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Chemical Structure| 29848-57-5

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Product Details of [ 29848-57-5 ]

CAS No. :29848-57-5
Formula : C7H5F2NO2
M.W : 173.12
SMILES Code : [O-][N+](=O)C1=CC=C(C=C1)C(F)F
MDL No. :MFCD16659620
InChI Key :RMHPWPAKPAVHTB-UHFFFAOYSA-N
Pubchem ID :640443

Safety of [ 29848-57-5 ]

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

Computational Chemistry of [ 29848-57-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.14
Num. rotatable bonds 2
Num. H-bond acceptors 4.0
Num. H-bond donors 0.0
Molar Refractivity 40.33
TPSA ?

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

45.82 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.33
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

2.63
Log Po/w (WLOGP)?

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

3.05
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.

2.61
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

0.55
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.03

Water Solubility

Log S (ESOL):?

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

-2.81
Solubility 0.269 mg/ml ; 0.00156 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.

-3.24
Solubility 0.099 mg/ml ; 0.000572 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

-2.38
Solubility 0.72 mg/ml ; 0.00416 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.

-5.49 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

2.0 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)

1.51

Application In Synthesis of [ 29848-57-5 ]

* 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 [ 29848-57-5 ]

[ 29848-57-5 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 555-16-8 ]
  • [ 29848-57-5 ]
YieldReaction ConditionsOperation in experiment
With diethylamino-sulfur trifluoride; In dichloromethane; at -70℃; To a mixture of 4-nitrobenzaldehyde (5.00 g, 33.10 mmol) in DCM (75 ml_) diethylaminosulfur trifluoride (6.40 g, 39.70 mmol) was added dropwise at -70 C. The mixture was stirred at the same temperature for 10 min. The cooling bath was removed and the mixture was stirred overnight. Concentrated aqueous NaHCC solution was added slowly to the mixture and the mixture was extracted with DCM (3 x 50 ml_). The combined organic layers were dried over anhydrous Na2S04, filtered and concentrated to dryness. The residue was purified by column chromatography (PE) to provide the title compound.
  • 2
  • [ 29848-57-5 ]
  • [ 114467-74-2 ]
  • 4
  • [ 5315-87-7 ]
  • [ 29848-57-5 ]
  • [ 555-16-8 ]
  • 5
  • [ 41159-02-8 ]
  • [ 29848-57-5 ]
  • 8
  • [ 500-11-8 ]
  • [ 29848-57-5 ]
YieldReaction ConditionsOperation in experiment
64% With Bis(1,5-cyclooctadiene)nickel(0); N,N,N,N,-tetramethylethylenediamine; In tetrahydrofuran; at 0 - 20℃; for 1h; General procedure: Bis (1,5-cyclooctadiene) nickel (1.4 mg, 0.005 mmol, 2.5 mol%),N, N?-tetramethylethylenediamine (0.6 mg, 0.005 mmol,2.5 mol%) in THF (1 mL)In addition to the THF solution of difluoroiodomethane (1.0-1.5 M, 0.20 mmol) in the resulting mixtureWas added at room temperature.Then cool down to 0 C,4- (Ethoxycarbonyl) phenylmagnesium bromide in THF(0.5M, 0.6 mL) was slowly added dropwise. Thereafter, the mixture was stirred at room temperature for 1 hour.After stopping the reaction, extract with ether,The ether layer is washed with brine,Dried over anhydrous magnesium sulfate.After filtration, the solvent was distilled off under reduced pressure,After filtration, the solvent was distilled off under reduced pressure,A crude product was obtained.The crude yield determined by NMR using trifluoromethylbenzene as an internal standard was 82%.The obtained crude product was purified using silica gel chromatography (hexane / ethyl acetate = 20/1) to obtain a colorless liquid target product (28.4 mg, 0.14 mmol, yield 71%).
  • 11
  • [ 29848-57-5 ]
  • [ 114467-81-1 ]
  • 12
  • [ 29848-57-5 ]
  • [ 114467-77-5 ]
  • 13
  • [ 29848-57-5 ]
  • [ 114467-86-6 ]
  • 14
  • [ 555-16-8 ]
  • 1-hydroxymethyl-3,3-dimethyl-norbornane-2<i>endo</i>-ol [ No CAS ]
  • [ 29848-57-5 ]
  • 15
  • Ethyl N-(p-difluoromethylphenyl)oxamide [ No CAS ]
  • [ 29848-57-5 ]
  • [ 555-16-8 ]
  • [ 4755-77-5 ]
  • 1-methyl-7-trifluoromethylquinoxaline-2(1H)-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
With HF; SF4; nitric acid; acetic anhydride; In ethanol; acetic acid; Those of the starting materials which are of the formula SPC10 are prepared by the following reaction scheme; SPC11 In a representative preparation, ethyl N-(4-difluoromethyl-2-nitrophenyl)oxamide was prepared as described below. p-Nitrobenzal fluoride (5 grams) (prepared by reaction of p-nitrobenzaldehyde with SF4 /HF) was hydrogenated over 200 mg. platinum oxide in 50 ml. of ethanol. The catalyst was removed by filtration and the ethanol, by evaporation. The residue was dissolved in 50 ml. of cold ether; to this solution was added a solution of ethyl oxalyl chloride (7 ml.) in 25 ml. of ether. The reaction mixture was stirred for 15 minutes, filtered, and evaporated to dryness. The residue, the desired ethyl N-(p-difluoromethylphenyl)oxamide product, was recrystallized from a mixture of ethanol and water, m.p. 110-114C. Ethyl N-(p-difluoromethylphenyl)oxamide (1 gram) was dissolved in 4 ml. of each of acetic acid and acetic anhydride and the mixture cooled to about 0-5C. Fuming nitric acid (1 ml.) mixed with acetic acid (2 ml.) was added portionwise to the cooled solution. An additional 1 ml. of fuming nitric acid was added one hour later. Two hours after the initial addition, the reaction mixture was poured into water, and the ethyl N-(4-difluoromethyl-2-nitrophenyl)oxamide product was collected, washed, and recrystallized from a mixture of ethanol and water, m.p. 113-115C. Those starting materials which are 1-methylquinoxalinones: SPC12 are prepared in accordance with the following procedures SPC13 The following preparation of 1-methyl-7-trifluoromethyl-2(1H)-quinoxalinone illlustrates the procedure.
  • 16
  • [ 1309-60-0 ]
  • [ 100-14-1 ]
  • [ 29848-57-5 ]
YieldReaction ConditionsOperation in experiment
With hydrogen fluoride; EXAMPLE 13 4-(Difluoromethyl)nitrobenzene from 4-(Chloromethyl)nitrobenzene STR14 The procedure of Example 1 was followed with 4-(chloromethyl)nitrobenzene(1.72 g, 0.01 mole), lead dioxide (7.2 g, 0.03 mole) and hydrogen fluoride (50 ml) for 22 hr at room temperature to give 1.68 g of crude product as a yellow oily solid.
  • 18
  • [ 206360-56-7 ]
  • [ 29848-57-5 ]
YieldReaction ConditionsOperation in experiment
79% With potassium fluoride; In N,N-dimethyl-formamide; at 170℃; for 12h;Inert atmosphere; Accordance with the above scheme, the 2-neck tube 2,2-difluoro-2-(4-nitrophenyl)acetic acid (Compound 4b; 65.1 mg, 0.3 mmol), potassium fluoride (87.2 mg, 1.5 mmol), DMF (1.2 mL ) were placed, under a nitrogen atmosphere and stirred for 12 hours at 170 C.. The reaction mixture was extracted with ethyl acetate, washed with water, and dried over anhydrous sodium sulfate. Ethyl acetate was distilled off under reduced pressure and purified by silica gel column chromatography to give 1-(difluoromethyl)-4-nitrobenzene (compound 5b) was obtained in 79% yield
  • 19
  • 2,2-difluoro-2-(4-nitrophenyl)acetic acid ethyl ester [ No CAS ]
  • [ 29848-57-5 ]
  • 20
  • difluoromethyl copper [ No CAS ]
  • [ 100-01-6 ]
  • [ 29848-57-5 ]
  • 21
  • [ 456-27-9 ]
  • [ 86340-78-5 ]
  • [ 29848-57-5 ]
  • 23
  • [ 555-16-8 ]
  • [ 500-11-8 ]
  • [ 29848-57-5 ]
  • 24
  • [ 636-98-6 ]
  • [bis(difluoromethyl)zinc(dmpu)2] [ No CAS ]
  • [ 29848-57-5 ]
  • 25
  • [ 636-98-6 ]
  • C8H18F4N2Zn [ No CAS ]
  • [ 29848-57-5 ]
  • 26
  • C8H18F4N2Zn [ No CAS ]
  • [ 586-78-7 ]
  • [ 29848-57-5 ]
  • 27
  • C8H18F4N2Zn [ No CAS ]
  • [ 100-00-5 ]
  • [ 29848-57-5 ]
  • 28
  • [ 636-98-6 ]
  • C20H28N2O4*CHF2Zn [ No CAS ]
  • [ 29848-57-5 ]
YieldReaction ConditionsOperation in experiment
8% With 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; copper(I) thiophene-2-carboxylate; at 20℃; for 48h; A test tube equipped with a stirrer was charged with difluoromethylzinc · 1,2-diamine complex (CF 2 HZn · N, N-bis (2,4-dimethoxybenzyl) ethane-1,2-diamine) (0.1 mmol), 4-nitroiodobenzene (25 mg, 0.1 mmol), copper thiophene- 10 mg, 0.1 mmol) and DMPU (1 mL), and the reaction was carried out at room temperature for 48 hours, then 1 M hydrochloric acid (5 mL) was added to stop the reaction. Diethyl ether (15 mL) was added thereto, the organic layer was separated, and the aqueous layer was extracted twice with diethyl ether (10 mL). Thereafter, all the organic layers were mixed, washed with saturated brine, dried over sodium sulfate, and the solvent was distilled off under reduced pressure. To the mixture obtained in this step, benzotrifluoride (BTF) was added as an internal standard substance and analyzed by FNMR, and it was confirmed that the yield of the target product was 8%. From the resulting mixture, 4-difluoronitrobenzene was separated and purified by column chromatography and identified by HNMR and FNMR
  • 29
  • [ 636-98-6 ]
  • C28H37CuF2N2(1+) [ No CAS ]
  • [ 29848-57-5 ]
  • 30
  • [ 19479-80-2 ]
  • [ 29848-57-5 ]
  • 31
  • [ 19479-80-2 ]
  • [ 500-11-8 ]
  • [ 29848-57-5 ]
  • [ 555-16-8 ]
  • 33
  • [ 636-98-6 ]
  • C7H17F2IN2Ni [ No CAS ]
  • [ 29848-57-5 ]
  • 35
  • [bis(difluoromethyl)zinc(dmpu)2] [ No CAS ]
  • [ 122-04-3 ]
  • [ 29848-57-5 ]
 

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