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Chemical Structure| 141-30-0 Chemical Structure| 141-30-0

Structure of 141-30-0

Chemical Structure| 141-30-0

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Product Details of [ 141-30-0 ]

CAS No. :141-30-0
Formula : C4H2Cl2N2
M.W : 148.98
SMILES Code : ClC1=NN=C(Cl)C=C1
MDL No. :MFCD00006466
InChI Key :GUSWJGOYDXFJSI-UHFFFAOYSA-N
Pubchem ID :67331

Safety of [ 141-30-0 ]

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

Computational Chemistry of [ 141-30-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 8
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 32.05
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.

1.69
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

0.7
Log Po/w (WLOGP)?

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

1.78
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.

1.21
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

2.34
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.55

Water Solubility

Log S (ESOL):?

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

-1.76
Solubility 2.59 mg/ml ; 0.0174 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.

-0.82
Solubility 22.6 mg/ml ; 0.152 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

-2.87
Solubility 0.203 mg/ml ; 0.00136 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.

-6.71 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

2.0
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)

1.72

Application In Synthesis of [ 141-30-0 ]

* 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 [ 141-30-0 ]
  • Downstream synthetic route of [ 141-30-0 ]

[ 141-30-0 ] Synthesis Path-Upstream   1~5

  • 1
  • [ 141-30-0 ]
  • [ 33097-39-1 ]
References: [1] Journal of Heterocyclic Chemistry, 2015, vol. 51, # 5, p. 1404 - 1409.
[2] Angewandte Chemie - International Edition, 2006, vol. 45, # 17, p. 2720 - 2725.
  • 2
  • [ 141-30-0 ]
  • [ 33097-38-0 ]
  • [ 33097-39-1 ]
References: [1] Tetrahedron Letters, 2000, vol. 41, # 35, p. 6763 - 6767.
[2] Tetrahedron, 2001, vol. 57, # 4, p. 739 - 750.
[3] Chemistry Letters, 1993, # 3, p. 509 - 512.
  • 3
  • [ 141-30-0 ]
  • [ 75-98-9 ]
  • [ 22808-29-3 ]
YieldReaction ConditionsOperation in experiment
64%
Stage #1: With ammonium peroxydisulfate; sulfuric acid; silver nitrate In water at 70℃; for 1 h;
Synthesis of Compound J.1. A flask was charged with 3,6-dichloropyridazine (1.49 g, 0.01 mol, 1.0 equiv), silver nitrate (0.17 g, 0.001 mol, 0.1 equiv), water (30 mL), pivalic acid (3.57 g, 0.035 mol, 3.5 equiv), and sulfuric acid (1.6 mL, 0.03 mol, 3.0 equiv). The mixture was heated to 70° C. and a solution of ammonium persulfate (2.28 g, 0.01 mol, 1.0 equiv) in water (10 mL) was added dropwise over ten minutes. The reaction was stirred at 70° C. for one hour and then cooled to RT. The reaction mixture was poured into ice water and then adjusted to pH 8 with aqueous ammonium hydroxide. The aqueous mixture was extracted with CH2Cl2 (2.x.250 mL). The combined organic extracts were filtered through a cotton plug, washed with aqueous 1 N NaOH (70 mL), dried over anhydrous MgSO4 and concentrated under reduced pressure. Purification by flash column chromatography (20percent EtOAc/hexanes) afforded the title compound (1.32 g, 64percent) as a white solid. 1H NMR: (CDCl3, 400 MHz) δ: 7.5 (s, 1H), 1.5 (s, 9H); Rf=0.5 (80percent EtOAc/hexanes).
64% With ammonium peroxydisulfate; sulfuric acid; silver nitrate In water at 70℃; for 1 h; A flask was charged with 3,6-dichloropyridazine (1.49 g, 0.01 mol, 1.0 equiv), silver nitrate (0.17 g, 0.001 mol, 0.1 equiv), water (30 mL), pivalic acid (3.57 g, 0.035 mol, 3.5 equiv), and sulfuric acid (1.6 mL, 0.03 mol, 3.0 equiv). The mixture was heated to 70° C. and a solution of ammonium persulfate (2.28 g, 0.01 mol, 1.0 equiv) in water (10 mL) was added dropwise over ten minutes. The reaction was stirred at 70° C. for one hr and then cooled to RT. The reaction mixture was poured into ice water and then adjusted to pH 8 with aqueous ammonium hydroxide. The aqueous mixture was extracted with CH2Cl2 (2.x.250 mL). The combined organic extracts were filtered through a cotton plug, washed with aqueous 1 N NaOH (70 mL), dried over anhydrous MgSO4 and concentrated under reduced pressure. Purification by flash column chromatography (20percent EtOAc/hexanes) afforded the title compound (1.32 g, 64percent) as a white solid. 1H NMR: (CDCl3, 400 MHz) δ: 7.5 (s, 1 H), 1.5 (s, 9 H); Rf=0.5 (80percent EtOAc/hexanes).
References: [1] Patent: US2009/5359, 2009, A1, . Location in patent: Page/Page column 39.
[2] Patent: US2009/36419, 2009, A1, . Location in patent: Page/Page column 84.
[3] Journal of Medicinal Chemistry, 2005, vol. 48, # 23, p. 7089 - 7092.
[4] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 20, p. 6030 - 6033.
  • 4
  • [ 141-30-0 ]
  • [ 22808-29-3 ]
References: [1] Patent: US4628088, 1986, A, .
  • 5
  • [ 141-30-0 ]
  • [ 7664-93-9 ]
  • [ 75-98-9 ]
  • [ 22808-29-3 ]
YieldReaction ConditionsOperation in experiment
53% With silver nitrate In hexane; water a
3,6-Dichloro-4-(1,1-dimethylethyl)pyridazine
Concentrated sulphuric acid (53.6 ml, 1.0 mol) was added carefully to a stirred suspension of 3,6-dichloropyridazine (50.0 g, 0.34 mol) in water (1.25 l).
This mixture was then heated to 70° C. (internal temperature) before the addition of trimethylacetic acid (47.5 ml, 0.41 mol).
A solution of silver nitrate (11.4 g, 0.07 mol) in water (20 ml) was then added over approximately one minute.
This caused the reaction mixture to become milky in appearance.
A solution of ammonium persulphate (230 g, 1.0 mol) in water (0.63 l) was then added over 20-30 minutes.
The internal temperature rose to approximately 85° C.
During the addition the product formed as a sticky precipitate.
Upon complete addition the reaction was stirred for an additional 10 minutes, then allowed to cool to room temperature.
The mixture was then poured onto ice and basified with concentrated aqueous ammonia, with the addition of more ice as required to keep the temperature below 10° C.
The aqueous was extracted with dichloromethane (3*300 ml).
The combined extracts were dried (MgSO4), filtered and evaporated to give 55.8 g of crude product as an oil.
This was purified by silica gel chromatography using 0-15percent ethyl acetate in hexane as eluent to give 37.31 g (53percent) of the desired compound.
Data for the title compound: 1H NMR (360 MHz, d6-DMSO) δ1.50 (9H, s), 7.48 (1H, s); MS (ES+) m/e 205 [MH]+, 207 [MH]+.
References: [1] Patent: US6630471, 2003, B1, .
 

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Technical Information

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