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Chemical Structure| 63845-72-7 Chemical Structure| 63845-72-7

Structure of 63845-72-7

Chemical Structure| 63845-72-7

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Product Details of [ 63845-72-7 ]

CAS No. :63845-72-7
Formula : C8H5BrN2
M.W : 209.04
SMILES Code : BrC1=NC=CC2=CC=CN=C12
MDL No. :MFCD12401002
InChI Key :ZMRBFCVWSDKLLT-UHFFFAOYSA-N
Pubchem ID :56689046

Safety of [ 63845-72-7 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 63845-72-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 10
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 47.24
TPSA ?

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

25.78 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.83
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

2.14
Log Po/w (WLOGP)?

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

2.39
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.

1.34
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

2.07

Water Solubility

Log S (ESOL):?

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

-3.16
Solubility 0.146 mg/ml ; 0.000697 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.

-2.31
Solubility 1.02 mg/ml ; 0.00486 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

-4.19
Solubility 0.0136 mg/ml ; 0.0000652 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.

-6.06 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)

1.76

Application In Synthesis of [ 63845-72-7 ]

* 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 [ 63845-72-7 ]

[ 63845-72-7 ] Synthesis Path-Downstream   1~3

  • 2
  • [ 1001014-83-0 ]
  • [ 63845-72-7 ]
  • 8-(4-(4-(pyridin-2-yl)-1-(pyridin-3-yl)-1H-imidazol-2-yl)phenyl)-1,7-naphthyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 160.0℃; for 2.0h;Microwave irradiation; Example 78; 8-(4-(4-f Dvridin-2-v»-1 -f Dvridin-3-vn-1 H-imidazol-2-vQphenvl V 1.7-naphthvridine; 2-(2-(4-(tributylstannyl)phenyl)-1-(pyridin-3-yl)-1 H-imidazol-4-yI)pyridine (180 mg, 0.31 mmol), 8-bromo-1 ,7-naphthyridine (77 mg, 0.37 mmol), tetrakis- (triphenylphosphine)palladium (38 mg, 0.033 mmol), CuI (17 mg, 0.092 mmol) and p-dioxane (4 mL) were heated by microwave at 160 0C for 2h. The mixture was concentrated and purified by RP-HPLC (basic conditions) giving a white solid. Yield 4 mg. 1H NMR (CDCI3) δ 9.03 (dd, 1 H, J = 1.7, 4 Hz), 8.75 (d, 1H, J = 5 Hz), 8.71-8.68 (m, 3H)1 8.43-8.40 (m, 2H)1 8.20 (dd, 1H, J = 2, 8.3 Hz), 8.15 (m, 2H), 8.05 (m, 1H), 7.68 (m, 1H), 7.64 (d, 1H, J = 5 Hz), 7.63-7.57 (m, 3H), 7.43-7.39 (m, 2H). HPLCMS 4.65 miϖ, m/e 427 (MH+)). ICSO = 3.26 nM
  • 3
  • C15H25N3O3 [ No CAS ]
  • [ 63845-72-7 ]
  • C23H29N5O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With chloro(2-dicyclohexylphosphino-2’,6’-diisopropoxy-1,1’-biphenyl)[2-(2’-amino-1,1‘-biphenyl)]palladium(II) 2nd generation; sodium t-butanolate; ruphos; In tetrahydrofuran; at 80.0℃; for 16.0h;Sealed tube; Inert atmosphere; General procedure: Step 1: To vials containing heterocyclic halide monomers (180 mmol, 1.5 equiv) and tBuONa (450 mmol, 3.0 equiv) were added 800 mL of a 0.19 M solution of amine template S15 (150 mmol, 1 equiv) in THF and 200 mL of a 0.03 M/0.03 M pre-mixed solution of RuPhos Pd-G2 (6.0 mmol, 0.4 equiv)/RuPhos (6.0 mmol, 0.4 equiv) in THF. The vials were capped and shaken at 80 oC for 16 h. The reactions were diluted with saturated NaHCO3 (aq) (1.0 mL) followed by extraction with EtOAc (3 × 1.0 mL). The combined organic extracts were concentrated and used in the next step without further purification. Step 2: To vials containing the Boc-protected intermediates (~100 mmol) was added premixed solutions of TFA in CH2Cl2 (v/v = 1/4, 1.5 mL). The capped vials were shaken at 30 oC for 2 h. All solvent was evaporated and the corresponding amine TFA salts were used in the next step without further purification. Step 3: To vials containing amine intermediate from Step 2 (~100 mmol, 1.0 equiv) in CH2Cl2 (0.1 M) was added Et3N (400 mmol, 4.0 equiv) and 500 mL of a 0.2 M trisphosgene solution (100 mmol, 1.0 equiv). The capped vials were stirred at 0 oC for 0.5 h. The reaction vials were diluted with water (1.0 mL) and extracted with CH2Cl2 (3 × 1.5 mL). The combined organic extracts were dried over MgSO4, filtered, and concentrated to give the crude carbamic chloride intermediate. To each vial was added 1.0 mL of a 0.6 M solution of amine monomer (600 mmol, 6.0 equiv) followed by addition of Et3N (200 umol, 2.0 equiv). The capped vials were shaken at 30 oC for 16 h. All solvent was evaporated and the corresponding final urea products were purified by preparative HPLC.
 

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Technical Information

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