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Chemical Structure| 1078-28-0 Chemical Structure| 1078-28-0

Structure of 1078-28-0

Chemical Structure| 1078-28-0

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Product Details of [ 1078-28-0 ]

CAS No. :1078-28-0
Formula : C11H11NO
M.W : 173.21
SMILES Code : COC1=CC2=C(C=C1)N=C(C)C=C2
MDL No. :MFCD00006761
InChI Key :NAGJQQFMJKMXJQ-UHFFFAOYSA-N
Pubchem ID :70648

Safety of [ 1078-28-0 ]

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

Computational Chemistry of [ 1078-28-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 10
Fraction Csp3 0.18
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 53.2
TPSA ?

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

22.12 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.33
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

2.56
Log Po/w (WLOGP)?

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

2.55
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.

1.78
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

2.91
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.43

Water Solubility

Log S (ESOL):?

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

-3.03
Solubility 0.162 mg/ml ; 0.000933 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.

-2.67
Solubility 0.368 mg/ml ; 0.00213 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

-4.21
Solubility 0.0107 mg/ml ; 0.0000615 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately 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

Yes
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.

-5.54 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)

1.21

Application In Synthesis of [ 1078-28-0 ]

* 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 [ 1078-28-0 ]

[ 1078-28-0 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 92-55-7 ]
  • [ 1078-28-0 ]
  • (E)-6-Methoxy-2-[2-(5-nitrofuran-2-yl)vinyl]quinoline [ No CAS ]
YieldReaction ConditionsOperation in experiment
83% With acetic anhydride; at 150℃; for 30h; General procedure: A mixture of 2-methylquinoline (5a, 0.14 g, 1 mmol), <strong>[92-55-7](5-nitrofuran-2-yl)methylene diacetate</strong> (0.72 g, 3 mmol) and acetic anhydride (30 mL) was heated at 150 C for 30 h (TLC monitoring). After cooling, the solvent was removed in vacuo to provide the crude product, which was purified by flash column chromatography (FC, silica gel use CH2Cl2 as eluent) to give 6a (0.22 g, 81%) as a yellow solid.
  • 2
  • [ 1078-28-0 ]
  • [ 5780-66-5 ]
  • C16H13N3O [ No CAS ]
YieldReaction ConditionsOperation in experiment
85% With toluene-4-sulfonamide; In toluene; at 120℃; for 12h;Inert atmosphere; A solution of 6-methoxy-2-methylquinoline (100 mg, 0.57 mmol), p-toluenesulfonamide (98.85 mg, 0.57 mmol) and pyrazine-2-carbaldehyde (61.5 mg, 0.57 mmol) in toluene (0.5 mL) was refluxed at 120° C. for 12 h in a reaction tube under nitrogen. After the mixture was cooled to room temperature, the solvent was removed under reduced pressure. Then the concentrate was purified by column chromatography with EtOAc/DCM (1:2, v/v) on silica gel, affording TZ-23-12 (127 mg, 85percent). 1H-NMR (400 MHz, CDCl3): delta 8.73 (d, J=1.3 Hz, 1H), 8.61-8.48 (m, 1H), 8.41 (d, J=2.5 Hz, 1H), 7.99 (dd, J=15.6, 8.9 Hz, 2H), 7.81 (dd, J=70.7, 15.9 Hz, 2H), 7.56 (d, J=8.5 Hz, 1H), 7.44-7.29 (m, 1H), 7.02 (d, J=2.8 Hz, 1H), 3.90 (s, 3H). 13C NMR (101 MHz, CDCl3) delta 158.00, 152.10, 150.82, 144.45, 144.36, 144.25, 143.24, 135.23, 134.77, 130.93, 128.79, 128.40, 122.74, 120.91, 104.99, 55.53.
  • 3
  • [ 6563-13-9 ]
  • [ 2181-42-2 ]
  • [ 14300-14-2 ]
  • [ 1078-28-0 ]
YieldReaction ConditionsOperation in experiment
With pyrrolidine; potassium-t-butoxide; In tetrahydrofuran; at 80℃; under 760.051 Torr; for 16h; General procedure: A coupling reaction between <strong>[6563-13-9]6-methoxyquinoline N-oxide</strong> (1a) and trimethylsulfonium iodide (2a) was performed. The results are shown in Table 1.As a result of screening various bases and solvents, the use of KOtBu base in THF promotes the coupling of 1a and 2a to be redox-neutral ( redox-neutral) and the reductive C2-methylated products 3a and 3aa were found to give in good yields (71%).After further optimization, it was found that the use of pyrrolidine as an additional base promotes a high level of yield (91%) and selectivity (15:1 ratio) for the production of 3a (entry 6).From the control entry 9, it was confirmed that the combination of KOtBu and pyrrolidine was essential for the binding of 1a and 2a.In addition, as shown in entry 10, 3a was formed in 95% yield within 3 hours with high chemical selectivity (18: 1).Satisfyingly, this transformation proceeded under mild reaction conditions (40 C.) to afford 3a with a selectivity of 20:1 ratio in 92% yield (entry 11).In addition, as a result of carrying out this reaction on a scale of 1 g, 3a was obtained in 84% yield with almost the same chemical selectivity of 20:1 (entry 12).
 

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Technical Information

Categories

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