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Chemical Structure| 37131-89-8 Chemical Structure| 37131-89-8

Structure of 37131-89-8

Chemical Structure| 37131-89-8

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Product Details of [ 37131-89-8 ]

CAS No. :37131-89-8
Formula : C5H2Cl2N2O2
M.W : 192.99
SMILES Code : ClC1=NC=C(C(=N1)Cl)C(=O)O
MDL No. :MFCD09999133
InChI Key :IVIHUCXXDVVSBH-UHFFFAOYSA-N
Pubchem ID :21941896

Safety of [ 37131-89-8 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Computational Chemistry of [ 37131-89-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 4.0
Num. H-bond donors 1.0
Molar Refractivity 39.01
TPSA ?

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

63.08 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.03
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

1.65
Log Po/w (WLOGP)?

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

1.48
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.

0.42
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

1.64
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.24

Water Solubility

Log S (ESOL):?

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

-2.41
Solubility 0.745 mg/ml ; 0.00386 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.

-2.59
Solubility 0.498 mg/ml ; 0.00258 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

-2.26
Solubility 1.06 mg/ml ; 0.00547 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.

-6.31 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.

0.56

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)

1.61

Application In Synthesis of [ 37131-89-8 ]

* 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 [ 37131-89-8 ]

[ 37131-89-8 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 23945-44-0 ]
  • [ 37131-89-8 ]
YieldReaction ConditionsOperation in experiment
65% With N,N-diethylaniline; trichlorophosphate; In N,N-dimethyl-formamide; at 90℃; for 2.66667h;Under cold conditions; To 10.0 g (64.06 mmol) of uracil-5-carboxylic acid (Aldrich Chemical Company) partially dissolved in 20 mL of DMF are added, under cold conditions, 59.7 mL (0.64 mol) of phosphorus oxychloride and 10.3 mL (64.7 mmol) of N,N-diethylaniline, and the mixture is then heated at 90° C. for 2 hours 40 minutes.After cooling to room temperature and evaporating off half the excess POCl3, the medium is poured onto ice and then extracted with ether.The ether phases are combined, dried over sodium sulfate, filtered and concentrated under vacuum. 8.1 g (41.97 mmol) of 2,4-dichloro-5-pyrimidinecarboxylic acid are obtained in a yield of 65percent.
With N,N-dimethyl-aniline; trichlorophosphate; at 110℃; for 4h;Cooling with ice; To a 25 ml three-necked flask was added uracil-5-carboxylic acid (1 g, 6.4 mmol)N, N-dimethylaniline (1.09 g, 9. 0 mmol) was added dropwise to a solution of phosphorus oxychloride (9.83 g, 64. lmmol) under ice-cooling.After the dropwise addition, the ice bath was heated to 110 ° C for 4 hours. After the reaction solution was cooled, it was slowly added to the ice water for quenching.The aqueous phase was extracted with ethyl acetate and the organic phase was washed twice with water, once with saturated brine, dried over anhydrous sodium sulfate and concentrated to give 960 mg of crude oil as an oil, 2,4-dichloro-5-pyrimidinecarboxylic acid Purification is used directly for the next step
  • 2
  • [ 2972-52-3 ]
  • [ 37131-89-8 ]
YieldReaction ConditionsOperation in experiment
93% With water; In diethyl ether; at 35℃; for 1h; To a solution of 9 g (42.8 mmol) of 2,4-dichloro-5-pyrimidinecarboxylic acid chloride (Manchester Organics Limited) in 60 mL of ether are added 10 mL of water and the reaction mixture is stirred vigorously at 35 C. for 1 hour. After addition of ether and separation of the phases by settling, the organic phase is dried over Na2SO4, filtered and concentrated under vacuum. 7.7 g of a colourless oil that solidifies rapidly in air, and which is used immediately in the following step, are obtained. Yield=93%.
With water; In tetrahydrofuran; at 20℃; for 0.83h; To a solution of the <strong>[2972-52-3]2,4-dichloropyrimidine-5-carbonyl chloride</strong> (24 mmol) in THF (24 ml) is added H2O (0.64 ml) at room temperature. The reaction mixture is stirred at room temperature for 0.83 h and then diluted with HaO. The mixture is extracted with AcOEt. The organic extracts are washed with brine, dried over Na2SO4, filtered, and concentrated in vacua to give the crude titled compound; 1H NMR (CDCI3) 5 6.80 (brs, 1H), 9.18 (s, 1H).
  • 3
  • [ 37131-89-8 ]
  • [ 2972-52-3 ]
YieldReaction ConditionsOperation in experiment
90% With thionyl chloride; at 80℃; for 4h; To a 50 ml three-necked flask was added successively the crude product (0.6 g, 3.1 mmol) in the previous step,Thionyl chloride (10 ml) and heated to 80 C for 4 hours.Concentrated to dryness under reduced pressure to give 0.6 g of 2,4-dichloro-5-pyrimidinecarboxylic acid chloride in a yield of 90%
With oxalyl dichloride; N,N-dimethyl-formamide; In dichloromethane; at 20℃; for 1h; To a solution of 2,4-dichloropyrimidine-5-carbonyl chloride(100 mg, 0.47 mmol) in DCM (10 mL) added ammonium thiocyanate(54 mg, 0.71 mmol, 1.5 equiv) dropwise under stirring. A dropof PEG-400 was added to the suspension, it was then stirred atroom temperature for 20 min. After consumption of the startingmaterial, 1-(cyclohexylmethyl)piperazine (86 mg, 0.47 mmol) wasadded. It was then stirred for 1 h at room temperature. The reactionmixture was then diluted with water (30 mL) and extracted withDCM (20 mL 3). The organic extracts were dried over anhydrousMgSO4 and concentrated under reduced pressure. The residue waspurified by column chromatography on silica gel to afford compoundB02 as a white solid (159 mg, yield 89%): EtOAc-PET (1:3,Rf 0.27); 1H NMR (400 MHz, CDCl3) d 9.36 (s, 1H), 4.17 (br, 2H),3.74 (br, 2H), 2.57 (s, 4H), 2.21 (s, 2H), 1.81e1.73 (m, 6H), 1.51 (br,1H), 1.35e1.23 (m, 2H), 0.92e0.88 (m, 2H); 13C NMR (151 MHz,CDCl3) d 167.3, 166.6, 162.3, 161.0, 160.0, 115.9, 65.0, 53.0, 52.8, 47.0,46.6, 35.0, 31.6, 26.7, 26.0; HRMS (CI) m/z [MH] calcd forC17H23ClN5OS, 380.1306; found, 380.1317.
With thionyl chloride;Reflux; To 2,4-dichloropyrimidine-5-carboxylic acid (1 g, 5.1817 mmol) was added thionyl chloride (13.120 g, 8 mL, 110.28 mmol) and the resulting suspension was refluxed overnight. The reaction mixture was concentrated under reduced pressure to provide 2,4- dichloropyrimidine-5-carbonyl chloride (1.31 g, 114%) 1H NMR (400 MHz, CDCl3) d 9.26 (s, 1H).
 

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Technical Information

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