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Chemical Structure| 69045-84-7 Chemical Structure| 69045-84-7

Structure of 69045-84-7

Chemical Structure| 69045-84-7

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Product Details of [ 69045-84-7 ]

CAS No. :69045-84-7
Formula : C6H2Cl2F3N
M.W : 215.99
SMILES Code : C1=C(C(F)(F)F)C=NC(=C1Cl)Cl
MDL No. :MFCD00042243
InChI Key :ABNQGNFVSFKJGI-UHFFFAOYSA-N
Pubchem ID :112234

Safety of [ 69045-84-7 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H227-H302+H332-H317-H318-H411
Precautionary Statements:P501-P261-P273-P272-P270-P210-P271-P264-P280-P302+P352-P370+P378-P391-P362+P364-P333+P313-P301+P312+P330-P304+P340+P312-P305+P351+P338+P310-P403+P235
Class:9
UN#:3082
Packing Group:

Computational Chemistry of [ 69045-84-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.17
Num. rotatable bonds 1
Num. H-bond acceptors 4.0
Num. H-bond donors 0.0
Molar Refractivity 39.26
TPSA ?

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

12.89 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.97
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

3.33
Log Po/w (WLOGP)?

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

4.56
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.

2.75
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

3.68
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.26

Water Solubility

Log S (ESOL):?

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

-3.58
Solubility 0.0567 mg/ml ; 0.000262 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.

-3.28
Solubility 0.114 mg/ml ; 0.000528 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

-4.15
Solubility 0.0153 mg/ml ; 0.0000708 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

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.

-5.25 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)

1.99

Application In Synthesis of [ 69045-84-7 ]

* 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 [ 69045-84-7 ]

[ 69045-84-7 ] Synthesis Path-Downstream   1~7

  • 1
  • [ 593-51-1 ]
  • [ 69045-84-7 ]
  • [ 89810-01-5 ]
  • 2
  • [ 69045-83-6 ]
  • [ 69045-84-7 ]
YieldReaction ConditionsOperation in experiment
92% With hydrogen fluoride; tungsten(VI) chloride; at 170 - 180℃; under 1500.15 Torr; for 5h;Autoclave; 26.5 g 0.1 mol <strong>[69045-83-6]2,3-dichloro-5-trichloromethylpyridine</strong>,0.2 g of tungsten hexachlor into the reactor,Heated to 170 C at atmospheric pressure,And then hydrogen fluoride (about 20 g)The reaction is terminated when the test product is no longer changed,Unreacted hydrogen fluoride,After condensing recovery,The generated hydrogen chloride can be absorbed and removed.The reaction solution was cooled to room temperature,Transferred to an autoclave,Heated to 180 C,Pressure 0.2MPa,Reaction 5h,Cooling down,Sampling analysis,Containing 2,3-dichloro-5-trifluoromethylpyridine 94%Yield 92%.
73% With pyridine; iron(III) chloride; hydrogen fluoride; at 130 - 175℃;Autoclave; EXAMPLE 3 Conversion of <strong>[69045-83-6]2,3-dichloro-5-(trichloromethyl)pyridine</strong> to 2,3-dichloro-5- (trifluoromethyl)pyridine. <strong>[69045-83-6]2,3-dichloro-5-(trichloromethyl)pyridine</strong> (5 g, 18.84 mmole), iron(III) chloride (0.153 g, 0.942 mmole) and hydrogen fluoride (2.423 g, 85 mmole) in pyridine solution (70%) was added to an autoclave and heated to 175 C over night. The autoclave was cooled to 130 C and left for stirring additional 5 hours, followed by cooling to 25 C and opened carefully leaving gas phase through a Caustic Lye scrubber. The crude was dissolved in dichloromethane, washed with 1 M NaOH (aq) and water. The organic phase was removed by distillation and the product was obtained by distillation (3.0 g, 73 % yield).
63.2% With hydrogen fluoride; antimonypentachloride; at 70 - 200℃; under 63756.4 Torr; for 30h; 500 g (3.08 mol) of 2-chloro-5-chloromethylpyridine (molecular weight: 162 g / mol) and 50 g (10% by weight) of copper oxide were charged into a 1 L four-necked flask equipped with a thermometer, a condenser and a mechanical stir And heated to 275 C, and then chlorinated by passing Cl 2 into the above solution, and the reaction was carried out for 60 hours to obtain 562 g (2.12 mol) of <strong>[69045-83-6]2,3-dichloro-5-trichloromethylpyridine</strong>. A solution of 562 g (2.12 mol) of <strong>[69045-83-6]2,3-dichloro-5-trichloromethylpyridine</strong> was heated to 70 C and added with 5 g of catalyst antimony pentachloride followed by 210 g (10.5 mol) of hydrogen fluoride at 200 C, 8.5 MPa pressure for 30 hours to give 421 g (1.95 mol) of 2,3-dichloro-5-trifluoromethylpyridine in a yield of 63.2% from 2-chloro-5-chloromethylpyridine,
With FeCl2; EXAMPLE 10 2,3-Dichloro-5-(trifluoromethyl)pyridine STR12 A 360 milliliter (ml) TEFLON PFA reaction flask, fitted with a PFA reflux condenser, an HF bleed tube, a magnetic stirrer and an optical pyrometer, was charged with 180 grams (g) of <strong>[69045-83-6]2,3-dichloro-5-(trichloromethyl)pyridine</strong> and 4.3 g (5 mole percent) of FeCl2. Anhydrous HF gas was introduced into the reaction mixture (~4 g/hr) below the surface of the liquid as the reaction mixture was heated to a temperature between 170 C. and 175 C. This temperature (170-175 C.) was maintained for a period of 70 hours with constant agitation. Standard gas-liquid chromatography (GLC) analysis of the product indicated that the reaction product contained:
With hydrogen fluoride; EXAMPLE 7 This Example illustrates the preparation of 2,3-dichloro-5-trifluoromethylpyridine by fluorination of <strong>[69045-83-6]2,3-dichloro-5-trichloromethylpyridine</strong>, using a fluorinating agent alternative to that of Example 6. 2,3-Dichloro-5-trichloromethylpyridine (35 g) was heated with anhydrous hydrogen fluoride (100 g) in an autoclave at 200 for 10 hours with stirring. The cooled reaction mixture was poured on to ice and neutralised with sodium hydroxide at 0. The mixture was extracted with methylene chloride (750 ml). The extracts were washed with water (500 ml), sodium carbonate solution (500 ml) and water (500 ml), dried, and evaporated. The remaining oil was distilled and the fraction of boiling point 77-83/25 Torr was collected and identified as the required pyridine derivative.
With hydrogen fluoride; at 170℃; for 11h; Take intermediate <strong>[69045-83-6]2,3-dichloro-5-trichloromethylpyridine</strong> 50g,After adding the catalyst, the temperature is raised to 170C.Slowly introduce anhydrous hydrogen fluoride gas,Reaction 11h, after the end of the reaction, neutralized with 5% sodium bicarbonate solution,Separate the organic phase, washed,The crude product obtained after drying was 2,3-dichloro-5-trifluoromethylpyridine as the desired material in an amount of 85% and the yield was 65%.

  • 3
  • [ 69045-84-7 ]
  • [ 154471-65-5 ]
  • 5-(3-chloro-5-trifluoromethyl-2-pyridyl)-1-methyl-3-trifluoromethyl-1H-pyrazole [ No CAS ]
  • 4
  • [ 1310-58-3 ]
  • [ 69045-84-7 ]
  • [ 94050-90-5 ]
  • [ 95977-29-0 ]
YieldReaction ConditionsOperation in experiment
In water; Preparation of R-(+)-2-[4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)-phenoxy]propionic acid In 200 ml of diemthylsulfoxide, 13 g of <strong>[94050-90-5]R-(+)-2-(4-hydroxyphenoxy)propionic acid</strong> and 9.45 g of potassium hydroxide powder were dissolved under nitrogen atmosphere. To this mixture, was added dropwise 15.5 g of 2,3-dichloro-5-trifluoromethyl pyridine at room temperature, and the resulting mixture was stirred at 70 C. for 15 hours. The thus obtained reaction mixture was poured into 1000 ml of water, followed by acidification with concentrated hydrochloric acid and by extraction with ether. The ether layer was dried over anhydrous magnesium sulfate and evaporated the solvent to obtain 20.9 g of R-(+)-2-[4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)-phenoxy]propionic acid.
  • 5
  • [ 7783-56-4 ]
  • [ 69045-83-6 ]
  • [ 69045-84-7 ]
YieldReaction ConditionsOperation in experiment
With antimonypentachloride; EXAMPLE 8 This Example further illustrates the preparation of 2,3-dichloro-5-trifluoromethylpyridine. Antimony trifluoride (61 g) was melted under a vacuum to remove moisture. The cooled material was broken up and heated to 65-70 while antimony pentachloride (6.6 g) was added dropwise with stirring. 2,3-Dichloro-5-trichloromethylpyridine (40 g) was then added dropwise to the mixture and the whole heated to 160 over 45 minutes. The mixture was cooled and steam distilled. The oil which distilled over was extracted with ether (2*100 ml). The ether extract was washed with tartaric acid solution then water, sodium bicarbonate, and water, and dried. The remaining oil was distilled. The fraction boiling at 71-80/18 Torr was identified as the required pyridine derivative.
  • 6
  • [ 69045-84-7 ]
  • [ 94050-90-5 ]
  • [ 95977-29-0 ]
YieldReaction ConditionsOperation in experiment
84.4% (R) -2- (4-hydroxyphenoxy) propionic acid (3.00 g), DMF (35 ml), slowly adding K2CO3 (4.55 g)70~80C , stirring 1h, by adding 2,3-dichloro-5-trifluoromethylpyridine (3.56g), keep 70 ~ 80 C stirring 8h, stopThe reaction was allowed to cool to room temperature, the mixture was poured into ice water (100 mL), adjusted to pH 4 to 5 using dilute hydrochloric acid, (R)-2-[4-(5-trifluoromethyl-3-chloropyridin-2-yloxy)phenoxy]propanone, and the organic phase was washed with water, Acid brown liquid 5.03g, yield 84.4%.
84.4% (R) -2- (4-hydroxyphenoxy) propionic acid (3 g),DMF (35 ml),K2CO3 (4.55 g) was added slowly,Heating up to 70 ~ 80 ,Stir for 1h,Was added dropwise 2,3-dichloro-5-trifluoromethylpyridine (3.56 g)Keep at 70 ~ 80 stirring 8h,Stop the reaction,Naturally cooled to room temperature,The mixture was poured into ice water (200 mL)The use of dilute hydrochloric acid to adjust the pH 4 to 5,Extracted with ethyl acetate,Organic phase washed,dry,(R) -2- [4- (5-trifluoromethyl-3-chloropyridin-2-yloxy) phenoxy] propionic acidBrown liquid5.03g,Yield 84.4%.
84.4% (R) -2- (4-hydroxyphenoxy) propionic acid (3 g),DMF (35 ml),K2CO3 (4.55 g) was added slowly,Heating up to 70 ~ 80 ,Stir for 1h,Was added dropwise 2,3-dichloro-5-trifluoromethylpyridine (3.56 g)Keep at 70 ~ 80 stirring 8h,Stop the reaction,Naturally cooled to room temperature,The mixture was poured into ice water (200 mL)The use of dilute hydrochloric acid to adjust the pH 4 to 5,Extracted with ethyl acetate,Organic phase washed,dry,5.03 g of (R) -2- [4- (5-trifluoromethyl-3-chloropyridin-2-oxy) phenoxy] propionic acidYield 84.4%.
84.4% (R) -2- (4-hydroxyphenoxy) propionic acid(3g),DMF (35 ml), slowly adding K2CO3 (4.55 g),The temperature was raised to 70 to 80 C, stirred for 1 h, and 2,3-dichloro-5-trifluoromethylpyridine (3.56 g)Keep at 70 ~ 80 stirring 8h,The reaction was stopped and the mixture was allowed to cool to room temperature and the mixture was poured into ice water (200 mL)The use of dilute hydrochloric acid to adjust the pH 4 to 5,Extracted with ethyl acetate, washed with organic phase, dried and desolved(R) -2- [4- (5-trifluoromethyl-3-chloropyridin-2-oxy) phenoxy] propionic acid brownThe color liquid was 5.03 g, 84.4% yield
84.4% (R) -2- (4-hydroxyphenoxy) propionic acid (3 g),DMF (35 ml), slowly adding K2CO3 (4.55 g),Heating up to 70 ~ 80 ,Stir for 1h,Was added dropwise 2,3-dichloro-5-trifluoromethylpyridine (3.56 g)Keep at 70 ~ 80 for 8h,Stop the reaction,Naturally cooled to room temperature,The mixture was poured into ice water (200 mL)The pH was adjusted to 4 to 5 using dilute hydrochloric acid, extracted with ethyl acetate,Organic phase washed,dry,(R) -2- [4- (5-trifluoromethyl-3-chloropyridin-2-yloxy) phenoxy]Propionic acid brown liquid 5.03 g,Yield 84.4%.
84.4% <strong>[94050-90-5](R)-2-(4-hydroxyphenoxy)propionic acid</strong> (3g),DMF (35ml),Slowly add K2CO3 (4.55g),Warm up to 70-80 C, stir for 1 h,Add 2,3-dichloro-5-trifluoromethylpyridine (3.56 g) dropwise, keep stirring at 70-80 C for 8 h, stop the reactionIt should be naturally cooled to room temperature, poured into ice water (200 mL), adjusted to pH 4-5 with dilute hydrochloric acid, with ethyl acetateExtraction, organic phase washing, drying, de-solubilization to obtain (R)-2-[4-(5-trifluoromethyl-3-chloropyridin-2-yloxy)phenoxy]propionic acidBrown liquid 5.03g, yield 84.4%
84.4% (R)-2 - (4 - hydroxy-phenoxy) propionic acid (3.00 g), DMF (35 ml), slowly adding K2CO3(4.55 G), heated to 70 - 80 C, stirring 1 h, added dropwise 2, 3 - dichloro -5 - trifluoro methyl pyridine (3.56 g), keep the 70 - 80 C stirring 8 h, stopping the reaction, natural cooling to room temperature, the mixture is poured into ice water (100 ml) in, using diluted hydrochloric acid to adjust the pH 4 - 5, extracted with ethyl acetate, the organic phase with water washing, drying, shall desolution (R)-2 - [4 - (5 - trifluoromethyl -3 - chloro pyridine -2 - yloxy) phenoxy] propionic acid brown liquid 5.03 g, yield 84.4%.

  • 7
  • [ 287114-25-4 ]
  • [ 69045-84-7 ]
  • tert-butyl [8-{3-chloro-5-(trifluoromethyl)pyridin-2-yl}azabicyclo[3.2.1]octan-3-yl]carbamate [ No CAS ]
 

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