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Chemical Structure| 205046-59-9

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Product Details of [ 205046-59-9 ]

CAS No. :205046-59-9
Formula : C10H5N3O2
M.W : 199.17
SMILES Code : N#CC1=C2N=CC=CC2=C([N+]([O-])=O)C=C1
MDL No. :MFCD27947097
InChI Key :UBENFVCBHLLYSK-UHFFFAOYSA-N
Pubchem ID :21874838

Safety of [ 205046-59-9 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P280-P305+P351+P338-P310

Computational Chemistry of [ 205046-59-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 15
Num. arom. heavy atoms 10
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 4.0
Num. H-bond donors 0.0
Molar Refractivity 55.28
TPSA ?

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

82.5 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.23
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

2.06
Log Po/w (WLOGP)?

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

2.01
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.

0.06
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

0.2
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.11

Water Solubility

Log S (ESOL):?

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

-2.8
Solubility 0.316 mg/ml ; 0.00159 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.

-3.42
Solubility 0.0755 mg/ml ; 0.000379 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

-3.17
Solubility 0.134 mg/ml ; 0.000673 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

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

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

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

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<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)

1.97

Application In Synthesis of [ 205046-59-9 ]

* 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 [ 205046-59-9 ]

[ 205046-59-9 ] Synthesis Path-Downstream   1~9

  • 1
  • [ 139366-35-1 ]
  • [ 205046-59-9 ]
YieldReaction ConditionsOperation in experiment
In N-methyl-acetamide; dichloromethane; Step 1: 8-Cyano-5-nitroquinoline 5.80 g of 8-bromo-5-nitroquinoline and 2.00 g of copper(I) cyanide in 15 ml of dimethylformamide were heated to 150 C. for 5 hours. After cooling, methylene chloride was added, insoluble particles were filtered off and the filtrate was concentrated. Yield: 3.90 g (1H-NMR (CDCl3; delta in ppm): 7.84 (m,1H); 8.37 (m,1H); 8.40 (m,1H); 9.00 (m,1H); 9.24 (m,1H))
  • 2
  • [ 205046-59-9 ]
  • [ 83848-59-3 ]
YieldReaction ConditionsOperation in experiment
Step 2: 5-Nitroquinoline-8-carboxylic Acid At 150 C., 1.50 g of <strong>[205046-59-9]8-cyano-5-nitroquinoline</strong> were added a little at a time to 3.50 g of 75% strength sulfuric acid. After stirring for one hour, the reaction mixture was cooled, poured into ice water and extracted with ethyl acetate. The organic phase was dried and the solvent was removed under reduced pressure. Yield: 1.1 g (Melting point: 210 C.) (1H-NMR (d6-DMSO; delta in ppm): 8.00 (m,1H); 8.49 (m,1H); 8.58 (m,1H); 9.01 (m,1H); 9.22 (m,1H); 15.0 (bs,1H))
Step 2: 5-Nitroquinoline-8-carboxylic acid At 150 C., 1.50 g of <strong>[205046-59-9]8-cyano-5-nitroquinoline</strong> were added a little at a time to 3.50 g of 75% strength sulfuric acid. After stirring for one hour, the reaction mixture was cooled, poured into ice water and extracted with ethyl acetate. The organic phase was dried and the solvent was removed under reduced pressure. Yield: 1.1 g (Melting point: 210 C.) (1H-NMR (d6-DMSO; delta in ppm): 8.00 (m,1H); 8.49 (m,1H); 8.58 (m,1H); 9.01 (m,1H); 9.22 (m,1H); 15.0 (bs,1H))
YieldReaction ConditionsOperation in experiment
76% 12C. 5-Nitroquinoline-8-carbonitrile To a suspension of compound 12B (600 mg, 2.75 mmol) in anhydrous THF (25 mL) cooled to -15 C. was added Et3N (0.46 mL, 3.3 mmol), followed by a dropwise addition of ethyl chloroformate (0.33 mL, 3.44 mmol). The reaction mixture was stirred at -15 C. for 30 min, then NH3 gas was bubbled into the reaction for 5 min followed by warming of the reaction to rt for 1 h. The solvent was evaporated to give 850 mg (>100%) of the amide as a yellow solid which was carried on to the next step without further purification. The amide (850 mg) was dissolved in pyridine (25 mL), and imidazole (377 mg, 5.49 mmol) was added. The mixture was cooled to -30 C. under nitrogen, POCl3 (1.01 mL, 10.7 mmol) was added and the reaction was warmed to 0 C. for 30 min, and then evaporated to dryness. The residue was chromatographed (silica gel) eluding with CH2Cl2 to afford the title compound (416 mg, 76%, 2 steps). LC/MS m/z 200 [M+H]+.
76% 12C. 5-Nitroquinoline-8-carbonitrile To a suspension of compound 12B (600 mg, 2.75 mmol) in anhydrous THF (25 mL) cooled to -15 C. was added Et3N (0.46 mL, 3.3 mmol), followed by a dropwise addition of ethyl chloroformate (0.33 mL, 3.44 mmol). The reaction mixture was stirred at -15 C. for 30 min, then NH3 gas was bubbled into the reaction for 5 min followed by warming of the reaction to rt for 1h. The solvent was evaporated to give 850 mg (>100%) of the amide as a yellow solid which was carried on to the next step without further purification. The amide (850 mg) was dissolved in pyridine (25 mL), and imidazole (377 mg, 5.49 mmol) was added. The mixture was cooled to -30 C. under nitrogen, POCl3 (1.01 mL, 10.7 mmol) was added and the reaction was warmed to 0 C. for 30 min, and then evaporated to dryness. The residue was chromatographed (silica gel) eluding with CH2Cl2 to afford the title compound (416 mg, 76%, 2 steps). LC/MS m/z 200 [M+H]+.
  • 4
  • [ 205046-59-9 ]
  • ammonium chloride [ No CAS ]
  • [ 7439-89-6 ]
  • [ 573758-03-9 ]
YieldReaction ConditionsOperation in experiment
5.09 g (100%) In tetrahydrofuran; ethanol; C. 5-Amino-quinoline-8-carbonitrile (464C) Compound 464B (6.00 g, 30.1 mmol) was dissolved in THF (150 mL) at reflux with mechanical stirring. EtOH (150 mL) was then added followed by aqueous ammonium chloride (2.4 g/225 mL water). The mixture was heated at 70 C. and then iron powder (325 mesh, 6.75 g, 120 mmol) was added with vigorous mechanical stirring. After 1 h, the reaction was cooled to 22 C. and filtered through Celite rinsing with methylene chloride. The filtrate was then concentrated to ~250 mL and the pH was adjusted to 10 by addition of 1N NaOH. The solution was then extracted with ethyl acetate (5*150 mL). The combined organic layers were washed once with brine (250 mL) and then dried over anhydrous magnesium sulfate. Concentration in vacuo gave 5.09 g (100%) of compound 464C as a yellow solid. HPLC: 99% at 1.143 min (retention time) (YMC S5 ODS column, 4.6*50 mm, eluding with 10-90% aqueous methanol over 4 min containing 0.2% phosphoric acid, 4 mL/min, monitoring at 220 nm). MS (ES): m/z 170.16 [M+H]+.
  • 5
  • bis(diphenylphosphino)ferrocene [ No CAS ]
  • tris(benzylidineacetone)dipalladium [ No CAS ]
  • [ 139366-35-1 ]
  • [ 205046-59-9 ]
YieldReaction ConditionsOperation in experiment
6.01 g (51%) In dichloromethane; N,N-dimethyl-formamide; B. 5-Nitro-quinoline-8-carbonitrile (464B) Compound 464A (15.0 g, 59.3 mmol) was dissolved in DMF (120 mL) and zinc cyanide (4.20 g, 35.9 mmol) was added. Bis(diphenylphosphino)ferrocene (3.00 g, 5.40 mmol) and tris(benzylidineacetone)dipalladium (3.00 g, 3.30 mmol) were then added and the reaction was heated to 100 C. for 1.5 h. The reaction was cooled to 22 C. and then poured into concentrated ammonium hydroxide (900 mL) resulting in an orange precipitate which was filtered and rinsed with cold water (1 L). The resulting precipitate was dissolved in methylene chloride, washed with brine (1*300 mL) and then dried over anhydrous sodium sulfate. Concentration in vacuo gave the crude material as an orange solid which was purified by flash chromatography on silica gel eluding with methylene chloride to give 6.01 g (51%) of compound 464B as a yellow solid. HPLC: 99% at 1.900 min (retention time) (YMC S5 ODS column, 4.6*50 mm, eluding with 10-90% aqueous methanol over 4 min containing 0.2% phosphoric acid, 4 mL/min, monitoring at 220 nm).
  • 9
  • 5-nitroquinoline-8-carboxamide [ No CAS ]
  • [ 205046-59-9 ]
 

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Technical Information

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