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Chemical Structure| 1122-17-4 Chemical Structure| 1122-17-4

Structure of 1122-17-4

Chemical Structure| 1122-17-4

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Product Details of [ 1122-17-4 ]

CAS No. :1122-17-4
Formula : C4Cl2O3
M.W : 166.95
SMILES Code : O=C(C(Cl)=C1Cl)OC1=O
MDL No. :MFCD00005520
InChI Key :AGULWIQIYWWFBJ-UHFFFAOYSA-N
Pubchem ID :70728

Safety of [ 1122-17-4 ]

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

Computational Chemistry of [ 1122-17-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 0
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 29.83
TPSA ?

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

43.37 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.83
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

1.55
Log Po/w (WLOGP)?

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

0.76
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.

0.61
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

1.93
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.14

Water Solubility

Log S (ESOL):?

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

-1.85
Solubility 2.35 mg/ml ; 0.0141 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.

-2.07
Solubility 1.42 mg/ml ; 0.0085 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

-1.7
Solubility 3.32 mg/ml ; 0.0199 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

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.

-6.22 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

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)

2.31

Application In Synthesis of [ 1122-17-4 ]

* 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 [ 1122-17-4 ]

[ 1122-17-4 ] Synthesis Path-Downstream   1~5

  • 2
  • [ 1122-17-4 ]
  • [ 1193-54-0 ]
YieldReaction ConditionsOperation in experiment
With ammonia; In acetic acid; at 108℃; for 1.5h; General procedure: To suspension of 16.7 g (0.1 mol) of dichloromaleic anhydride in 60 g of glacial acetic acid was added dropwise 0.1 mol of the corresponding amine. The mixture was stirred for 30 min at 85 and for 90 min at 108. Then the mixture was cooled while stirred to 10, the precipitate was filtered off, washed with water, and dried in a vacuum at 60.
  • 3
  • [ 1122-17-4 ]
  • [ 371-40-4 ]
  • [ 41205-21-4 ]
YieldReaction ConditionsOperation in experiment
99.2% In water; EXAMPLE 4 10g (0.06 mol) of 2,3-dichloromaleic anhydride was dissolved in 200 ml of water. Then to the resulting solution 5.55g (0.05 mol) of 4-fluoroaniline was added dropwise over a period of 5 min. at room temperature under agitation. The mixture was then allowed to react for 2 hours at reflux temperatures. Upon cooling the reaction mixture, precipitated crystal was separated by filtration to obtain 12.9g of N-(4-fluorophenyl)-2,3-dichloromaleimide melting at 240-243 C (not corrected) at a yield of 99.2%. An anaylsis by gas chromatography showed the product had a purity of 99.3%.
99.1% In water; EXAMPLE 5 5.55g (0.05 mol) of 4-fluoroaniline was emulsified in 150 ml of water. Then to the resulting emulsion 10g (0.06 mol) of 2,3-dichloromaleic anhydride in 50 ml of water was added dropwise over a period of 30 min. at room temperatures under agitation. The mixture was then allowed to react at reflux temperatures. Upon cooling the reaction mixture, a crystal was removed out, which was separated by filtration to obtain 12.9g of N-(4-fluorophenyl)-2,3-dichloromaleimide melting at 240-243 C (not corrected) at a yield of 99.1%. An analysis by gas chromatography showed the product had a purity of 98.6%.
98.4% In water; EXAMPLE 2 10g (0.06 mol) of 2,3-dichloromaleic anhydride was dissolved in 100 ml of water. Then, to the resulting solution 5.55g (0.05mol) of 4-fluoroaniline was added dropwise over a period of 5 min. at room temperatures under agitation. The mixture was allowed to react for 2 hours at 80 C. Upon cooling the reaction mixture, a crystal was separated out, which was then separated by filtration to obtain 12.8g of N-(4-fluorophenyl)-2,3-dichloromaleimide melting at 239-242 C (not corrected) at a yield of 98.4%. An analysis by gas chromatography showed the product had a purity of 98.7%.
91.5% In water; EXAMPLE 3 10g (0.06 mol) of 2,3-dichloromaleic anhydride was dissolved in 100 ml of water. Then to the resulting solution 5.55g (0.05 mol) of 4-fluoroaniline was added dropwise over a period of 5 min. at room temperatures under agitation. The mixture was then allowed to react for 15 hours at 60 C. Upon cooling the reaction mixture, precipitated crystal was separated by filtration to obtain 11.9g of N-(4-fluorophenyl)-2,3-dichloromaleimide melting at 239-242 C (not corrected) at a yield of 91.5%. An analysis by gas chromatography showed the product had a purity of 97.9%.

  • 4
  • [ 1122-17-4 ]
  • [ 2100-42-7 ]
  • [ 608-44-6 ]
  • [ 20103-10-0 ]
  • [ 32741-27-8 ]
  • [ 824-69-1 ]
  • [ 14918-69-5 ]
  • [ 15012-64-3 ]
  • [ 123-31-9 ]
  • [ 615-67-8 ]
YieldReaction ConditionsOperation in experiment
1%; 3%; 42%; 5%; 2%; 2.5%; 10%; 20% With aluminum (III) chloride; iron(III) chloride; sodium chloride; In melt; at 150 - 185℃; for 0.166667h; General procedure: A mixture of substrate 7 (1.38 g, 8.0 mmol) and anhydride 9 (2.67 g, 16.0 mmol) was added to the melt of anhydrous AlCl3 (8.54 g, 64.0 mmol), NaCl (1.87 g, 32.0 mmol) and anhydrous FeCl3 (1.30 g, 8.0 mmol) with vigorous stirring at 150 C, the temperature of the mixture was increased to 180-185 C and maintained for 10 min. Then, the reaction mixture was cooled to room temperature, treated with 10% aqueous HCl (60 mL), and allowed to stand for 12 h. The product formed was separated, washed with hot (55-60 C) water (10×40 mL), dried to the constant weight, and subjected to chromatography on a column with SiO2. The elution with the mixture of hexane-benzene (10 : 1) gave compound 2 (0.066 g, 2.5%), the elution with the mixture of hexane-benzene (4 : 1) gave compound 1 (0.99 g, 42%), the elution with benzene gave compound 10 (0.045 g, 2%) identical to the sample described above. The combined acidic mother liquor and washing water (460 mL) were extracted with AcOEt (6×50 mL), the combined extracts were washed with saturated aqueous NaCl (3×50 mL), and dried with Na2SO4. The solvent was evaporated at reduced pressure, the residue was subjected to chromatography on a column with SiO2. The elution with the mixture of hexane-acetone (9 : 1) gave compound 14 (0.057 g, 5%), the elution with the mixture of hexane-acetone (8 : 1) gave compound 15 (0.034 g, 3%), the elution with the mixture of hexane-acetone (7 : 1) gave compound 16 (0.011 g, 1%), the elution with the mixture of hexane-acetone (5 : 1) gave compound 12 (0.232 g, 20%), and the elution with the mixture of hexane-acetone (4 : 1) gave compound 13 (0.07 g, 10%) identical to the sample described above.
  • 5
  • [ 1122-17-4 ]
  • [ 39542-66-0 ]
  • [ 608-94-6 ]
  • [ 32741-27-8 ]
  • [ 15012-64-3 ]
  • [ 615-67-8 ]
YieldReaction ConditionsOperation in experiment
34%; 34%; 32%; 1% With aluminum (III) chloride; sodium chloride; In melt; at 150 - 180℃; for 0.025h; General procedure: A mixture of substrate 8 (2.07 g, 10.0 mmol) and anhydride 9 (3.34 g, 20.0 mmol) was added to the melt of anhydrous AlCl3 (8.54 g, 64.0 mmol) and NaCl (8.54 g, 64.0 mmol) with vigorous stirring at 150 C, the temperature of the mixture was increased to 175-180 C and maintained for 1.5 min. The workup similar to that described above for cycloacylation of substrate 7 gave a mixture of products, which was subjected to chromatography on a column with SiO2. The elution with the mixture of hexane-benzene (10 : 1) gave compound 2 (1.05 g, 32%), the elution with the mixture of hexane-benzene (4 : 1) gave compound 1 (0.34 g, 34%) identical to the sample described above. The combined acidic mother liquor and washing water (460 mL) were extracted according to procedure described above for cycloacylation of substrate 7 in the presence of FeCl3 to isolate a mixture of products, which was subjected to chromatography on a column with SiO2. The elution with the mixture of hexane-acetone (10 : 1) gave hydroquinone 17 (0.238 g, 34%), the elution with the mixture of hexane-acetone (5 : 1) gave hydroquinone 12 (0.01 g, 1%) identical to the sample described above. The same amount of the reagents heated at 175-180 C for the longer time of 3 min led to the formation of a mixture of products, which was subjected to chromatography on a column with SiO2. The elution with the mixture of hexane-benzene (10 : 1) gave compound 2 (0.033 g, 1%), the elution with the mixture of hexane-benzene (4 : 1) gave compound 1 (1.51 g, 52%), the elution with benzene gave compound 10 (0.152 g, 6%), and the elution with the mixture of benzene-acetone 1 : 1 gave compound 11 (0.014 g, 0.5%) identical to the sample described above.
 

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