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Chemical Structure| 14160-91-9 Chemical Structure| 14160-91-9

Structure of 14160-91-9

Chemical Structure| 14160-91-9

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Product Details of [ 14160-91-9 ]

CAS No. :14160-91-9
Formula : C6H4Cl2N2O
M.W : 191.01
SMILES Code : CC1=NC(Cl)=C(C=O)C(Cl)=N1
MDL No. :MFCD09909782
InChI Key :DOMBYPXLCGLBRD-UHFFFAOYSA-N
Pubchem ID :23035630

Safety of [ 14160-91-9 ]

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

Computational Chemistry of [ 14160-91-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.17
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 42.41
TPSA ?

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

42.85 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.57
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

1.99
Log Po/w (WLOGP)?

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

1.9
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.

0.52
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

2.76
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.75

Water Solubility

Log S (ESOL):?

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

-2.62
Solubility 0.463 mg/ml ; 0.00242 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.

-2.52
Solubility 0.582 mg/ml ; 0.00305 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

-3.22
Solubility 0.114 mg/ml ; 0.000598 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

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

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)

1.58

Application In Synthesis of [ 14160-91-9 ]

* 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 [ 14160-91-9 ]

[ 14160-91-9 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 1194-22-5 ]
  • [ 14160-91-9 ]
  • 2
  • [ 68-12-2 ]
  • [ 1194-22-5 ]
  • [ 14160-91-9 ]
YieldReaction ConditionsOperation in experiment
59% With trichlorophosphate; at 0℃;Reflux; To POCl3 (60.6g, 397mmol) was added dropwise DMF (9.8g, 135mmol) at 0C. The resulting suspension was stirred at the same temperature for 1h. Then <strong>[1194-22-5]2-methylpyrimidine-4,6-diol</strong> 64 (10g, 79mmol) was added in portions and stirred at room temperature for 1h, followed by stirring at reflux overnight. The reaction solution was concentrated and diluted with cold ethyl acetate (100mL). This solution was added dropwise into ice-water and filtered. The filtrate was extracted with ethyl acetate (200mL). The organic layer was dried over Na2SO4, filtered and evaporated to give the desired product (9g, 59%) as a yellow oil. 1H NMR (400MHz, CDCl3) delta 10.41 (s, 1H), 2.75 (s, 3H). 13C NMR (150MHz, CDCl3) delta 185.7, 171.6, 162.6, 121.9, 26.1. MS (ESI/APCI) m/z 222.8 [M+MeOH+H]+.
45% With trichlorophosphate; at 10 - 120℃; for 11h; Reference Example 1 Production of 4,6-dichloro-2-methylpyrimidine-5-carbaldehyde To ice-cooled phosphorus oxychloride (52.2 g, 340 mmol) was added dropwise DMF (3.10 mL, 40 mmol), and the mixture was stirred at room temperature for 30 min. 4,6-Dihydroxy-2-methylpyrimidine (5.04 g, 40 mmol) was added by small portions, and the mixture was stirred at room temperature for 1 hr and then at 120C for 10 hr. After cooling, the reaction mixture was poured into ice. Ethyl acetate and diethyl ether were added thereto, and the insoluble material was filtered off, and the filtrate was extracted 3 times with ethyl acetate/diethyl ether=1/4 solution. The extract was washed successively with water and brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluate, hexane:ethyl acetate=95:5?75:25) to give the title compound (3.46 g, 45%) as a yellow solid. 1H NMR (300 MHz, CDCl3) delta:2.78 (3 H, s), 10.44 (1 H, s).
10 g To POCl3(60.6 g, 396.5 mmol) was added dropwise DMF (9.8 g, 134.8 mmol) at 0C. The resulting suspension was stirred at the same temperature for lh. Then <strong>[1194-22-5]2-methylpyrimidine-4,6-diol</strong> (10 g, 79.3 mmol) was added in portions and stirred at room temperature for lh, after that, stirred at 105 C overnight. The reaction solution was concentrated and diluted with cold ethyl acetate (lOOmL). This solution was added dropwise into ice-water, filtered and the filtrate was extracted with ethyl acetate (200 mL). The combined organic layer was dried over Na2S04, filtered and evaporated to give a yellow oil (10 g). This oil was dissolved in THF (50 mL) and water (10 mL), and NaBH4(4 g, 104.7 mmol) was added in portions at 0C. The resulting suspension was stirred at the same temperature for 30min. Water (50 mL) was added, and extracted with ethyl acetate (50 mL). The organic layer was dried over Na2S04, filtered and evaporated. The residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate = 10/1) to give the desired product (2 g, 20%) as a yellow solid.
 

Historical Records

Technical Information

Categories

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[ 14160-91-9 ]

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