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Chemical Structure| 38427-94-0

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Product Details of [ 38427-94-0 ]

CAS No. :38427-94-0
Formula : C10H14N2O2
M.W : 194.23
SMILES Code : O=C(OC(C)(C)C)NC1=NC=CC=C1
MDL No. :MFCD03411622
InChI Key :ORUGTGTZBRUQIT-UHFFFAOYSA-N
Pubchem ID :11206349

Safety of [ 38427-94-0 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H317
Precautionary Statements:P280

Computational Chemistry of [ 38427-94-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 6
Fraction Csp3 0.4
Num. rotatable bonds 4
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 54.48
TPSA ?

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

51.22 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.11
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

2.0
Log Po/w (WLOGP)?

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

2.24
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.

1.24
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

1.12
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.74

Water Solubility

Log S (ESOL):?

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

-2.36
Solubility 0.853 mg/ml ; 0.00439 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.

-2.7
Solubility 0.386 mg/ml ; 0.00199 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

-2.98
Solubility 0.204 mg/ml ; 0.00105 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.

-6.06 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)

2.23

Application In Synthesis of [ 38427-94-0 ]

* 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 [ 38427-94-0 ]

[ 38427-94-0 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 504-29-0 ]
  • [ 24424-99-5 ]
  • [ 6268-43-5 ]
  • [ 38427-94-0 ]
  • 2
  • [ 38427-94-0 ]
  • [ 863753-35-9 ]
YieldReaction ConditionsOperation in experiment
Under a nitrogen atmosphere, a solution of tert-butyl iV-(2-ρyridyl)carbamate (15.71 g, 80.9 mmol) and iV.ΛζN'.N'-tetramethylethylenediamine (TMEDA) (25.3 g, 218 mmol) in THF (400 mL) was cooled to -78 0C. M-Butyllithium (81 mL of a 2.5 M solution in hexanes) was added dropwise over a period of 20 minutes. The solution was stirred for ten minutes, and then the addition funnel was rinsed with additional THF (20 mL). The solution was warmed to -6 0C, stirred for two hours, and cooled again to -78 0C. Triisopropyl borate (57.7 g, 307 mmol) was added over a period often minutes. The resulting solution was warmed to 00C and then poured into saturated aqueous ammonium chloride (500 mL). A yellow solid formed and was stirred with diethyl ether (300 mL), isolated by filtration, washed with diethyl ether and water, and air-dried overnight to provide 2-ført-butoxycarbonylamino-3-pyridylboronic acid as a yellow solid.
Manufacturing Example 1-7-22-N-butoxycarbonyl-3-pyridineboronic acid; A tetrahydrofuran solution (400 mL) of pyridin-2-yl-carbamic acid tert-butyl ester (16 g) described in Manufacturing Example 1-7-1 and N,N,N',N'-tetramethylethylenediamine (25 g) was cooled to -70 C., n-butyl lithium (78 mL, 2.64M heptane solution) was then added dropwise over a period of 1 hour, which was stirred for 10 minutes. This mixture was warmed to a temperature between -10 C. and -6 C., which was stirred for 2 hours at that temperature. The solution was again cooled to -70 C., and triisobutyl borate (58 g) was added dropwise over a period of 1 hour. This mixture was warmed to 0 C., and then a saturated ammonium chloride aqueous solution was added thereto. Ether was added to the yellow solid thus produced, which was stirred, and the solid was then collected by filtration and washed with ether and water. This solid was dried under a reduced pressure, so as to obtain the title compound (14 g).1H-NMR spectrum (DMSO-d6) δ (ppm): 1.32-1.41 (9H, m), 6.80-6.84 (1H, m), 7.95-8.13 (2H, m).
A solution of pyridin-2-yl-carbamic acid tert-butyl ester described in Preparation Example 4-1-1 (16 g) and N,N,N',N'-tetramethyl ethylenediamine (25 g) in tetrahydrofuran (400 mL) was cooled to -70 C., n-butyl lithium (78 mL, 2.64M heptane solution) was then added thereto dropwise over one hour, and stirred for 10 minutes. This mixture was heated to between -10 C. and -6 C., and stirred at this temperature for two hours. Again, this solution was cooled to 70 C., and triisobutyl borate (58 g) was added thereto dropwise over one hour. This mixture was heated to 0 C., then, a saturated aqueous ammonium chloride was added thereto. To the produced yellow solid was added ether, and stirred, and then, a solid was recovered by filtration and washed with ether and water. This solid was in vacuo to obtain the title compound (14 g). 1H-NMR Spectrum (DMSO-d6) δ (ppm): 1.32-1.41 (9H, m), 6.80-6.84 (1H, m), 7.95-7.8.13 (2H, m).
  • 3
  • [ 13195-76-1 ]
  • [ 38427-94-0 ]
  • [ 863753-35-9 ]
YieldReaction ConditionsOperation in experiment
Manufacturing Example 2-7-2 2-N-t-butoxycarbonyl-3-pyridineboronic acid; A solution of tetrahydrofuran (400 mL) of pyridin-2-yl-carbamic acid tert-butyl ester (16 g) described in Manufacturing Example 2-7-1 and N,N,N',N'-tetramethylethylene diamine (25 g) was cooled to -70 C., n-butyl lithium (78 mL, 2.64 M heptane solution) was added dropwise for 1 hour, and the mixture was stirred for 10 minutes. This mixture was then warmed to between -10 C. and -6 C., and stirred at that temperature for 2 hours. The solution was then cooled again to -70 C., and triisobutyl borate (58 g) was added dropwise for 1 hour. The mixture was warmed to 0 C., and saturated aqueous ammonium chloride solution was added thereto. To the resulting yellow solids was added ether and then stirred, and the solids were filtered out and washed with ether and water. The solids were dried under a reduced pressure to obtain the title compound (14 g).1H-NMR Spectrum (DMSO-d6) δ (ppm): 1.32-1.41 (9H, m), 6.80-6.84 (1H, m), 7.95-7.8.13 (2H, m).
Manufacturing Example 1-7-2 2-tert-butoxycarbonylamino-3-pyridineboronic acid A solution of tetrahydrofuran (400 mL) of pyridin-2-yl-carbamic acid tert-butyl ester (16 g) described in Manufacturing Example 1-7-1 and N,N,N',N'-tetramethylethylene diamine (25 g) was cooled to -70 C., n-butyl lithium (78 mL, 2.64 M heptane solution) was added dropwise for 1 hour, and the mixture was stirred for 10 minutes. This mixture was then warmed to between -10 C. and -6 C., and stirred at that temperature for 2 hours. The solution was then cooled again to -70 C., and triisobutyl borate (58 g) was added dropwise for 1 hour. The mixture was warmed to 0 C., and saturated aqueous ammonium chloride solution was added thereto. To the resulting yellow solids was added ether and then stirred, and the solids were filtered and washed with ether and water. The solids were dried under a reduced pressure to obtain the title compound (14 g). 1H-NMR Spectrum (DMSO-d6) δ (ppm): 1.32-1.41 (9H, m), 6.80-6.84 (1H, m), 7.95-7.8.13 (2H, m).
  • 4
  • [ 23784-96-5 ]
  • [ 38427-94-0 ]
  • tert-butyl [(5-chlorothiophen-2-yl)methyl](pyridin-2-yl)carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
89% To the reaction flask was added tert-butyl pyridin-2-ylcarbamate (0.7 g, 3.6 mmol), DMF (10 mL), and sodium hydride (0.32 g, 8 mmol, 60%).Stir at room temperature for 20 minutes, cool to 0 C in an ice bath.2-Chloro-5-chloromethylthiophene (0.6 g, 3.6 mmol) in DMF (5 mL) was slowly added dropwise.Stir at room temperature overnight.Ethyl acetate (100 ml) and water (50 ml) were added to the mixture. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, and evaporated. Washing liquid: ethyl acetate: petroleum ether = 1:5), 1 g of butter was obtained, yield: 89%.
 

Historical Records

Technical Information

Categories

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