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Chemical Structure| 65094-22-6 Chemical Structure| 65094-22-6

Structure of 65094-22-6

Chemical Structure| 65094-22-6

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Product Details of [ 65094-22-6 ]

CAS No. :65094-22-6
Formula : C5H10BrF2O3P
M.W : 267.01
SMILES Code : CCOP(=O)(OCC)C(F)(F)Br
MDL No. :MFCD00069118
InChI Key :QRADKVYIJIAENZ-UHFFFAOYSA-N
Pubchem ID :144101

Safety of [ 65094-22-6 ]

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

Computational Chemistry of [ 65094-22-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 0
Fraction Csp3 1.0
Num. rotatable bonds 5
Num. H-bond acceptors 5.0
Num. H-bond donors 0.0
Molar Refractivity 44.99
TPSA ?

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

45.34 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.3
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

1.83
Log Po/w (WLOGP)?

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

4.04
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.

1.32
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

1.28
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.15

Water Solubility

Log S (ESOL):?

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

-2.32
Solubility 1.28 mg/ml ; 0.0048 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.

-2.4
Solubility 1.06 mg/ml ; 0.00396 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

-2.42
Solubility 1.01 mg/ml ; 0.00377 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.

-6.63 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

0.0
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

2.0 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<0.0
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)

3.53

Application In Synthesis of [ 65094-22-6 ]

* 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 [ 65094-22-6 ]

[ 65094-22-6 ] Synthesis Path-Downstream   1~11

  • 1
  • [ 65094-22-6 ]
  • [ 181765-85-5 ]
  • [ 1369842-51-2 ]
  • 2
  • [ 65094-22-6 ]
  • [ 181765-85-5 ]
  • [ 1369842-65-8 ]
  • 3
  • [ 65094-22-6 ]
  • [ 18362-30-6 ]
  • 2-chloro-6-(difluoromethoxy)benzaldehyde [ No CAS ]
YieldReaction ConditionsOperation in experiment
68% With water; potassium hydroxide; In acetonitrile; at 0℃; To a 250 mL round-bottom flask was added <strong>[18362-30-6]2-chloro-6-hydroxybenzaldehyde</strong> 15a (6 g, 38.32 mmol, 1.0 equiv.) and CH3CN (200 mL), followed by the dropwise addition of potassium hydroxide (21.54 g, 383,89 rnmol, 10.0 equiv.) at 0 C. Water (20 mL) was then added, followed by the dropwise addition of diethyl (bromodifluoromethyl)phosphonate (16.38 g, 61.35 mmol, 1.6 equiv.) and the reaction mixture was stirred 30 min at 0 C. The resulting mixture was quenched with H2O (100 mL) and extracted with ethyl acetate (300 mL x 2). The combined organic layers were washed with brine (300 mL x 2), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The crude product (10 mL) was purified by Flash-Prep- HPLC using the following conditions: Column, silica gel; mobile phase, eiuting with PE:EtOAc = 100:0 to 87: 13 over 14 min; Detector, UV 254 nm to provide 2-chloro-6- (difluoromethoxy)benzaldehyde 15b (5.4 g, 68%) as a yellow oil.
53% To <strong>[18362-30-6]2-chloro-6-hydroxy-benzaldehyde</strong> (20 g, 128.2 mmol) in MeCN (150 mL) was added an aqueous solution of potassium hydroxide (71.7 g, 1282 mmol) in water (50 mL) at 0C and the reaction mixture was stirred at 0C for 10 minutes. Diethyl (bromodifluoromethyl) phosphonate (36.4 mL, 205.1 mmol) was added at 0C. The reaction mixture was stirred at 0C for 30 minutes. After completion of reaction (monitored by TLC), the reaction mixture was poured into water (500 mL). The aqueous layer was extracted with ethyl acetate (1 L X 2). The organic layer was washed with water (500 mL), brine (500 mL) and dried over anhydrous sodium sulphate. The organic layer was evaporated underreduced pressure to yield the crude product which was purified by column chromatography (Si02, 5% EtOAc in hexane) yielding the title compound (13.9g, 53%) as a yellow oil. 1H NMR (400 MHz, CDC13) oe 10.46 (s, 1H), 7.49 (t, J8.2 Hz, 1H), 7.37 (dd, J 8.1, 1.1 Hz, 1H), 7.20 (m, 1H), 6.61 (t, 1H).
53% To <strong>[18362-30-6]2-chloro-6-hydroxy-benzaldehyde</strong> (20 g, 128.2 mmol) in MeCN (150 mL) was added an aqueous solution of potassium hydroxide (71.7 g, 1282 mmol) in water (50 mL) at 0C and the reaction mixture was stirred at 0C for 10 mi Diethyl (bromodifluoro methyl) phosphonate (36.4 mL, 205.1 mmol) was added at 0C. The reaction mixture was stirred at 0C for 30 mm. After completion of reaction (monitored by TLC), the reaction mixturewas poured into water (500 mL). The aqueous layer was extracted with ethyl acetate (1 L X 2). The organic layer was washed with water (500 mL), brine (500 mL) and dried over anhydrous sodium sulphate. The organic layer was evaporated under reduced pressure to yield the crude product which was purified by column chromatography (Si02, 5% EtOAc in hexane) yielding the title compound (13.9g, 53% yield) as a yellow oil.1H NMR (400 MHz, CDC13) oe 10.46 (s, 1H), 7.49 (t, J 8.2 Hz, 1H), 7.37 (dd, J 8.1, 1.1 Hz, 1H), 7.20 (m, 1H), 6.61 (t, 1H).
53% With potassium hydroxide; In water; acetonitrile; at 0℃; for 0.666667h; To <strong>[18362-30-6]2-chloro-6-hydroxybenzaldehyde</strong> (20 g, 128.2 mmol) in acetonitrile (150 mL) was added a solution of potassium hydroxide (71.7 g, 1282 mmol) in water (50 mL) at 0C. The reaction mixture was stirred at 0C for 10 minutes, then diethyl (bromo- - - (0850) difluoromethyl)phosphonate (36.4 mL, 205.1 mmol) was added at 0C. The reaction mixture was stirred at 0C for 30 minutes, then poured into water (500 mL). The aqueous layer was extracted with EtOAc (2 x 1 L). The organic layer was washed with water (500 mL) and brine (500 mL), then dried over anhydrous sodium sulphate and filtered. The organic layers were evaporated under reduced pressure. The resulting crude residue was purified by column chromatography (Si02, 5% EtOAc in hexane) yielding the title compound (13.9 g, 53%) as a yellow oil. deltaEta (400 MHz, CDC13) 10.46 (s, 1H), 7.49 (t, J 8.2 Hz, 1H), 7.37 (dd, J 8.1, 1.1 Hz, 1H), 7.20 (m, 1H), 6.61 (t, 1H).
53% To <strong>[18362-30-6]2-chloro-6-hydroxybenzaldehyde</strong> (20 g, 128.2 mmol) in acetonitrile (150 mL)was added a solution of potassium hydroxide (71.7 g, 1282 mmol) in water (50 mL) at0C. The reaction mixture was stirred at 0C for 10 minutes, then diethyl (bromodifluoromethyl)phosphonate (36.4 mL, 205.1 mmol) was added at 0C. The reaction mixture was stirred at 0C for 30 minutes, then poured into water (500 mL). The aqueous layer was extracted with EtOAc (2 x 1 L). The organic layer was washed with water (500mL) and brine (500 mL), then dried over anhydrous sodium sulphate and filtered. The organic layers were evaporated under reduced pressure. The resulting crude residue was purified by column chromatography (Si02, 5% EtOAc in hexane) yielding the title compound (13.9 g, 53%) as a yellow oil. oH (400 MHz, CDC13) 10.46 (s, 1H), 7.49 (t, J 8.2 Hz, 1H), 7.37 (dd, J8.1, 1.1 Hz, 1H), 7.20 (m, 1H), 6.61 (t, 1H).

  • 4
  • [ 65094-22-6 ]
  • [ 855836-62-3 ]
  • 2-bromo-1-chloro-3-(difluoromethoxy)benzene [ No CAS ]
YieldReaction ConditionsOperation in experiment
87% With potassium hydroxide; In water; acetonitrile; at -78 - 20℃; for 16.3333h;Inert atmosphere; To a co?d (-780) souton of 2-bromo-3-choropheno (1.0 g, 4.8 mmo) and potassium hydroxide (5.4 g, 96.4 mmo) nacetonftre (40 mL) and water (40 mL) was added dethy(bromodWuoromethy)phosphonate (1.7 mL, 9.6 mmo) at once. After 20 rnnutes the reacton mixture was warmed to rt and sUrred for 16 h. The mixture was then dHuted w[thwater and extracted with EtOAc (x 3). The combined organic extracts were diled over Na2SO4 and concentrated to obtain the product as an o (1.2 g, 87% yed), which was used drecUy n the next reaction. 1H NMR (500 MHz, CDC3) 5 738 7.33 (m, I H), 730 7.23 (m, IH), 7.13 (rn, J = 8.3, 1,1 Hz, I H), 6.54 (t, J = 73.1 Hz, IH).
  • 5
  • [ 65094-22-6 ]
  • [ 78137-76-5 ]
  • [ 865886-84-6 ]
YieldReaction ConditionsOperation in experiment
With potassium hydroxide; In water; acetonitrile; at -30 - 20℃; for 0.5h; 3.62. Compound 63: (lR,2R)-N-(6-((5-(difluoromethoxy)-2-ethylphenyl)(methyl)amino)-l-methyl- lH-imidazo[4,5-c]pyridin-4-yl)-2-fluorocyclopropanecarboxamide 3.62.1. Step i): l-Bromo-4-difluoromethoxy-2-nitro-benzene Diethyl(bromodifluoromethyl)phosphonate (2 eq, 1.64mL) is added to a cooled (-30 °C) solution of 4-Bromo-3-nitro-phenol (1 eq, 1.0 g) and KOH (20 eq, 5.17 g) in MeCN/water (46 mL; 1 :1) and the reaction mixture is allowed to warm to room temperature. After 30 min, the mixture is diluted with Et20, the organic phase is separated and the water phase is washed with a further amount of Et20. The combined organics are dried and concentrated. The residue is purified by silica chromatography (5-50 percent EtOAc in petroleum ether) to give the desired product.
  • 6
  • [ 1075-35-0 ]
  • [ 65094-22-6 ]
  • 5-chloro-3-((difluoromethyl)thio)-2-methyl-1H-indole [ No CAS ]
  • 7
  • [ 65094-22-6 ]
  • [ 145349-76-4 ]
  • C10H10F4S [ No CAS ]
  • 8
  • [ 65094-22-6 ]
  • [ 145349-76-4 ]
  • C11H10F4OS [ No CAS ]
  • 9
  • [ 65094-22-6 ]
  • [ 145349-76-4 ]
  • (4-(difluoromethyl)phenyl)(ethyl)sulfane [ No CAS ]
  • 10
  • [ 14040-11-0 ]
  • [ 65094-22-6 ]
  • [ 145349-76-4 ]
  • C10H10F2OS [ No CAS ]
  • 11
  • [ 65094-22-6 ]
  • [ 149-30-4 ]
  • [ 943-08-8 ]
YieldReaction ConditionsOperation in experiment
89% General procedure: The starting material (2 mmol) was added to a sealed tube holding 20 mL of a 1:1 mixture of acetonitrile/water and KOH (40 mmol), whichwas cooled using an ice bath. The mixture was vigorously mixed for 15min and then phosphonate 1 (4 mmol) was added to the mixture in oneportion, and mixing and cooling was maintained for an additional 15 -60 min, followed by ~30 min - 2.5 h at r.t. The reaction mixture wasthen diluted with ether (10 mL) and the organic phase separated. Thewater phase was further washed with ether (10 mL). The combinedorganic phase was dried over anhydrous Na2SO4 and the solvent evaporatedto provide a crude product which was purified using columnchromatography on silica gel
 

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