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Type HazMat fee for 500 gram (Estimated)
Excepted Quantity USD 0.00
Limited Quantity USD 15-60
Inaccessible (Haz class 6.1), Domestic USD 80+
Inaccessible (Haz class 6.1), International USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic USD 100+
Accessible (Haz class 3, 4, 5 or 8), International USD 200+
Chemical Structure| 405224-23-9 Chemical Structure| 405224-23-9

Structure of 405224-23-9

Chemical Structure| 405224-23-9
Product Citations

Alternative Products

Product Details of [ 405224-23-9 ]

CAS No. :405224-23-9
Formula : C6H2BrClN2
M.W : 217.45
SMILES Code : N#CC1=C(Cl)N=CC(Br)=C1
MDL No. :MFCD09801046
InChI Key :MQOHJAYYYVQBSH-UHFFFAOYSA-N
Pubchem ID :21948269

Safety of [ 405224-23-9 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H301-H315-H318-H335
Precautionary Statements:P280-P301+P310+P330-P302+P352-P305+P351+P338+P310
Class:6.1
UN#:2811
Packing Group:

Computational Chemistry of [ 405224-23-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 41.66
TPSA ?

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

36.68 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.7
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

2.22
Log Po/w (WLOGP)?

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

2.37
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.

1.16
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

2.65
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.02

Water Solubility

Log S (ESOL):?

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

-3.03
Solubility 0.203 mg/ml ; 0.000932 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.

-2.63
Solubility 0.515 mg/ml ; 0.00237 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

-3.59
Solubility 0.0564 mg/ml ; 0.000259 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

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.

-6.05 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

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)

1.89

Application In Synthesis of [ 405224-23-9 ]

* 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 [ 405224-23-9 ]

[ 405224-23-9 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 405224-22-8 ]
  • [ 405224-23-9 ]
YieldReaction ConditionsOperation in experiment
84% With phosphorus pentachloride; In trichlorophosphate;Reflux; 5-Bromo-2-chloronicotinonitrile (13) Compound 12 (69 mg, 0.35 mmol) and PCl5(109 mg, 0.52 mmol) were refluxed in POCl3 (5 mL) overnight. Themixture was cooled to room temperature and added to ice water in drops slowly,basified with NaOH (4 M)to pH 8, and extracted with CH2Cl2 (3×30 mL). Thecombined extracts were washed with aqueous NaHCO3, brine, dried overanhydrous Na2SO4, and concentrated in vacuum.Purification by chromatography (PE/EA = 20:1) provided compound 13 (63 mg, 84percent) as a yellow solid. MP:138~139°C. 1H NMR (400 MHz, CDCl3): delta 8.66 (d, J = 2.4 Hz, 1H), 8.12 (d, J = 2.4 Hz,1H).6
With phosphorus pentachloride; trichlorophosphate; for 3.0h;Heating / reflux; 5-Bromo-2-chloro-nicotinonitrile 5-Bromo-2-oxo-1,2 dihydro-pyridine-3-carbonitrile (33 g, 166 mmol) was added to a suspension of PCl5 (96.6 g, 464 mmol) in POCl3 (20 ml, 216 mmol). The mixture was stirred at reflux for 3 hours, cooled to room temperature and then poured slowly into ice/water. The resulting solid was fitered, washed with water, and dried in vacuo to afford the title compounid. 1H NMR delta (d6 DMSO) 8.7 (d, 1H), 8.1 (d, 1H).
  • 2
  • [ 709652-82-4 ]
  • [ 405224-23-9 ]
YieldReaction ConditionsOperation in experiment
88% With hydrogenchloride; sodium nitrite; In water; at -5 - 20℃; To a stirred solution of compound 2 (4.6 g) in HC1 (48.4 mL ) was added sodium nitrite ( 5.3 mL ) dropwise at-5 C. The reaction mixture was stirred at room temperature for 2h. The resulting solids were collected by filtration and dried in vacuum to give compound 3 (4.4 g, 88%).
88% With hydrogenchloride; sodium nitrite; In water; at -5 - 20℃; for 2h; Step-2 [0069] To a stirred solution of compound 2 (4.6 g) in HCl (48.4 mL) was added sodium nitrite (5.3 mL) dropwise at -5 C. The reaction mixture was stirred at room temperature for 2 h. The resulting solids were collected by filtration and dried in vacuum to give compound 3 (4.4 g, 88%).
70% With hydrogenchloride; sodium nitrite; In water; at 0℃; Example 2; 5-bromo-2-chloropyridine-3-carbonitrile (3) ; [00141] Compound 2 was dissolved in cone. HCl at O2C, to which 1.1 equivalent of NaNO2 in H2O was added dropwise. Precipitation was formed. The white solid was filtered off, which gave the title compound 3. Overall yield was 70%.
  • 3
  • [ 1209780-71-1 ]
  • [ 405224-23-9 ]
  • tert-butyl 4-[(5-bromo-3-cyanopyridin-2-yl)oxy]-3,3-difluoropiperidine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
39% With potassium tert-butylate; In tetrahydrofuran; at 90℃; for 0.25h;Microwave irradiation; Method 64 [00589] 2-(azetidin-3-yloxy)-5-[2-([4-[4-(oxetan-3-yl)piperazin-l- yl]phenyl]amino)pyrimidin-4-yl]benzonitrile : To a solution of 5-bromo-2-chloropyridine-3- carbonitrile (950 mg, 4.37 mmol) in THF (15 mL) was added tert-butyl 3,3-difluoro-4- hydroxypiperidine-l-carboxylate (1250 mg, 5.27 mmol), and t-BuOK (1230 mg, 10.97 mmol) at room temperature. The reaction mixture was irradiated with microwave for 15 min at 90 C. When the reaction was done, the solids were filtered out and the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography eluting with EtOAc in hexane (0% to 10% gradient) to yield tert-butyl 4-[(5-bromo-3-cyanopyridin-2-yl)oxy]-3,3- difluoropiperidine- l-carboxylate as a light yellow oil (725 mg, 39%). MS: m/z = 440.0 [M+H]+.
  • 4
  • [ 1209780-71-1 ]
  • [ 405224-23-9 ]
  • C22H30BF2N3O5 [ No CAS ]
 

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Technical Information

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