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Chemical Structure| 83942-10-3 Chemical Structure| 83942-10-3

Structure of 83942-10-3

Chemical Structure| 83942-10-3

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Product Details of [ 83942-10-3 ]

CAS No. :83942-10-3
Formula : C5H4Cl2N2
M.W : 163.01
SMILES Code : ClC1=NC=NC(=C1Cl)C
MDL No. :MFCD09909763
InChI Key :SIUNBOQRQYAIJI-UHFFFAOYSA-N
Pubchem ID :11789537

Safety of [ 83942-10-3 ]

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

Computational Chemistry of [ 83942-10-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 6
Fraction Csp3 0.2
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 37.02
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.

1.89
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

2.19
Log Po/w (WLOGP)?

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

2.09
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.

1.16
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

2.67
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.0

Water Solubility

Log S (ESOL):?

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

-2.72
Solubility 0.308 mg/ml ; 0.00189 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.

-2.37
Solubility 0.703 mg/ml ; 0.00431 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

-3.26
Solubility 0.0892 mg/ml ; 0.000547 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.

-5.74 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)

1.43

Application In Synthesis of [ 83942-10-3 ]

* 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 [ 83942-10-3 ]

[ 83942-10-3 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 7752-72-9 ]
  • [ 83942-10-3 ]
YieldReaction ConditionsOperation in experiment
88.5% With trichlorophosphate; In toluene;Reflux; 2) The Preparation of Intermediate 4,5-dichloro-6-methylpyrimidine 50 ml of POCl3 was added dropwise to a solution of 14.5 g (0.1 mol) of <strong>[7752-72-9]4-hydroxyl-5-chloro-6-methylpyrimidine</strong> in 50 mL of toluene, the mixture was refluxed for 5-7 h after addition. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was concentrated under reduced pressure to remove toluene and extra POCl3, and then poured into ice water. The water phase was extracted with ethyl acetate (3*50 ml), the organic phases were emerged, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was purified through silica column to give 14.43 g as yellow liquid with yield of 88.5%.
88.5% With trichlorophosphate; In toluene;Reflux; The preparation of intermediate 4,5-dichloro-6-methylpyrimidine ;50ml of POCl3 was added dropwise to a solution of 14.5g ( 0.lmol ) of <strong>[7752-72-9]4-hydroxyl-5-chloro-6-methylpyrimidine</strong> in 50 mL of toluene, the mixture was refluxed for 5-7 hrs after addition. ;After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was concentrated under reduced pressure to remove toluene and extra POCl3, and then poured into ice water. ;The water phase was extracted with ethyl acetate (3x50mL), the organic phases were emerged, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was purified through silica column to give 14.43g as yellow liquid with yield of 88.5%.
88.5% With trichlorophosphate; In toluene;Reflux; Enzymatic reaction; 2) Preparation of 4,5-dichloro-6-methylpyrimidineThe 14.5g (0.1mol) <strong>[7752-72-9]4-hydroxy-5-chloro-6-methylpyrimidine</strong> dissolved in 50ml of toluene, was added dropwise with stirring to the reaction flask 50ml of phosphorus oxychloride dropwise at reflux temperature the reaction completion 5-7 hours after, TLC monitored the reaction is complete. The toluene was evaporated under reduced pressure and an excess of phosphorus oxychloride, while stirring the reaction was poured into ice water, the aqueous phase was extracted with (3 × 50ml) and extracted with ethyl acetate, the combined organic phase was dried over anhydrous magnesium sulfate, filtered, desolvation . The residue was purified by column chromatography (eluent, ethyl acetate and petroleum ether (boiling range 60-90 ), the volume ratio of 1: 4) was isolated as a yellow liquid 14.43g, yield 88.5%.
88.5% With trichlorophosphate; In toluene; at 5 - 7℃;Reflux; 14.5g (0.1mol) 4- hydroxy-5-chloro-6-methylpyrimidine dissolved in 50ml of toluene, was added dropwise with stirring to the reaction flask 50ml phosphorus oxychloride, after dropwise addition the reaction heated at reflux for 5-7 hours, TLC monitored after completion of the reaction. Toluene was evaporated under reduced pressure and excess phosphorus oxychloride, with stirring the reaction was poured into ice water, the aqueous phase was extracted with ethyl acetate (3 × 50ml), the combined organic phase was dried over anhydrous magnesium sulfate, filtered, and dissolved. The residue was purified by column chromatography (eluent, ethyl acetate and petroleum ether (boiling range 60-90 deg. C), the volume ratio of 1: 4) was isolated as a yellow liquid 14.43g, yield 88.5%.
88.5% With trichlorophosphate; In toluene;Reflux; The 14.5g (0.1mol) 4- hydroxy-5-chloro-6-methylpyrimidine dissolved in 50ml of toluene, was added dropwise with stirring to the reaction flask 50ml of phosphorus oxychloride dropwise at reflux temperature the reaction completion 5-7 hours . After completion of the reaction was monitored by TLC, toluene was distilled off under reduced pressure and an excess of phosphorus oxychloride, while stirring the reaction was poured into ice water, the aqueous phase was extracted with (3 × 50ml) and extracted with ethyl acetate, the combined organic phase was dried over anhydrous magnesium dried, filtered, removing solvent. The residue was purified by column chromatography (eluent, ethyl acetate and petroleum ether, the volume ratio of 1: 5) was isolated yellow liquid 14.43 g, 88.5% yield.
88.5% With trichlorophosphate; In toluene;Reflux; 50 ml of POCl3 was added dropwise to a solution of 14.5 g (0.1 mol) of <strong>[7752-72-9]4-hydroxyl-5-chloro-6-methylpyrimidine</strong> in 50 mL of toluene, the mixture was refluxed for 5-7 h after addition. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was concentrated under reduced pressure to remove toluene and extra POCl3, and then poured into ice water. The water phase was extracted with ethyl acetate (3*50 mL), the organic phases were emerged, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was purified through silica column (ethyl acetate/petroleum ether=1:5, as an eluent) to give 14.43 g as yellow liquid with yield of 88.5%.
88.5% With trichlorophosphate; In toluene;Reflux; Dissolve 14.45 g (0.1 mol) of <strong>[7752-72-9]4-hydroxy-5-chloro-6-methylpyrimidine</strong> in 50 ml of toluene and stir it under anti-flask50 ml of phosphorus oxychloride was added dropwise, and the reaction was heated to reflux for 5-7 hours. TLC was monitored after the reaction was completed. Vacuum distillation of toluene andThe amount of phosphorous oxychloride was poured into ice water with stirring, the aqueous phase was extracted with (3×50 ml) ethyl acetate, and the organic phases were combined.Anhydrous magnesium sulfate drying and desolventization. Chromatographic separation of the yellow liquid 14.43g, the yield of 88.5%.
88.5% With trichlorophosphate; In toluene;Reflux; Dissolve 14.5 g (0.1 mol) of <strong>[7752-72-9]4-hydroxy-5-chloro-6-methylpyrimidine</strong> in 50 ml of toluene, add 50 ml ofphosphorus oxychloride to the reaction flask with stirring, and then heat up to reflux for 5-7 hours. After TLC monitoring was completed, toluene and excess phosphorus oxychloride were distilled off underreduced pressure. The reaction was poured into ice water with stirring. The aqueous phase was extracted with(3×50 ml) ethyl acetate, and the organic phases were combined and dried over anhydrous magnesium sulfate.Dry, filter, and dissolve. The residue was purified by column chromatography (eluent: ethyl acetate and petroleum ether, 1 : 5 in volume) to give 14.43 g of a yellow liquid, yield 88.5%.
88.5% With trichlorophosphate; In toluene;Reflux; 50 ml of POCl3 was added dropwise to a solution of 14.5 g (0.1 mol) of <strong>[7752-72-9]4-hydroxyl-5-chloro-6-methylpyrimidine</strong> in 50 mL of toluene, the mixture was refluxed for 5-7 h after addition. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was concentrated under reduced pressure to remove toluene and extra POCl3, and then poured into ice water. The water phase was extracted with ethyl acetate (3*50 mL), the organic phases were merged, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was purified through silica column (ethyl acetate/petroleum ether=1:5, as an eluent) to give14.43 g as yellow liquid with yield of 88.5%.
88.5% With trichlorophosphate; In toluene;Reflux; 14.5 g (0.1 mol) of <strong>[7752-72-9]4-hydroxy-5-chloro-6-methylpyrimidine</strong> was dissolved in 50 ml of toluene solution.50 ml of phosphorus oxychloride was added dropwise to the reaction flask under stirring, and the mixture was heated under reflux for 5-7 hours.After the TLC monitoring reaction was completed, toluene and excess phosphorus oxychloride were distilled off under reduced pressure, and the reactant was poured into ice water with stirring.The aqueous phase was extracted with ethyl acetate (3 × 50ml), the organic phases were combined, dried over anhydrous magnesium sulfate, filtered, desolventized.Residue column chromatography (eluent is ethyl acetate and petroleum ether,Volume ratio of 1: 5) to give yellow liquid was isolated 14.43g, yield 88.5%.
88.5% With trichlorophosphate; In toluene;Reflux; Dissolve 14.5g (0.1mol) <strong>[7752-72-9]4-hydroxy-5-chloro-6-methylpyrimidine</strong> in 50ml toluene solution,Under stirring, 50ml of phosphorus oxychloride was dropped into the reaction bottle, and the temperature was raised and the reaction was refluxed for 5-7 hours.After the reaction was monitored by TLC, toluene and excess phosphorus oxychloride were distilled off under reduced pressure.The reaction was poured into ice water with stirring, the aqueous phase was extracted with (3 × 50 ml) ethyl acetate, the organic phases were combined, dried over anhydrous magnesium sulfate, filtered and desolvated.The residue was separated by column chromatography (eluent was ethyl acetate and petroleum ether, volume ratio was 1: 5) to obtain a yellow liquid 14.43g, yield 88.5%.
88.5% With trichlorophosphate; In toluene;Reflux; Dissolve 14.5g (0.1mol) of <strong>[7752-72-9]4-hydroxy-5-chloro-6-methylpyrimidine</strong> in 50ml of toluene solution, drop 50ml of phosphorus oxychloride into the reverse bottle with stirring, and after heating up, reflux and react for 5-7 hours , After the reaction was monitored by TLC. Toluene and excess phosphorus oxychloride were distilled off under reduced pressure, the reaction was poured into ice water with stirring, the aqueous phase was extracted with (3 × 50 ml) ethyl acetate, the organic phases were combined, dried over anhydrous magnesium sulfate, filtered and desolvated . Column chromatography of the residue (eluent is ethyl acetate and petroleum ether (boiling range 60-90 C), volume ratio is 1: 5) to obtain a yellow liquid 14.43g, yield 88.5%.
With trichlorophosphate; In toluene;Reflux; General procedure: POCl3 (100 mL) was added dropwise to a solution of M-2 (0.36 mol)in toluene (150 mL), the mixture was refluxed for 3-5 h. The reactionmixture was concentrated under reduced pressure to remove tolueneand extra POCl3, and then poured into ice water. The water phase wasextracted with ethyl acetate (3 × 50 mL), the emerged organic phasewas successively washed with saturated sodium bicarbonate, dried overanhydrous magnesium sulfate, filtered and then concentrated underreduced pressure. The residue was purified through silica column togive M-3 as yellow liquid.

 

Historical Records

Technical Information

Categories

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[ 83942-10-3 ]

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