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Chemical Structure| 3819-88-3 Chemical Structure| 3819-88-3

Structure of 3819-88-3

Chemical Structure| 3819-88-3
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Product Details of [ 3819-88-3 ]

CAS No. :3819-88-3
Formula : C6H3FINO2
M.W : 267.00
SMILES Code : O=[N+](C1=CC(I)=CC(F)=C1)[O-]
MDL No. :MFCD00007219
InChI Key :MXPYCSFCKXSPAB-UHFFFAOYSA-N
Pubchem ID :259086

Safety of [ 3819-88-3 ]

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

Computational Chemistry of [ 3819-88-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 47.94
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.

1.68
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

2.5
Log Po/w (WLOGP)?

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

2.76
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.

3.04
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

1.09
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.21

Water Solubility

Log S (ESOL):?

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

-3.41
Solubility 0.104 mg/ml ; 0.000391 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.

-3.11
Solubility 0.208 mg/ml ; 0.00078 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

-3.01
Solubility 0.262 mg/ml ; 0.000982 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

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.

-6.15 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

3.0 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)

2.45

Application In Synthesis of [ 3819-88-3 ]

* 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 [ 3819-88-3 ]

[ 3819-88-3 ] Synthesis Path-Downstream   1~5

  • 1
  • [ 3819-88-3 ]
  • [ 660-49-1 ]
YieldReaction ConditionsOperation in experiment
91% With tin(II) chloride dihdyrate; In ethanol; for 1.5h;Reflux; Example 2Synthesis of 3-fluoro-5-iodo-N,N-dimethylaniline (VMY-2-119): The suspension of l-fluoro-3-iodo-5 -nitrobenzene (0.5 g, 1.87 mmol) and SnCl2'2H20 (1.5 g, 6.64 mmol) in EtOH (10 mL) was heated to reflux for 1.5 h. The solvent was removed and the crude mixture was diluted with ether, washed with 4 N NaOH and brine. The ether layer was- 42 -B4067289v2 separated and dried over Na2S04, filtered, concentrated to yield amine compound as a solid (0.4 g, 91%). The crude product was used without purification.A solution of above amine (0.4 g, 1.69 mmol) and iodomethane (0.719 g, 5 mmol) in dimethylformamide (DMF; 10 mL) containing potassium carbonate (0.46 g, 3.38 mmol) was stirred for 48 h at room temperature. Water (lOmL) was then added and the solution was extracted with ether three times. The organic extracts washed with water, brine, dried over Na2S04, filtered and concentrated. The crude product was purified by column chromatography to yield VMY-2-119 as a liquid (0.23 g, 52%). 1H NMR (399 MHz) ? 6.69 - 6.63 (m, 2H), 6.22 (dt, J = 12.5, 2.3, 1H), 2.83 (s, 6H). 13C NMR (100 MHz) ? 163.33(d, JF-C=245 Hz), 152.49(d, J=l lHz) 116.91 (d, J = 2.4), 112.12(d, J=24 Hz), 98.73(d, J=26Hz), 94.24(d, J=l l Hz), 40.21 (s, 3H).
Production Example 341 3-Fluoro-5-iodophenylamine 3.2 g crude title compound (yellow oil) was obtained from 3.0 g of 3-fluoro-5-iodonitrobenzene by the same reaction as in Production Example 335.1H-NMR (CDCl3) delta: 3.78(brs, 2H), 6.28-6.35(m, 1H), 6.75-6.84(m, 2H)
With iron; acetic acid; In tetrahydrofuran; water; at 40℃; 3-Iodo-5-fluoro-1-nitrobenzene (5.2 g; 19.48 mmol) is dissolved in a 4/3 water/tetrahydrofuran mixture. Powdered iron (8.7 g; 156 mmol), followed by acetic acid (4.5 ml) are added at room temperature and the suspension formed is stirred overnight at 40 C. The reaction mixture is filtered over diatomaceous earth and poured on to water. The mixture is extracted with ethyl acetate and the combined organic phases are dried over sodium sulphate, filtered and concentrated. The residue is chromatographed over silica gel with n-hexane/ethyl acetate (3/1). The pure fractions are combined and the solvent is evaporated off. The residue is diluted with methylene chloride (30 ml), and pyridine (4,0 ml; 49.5 mmol) and trifluoroacetic anhydride (3.44 ml; 24.7 mmol) are added and the mixture is stirred for one hour at room temperature. The reaction solution is poured on to aqueous hydrochloric acid (1 M; 50 ml) and the mixture is extracted twice with ethyl acetate (50 ml). The combined organic phases are dried over sodium sulphate, filtered and concentrated. The residue is chromatographed over silica gel with n-hexanelethyl acetate (9/1). The pure fractions are combined and the solvent is evaporated off. [00367] Yield: 5.40 g (98%) as a white solid. [00368] MS: 333 (M)
  • 2
  • [ 3819-88-3 ]
  • [ 544-92-3 ]
  • [ 110882-60-5 ]
  • 3
  • [ 3819-88-3 ]
  • [ 557-21-1 ]
  • [ 110882-60-5 ]
YieldReaction ConditionsOperation in experiment
90% tetrakis(triphenylphosphine) palladium(0); In DMF (N,N-dimethyl-formamide); at 80℃; EXAMPLE 1; Step 1; To a solution of 1.0 eq 1A in dry DMF (0.37 M) was added Zn(CN)2 (0.92 eq) and Pd(PPh3)4 (0.058 eq). The reaction mixture was purged with nitrogen and heated to 80° C. overnight. An additional 0.023 eq of Pd(PPh3)4 was then added and the reaction was heated for another 6 hrs. The reaction mixture was then cooled to RT, diluted with 15 volumes of EtOAc (based on 1A) and the organic layer was washed 3 times with water and once with brine. The organic layer was dried over sodium sulfate, filtered and concentrated. Purification by chromatography over silica gel using 10percent Et2O/hexane as the eluant provided 1B as a solid (90percent).
90% tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 80℃; To a solution of 1.0 eq IA in dry DMF (0.37 M) was added Zn(CN)2 (0.92 eq) and Pd(PPh3)4 (0.058 eq). The reaction mixture was purged with nitrogen and heated to 800C overnight. An additional 0.023 eq of Pd(PPh3)4 was then added and the reaction was heated for another 6 hrs. The reaction mixture was then cooled to RT, diluted with 15 volumes of EtOAc (based on IA) and the organic layer was washed 3 times with water and once with brine. The organic layer was dried over sodium sulfate, filtered and concentrated. Purification by <n="54"/>chromatography over silica gel using 10percent Et2psi/hexane as the eluant provided IB as a solid (90percent).
90% tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 80℃; To a solution of 1.0 eq IA in dry DMF (0.37 M) was added Zn(CN)2 (0.92 eq) and Pd(PPli3)4 (0.058 eq). The reaction mixture was purged with nitrogen and heated to 800C overnight. An additional 0.023 eq of Pd(PPh3)4 was then added and the reaction was heated for another 6 hrs. The reaction mixture was then cooled to RT, diluted with 15 volumes of EtOAc (based on IA) and the organic layer was washed 3 times with water and once with brine. The organic layer was dried over sodium sulfate, filtered and concentrated. Purification by chromatography over silica gel using 10percent Et2O/hexane as the eluant provided IB as a solid (90percent).
90% tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 80℃; To a solution of 1.0 eq IA in dry DMF (0.37 M) was added Zn(CN)2 (0.92 eq) and Pd(PPhj)4 (0.058 eq). The reaction mixture was purged with nitrogen and heated to 800C overnight. An additional 0.023 eq of Pd(PPh3)4 was then added and the reaction was heated for another 6 hrs. The reaction mixture was then cooled to RT, diluted with 15 volumes of EtOAc (based on IA) and the organic layer was washed 3 times with water and once with brine. The organic layer was dried over sodium sulfate, filtered and concentrated. Purification by chromatography over silica, gel using 10percent Et2O/hexane as the eluant provided IB as a solid (90percent).
90% tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide;Heating / reflux; Example 1 Step 1. To a solution of 1.0 eq IA in dry DMF (0.37 M) was added Zn(CN)2 (0.92 eq) and Pd(PPlIa)4 (0.058 eq). The reaction mixture was purged with nitrogen and heated to 800C overnight. An additional 0.023 eq of Pd(PPh3)4 was then added and the reaction was heated for another 6 hrs. The reaction mixture was then cooled to RT, diluted with 15 volumes of EtOAc (based on IA) and the organic layer was washed 3 times with water and once with brine. The organic layer was dried over sodium sulfate, filtered and concentrated. Purification by chromatography over silica gel using 10percent E_2psi/hexane as the eluant provided IB as a solid (90percent).

  • 4
  • zinc cyanide [ No CAS ]
  • [ 3819-88-3 ]
  • [ 110882-60-5 ]
YieldReaction ConditionsOperation in experiment
90% tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 80℃; EXAMPLE 1; Step 1 To a solution of 1.0 eq 1A in dry DMF (0.37 M) was added Zn(CN)2 (0.92 eq) and Pd(PPh3)4 (0.058 eq). The reaction mixture was purged with nitrogen and heated to 80° C. overnight. An additional 0.023 eq of Pd(PPh3)4 was then added and the reaction was heated for another 6 hrs. The reaction mixture was then cooled to RT, diluted with 15 volumes of EtOAc (based on 1A) and the organic layer was washed 3 times with water and once with brine. The organic layer was dried over sodium sulfate, filtered and concentrated. Purification by chromatography over silica gel using 10percent Et2O/hexane as the eluant provided 1B as a solid (90percent).
  • 5
  • [ 3819-88-3 ]
  • copper(l) cyanide [ No CAS ]
  • [ 110882-60-5 ]
YieldReaction ConditionsOperation in experiment
With copper(l) cyanide; In N,N-dimethyl-formamide; 1) Preparation of 3-Fluoro-5-nitrobenzonitrile Copper cyanide (5.03 g) was dried overnight and mixed with 15.0 g of 1-fluoro-3-iodo-5-nitrobenzene and 120 ml of dimethylformamide. The mixture was heated under reflux for 3 hours. After cooling, the reaction mixture was poured into ice-water containing about 4N hydrochloric acid, followed by stirring vigorously for 1 hour. Ethyl ether was added to the reaction mixture, followed by stirring vigorously for 1.5 hours. The insoluble matter was removed by filtration using Celite, and the filtrate was extracted with ethyl ether repeatedly. The ethyl ether layer was washed with water and a saturated sodium chloride aqueous solution, and dried over anhydrous sodium sulfate. The solvent was removed by evaporation. The residue was subjected to silica gel column chromatography using a mixture of hexane-ethyl acetate (50:3 by volume) as an elude. The fraction containing the desired compound was concentrated to afford 8.00 g of the title compound. 1H-NMR (CDCl3) delta: 7.73 (dd, 1H, J=7, 1.5 Hz), 8.21 (dt, J=8, 2 Hz), 8.36 (m, 1H)
 

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