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Structure of 937602-15-8

Chemical Structure| 937602-15-8

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Product Details of [ 937602-15-8 ]

CAS No. :937602-15-8
Formula : C7H7F3N2
M.W : 176.14
SMILES Code : FC(C1=CN=C(NC)C=C1)(F)F
MDL No. :MFCD08689790
InChI Key :ALRNMRIFTCZDDH-UHFFFAOYSA-N
Pubchem ID :18526206

Safety of [ 937602-15-8 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 937602-15-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.29
Num. rotatable bonds 2
Num. H-bond acceptors 4.0
Num. H-bond donors 1.0
Molar Refractivity 38.54
TPSA ?

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

24.92 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.61
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

2.05
Log Po/w (WLOGP)?

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

3.1
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.

1.65
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

2.02
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.09

Water Solubility

Log S (ESOL):?

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

-2.46
Solubility 0.609 mg/ml ; 0.00345 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.

-2.2
Solubility 1.11 mg/ml ; 0.00628 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

-3.35
Solubility 0.0792 mg/ml ; 0.00045 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

No
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.

-5.92 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)

1.8

Application In Synthesis of [ 937602-15-8 ]

* 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 [ 937602-15-8 ]

[ 937602-15-8 ] Synthesis Path-Downstream   1~11

  • 1
  • [ 79-16-3 ]
  • [ 52334-81-3 ]
  • [ 937602-15-8 ]
  • 2
  • [ 123-39-7 ]
  • [ 52334-81-3 ]
  • [ 937602-15-8 ]
  • 3
  • [ 52334-81-3 ]
  • [ 74-89-5 ]
  • [ 937602-15-8 ]
YieldReaction ConditionsOperation in experiment
In 1-methyl-pyrrolidin-2-one; water; at 20℃; for 3h; Reference Production Example 6; To a mixture of 18.2 of 2-chloro-5- trifluoromethylpyridine and 100 ml of N- methylpyrrolidone was added 23.3 g of a 40% methylamine aqueous solution, and the mixture was stirred for 3 hours at room temperature. Water was poured, and the mixture was extracted three times with ethyl acetate. The combined organic layers were dried over magnesium sulfate, then, concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to obtain 17.3 g of N-methyl-(5- trifluoromethylpyridine-2-yl) -amine .Me1H-NMR (CDCl3) delta: 8.34 (s, IH), 7.60 (dd, J=8.8, 2.4Hz, IH), 6.40 (d, J=8.8Hz, IH), 4.89(br s, IH), 2.97 (d, J=5.1Hz, 3H)
  • 4
  • [ 937602-15-8 ]
  • [ 175277-21-1 ]
YieldReaction ConditionsOperation in experiment
With sulfuric acid; nitric acid; at 80℃; for 2h; Into a mixture of 17.3 g of N-methyl(5- trifluoromethylpyridin-2-yl) -amine and 100 ml of sulfuric acid was dropped 12.3 g of nitric acid, then, the mixture was stirred for 2 hours while heating at 800C. After cooling down to room temperature, water was poured into the reaction mixture, and the deposited precipitate was filtrated, then, washed with water, then, dried under reduced pressure to obtain 18.8 g of N-methyl (3-nitro-5-trifluoromethylpyridin-2-yl) -amine.1H-NMR (CDCl3 ) delta: 8.66-8.64 (m, 2H) , 8.43 (br s, IH) , 3.23 (d, J=4.9Hz, 3H)
  • 5
  • [ 937602-15-8 ]
  • [ 1421952-02-4 ]
  • 3-ethylsulfanyl-N-methyl-5-trifluoromethyl-N-(5-trifluoromethylpyridin-2-yl)picolinamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
0.18 g With pyridine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; at 20℃; for 3h; Production Example 15 [0734] A mixture of 0.35 g of <strong>[937602-15-8]2-methylamino-5-trifluoromethylpyridine</strong>, 0.50 g of 3-ethylsulfanyl-5-trifluoromethylpicolinic acid, 0.46 g of EDCI hydrochloride, 0.02 g of HOBt and 3 mL of pyridine was stirred at room temperature for 3 hours. A saturated aqueous sodium bicarbonate solution was poured to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure, and the resulting residue was applied to a silica gel column chromatography to obtain 0.18 g of 3-ethylsulfanyl-N-methyl-5-trifluoromethyl-N-(5-trifluorome thylpyridin-2-yl)picolinamide (hereinafter, referred to as Compound of Present Invention 24). Compound of Present Invention 24 [0735] 1H-NMR(CDCl3)delta: 8.54-8.47(2H, m), 7.89-7.81(2H, m), 7.61(1H, s), 3.55(3H, s), 3.02(2H, q), 1.35(3H, t).
  • 6
  • [ 937602-15-8 ]
  • [ 1421952-02-4 ]
  • 3-ethylsulfonyl-N-methyl-5-trifluoromethyl-N-(5-trifluoromethylpyridin-2-yl)picolinamide [ No CAS ]
  • 7
  • [ 937602-15-8 ]
  • [ 126917-10-0 ]
  • 2-fluoro-N-methyl-4-(trifluoromethyl)-N-(5-(trifluoromethyl)pyridin-2-yl)benzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
47% With dmap; triethylamine; In tetrahydrofuran; at 20℃; for 3h;Cooling with ice; Example 1-1 (0142) Production Method of 2-fluoro-N-methyl-4-(trifluoromethyl)-N-(5-(trifluoromethyl)pyridin-2-yl)benzamide (0143) 2-Fluoro-4-trifluoromethyl benzoyl chloride (409 mg) and a THF (1 mL) solution were added to a mixture of <strong>[937602-15-8]N-methyl-5-(trifluoromethyl)pyridin-2-amine</strong> (264 mg), THF (4 mL) and triethylamine (1 mL) under ice cooling. After heating to room temperature, N,N-dimethyl aminopyridine (50 mg) was added, and the resulting mixture was stirred for 3 hours. Water was added to the reaction mixture, and extraction with ethyl acetate was performed. The organic layer was dried over anhydrous magnesium sulfate and then concentrated in vacuo. The resulting residue was subjected to column chromatography to give the desired compound (260 mg, yield: 47%).
  • 8
  • [ 937602-15-8 ]
  • 2-(ethylsulfonyl)-N-methyl-4-(trifluoromethyl)-N-(5-(trifluoromethyl)pyridin-2-yl)benzamide [ No CAS ]
  • 2-(ethylsulfinyl)-N-methyl-4-(trifluoromethyl)-N-(5-(trifluoromethyl)pyridin-2-yl)benzamide [ No CAS ]
  • 9
  • [ 937602-15-8 ]
  • 2-(ethylthio)-N-methyl-4-(trifluoromethyl)-N-(5-(trifluoromethyl)pyridin-2-yl)benzamide [ No CAS ]
  • 10
  • [ 75-44-5 ]
  • [ 937602-15-8 ]
  • [ 204452-91-5 ]
  • C19H21F3N4O3 [ No CAS ]
  • 11
  • [ 937602-15-8 ]
  • [ 204452-91-5 ]
  • 7-formyl-N-methyl-N-(5-(trifluoromethyl)pyridin-2-yl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide [ No CAS ]
 

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