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Chemical Structure| 20348-23-6

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Product Details of [ 20348-23-6 ]

CAS No. :20348-23-6
Formula : C7H8N2O
M.W : 136.15
SMILES Code : C1COC2=CC=CN=C2N1
MDL No. :MFCD09025907
InChI Key :QQVXDMFULJVZLA-UHFFFAOYSA-N
Pubchem ID :13196538

Safety of [ 20348-23-6 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302+H312+H332-H315-H319-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 20348-23-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.29
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 40.86
TPSA ?

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

34.15 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.44
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

0.91
Log Po/w (WLOGP)?

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

0.31
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.

0.28
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

1.43
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.87

Water Solubility

Log S (ESOL):?

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

-1.7
Solubility 2.71 mg/ml ; 0.0199 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.

-1.21
Solubility 8.34 mg/ml ; 0.0613 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

-2.34
Solubility 0.627 mg/ml ; 0.0046 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.

-6.48 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)

2.18

Application In Synthesis of [ 20348-23-6 ]

* 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 [ 20348-23-6 ]

[ 20348-23-6 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 20348-09-8 ]
  • [ 20348-23-6 ]
YieldReaction ConditionsOperation in experiment
85% a) 3,4-Dihydro-2H-pyrido[3,2-&][l,4]oxazine; To an ice-cold solution of 4H-rhoyrido[3,2-][l,4]oxazin-3-one (5.00 g, 33.3 mmol) in TetaF (40 mL) was added lithium aluminum hydride (66.6 mL of a 1.0 M solution in TetaF, 66.6 mmol). Following the addition, the solution was heated to reflux. After 18 h, the solution was cooled to 00C and quenched the reaction with H2O (4 mL) followed by NaOH (4 mL, 15%) and H2O (10 mL). The resulting slurry was filtered over Celite and the filtrate concentrated to give the title compound (3.87 g, 85%) as a blue-gray powder: 1H NMR (500 MHz, OMSO-d6) delta 7.53 (dd, J= 4.5, 1.0 Hz, IH), 6.90-6.89 (m, IH), 6.61 (br s, IH), 6.44 (dd, J= 8.0, 3.0 Hz, IH), 4.08 (t, J= 4.5 Hz, 2H), 3.39-3.36 (m, 2H); MS (ESI) m/e 31 (M + eta)
79% With sodium hydroxide; LiAlH4; In tetrahydrofuran; a) 3,4-Dihydro-2H-pyrido[3,2-b]-1,4-oxazine To a suspension of 2H-pyrido[3,2-b]-1,4-oxazin-3(4H)-one (2.0 g, 13.3 mmole) in dry THF (40 mL) was added a solution of LiAlH4 in THF (1.0 M, 26.6 mL, 26.6 mmole) slowly at 0C. After 1 hr the mixture was quenched with 2.0 M NaOH until a solid formed. The mixture was dried (MgSO4), filtered, and concentrated under reduced pressure to give the title compound (1.44 g, 79%) as a white solid which was sufficiently pure for use in the next step: MS (ES) m/e 137 (M + H)+.
With sodium hydroxide; In tetrahydrofuran; water; Step 1 Production of 3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine Lithium aluminum hydride (2 g) was suspended in tetrahydrofuran (80 mL), and <strong>[20348-09-8]4H-pyrido[3,2-b][1,4]oxazin-3-one</strong> (3.956 g) was added under ice-cooling by small portions. After heating under reflux for 2 hrs, water (2 mL), 15% aqueous sodium hydroxide (2 mL) and water (6 mL) were successively added under ice-cooling, and the mixture was stirred at room temperature. The mixture was dried over anhydrous sodium sulfate. The solvent was evaporated, and the residue was purified by silica gel chromatography (n-hexane-ethyl acetate=1:9) to give the title compound (3.407 g) as a white solid.
Step 1 Production of 3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine Lithium aluminum hydride (2 g) was suspended in tetrahydrofuran (80 mL), and <strong>[20348-09-8]4H-pyrido[3,2-b][1,4]oxazin-3-one</strong> (3.956 g) was added under ice-cooling by small portions. After heating under reflux for 2 hrs, water (2 mL), 15% aqueous sodium hydroxide (2 mL) and water (6 mL) were successively added under ice-cooling, and the mixture was stirred at room temperature. The mixture was dried over anhydrous sodium sulfate. The solvent was evaporated, and the residue was purified by silica gel chromatography (n-hexane-ethyl acetate=1:9) to give the title compound (3.407 g) as a white solid.
Step 1 Production of 3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine Lithium aluminum hydride (2 g) was suspended in tetrahydrofuran (80 mL), and <strong>[20348-09-8]4H-pyrido[3,2-b][1,4]oxazin-3-one</strong> (3.956 g) was added under ice-cooling by small portions. After heating under reflux for 2 hrs, water (2 mL), 15% aqueous sodium hydroxide (2 mL) and water (6 mL) were successively added under ice-cooling, and the mixture was stirred at room temperature. The mixture was dried over anhydrous sodium sulfate. The solvent was evaporated, and the residue was purified by silica gel chromatography (n-hexane-ethyl acetate=1:9) to give the title compound (3.407 g) as a white solid.

  • 2
  • [ 20348-23-6 ]
  • [ 252742-72-6 ]
  • C10H11N5O2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
36% A solution of 33A (0.105 g 0.77 mmol) in DMF (5 mL) was treated with KN(SiMe3)2 (0.5 M/toluene, 1.8 mL, 0.93 mmol), stirred at 0° C. for 20 min, and then treated with 33B (0.155 g 1.16 mmol, Tetrahedron Letters 2000, 41, 8661). The reaction was warmed to 20° C., stirred 2 h, and concentrated. The residue was then treated with 0.5 N NaOH (10 mL) and washed with CH2Cl2 (3.x.). The aqueous layer was concentrated and subjected to chromatography (20-80percent EtOAc/hexanes) to provide 33 as a white solid (0.065 g, 36percent). LMCS m/z 234 (MH+).
  • 3
  • [ 959992-62-2 ]
  • [ 20348-23-6 ]
  • 4
  • [ 959992-62-2 ]
  • [ 20348-23-6 ]
  • 6-(dimethoxymeth-13C-yl)-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine [ No CAS ]
 

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Technical Information

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