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Chemical Structure| 1099597-32-6

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Product Details of [ 1099597-32-6 ]

CAS No. :1099597-32-6
Formula : C7H3BrClF3
M.W : 259.45
SMILES Code : FC(F)(F)C1=C(Br)C=C(Cl)C=C1
MDL No. :MFCD09839109
InChI Key :ZIPJFBGICWZITF-UHFFFAOYSA-N
Pubchem ID :20269857

Safety of [ 1099597-32-6 ]

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

Computational Chemistry of [ 1099597-32-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
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 44.15
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.

2.39
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

4.13
Log Po/w (WLOGP)?

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

5.27
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.

4.66
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

4.17
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

4.12

Water Solubility

Log S (ESOL):?

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

-4.35
Solubility 0.0115 mg/ml ; 0.0000442 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.

-3.84
Solubility 0.0378 mg/ml ; 0.000146 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

-4.75
Solubility 0.00456 mg/ml ; 0.0000176 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.

-4.95 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

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)

1.58

Application In Synthesis of [ 1099597-32-6 ]

* 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 [ 1099597-32-6 ]

[ 1099597-32-6 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 445-14-7 ]
  • [ 1099597-32-6 ]
YieldReaction ConditionsOperation in experiment
100% Example 5 3-((5-chloro-2-(trifluoromethyl)phenyl)ethvnyl)-5-(l-(piperidin-4-yl)-lH-pyrazol-4- yl)-lH-pyrrolor2,3-b1pyridine Step 1) 2-bromo-4-chloro-l-(trifluoromethyl)benzene To a stirred solution of 40percent HBr (2.20 mL, 15.34 mmol) in 0 (2 mL) was added 2-amino-4- chlorobenzotrifluoride (0.50 g, 2.56 mmol) at 0 °C. Then a solution of sodium nitrite (0.21 g, 3.07 mmol) in H20 (2 mL) was added dropwise at 0 °C. The mixture was stirred at 0 °C for a further 0.5 hours, a solution of cuprous bromide (0.63 g, 4.35 mmol) in 40percent HBr (2.20 mL, 15.34 mmol) and H20 (3 mL) was added. The mixture was stirred at 75 °C for 3 hours, then cooled to rt, and extracted with EtOAc (40 mL x 4). The combined organic phases were washed with brine (80 mL x 2), dried over anhydrous Na2S04 and concentrated in vacuo to give the title compound as a yellow liquid (0.76 g, 100percent). GC -MS: 257.9.
100% 40percent HBr (2.20 mL, 15.34 mmol) was dissolved in H2O (2 mL), then at 0 ° C,2-Amino-4-chlorobenzotrifluoride (0.50 g, 2.56 mmol) was added to the reaction mixture, followed by 0 ° C,An aqueous solution of sodium nitrite (sodium nitrite (0.21 g, 3.07 mmol) dissolved in 2 mL of water) was added dropwise to the reaction mixture.After the reaction solution was stirred at 0 ° C for half an hour, additional cuprous bromide (0.63 g, 4.35 mmol) of 40percent HBr (2.20 mL, 15.34 mmol) andA mixed solution of H2O (3 mL).The reaction solution was stirred at 75 ° C for 3 hours, and then cooled to room temperature.It was then extracted with ethyl acetate (40 mL x 4).The combined organic phases were washed with brine (80 mL x 2).Dry with anhydrous Na2SO4,The title compound was obtained as a yellow liquid after concentration under reduced pressure.(0.76g, 100percent).
  • 2
  • [ 1099597-32-6 ]
  • [ 475275-69-5 ]
  • 5-chloro-4-[5-chloro-2-(trifluoromethyl)phenyl]-2-methoxypyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium dihydrogenphosphate; chloro(2-dicyclohexylphosphino-2?,4?,6?-triisopropyl-1,1?-biphenyl)[2-(2?-amino-1,1?-biphenyl?)]palladium(II); In tetrahydrofuran; water; at 60℃;Inert atmosphere; Sonication; General procedure: [0550] In a flask which had been dried by heating andflushed with argon, 1.0 eq. of the appropriate boronic acids,1.0 eq. of the aryl bromide or aryl iodide and 0.05 eq. ofXPhos precatalyst [(2'-aminobiphenyl-2-yl)( chloro )palladium/dicyclohexyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphane(1:1)], J. Am. Chern. Soc. 2010, 132, 14073-14075]were initially charged. The flask was then evacuated threetimes and in each case vented with argon. THF (about 12ml/mmol) which had been degassed in an ultrasonic bath and3.0 eq. of aqueous potassium phosphate solution (0.5 molar)were added, and the reaction mixture was stirred at 60 C.Water and ethyl acetate were then added to the reaction mixture.After phase separation, the aqueous phase was extractedonce with ethyl acetate. The combined organic phases weredried (sodium sulphate), filtered and concentrated underreduced pressure. The crude product was then purified eitherby flash chromatography (silica gel 60, mobile phase: cyclohexane/ethyl acetate mixtures or dichloromethane/methanolmixtures) or by preparative HPLC (Reprosil CIS, water/acetonitrilegradient or water/methanol gradient).
193 mg With potassium phosphate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In tetrahydrofuran; water; at 60℃;Inert atmosphere; Sonication; General procedure: General Method 2B: Suzuki coupling In a flask whichhad been dried by heating and flushed with argon, 1.0 eq. of the appropriateboronic acids, 1.0 eq. of the aryl bromide or aryl iodide and 0.05 eq. of XPhosprecatalyst[(2'-aminobipheny1-2-y1)(chloro)palladium/dicyclohexyl(2',4',61-triisopropylbipheny1-2-yl)phosphane(1:1)], J. Am. Chem. Soc. 2010, 132, 14073-14075] were initially charged. Theflask was then evacuated three times and in each case vented with argon. THF(about 12 ml/mmol) which had been degassed in an ultrasonic bath and 3.0 eq. ofaqueous potassium phosphate solution (0.5 molar) were added, and the reactionmixture was stirred at 60 C. Water and ethyl acetate were then I uiu fore=countries added to the reaction mixture. After phase separation, the aqueousphase was extracted once with ethyl acetate. The combined organic phases weredried (sodium sulphate), filtered and concentrated = under reduced pressure.The crude product was then purified either by flash chromatography (silica gel60, mobile phase: cyclohexane/ethyl acetate mixtures ordichloromethane/methanol mixtures) or by preparative HPLC (Reprosil C18,water/acetonitrile gradient or water/methanol gradient).443 mg (2.20 mmol) of5-chloro-2-methoxypyridin-4-ylboronic acid and 571 mg (2.20 mmol) of2-bromo-4-chloro-1-(trifluoromethyl)benzene in the presence of XPhosprecatalyst were reacted according to General Method 2B.Yield: 193 mg (purity 93%, 25% of theory)
 

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