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Chemical Structure| 56741-94-7

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Product Details of [ 56741-94-7 ]

CAS No. :56741-94-7
Formula : C10H9N3O
M.W : 187.20
SMILES Code : O=C1NC(N)=NC(C2=CC=CC=C2)=C1
MDL No. :MFCD00466412
InChI Key :KXYGHDWFGFZJPJ-UHFFFAOYSA-N
Pubchem ID :135420365

Safety of [ 56741-94-7 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302+H312+H332-H315-H319-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 56741-94-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 12
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 2.0
Molar Refractivity 54.7
TPSA ?

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

71.77 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.08
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

0.34
Log Po/w (WLOGP)?

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

1.03
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.

0.99
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

1.88
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.06

Water Solubility

Log S (ESOL):?

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

-1.78
Solubility 3.08 mg/ml ; 0.0165 mol/l
Class?

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

Very soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-1.41
Solubility 7.26 mg/ml ; 0.0388 mol/l
Class?

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

Very 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

-3.72
Solubility 0.0358 mg/ml ; 0.000191 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

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.

-7.2 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

0.0 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)

1.88

Application In Synthesis of [ 56741-94-7 ]

* 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.

  • Upstream synthesis route of [ 56741-94-7 ]
  • Downstream synthetic route of [ 56741-94-7 ]

[ 56741-94-7 ] Synthesis Path-Upstream   1~10

  • 1
  • [ 94-02-0 ]
  • [ 56741-94-7 ]
YieldReaction ConditionsOperation in experiment
86%
Stage #1: for 1 h; Heating / reflux
Stage #2: at 45℃; Heating / reflux
Intermediate 1A : Preparation of 4-chloro-6-phenylpyrimidin-2-amine; A suspension of guanidine carbonate (3.60 g, 20 mmol) in ethanol (120 mL) and toluene (20 mL) was refluxed under nitrogen for 1 h, during which time about 50 mL of solvent was removed by distillation. After the mixture was cooled to 45 °C, ethyl 3-oxo-3- phenylpropanoate (7.68 g, 40 mmol) was added and the solution was heated at reflux overnight. The desired product precipitated as a white solid during the reaction. Water (50 mL) was added to the reaction and the mixture was refluxed for an additional 30 min. After cooling to rt, the mixture was neutralized with 1N HC1 and placed in the refrigerator for 6 h. The solid was filtered, washed with water followed by ether and dried at 60 °C under vacuum to give the product as white solid (6.45 g, 86percent). MS ES: 188 (M+H) +, calcd 188; RT = 0.91 min; TLC (CH2C12/2M NH3 in MeOH 95/5) Rf = 0.10. A mixture of the above product (6.0 g, 32 mmol) and POC13 (100 mL) was heated at reflux for 1 h. The majority of the POC13 was removed in vacuo and the residue was diluted with EtOAc and poured over an ice/saturated NaHC03 solution. The aqueous layer was extracted with EtOAc and the combined organic layers were washed with brine, dried (Na2SO4), and concentrated. The crude organic concentrate was re-crystallized from EtOAc/ether to give the product 1A as an off-white powder (2. 8 g, 43percent). MS ES: 206 (M+H) +, calcd 206; RT = 2.49 min; TLC (CH2C12/2M NH3 in MeOH 95/5) Rf = 0.72. (Reference 1: H. L. Skulnick, S. D. Weed, E. E. Edison, H. E. Renis, W. Wierenga, and D. A. Stringfellow, J ; Med. Cllem. 1985, 28,1854-1869).
References: [1] Patent: WO2005/35507, 2005, A2, . Location in patent: Page/Page column 52.
  • 2
  • [ 593-85-1 ]
  • [ 94-02-0 ]
  • [ 56741-94-7 ]
YieldReaction ConditionsOperation in experiment
70% at 80℃; Inert atmosphere General procedure: To a suspension of guanidine carbonate (1.5-5 eq) in ethanol (2 mL/mmol) was added γ-aryl-β-ketoester (1.43-26.6 mmol), and the reaction mixture heated at 80 °C for 15-64 h. Followingreaction completion by TLC, the mixture was cooled to ambient temperature, filtered and thesolid triturated with water (5-20 mL) and acetone (5-20 mL) to give the title compound.
References: [1] Tetrahedron, 2015, vol. 71, # 39, p. 7339 - 7343.
[2] Journal of the American Chemical Society, 1998, vol. 120, # 27, p. 6761 - 6769.
[3] Justus Liebigs Annalen der Chemie, 1891, vol. 262, p. 365.
[4] Journal fuer Praktische Chemie (Leipzig), 1893, vol. &lt;2&gt; 47, p. 203.
  • 3
  • [ 614-27-7 ]
  • [ 113-00-8 ]
  • [ 56741-94-7 ]
YieldReaction ConditionsOperation in experiment
800 mg With sodium methylate In methanol at 65℃; Inert atmosphere A mixture of methyl 3-oxo-3-phenylpropanoate (2.0 g) , guanidine (2.02 g) and sodium methanolate (1.12 g) in methanol (50 mL) was stirred at 65°C overnight under a nitrogen atmosphere. The reaction mixture was evaporated under reduced pressure. The residue was purified by washed with methanol: ethyl acetate (1:10) as eluent to give the desired compound (800 mg) as a white solid. LC-MS m/z [M+H]+ = 188 (calc=188) (ES+)
References: [1] Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 5, p. 1315 - 1321.
  • 4
  • [ 50-01-1 ]
  • [ 94-02-0 ]
  • [ 56741-94-7 ]
References: [1] RSC Advances, 2014, vol. 4, # 29, p. 15087 - 15090.
  • 5
  • [ 124-46-9 ]
  • [ 94-02-0 ]
  • [ 56741-94-7 ]
References: [1] Patent: US2001/27196, 2001, A1, .
  • 6
  • [ 56741-95-8 ]
  • [ 98-80-6 ]
  • [ 66376-75-8 ]
  • [ 56741-94-7 ]
References: [1] Bioorganic and Medicinal Chemistry, 2000, vol. 8, # 4, p. 739 - 750.
  • 7
  • [ 593-84-0 ]
  • [ 94-02-0 ]
  • [ 56741-94-7 ]
References: [1] Journal of the American Chemical Society, 1914, vol. 36, p. 1205.
  • 8
  • [ 94-02-0 ]
  • [ 113-00-8 ]
  • [ 56741-94-7 ]
References: [1] Journal of Medicinal Chemistry, 1980, vol. 23, # 3, p. 237 - 239.
[2] Journal of Medicinal Chemistry, 1985, vol. 28, # 12, p. 1864 - 1869.
  • 9
  • [ 93-58-3 ]
  • [ 56741-94-7 ]
References: [1] Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 5, p. 1315 - 1321.
  • 10
  • [ 56741-95-8 ]
  • [ 56741-94-7 ]
References: [1] Analytical Chemistry, 1980, vol. 52, # 12, p. 1931 - 1934.
 

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