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Chemical Structure| 80194-83-8

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Product Details of [ 80194-83-8 ]

CAS No. :80194-83-8
Formula : C12H9ClN2O
M.W : 232.67
SMILES Code : O=C(NC1=CC=CC=C1)C2=CC=NC(Cl)=C2
MDL No. :MFCD09817650
Boiling Point : No data available
InChI Key :LTAXNWGTCKPZGT-UHFFFAOYSA-N
Pubchem ID :15075715

Safety of [ 80194-83-8 ]

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

Computational Chemistry of [ 80194-83-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 16
Num. arom. heavy atoms 12
Fraction Csp3 0.0
Num. rotatable bonds 3
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 63.46
TPSA ?

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

41.99 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.98
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

3.47
Log Po/w (WLOGP)?

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

2.8
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.

2.01
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

2.69
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.59

Water Solubility

Log S (ESOL):?

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

-3.83
Solubility 0.0348 mg/ml ; 0.000149 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.

-4.03
Solubility 0.0215 mg/ml ; 0.0000925 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately 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

-5.17
Solubility 0.00159 mg/ml ; 0.00000684 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

Yes
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.

-5.26 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)

1.7

Application In Synthesis of [ 80194-83-8 ]

* 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.

  • Upstream synthesis route of [ 80194-83-8 ]

[ 80194-83-8 ] Synthesis Path-Upstream   1~7

  • 1
  • [ 65287-34-5 ]
  • [ 62-53-3 ]
  • [ 80194-83-8 ]
YieldReaction ConditionsOperation in experiment
92% With N-ethyl-N,N-diisopropylamine In 1,2-dichloro-ethane at 0 - 95℃; for 2 h; To the sol. of 2-chloroisonicotinoyl chloride (Anderson, W. K. , Dean, D. C. , Endo, T., J Med Chem., 1990,33, 1667,10 g, 56.8 mmol) in 1,2-dichloroethane (100 mL) was added at 0 °C a sol. of aniline (5.70 mL, 62.5 mmol) and DIPEA (10.2 ml, 59.6 mmol) in 1,2-dichloroethane (10 ml) during ca. 30 min. The reaction was stirred at 0 °C for ca. 30 min and subsequently for 1 h at 95 °C. Water (30 mL) was added at rt and the mixture was filtered-off. The filtrate was extracted with CH2Cl2 (200 mL). The combined org. extracts were dried over MgS04, filtered, and the solvents were removed under reduced pressure. The residue was crystallized from MeOH/water 1: 10 (110 mL), yielding the title compound (12.12 g, 92percent). LC-MS: RT = 0.87 min; ES+ = 233.1.
92% With N-ethyl-N,N-diisopropylamine In 1,2-dichloro-ethane at 0 - 95℃; for 2 h; 2-Chloro-N-phenylisonicotinamide (N); To the sol. of 2-chloro-isonicotinoyl chloride (Anderson, W. K. , Dean, D. C. , Endo, T., J. Med. Chem., 1990, 33, 1667,10 g, 56.8 mmol) in 1,2-dichloroethane (100 mL) was added at 0 °C a sol. of aniline (5.70 mL, 62.5 mmol) and DIPEA (10.2 ml, 59.6 mmol) in 1,2- dichloroethane (10 ml) during ca. 30 min. The reaction was stirred at 0 °C for ca. 30 min and subsequently for 1 h at 95 °C. Water (30 mL) was added at rt and the mixture was filtered-off. The filtrate was extracted with CH2CI2 (200 mL). The combined org. extracts were dried over MgS04, filtered, and the solvents were removed under reduced pressure. The residue was crystallized from MeOH/water 1: 10 (110 mL), yielding the title compound (12.12 g, 92percent). LC-MS: RT = 0.87 min; ES+ = 233.1
92% With N-ethyl-N,N-diisopropylamine In 1,2-dichloro-ethane at 0 - 95℃; for 2 h; 2-Chloro-N-phenylisonicotinamide (N) To the sol. of 2-chloro-isonicotinoyl chloride (Anderson, W. K. , Dean, D. C. , Endo, T., J. Med. Chem., 1990,33, 1667,10 g, 56. 8 mmol) in 1,2-dichloroethane (100 mL) was added at 0 °C a sol. of aniline (5.70 mL, 62.5 mmol) and DIPEA (10.2 ml, 59.6 mmol) in 1,2- dichloroethane (10 ml) during ca. 30 min. The reaction was stirred at 0 °C for ca. 30 min and subsequently for 1 h at 95 °C. Water (30 mL) was added at rt and the mixture was filtered-off. The filtrate was extracted with CH2C12 (200 mL). The combined org. extracts were dried over MgS04, filtered, and the solvents were removed under reduced pressure. The residue was crystallized from MeOH/water 1: 10 (110 mL), yielding the title compound (12.12 g, 92percent). LC-MS: RT = 0.87 min; ES+ = 233.1.
92% With N-ethyl-N,N-diisopropylamine In 1,2-dichloro-ethane at 0 - 95℃; for 2 h; 2-Chloro-N-phenylisonicotinamide (N) To the sol. of 2-chloro-isonicotinoyl chloride (Anderson, W. K., Dean, D. C., Endo, T., J Med Chem., 1990, 33, 1667,10 g, 56. 8 mmol) in 1,2-dichloroethane (100 mL) was added at 0 °C a sol. of aniline (5.70 mL, 62.5 mmol) and DIPEA (10.2 ml, 59.6 mmol) in 1,2-dichloroethane (10 ml) during ca. 30 min. The reaction was stirred at 0 °C for ca. 30 min and subsequently for 1 h at 95 °C. Water (30 mL) was added at rt and the mixture was filtered-off. The filtrate was extracted with CH2Cl2 (200 mL). The combined org. extracts were dried over MgS04, filtered, and the solvents were removed under reduced pressure. The residue was crystallized from MeOH/water 1: 10 (110 mL), yielding the title compound (12.12 g, 92percent). LC-MS: RT = 0. 87 min; ES+ = 233.1.
92% at 0 - 95℃; for 2 h; 2-Chloro-N-phenylisonicotinamide (N); To the sol. of 2-chloro-isonicotinoyl chloride (Anderson, W. K., Dean, D. C. , Endo, T., J Med. Chem., 1990, 33, 1667,10 g, 56. 8 mmol) in 1,2-dichloroethane (100 mL) was added at 0 °C a sol. of aniline (5.70 mL, 62.5 mmol) and DIPEA (10.2 ml, 59.6 mmol) in 1,2- dichloroethane (10 ml) during ca. 30 min. The reaction was stirred at 0 °C for ca. 30 min and subsequently for 1 h at 95 °C. Water (30 mL) was added at rt and the mixture was filtered-off. The filtrate was extracted with CH2C12 (200 mL). The combined org. extracts were dried over MgS04, filtered, and the solvents were removed under reduced pressure. The residue was crystallized from MeOH/water 1: 10 (110 mL), yielding the title compound (12.12 g, 92percent). LC-MS: RT = 0.87 min; ES+ = 233. 1.

References: [1] Patent: WO2005/40120, 2005, A1, . Location in patent: Page/Page column 23.
[2] Patent: WO2005/40165, 2005, A1, . Location in patent: Page/Page column 22.
[3] Patent: WO2005/40173, 2005, A1, . Location in patent: Page/Page column 33-34.
[4] Patent: WO2005/54243, 2005, A1, . Location in patent: Page/Page column 24-25.
[5] Patent: WO2005/54244, 2005, A2, . Location in patent: Page/Page column 23.
[6] Patent: WO2012/142513, 2012, A1, . Location in patent: Page/Page column 426-427.
  • 2
  • [ 201230-82-2 ]
  • [ 62-53-3 ]
  • [ 80194-83-8 ]
YieldReaction ConditionsOperation in experiment
36% With palladium diacetate; triethylamine; triphenylphosphine In N,N-dimethyl-formamide at 50℃; for 46 h; Autoclave General procedure: In a typical experiment, Pd(OAc)2 (5.6 mg, 0.025 mmol), triphenylphosphine (13.1 mg, 0.05 mmol), 2,5-diiodopyridine(331 mg, 1 mmol), 2,3-diiodopyridine (331 mg, 1 mmol) or 2-chloro-3,4-diiodopyridine (182.75 mg, 0.5 mmol), amine nucleophile (see above in the tables; 3 mmol of a/2 mmol of b/1.5 mmol of c,d/1.1 mmol of e,f,g,h) and triethylamine (0.5 mL) were dissolved in DMF (10 mL) under argon in a 100 mL autoclave. The atmosphere was changed to carbon monoxide and the autoclave was pressurized to the given pressure by carbon monoxide. The reaction was conducted for the given reaction time upon stirring at 50 C andanalysed by GC-MS (internal standard: naphthalene). The mixture was then concentrated and evaporated to dryness and worked-up as described in Section 4.2.
References: [1] Tetrahedron, 2017, vol. 73, # 15, p. 2131 - 2138.
  • 3
  • [ 14178-44-0 ]
  • [ 80194-83-8 ]
References: [1] Tetrahedron, 1989, vol. 45, # 23, p. 7469 - 7476.
  • 4
  • [ 6313-54-8 ]
  • [ 80194-83-8 ]
References: [1] Patent: WO2012/142513, 2012, A1, .
  • 5
  • [ 55-22-1 ]
  • [ 80194-83-8 ]
References: [1] Tetrahedron, 1989, vol. 45, # 23, p. 7469 - 7476.
  • 6
  • [ 14254-57-0 ]
  • [ 80194-83-8 ]
References: [1] Tetrahedron, 1989, vol. 45, # 23, p. 7469 - 7476.
  • 7
  • [ 3034-31-9 ]
  • [ 80194-83-8 ]
References: [1] Tetrahedron, 1989, vol. 45, # 23, p. 7469 - 7476.
 

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