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Chemical Structure| 1079843-62-1 Chemical Structure| 1079843-62-1

Structure of 1079843-62-1

Chemical Structure| 1079843-62-1

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Product Details of [ 1079843-62-1 ]

CAS No. :1079843-62-1
Formula : C12H14F2N2O3
M.W : 272.25
SMILES Code : O=C(OC(C)(C)C)NNC(C1=CC(F)=CC=C1F)=O
MDL No. :MFCD23700206
Boiling Point : No data available
InChI Key :PAPCXRVVAHZZHH-UHFFFAOYSA-N
Pubchem ID :66806144

Safety of [ 1079843-62-1 ]

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

Computational Chemistry of [ 1079843-62-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 19
Num. arom. heavy atoms 6
Fraction Csp3 0.33
Num. rotatable bonds 6
Num. H-bond acceptors 5.0
Num. H-bond donors 2.0
Molar Refractivity 63.1
TPSA ?

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

67.43 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.28
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

2.3
Log Po/w (WLOGP)?

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

2.97
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.

2.91
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

1.75
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.44

Water Solubility

Log S (ESOL):?

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

-2.81
Solubility 0.417 mg/ml ; 0.00153 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.

-3.35
Solubility 0.121 mg/ml ; 0.000443 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

-3.91
Solubility 0.0336 mg/ml ; 0.000124 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

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.

-6.33 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)

2.53

Application In Synthesis of [ 1079843-62-1 ]

* 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 [ 1079843-62-1 ]

[ 1079843-62-1 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 870-46-2 ]
  • [ 2991-28-8 ]
  • [ 1079843-62-1 ]
YieldReaction ConditionsOperation in experiment
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride;dmap; In tetrahydrofuran; N,N-dimethyl-formamide; at 20℃; for 3h; To a solution of 5.Og (31.6 mmol) of <strong>[2991-28-8]2,5-difluorobenzoic acid</strong> (1-1) in 2OmL of 1: 1 THF/DMF was added 4.39g (33.2 mmol) of t-butylcarbazate, 6.67g (34.8 mmol) of EDCI, and 50 mg of DMAP. After stirring for 3h at room temperature, the reaction was dumped into ice water and extracted three times with ether. The combined organic phases were washed two times with 10percent citric acid, two times with saturated NaHCO3, once with water, once with brine, and then dried over MgSO4. Concentration by rotary evaporation provided the BOC-protected acyl hydrazine as a white solid. To a solution of 1.5g (5.5 mmol) of this material in 20 mL of CH2Cl2, cooled to 00C, was added 10 mL of trifluoroacetic acid, and the resultant mixture was allowed to stir for 2 h at that temperature. The volatiles were removed by rotary evaporation, the residue was partitioned between EtOAc and aqueous NaHCO3, the layers were separated, and the aqueous phase was extracted two more times with EtOAc. The combined organic phases were washed twice with saturated NaHCO3, brine, dried over Na2SO4, and concentrated to provide 663mg (3.85 mmol) of 2,5-difluorobenzohydrazide (1-2) as a white solid. This material was dissolved in 30 mL of EtOH, and then 1.5 mL of HOAc was added, followed by 390 muL (3.85 mmol) of benzaldehyde. After stirring for Ih at room temperature, the solvents were removed by rotary evaporation, and the residue was triturated with Et2O to provide the imine as a white powder. A portion of this imine (225mg, 0.86 mmol) was dissolved in 3 mL of acetic anhydride and heated at 125 0C for 2h After cooling to room temperature, the volatiles were removed by rotary evaporation, the residue was dissolve in EtOAc, washed twice with saturated NaHCO3, water, dried over Na2SO4, and concentrated. The residue was then purified by column chromatography with a gradient of EtOAc in hexanes to provide (1-3) as a white solid. IH NMR (500 MHz, CDC13): delta 7.6 -7.4 (m, 6H), 7.2 (m, 2H), 7.1 (s, IH), 2.4 (s, 3H) ppm. HRMS (ES) calc'd M + H for C16H12F2N2O2: 303.0940; found 303.0926.
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride;dmap; In tetrahydrofuran; N,N-dimethyl-formamide; for 16h; Step B: Preparation of <strong>[2991-28-8]2,5-difluorobenzoic acid</strong> hydrazide: To a solution of<strong>[2991-28-8]2,5-difluorobenzoic acid</strong> (3.5 g, 22 mmol) in THF/DMF (20 mL/20 mL) was added EDCI (4.7 g, 24 mmol), DMAP (50 mg) and NH2NHBoC (3.07 g, 23.2 mmol). After stirring for 16 hours, the reaction was quenched with water (30 mL) and diluted with EtOAc (30 mL). The organic layer was then washed with HCl (0.5 M, 20 mL), saturated NaHCO3 (20 mL), and brine (20 mL). The organic layer was then dried over Na2SO4, filtered and concentrated under reduced pressure to afford the crude Boc-protected product, which was then dissolved in DCM (60 mL) at 0 °C. TFA (50 mL) was added to the above DCM solution. After stirring for 2 hours, the reaction mixture was concentrated and the residue was dissolved in DCM (60 mL). The solution was washed with saturated NaHCO3 (40 mL) and dried over Na2SO4, filtered and concentrated under reduced pressure to afford the desired crude product.
 

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