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Chemical Structure| 10201-71-5 Chemical Structure| 10201-71-5

Structure of 10201-71-5

Chemical Structure| 10201-71-5

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Product Details of [ 10201-71-5 ]

CAS No. :10201-71-5
Formula : C6H8N2O
M.W : 124.14
SMILES Code : NC1=NC=CC=C1OC
MDL No. :MFCD07374874
InChI Key :HNAYRVKSWGSQTP-UHFFFAOYSA-N
Pubchem ID :9920384

Safety of [ 10201-71-5 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P264-P270-P271-P280-P301+P312-P302+P352-P304+P340-P305+P351+P338-P330-P332+P313-P337+P313-P362-P403+P233-P405-P501

Computational Chemistry of [ 10201-71-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 6
Fraction Csp3 0.17
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 35.13
TPSA ?

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

48.14 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.35
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

0.48
Log Po/w (WLOGP)?

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

0.68
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.

-0.07
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

0.64
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.62

Water Solubility

Log S (ESOL):?

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

-1.34
Solubility 5.68 mg/ml ; 0.0458 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.

-1.06
Solubility 10.8 mg/ml ; 0.087 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

-1.75
Solubility 2.21 mg/ml ; 0.0178 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.

-6.72 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)

1.68

Application In Synthesis of [ 10201-71-5 ]

* 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 [ 10201-71-5 ]

[ 10201-71-5 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 10201-71-5 ]
  • [ 6914-71-2 ]
  • 1-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridine-2-yl)cyclopropanecarboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
58% Preparation of l-(8-methoxy-[l,2,41triazolo[l,5-a1pyridine-2-yl)cyclopropanecarboxylic acid (a compound of formula (VI))Half of the solution of 3-methoxypyridine-2-amine in methanol (80kg methanol solution containing 6.21kg substance, 50.0mol) was transferred to a reactor. The temperature of the solution was adjusted to 16-20°C, and hydroxylamine-O-sulfonic acid (6.21kg, 54.9mol) was added in two equal portions keeping the temperature below 30°C. The temperature of the solution was adjusted to 16-20°C, and l,8-diazabicyclo[5.4.0]undec- 7-ene (8.40kg, 55.2mol) was added using a pump over at least 60 minutes keeping the temperature below 30°C. The mixture was then stirred at approximately 38-42°C for 48 hours. A sample was withdrawn and concentrated to dryness, and NMR of the residue showed 75percent amination of the pyridine nitrogen. l,8-diazabicyclo[5.4.0]undec-7-ene (8.36kg, 54.9mol) was added using a pump over at least 60 minutes keeping the temperature below 30°C. Then dimethyl cyclopropane-1,1- dicarboxylate (15.80kg, 99.7mol) was added, and the mixture was heated to 65-70°C and stirred for at least 16 hours. The mixture was cooled to 20-25°C and sodium hydroxide (20percent solution in water, 75.0kg) was added over at least 60 minutes keeping the temperature below 40°C. The mixture was distilled at?40°C under vacuum to a final volume of 80L, 93.8kg of distillate was collected. LC-MS (Method B) showed full hydrolysis of the intermediate methyl l-(8-methoxy-[l,2,4]triazolo[l,5-a]pyridin-2- yl)cyclopropanecarboxylate to the title compound. The temperature of the mixture was adjusted to 20-25°C and water (46kg) and ethyl acetate (55.5kg) were added. The mixture was stirred for approximately 15 minutes, and then the phases were allowed to settle. The phases were separated and the water phase was extracted with another portion of ethyl acetate (55.5kg), and the phases were separated. The temperature of the water phase was adjusted to 20-25°C and 6M sulfuric acid (65.4kg) was added with cooling over at least 60 minutes keeping the temperature below 25°C, pH of the mixture was then The procedure above was repeated with the second half of the solution of 3-methoxy- pyridine-2-amine in methanol (80kg methanol solution), giving a second portion of the raw product of the title compound. A reactor was charged with water (124kg) and the two portions of raw product were added. The mixture was stirred for at least 30 minutes. The product was isolated by filtration, washed with water (25kg), and dried at elevated temperature under vacuum. Yield 5.48kg (24percent). ^-NMR conformed to NMR for the small batch of the title compound above. Assay by ^-NMR (DMSO-d5, method B): 102 wtpercent. A second crop of product was isolated from the mother liquors from the two portions of raw product by adjusting the pH to 2.5 - 3. The product was isolated by filtration and re- suspended in water. The product was isolated by filtration, washed with water and dried under vacuum. Yield 5.76kg (25percent). ^-NMR conformed to NMR for the small batch of the title compound above. Assay by ^-NMR (DMSO-d6, method B): 101 wtpercent.
 

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Technical Information

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