  • [ 1232028-14-6 ]
YieldReaction ConditionsOperation in experiment
With triethylamine; at 20℃; for 0.5h; Step 3 Synthesis of 3,5-Dimethyl-4-(2-trifluoromethyl-benzoyl)-piperazine-1-carboxylic acid tert-butyl ester Triethyl amine (55.6 mg, 0.07 mL, 0.55 mmol) was added to a stirred solution of 2,5-dimethyl-piperazine-1-carboxylic acid tert-butyl ester (98.6 mg, 0.45 mmol) followed by 2-trifluoromethyl-benzoyl chloride (95.6 mg, 0.45 mmol) and the resulting mixture was stirred at room temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure to get the residue. The residue thus obtained was purified by column chromatography using 60-120 silica gel and 50percent ethyl acetate in hexane to afford 74 mg (41.71percent yield) of 3,5-dimethyl-4-(2-trifluoromethyl-benzoyl)-piperazine-1-carboxylic acid tert-butyl ester. LCMS Purity: 96.7percent.
  • 4
  • [ 52562-19-3 ]
  • [ 312-94-7 ]
  • N-(2-(prop-1-en-2-yl)phenyl)-2-(trifluoromethyl)benzamide [ No CAS ]
  • 5
  • [ 28466-26-4 ]
  • [ 312-94-7 ]
  • N-(1H-pyrazol-4-yl)-2-(trifluoromethyl)benzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
96% At room temperature, 10.40 g (49 8 mmol) of 2-trifluoromethylbenzoyl chloride were added dropwise to a solution of 1.38 g (16.6 mmol) of <strong>[28466-26-4]4-aminopyrazole</strong> and 10.30 g (74.7 mmol) of potassium carbonate in 40 ml of acetonitrile. The mixture was stirred at room temperature overnight and then concentrated on a rotary evaporator. The crude product was stirred at room temperature with 41 ml of methanol and 41 ml of 2N aqueous sodium hydroxide solution for 2 h. The mixture was concentrated and then extracted repeatedly with ethyl acetate. The organic phase was washed with saturated sodium chloride solution and dried with magnesium sulphate. Concentration of the solution gave 2.41 g (96% pure, 55% of theory) of N-(1H-pyrazol-4-yl)-2-(trifluoromethyl)benzamide HPLC: logP(HCOOH)=1.21, logP(neutral)=1.22; mass(m/z): 256(M+H)+; 1H NMR: 400 MHz, DMSO-D6, delta: 12.67 (s,1H), 10.56 (s,1H), 7.94 (s, 1H), 7.82 (d, 1H), 7.77 (t, 1H), 7.65 (m, 1H) 7.55 (s,1H)
  • 6
  • [ 5319-77-7 ]
  • [ 312-94-7 ]
  • N-(5-(methylthio)-1,3,4-thiadiazol-2-yl)-2-(trifluoromethyl)benzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
84.6% With potassium carbonate; In toluene; at 20℃; 2-Amino-5-methylindolyl-1,3,4-thiadiazole (2.6 mmol), potassium carbonate (3.9 mmol) and toluene(20mL) as a solvent, put in a 100mL three-neck bottle. After the solid was completely dissolved, 2-(trifluoromethyl)benzoyl chloride (2.6 mmol) was added dropwise, and the mixture was reacted at room temperature. TLC followed the progress of the reaction. After the reaction was completed, the reaction was stopped, the solvent was removed under reduced pressure, and the mixture was washed with water (30 mL), filtered and washed with water to obtain a crude product. N-(5-(methylthio)-1,3,4-thiadiazol-2-yl)-2-(trifluoromethyl)benzamide. Yield 84.6%.
 

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