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Chemical Structure| 6960-17-4 Chemical Structure| 6960-17-4

Structure of 6960-17-4

Chemical Structure| 6960-17-4

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Product Details of [ 6960-17-4 ]

CAS No. :6960-17-4
Formula : C6H9N3O2
M.W : 155.16
SMILES Code : NC1=NC(OC)=NC=C1OC
MDL No. :MFCD20486065
InChI Key :XOJPOIGPYBYDJF-UHFFFAOYSA-N
Pubchem ID :250370

Safety of [ 6960-17-4 ]

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

Computational Chemistry of [ 6960-17-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.33
Num. rotatable bonds 2
Num. H-bond acceptors 4.0
Num. H-bond donors 1.0
Molar Refractivity 39.42
TPSA ?

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

70.26 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.67
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

0.13
Log Po/w (WLOGP)?

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

0.08
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.

-0.67
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

0.14
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.27

Water Solubility

Log S (ESOL):?

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

-1.16
Solubility 10.8 mg/ml ; 0.0699 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.

-1.16
Solubility 10.7 mg/ml ; 0.0689 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

-1.53
Solubility 4.54 mg/ml ; 0.0292 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.

-7.15 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)

2.51

Application In Synthesis of [ 6960-17-4 ]

* 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.

  • Upstream synthesis route of [ 6960-17-4 ]

[ 6960-17-4 ] Synthesis Path-Upstream   1~2

  • 1
  • [ 16182-04-0 ]
  • [ 6960-17-4 ]
  • [ 219715-62-5 ]
YieldReaction ConditionsOperation in experiment
70.4%
Stage #1: at 27 - 87℃;
Stage #2: at 40℃;
Stage #3: With hydroxylamine In water; toluene at 68 - 81℃;
Example 4
Preparation of 2-amino-5,8-dimethoxy[1,2,4]triazolo[1,5-c]pyrimidine (Ia)
To a 700 mL jacketed vessel equipped with a mechanical stirrer, a dual pH/temperature probe, a nitrogen inlet, and a reflux condenser was added sequentially 27.9 g (0.180 mol) of 4-amino-2,5-dimethoxypyrimidine followed by 165.4 g (0.207 mol) of 16.4 wt percent ethoxy carbonylisothiocyanate solution in toluene.
The reaction mixture was heated to gentle reflux (87 ° C.) for 7 h at which time liquid chromatographic (LC) analysis indicated ˜95percent conversion of starting 4-amino-2,5-dimethoxypyrimidine.
The reaction mixture was cooled to 27 ° C. and allowed to stand overnight.
The mixture was heated to 40° C. and then 114.2 g (6.34 mol) of deionized water was added to the mixture.
After heating to reflux (˜68° C.).
, 14.3 g (0.217 mol) of a 50 wt percent aqueous hydroxylamine solution was continuously added over a 2 h 15 min period via a peristaltic pump.
During the course of the amine addition, the reaction pH rose from 4.44 to 6.95.
After complete addition of hydroxylamine, the pump line was flushed with 4.8 g (0.266 mol) of deionized water, the reaction mixture was heated to 81° C., and then stirred an additional 3 h during which time the reaction pH naturally raised to 7.40.
The reaction mixture was cooled to ambient temperature (26° C.).
The reaction mixture was then suction transferred into a temporary holding vessel.
The reactor was washed with two 30 g portions of water.
These water washes were combined with the reaction mixture.
The combined mixture was suctioned filtered through a coarse Buchner funnel (filtration time about 30 seconds), and the filtrate was collected and filtered a second time through the cake.
A final displacement cake wash with ˜40 g of methanol was performed and the product was dried at 60° C. under vacuum (˜<10 mm Hg; 1333 Pa) to afford 25.37 g of 2-amino-5,8-dimethoxy[1,2,4]triazolo[1,5-c]pyrimidine as a light cream colored solid. NMR analysis (using benzyl acetate as an internal standard) indicated an 97.3percent purity of 2-amino-5,8-dimethoxy[1,2,4]triazolo[1,5-c]pyrimidine active which corresponds to a 70.4percent yield.
References: [1] Patent: US2014/81024, 2014, A1, . Location in patent: Paragraph 0027.
  • 2
  • [ 6960-17-4 ]
  • [ 219715-62-5 ]
References: [1] Patent: US2011/295003, 2011, A1, .
 

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Technical Information

Categories

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