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Structure of 98349-25-8

Chemical Structure| 98349-25-8

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Product Details of [ 98349-25-8 ]

CAS No. :98349-25-8
Formula : C15H13F2NO3
M.W : 293.27
SMILES Code : O=C(C1=CN(C2CC2)C3=C(C=C(F)C(F)=C3)C1=O)OCC
MDL No. :MFCD01646378
InChI Key :QYGNYHKBMNUIJN-UHFFFAOYSA-N
Pubchem ID :9817544

Safety of [ 98349-25-8 ]

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

Computational Chemistry of [ 98349-25-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 21
Num. arom. heavy atoms 10
Fraction Csp3 0.33
Num. rotatable bonds 4
Num. H-bond acceptors 5.0
Num. H-bond donors 0.0
Molar Refractivity 72.97
TPSA ?

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

48.3 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.95
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

1.97
Log Po/w (WLOGP)?

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

3.57
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.

2.56
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

3.58
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.93

Water Solubility

Log S (ESOL):?

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

-2.99
Solubility 0.302 mg/ml ; 0.00103 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.

-2.61
Solubility 0.72 mg/ml ; 0.00246 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

-4.41
Solubility 0.0113 mg/ml ; 0.0000385 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

Yes
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.

-6.69 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

0.0
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<0.0
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)

2.37

Application In Synthesis of [ 98349-25-8 ]

* 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 [ 98349-25-8 ]

[ 98349-25-8 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 98349-25-8 ]
  • [ 93107-30-3 ]
YieldReaction ConditionsOperation in experiment
With sulfuric acid; sodium acetate; acetic acid; In water; Example 2 1500 g of ethyl 1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylate, 128.4 g of water, and 4500 g of acetic acid were introduced and 53 g of sulfuric acid were added. The mixture was heated at reflux for 4 hours. 2020 ml of distillate were then distilled off until a bottom temperature of 109 C. was reached. The suspension was then cooled to 80 C. and 2204 g of 4% strength by weight sodium acetate solution were added dropwise. The pH was then in the range 3 to 4. The mixture was then cooled to 20 C. and the solid was filtered off with suction. The. solid was washed with 2000 ml of water and dried in vacuo at 50 C. 1329 g of 1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid were isolated, which corresponds to a yield of 98%.
In hydrogenchloride; 1-Cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid A suspension of 4.1 g (13.3 mmol) of ethyl 1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylate in 150 ml of 6N hydrochloric acid was refluxed for six hours, then cooled to room temperature. The solids were filtered, washed with water and ether, and dried to give 3.2 g of the title compound, mp >300 C. The following compounds were prepared in a similar fashion:
With sulfuric acid; In water; acetic acid; EXAMPLE 10 1-Cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid A solution of 6,8 g of 1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, ethyl ester in a mixture of 46 ml of glacial acetic acid, 35 ml of water and 4.5 ml of concentrated sulfuric acid was refluxed for 1.5 hours. The resulting suspension was cooled in an ice bath, the solid collected, washed with cold water, dried and recrystallized from hot dimethylformamide, giving 5 g of the desired compound, mp 288-290 C.
With hydrogenchloride; water; acetic acid; for 2.5h;Reflux; Crude compound 1.3 (700 mg, 2.39 mmol, 1 eq) was refluxed with concentrated HC1 mL) and concentrated AcOH (13 mL) for 2.5 hours. The mixture was allowed tocool to room temperature, and the resulting precipitate was filtered, washed with water ( mL) and dried to give the crude product 1.4 mg, 90.4 % yield) as a white solid which was used in the successive reaction without further purification. 1H NMR (400 MHz, TFA-cl) 6 9.34 (ci, J = 3.53 Hz, 1H), 8.32 - 8.40 (m, 2H), 3.99 - 4.06 (m, 1H), 1.54 - 1.62 (m, 2H), 1.35 (br. 5., 2H); JR (umax/cm1) 1719, 1614, 1556, 1421, 1332, 1303, 1289, 1231, 1204, 1056, 1033, 1020, 891, 806, 778, 748, 719, 606; LC-MSRetention time 3.37 minutes, found 265.9 [M+H] calculated for C13H9F2N03266.22[M+H].
In sulfuric acid; A suspension of 7.85 g of 1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, ethyl ester in 220 ml of 2N sulfuric acid was heated at 100 C. overnight, then cooled in an ice bath. The solid was collected, washed with water and dried, giving 6.81 g of the desired compound, mp 292-293 C.

 

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