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Chemical Structure| 13223-43-3 Chemical Structure| 13223-43-3

Structure of 13223-43-3

Chemical Structure| 13223-43-3

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Product Details of [ 13223-43-3 ]

CAS No. :13223-43-3
Formula : C7H9N5O2
M.W : 195.18
SMILES Code : NC1=NN2C(OC)=CC(OC)=NC2=N1
MDL No. :MFCD09033220
InChI Key :SJEIPAUSEWIHJI-UHFFFAOYSA-N
Pubchem ID :11194901

Safety of [ 13223-43-3 ]

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

Computational Chemistry of [ 13223-43-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 9
Fraction Csp3 0.29
Num. rotatable bonds 2
Num. H-bond acceptors 5.0
Num. H-bond donors 1.0
Molar Refractivity 48.17
TPSA ?

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

87.56 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.61
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

0.36
Log Po/w (WLOGP)?

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

-0.27
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.

0.05
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

-0.8
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.19

Water Solubility

Log S (ESOL):?

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

-1.62
Solubility 4.68 mg/ml ; 0.024 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.

-1.76
Solubility 3.36 mg/ml ; 0.0172 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

-1.24
Solubility 11.2 mg/ml ; 0.0574 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

No
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.

-7.23 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)

2.61

Application In Synthesis of [ 13223-43-3 ]

* 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.

  • Upstream synthesis route of [ 13223-43-3 ]
  • Downstream synthetic route of [ 13223-43-3 ]

[ 13223-43-3 ] Synthesis Path-Upstream   1~3

  • 1
  • [ 102739-44-6 ]
  • [ 13223-43-3 ]
YieldReaction ConditionsOperation in experiment
91.5%
Stage #1: With hydroxylamine hydrochloride In ethanol at 60℃; for 0.5 h;
Stage #2: With triethylamine In ethanol for 5 h; Reflux
A solution of 3a (114.5 g,0.4 mol) and hydroxylamine hydrochloride (40.3 g, 0.58 mol) in EtOH (600 mL) was stirred vigorously for 0.5 h at 60 C, then triethylamine (58.7 g, 0.58 mol) was added dropwise into the mixture. The resultant mixture was refluxed for 5 h, then cooling to the room temperature. The white solid product of4a was collected by filtration and washed using 200 mL water, yield 71.4 g (91.5percent);
91.5% With hydroxylamine hydrochloride; triethylamine In ethanol at 60℃; for 5.5 h; Reflux In 1000mL equipped with a stirrer, thermometer, reflux condenser, droppingfunnel, 4-neck flask, was added 600mL ethanol, N- (4,6- dimethoxy-pyrimidin-2-yl) -N'-ethoxycarbonyl thiourea 114.5g (0.4mol), hydroxylamine hydrochloride 40.3g (0.58mol),heated to 60 , was added dropwise 58.7g (0.58mol) of triethylamine, 0.5H addition wascomplete, the reaction was refluxed 5H, until starting material N- ( after 4,6-dimethoxy-pyrimidin-2-yl) -N'-ethoxycarbonyl thiourea reaction was complete, cooled toroom temperature filtration and dried 200mL, 50 water washing was stirred 20min,filtered dried to give the product 71.4 g, a purity of 98.6percent, a yield of about 91.5percent.
82% With hydroxylamine hydrochloride; N-ethyl-N,N-diisopropylamine In ethanol 2.
Preparation of 2-amino-5,7-dimethoxy[1,2,4]-triazolo[1,5-a]pyrimidine
Ethyl N-[N'-(4,6-dimethoxypyrimidin-2-yl)-thiocarbamoyl]carbamate (0.50 g, 1.7 mmol) was mixed with ethanol (5 mL).
To this mixture was added hydroxylamine hydrochloride (0.12 g, 1.7 mmol) and diisopropylethylamine (0.30 mL, 1.7 mmol).
The resulting mixture was allowed to stir at room temperature.
After 2.5 hours, additional diisopropylethylamine (0.30 mL, 1.7 mmol) was added to the mixture.
After 48 hours the ethanol was removed in vacuo and the residue was partitioned between H2O and Et2O to give a powder.
The powder was filtered and dried to afford the product as a tan powder (0.27 g, 82percent).
mp 215-220° C. 1H NMR (DMSO-d6): δ 6.04 (s, 1H); 5.97 (bs, 2H); 4.04 (s, 3H).
References: [1] Heterocycles, 2016, vol. 92, # 5, p. 829 - 843.
[2] Patent: CN105399746, 2016, A, . Location in patent: Paragraph 0077-0078.
[3] Patent: US2002/111361, 2002, A1, .
  • 2
  • [ 36315-01-2 ]
  • [ 16182-04-0 ]
  • [ 13223-43-3 ]
YieldReaction ConditionsOperation in experiment
91.1%
Stage #1: at 78℃; for 5.33333 h; Heating / reflux
Stage #2: With hydroxyammonium sulfate In water; ethyl acetate at 71℃; Heating / reflux
Stage #3: With sodium carbonate In water; ethyl acetate at 71℃; for 7 h; Heating / reflux
One pot procedure for the synthesis of 2-amino-5,7-dimethoxy [1,2, 4] triazolopyrimidine (ADTP) from 2-amino-4,6-dimethoxypyrimidine (ADP) 11. 9 g (0.075 mol) ADP was dissolved in 68 g ethyl acetate. 11 g (0.0825 mol) ethoxycarbonyl isothiocyanate was added within 20 min. at 78°C (no exotherm). The mixture was stirred over 5 h at reflux (78-79°C). 49.2 g (0.075 mol) hydroxylammonium sulfate (25 percent solution in water) were added and the mixture heated to 71°C (reflux aceotrope). 50 g (0.1 mol) diluted caustic soda (2 mot/1) was added within 1 h to establish the pH from 1.3 to 6.5 and hold at 6.5-7. 0 (offgas C02 and H2S, slightly exotherm). The mixture was stirred over 6 h under reflux (71°C) for reaction completion. The mixture was cooled down over night to 20°C. The product (ADTP) was filtrated and washed 3 times with each 25 g water to remove the salt (Na content after first wash 0.42 percent, after second 0.20 percent, after third 0.025 percent). Finally the solid ADTP was dried. Yield : 91.1 percent in respect to ADP, purity 95.3 percent (quantitative HPLC assay).
References: [1] Patent: WO2005/63753, 2005, A1, . Location in patent: Page/Page column 6.
  • 3
  • [ 13223-25-1 ]
  • [ 13223-43-3 ]
References: [1] Organic Process Research and Development, 2006, vol. 10, # 6, p. 1167 - 1171.
 

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Technical Information

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