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Chemical Structure| 217959-45-0

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Product Details of [ 217959-45-0 ]

CAS No. :217959-45-0
Formula : C5H3F3OS
M.W : 168.14
SMILES Code : FC(C1=CC(O)=CS1)(F)F
MDL No. :MFCD07779810
InChI Key :JFSLKQBFXHGCHW-UHFFFAOYSA-N
Pubchem ID :11084273

Safety of [ 217959-45-0 ]

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

Computational Chemistry of [ 217959-45-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 5
Fraction Csp3 0.2
Num. rotatable bonds 1
Num. H-bond acceptors 4.0
Num. H-bond donors 1.0
Molar Refractivity 31.34
TPSA ?

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

48.47 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.51
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

2.17
Log Po/w (WLOGP)?

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

3.62
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.

1.55
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

3.11
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.39

Water Solubility

Log S (ESOL):?

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

-2.55
Solubility 0.47 mg/ml ; 0.0028 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.

-2.82
Solubility 0.254 mg/ml ; 0.00151 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

-1.97
Solubility 1.8 mg/ml ; 0.0107 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.

-5.78 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.

1.0 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)

2.32

Application In Synthesis of [ 217959-45-0 ]

* 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 [ 217959-45-0 ]

[ 217959-45-0 ] Synthesis Path-Downstream   1~8

  • 1
  • 3-Hydroxy-5-trifluoromethyl-2-thiophenecarboxylic Acid [ No CAS ]
  • [ 217959-45-0 ]
YieldReaction ConditionsOperation in experiment
82% EXAMPLE 9 Preparation of 4-Hydroxy-2-(trifluoromethyl)thiophene STR23 Neat 3-hydroxy-5-trifluoromethyl-2-thiophenecarboxylic acid (180 g, 0.849 mol) is slowly heated under argon to give rapid evolution of gas at 90 C. Heating at 90 C. is continued for an additional 3.5 hours. The resultant oil is vacuum distilled through a 6 inch Vigreaux column packed with 1/4 inch glass cylinders to give the title product as a clear liquid, 118 g (82% yield), bp 70-74 C./4 mm Hg, identified by 1 H-NMR and 13 C-NMR analysis.
  • 2
  • [ 157162-16-8 ]
  • [ 217959-45-0 ]
  • 3
  • [ 358-23-6 ]
  • [ 217959-45-0 ]
  • [ 827322-77-0 ]
YieldReaction ConditionsOperation in experiment
92% With pyridine; In dichloromethane; at 0 - 20℃; for 3.0h; TRIFLUOROMETHANESULFONIC anhydride (12 ML, 92. 8 mmol, 2 eq. ) was added drop- wise to a 0 C solution of <strong>[217959-45-0]3-hydroxy-5-trifluoromethylthiophene</strong> (7. 8 g, 46.4 mmol, prepared as in Synthesis 2000 get reference), pyridine (7.4 M 1, 9 2. 8 M MOL, 2 eq. ), and DICHLOROMETHANE (230 ML). The mixture was allowed to warm to rt and maintained for 3 h. At this time, the solution was diluted with DICHLOROMETHANE (200 ML), washed with brine (100 ML), 1 M HCI (100 ml), and brine (100 ML). The organic layer was dried (MGS04), filtered, and concentrated to yield 1 as a reddish-orange oil (12. 8 g, 92 %).
  • 4
  • [ 1513-65-1 ]
  • [ 217959-45-0 ]
  • [ 653601-80-0 ]
  • 5
  • [ 653593-13-6 ]
  • [ 217959-45-0 ]
  • 5-methyl-2-(4-trifluoromethyl-1H-pyrazol-1-yl)-4-(5-trifluoromethyl-3-thienyloxy)pyrimidine [ No CAS ]
  • 6
  • 5-methoxy-4-methylsulfonyl-2-(4-trifluoromethyl-1H-pyrazol-1-yl)pyrimidine [ No CAS ]
  • [ 217959-45-0 ]
  • 5-methoxy-2-(4-trifluoromethyl-1H-pyrazol-1-yl)-4-(5-trifluoromethyl-3-thienyloxy)pyrimidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
74% 3-Hydroxy-5-trifluoromethylthiophen A mixture of 1G (7.75 g) and tetrachloromethane (50 ml) was treated with iodotrimethylsilane (12.30 ml) and heated to 60 C. for 12 hours. The reaction mixture was stirred at room temperature for 12 hours. Water (50 ml) was added and the resulting reaction mixture was extracted with dichloromethane three times. The combined organic phases were washed with water and dried. The crude reaction mixture was eluted through hexane (100 g/silica gel) to remove benzyliodide and then with diethyl ether. The etheral phases were concentrated and distilled in vacuo to give the product (3.33 g, 74%) having a boiling point of 65-66 C. at 4 mm.
74% 2D 3-Hydroxy-5-trifluoromethylthiophen A mixture of 2G (7.75 g) and tetrachloromethane (50 ml) was treated with iodotrimethylsilane (12.30 ml) and heated to 60 C for 12 hours. The reaction mixture was stirred at room temperature for 12 hours. Water (50 ml) was added and the resulting reaction mixture was extracted with dichloromethane three times. The combined organic phases were washed with water and dried. The crude reaction mixture was eluted through hexane (100 g/silica gel) to remove benzyliodide and then with diethyl ether. The etheral phases were concentrated and distilled in vacuo to give the product (3.33 g, 74 %) having a boiling point of 65-66 C at 4 mm.
74% 3-Hydroxy-5-trifluoromethylthiophen A mixture of 5G (7.75 g) and tetrachloromethane (50 ml) was treated with iodotrimethylsilane (12.30 ml) and heated to 60 C for 12 hours. The reaction mixture was stirred at room temperature for 12 hours. Water (50 ml) was added and the resulting reaction mixture was extracted with dichloromethane three times. The combined organic phases were washed with water and dried. The crude reaction mixture was eluted through hexane (100 g/silica gel) to remove benzyliodide and then with diethyl ether. The etheral phases were concentrated and distilled in vacuo to give the product (3.33 g, 74 %) having a boiling point of 65-66 C at 4 mm.
1.18 g (82%) 5D 3-Hydroxy-5-trifluoromethylthiophen 5C (1.80 g) was slowly heated under argon. Evolution of gas was observed at 90 C. Heating was continued for additional 3.5 hours at 90 C. The resulting oil was distilled under reduced pressure (boiling point 70-74 C. at 4 mm) to yield 1.18 g (82 %) of compound 5D.
1.18 g (82%) 1D 3-Hydroxy-5-trifluoromethylthiophen 1C (1.80 g) was slowly heated under argon. Evolution of gas was observed at 90 C. Heating was continued for additional 3.5 hours at 90 C. The resulting oil was distilled under reduced pressure (boiling point 70-74 C. at 4 mm) to yield 1.18 g (82%) of compound 1D.
1.18 g (82%) 2D 3-Hydroxy-5-trifluoromethylthiophen 2C (1.80 g) was slowly heated under argon. Evolution of gas was observed at 90 C. Heating was continued for additional 3.5 hours at 90C. The resulting oil was distilled under reduced pressure (boiling point 70-74 C at 4 mm) to yield 1.18 g (82 %) of compound 5D .
1.18 g (82%) 5D 3-Hydroxy-5-trifluoromethylthiophen 5C (1.80 g) was slowly heated under argon. Evolution of gas was observed at 90 C. Heating was continued for additional 3.5 hours at 90C. The resulting oil was distilled under reduced pressure (boiling point 70-74 C at 4 mm) to yield 1.18 g (82 %) of compound 5D .

  • 8
  • [ 1140520-39-3 ]
  • [ 217959-45-0 ]
  • N-[(5-methyl-4-[5-(trifluoromethyl)-3-thienyl]oxy}pyrimidin-2-yl)methyl]cyclopropanecarboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
18% With potassium carbonate; In acetonitrile; for 8.0h;Heating / reflux; 3. Preparation of N-[(5-methyl-4-[5-(trifluoromethyl)-3-thienyl]oxy}pyrimidin-2-yl)methyl]cyclopropanecarboxamide, (Example No. 206 from Table 2); A mixture of 0.2 g (1.23 mmol) of <strong>[217959-45-0]3-hydroxy-5-trifluoromethylthiophene</strong>, 0.33 g (1.23 mmol) of N-[5-methyl-4-(methylsulfonyl)pyrimidin-2-yl]methyl}cyclopropane-carboxamide and 0.34 g (2.45 mmol) of K2CO3 in 20 ml of acetonitrile is stirred under reflux for 8 h and then allowed to stand overnight. The mixture is then poured into 20 ml of water and extracted four times with 20 ml of CH2Cl2. The combined organic phases are dried over Na2SO4 and concentrated. Chromatographic purification on silica gel using EA gives 0.08 g (18%) of product. 1H-NMR: delta [CDCl3] 0.75 (m, 2H), 0.92 (m, 2H), 1.40 (m, 1H), 2.30 (s, 1H), 4.58 (d, 2H), 6.65 (bs, 1H), 7.38 (m, 1H), 7.40 (m, 1H), 8.20 (s, 1H).
 

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