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Chemical Structure| 352-34-1 Chemical Structure| 352-34-1
Chemical Structure| 352-34-1

1-Fluoro-4-iodobenzene

CAS No.: 352-34-1

4.5 *For Research Use Only !

Cat. No.: A214100 Purity: 98% (stabilized with Copper chip)

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Product Details of [ 352-34-1 ]

CAS No. :352-34-1
Formula : C6H4FI
M.W : 222.00
SMILES Code : FC1=CC=C(I)C=C1
MDL No. :MFCD00001052
Boiling Point : No data available
InChI Key :KGNQDBQYEBMPFZ-UHFFFAOYSA-N
Pubchem ID :9605

Safety of [ 352-34-1 ]

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

Calculated chemistry of [ 352-34-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 8
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 1.0
Num. H-bond donors 0.0
Molar Refractivity 39.12
TPSA ?

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

0.0 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.07
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

2.87
Log Po/w (WLOGP)?

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

2.85
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.

3.64
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

3.29
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.94

Water Solubility

Log S (ESOL):?

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

-3.58
Solubility 0.0585 mg/ml ; 0.000263 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.

-2.53
Solubility 0.656 mg/ml ; 0.00296 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

-3.63
Solubility 0.0516 mg/ml ; 0.000232 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

Low
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.

-5.62 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

1.0 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)

2.16

Application In Synthesis [ 352-34-1 ]

* 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 [ 352-34-1 ]

[ 352-34-1 ] Synthesis Path-Downstream   1~26

  • 1
  • [ 352-34-1 ]
  • [ 108-95-2 ]
  • [ 10540-41-7 ]
  • [ 324-94-7 ]
  • [ 80254-62-2 ]
  • 2
  • [ 352-34-1 ]
  • [ 102664-66-4 ]
  • N,N',N''-Tris-(4-fluoro-phenyl)-N,N',N''-triphenyl-benzene-1,3,5-triamine [ No CAS ]
  • 3
  • [ 352-34-1 ]
  • [ 119838-38-9 ]
  • [ 138500-85-3 ]
  • (2S,5S)-2-tert-Butyl-5-(4'-fluoro-biphenyl-4-ylmethyl)-3-methyl-4-oxo-imidazolidine-1-carboxylic acid tert-butyl ester [ No CAS ]
  • 5
  • [ 5918-93-4 ]
  • [ 352-34-1 ]
  • 4-(4-fluorophenyl)-1H-imidazol-2(3H)-one [ No CAS ]
  • 7
  • [ 52522-41-5 ]
  • [ 352-34-1 ]
  • [ 13406-29-6 ]
  • [ 180891-60-5 ]
  • 8
  • [ 352-34-1 ]
  • [ 192945-49-6 ]
  • [ 1194019-74-3 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate;copper(l) iodide; trans-N,N'-dimethylcyclohexane-1,2-diamine; In N,N-dimethyl-formamide; at 120℃; for 3h;Sealed tube; Inert atmosphere; A mixture of lH-<strong>[192945-49-6]indazole-4-carboxylic acid methyl ester</strong> (5.0 g, 28 mmol), copper iodide (5.7 g, 3.0 mmol), potassium carbonate (4.15 g, 30.0 mmol) and 4- fluoroiodobenzene (3.47 g, 30.0 mmol) is charged in a sealed tube at room temperature. The tube is evacuated, back-filled with argon and dimethylformamide (20 mL) is added followed by rac-trans-N,N'-dimethylcyclohexane-l,2-diamine (0.93 g, 6.5 mmol). The solution is stirred at 120C for 3 hours, then cooled to room temperature and diluted with water (50 mL) and ethyl acetate (80 mL). The organic layer is separated, washed with brine (30 mL), and dried over sodium sulfate. The crude product is filtered, concentrated and purified by silica gel chromatography eluting with a gradient of 0-30% ethyl acetate in hexanes to afford l-(4-fluoro- phenyl)-lH-<strong>[192945-49-6]indazole-4-carboxylic acid methyl ester</strong>.
With potassium carbonate;trans-N,N'-dimethyl-1,2-cyclohexyldiamine; copper(l) iodide; at 20 - 120℃;Inert atmosphere; sealed tube; A mixture of lH-<strong>[192945-49-6]indazole-4-carboxylic acid methyl ester</strong> (5.0 g, 28 mmol), copper(I) iodide (5.7 g, 3.0 mmol), potassium carbonate (4.15 g, 30.0 mmol) and A- fluoroiodobenzene (3.47 g, 30.0 mmol) was charged in a sealed tube at room temperature. The tube was evacuated, back-filled with argon and dimethylformamide (20 mL) was added followed by rac-trans-N,N'-dimethylcyclohexane-l,2-diamine (0.93 g, 6.5 mmol). The solution was stirred at 120 0C for 3 hours. The solution was cooled to room temperature and diluted with water (50 mL) and ethyl acetate (80 mL). The organic layer was separated, washed with brine (30 mL), and dried over sodium sulfate. The crude product was filtered, concentrated and purified by silica gel chromatography eluting with a gradient of 0-30% ethyl acetate in hexanes to afford l-(4-fluoro-phenyl)-lH-indazole-4- carboxylic acid methyl ester.
  • 9
  • [ 352-34-1 ]
  • [bis(1,10-phenanthroline)Cu][bis(p-fluorophenoxide)Cu] [ No CAS ]
  • [ 330-93-8 ]
  • 10
  • [ 352-34-1 ]
  • [ 2914-69-4 ]
  • (S)-4-(4-fluorophenyl)-3-butyn-2-ol [ No CAS ]
  • 11
  • [ 352-34-1 ]
  • [ 192945-49-6 ]
  • [ 1194019-76-5 ]
  • 12
  • [ 352-34-1 ]
  • [ 7768-28-7 ]
  • [ 132194-67-3 ]
  • 13
  • [ 352-34-1 ]
  • [ 154258-82-9 ]
  • 14
  • [ 352-34-1 ]
  • [ 201230-82-2 ]
  • [ 100-44-7 ]
  • [ 347-84-2 ]
  • 15
  • [ 352-34-1 ]
  • [ 52090-69-4 ]
  • [ 1383734-99-3 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate;copper(l) iodide; cis-N,N'-dimethyl-1,2-diaminocyclohexane; In N,N-dimethyl-formamide; at 130.0℃; for 1.0h;microwave irradiation; J-3 (1.50 g, 8.56 mmol) and K2CO3 (1.50 g, 10.9 mmol) in methanol (20 mL) is warmed at reflux for 5 minutes. The mixture is filtered and concentrated to provide J-4. J-4 (1.10 g, 8.26 mmol), Oil (980.0 mg, 5.15 mmol), K2CO3 (2.75 g, 19.9 mmol), N,N- dimethyl-l,2-diaminocyclohexane (150.0 muL, 0.95 mmol) and 4-fluoroiodobenzene (2.40 g, 10.8 mmol) in DMF (13 mL) is warmed at 130C in a microwave reactor. After 1 hour, the reaction is diluted with saturated aqueous NH4C1 (50 mL) and then NaHCO3 is added and the mixture is extracted with EtOAc (3 x 50 mL). The combined organic layers are washed with saturated aqueous NH4C1 (3 x 40 mL), dried over magnesium sulfate, filtered and concentrated. The residue is purified by silica gel chromatography eluting with a gradient of 0-50% EtOAc in hexanes and crystallized from ether-hexanes to provide J-6.
  • 16
  • [ 352-34-1 ]
  • [ 172732-52-4 ]
  • [ 343-01-1 ]
  • 17
  • [ 352-34-1 ]
  • [ 172732-52-4 ]
  • [ 89346-55-4 ]
  • 18
  • [ 20358-03-6 ]
  • [ 352-34-1 ]
  • [ 1453813-84-7 ]
  • 19
  • [ 352-34-1 ]
  • [ 546-43-0 ]
  • (3aR,5S,8aR,9aR,E)-3-(4-fluorobenzylidene)-5,8a-dimethyl-3,3a,6,7,8,8a,9,9a-octahydronaphtho[2,3-b]furan-2(5H)-one [ No CAS ]
  • (5S,8aR,9aS)-3-(4-fluorobenzyl)-5,8a-dimethyl-6,7,8,8a,9,9a-hexahydronaphtho[2,3-b]furan-2(5H)-one [ No CAS ]
  • (5S,8aR,9aS)-3,5,8a-trimethyl-6,7,8,8a,9,9a-hexahydronaphtho[2,3-b]furan-2(5H)-one [ No CAS ]
  • (2S,3S,3a'R,5R,5'S,8aS,8a'R,9aR,9a'R)-3-(4-fluorophenyl)-5,5',8a,8a'-tetramethyl-3,3a',5,5',6,6',7,7',8,8a,8',8a',9,9a,9',9a'-hexadecahydro-1H,2'H-spiro[anthracene-2,3'-naphtho[2,3-b]furan]-2'-one [ No CAS ]
  • 20
  • [ 352-34-1 ]
  • [ 5932-27-4 ]
  • [ 115342-25-1 ]
YieldReaction ConditionsOperation in experiment
77% With copper(l) iodide; potassium carbonate; (1S,2S)-N,N'-dimethyl-1,2-diaminocyclohexane; In toluene; at 110℃; for 2h; To a solution of 1-fluoro-4-iodo-benzene (1.47 g, 6.6 mmol, 1.3 eq) and <strong>[5932-27-4]ethyl 1H-pyrazole-3-carboxylate</strong> (0.71 g, 5.1 mmol, 1 eq) in 15 mL of toluene was added CuI (0.19 g, 1.0 mmol, 0.2 eq), trans-N,-N-dimethylcyclohexane 1,2-diamine (0.4 mL, 2.5 mmol, 0.2 eq), and potassium carbonate (1.4 g, 10 mmol, 2 eq). The reaction mixture was heated at 110° C. for 2 d then filtered and concentrated. The residue was purified by silica gel column chromatography (hex:EtoAc 4:1) to afford ethyl 1-(4-fluorophenyl)pyrazole-3-carboxylate (0.92 g, 3.9 mmol, 77percent).
  • 21
  • [ 352-34-1 ]
  • [ 201230-82-2 ]
  • [ 6638-79-5 ]
  • [ 116332-54-8 ]
  • 22
  • [ 2622-63-1 ]
  • [ 352-34-1 ]
  • 2-(4'-fluorobiphenyl-2-yl)-1-methyl-1H-benzoimidazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
77% With [ruthenium(II)(eta6-1-methyl-4-isopropyl-benzene)(chloride)(mu-chloride)]2; potassium carbonate; triphenylphosphine; In benzene; at 150℃; for 24h;Sealed tube; General procedure: In a 30-mL sealed tube, <strong>[2622-63-1]1-methyl-2-phenylbenzimidazole</strong> (1, 0.25mmol), [RuCl2(p-cymene)]2 (0.0125 mmol), Ph3P (0.075 mmol),K2CO3 (0.50 mmol), and iodoarene (0.25 mmol) were combined inanhydrous benzene (2 mL) under air. The mixture was then stirredat 150 °C for 24 h. The mixture was cooled to r.t., diluted with EtOAc, and filtered through a small pad of Celite. The filtrate was concentrated in vacuo and purified by flash chromatography (silicagel, EtOAc?hexane) to give the analytically pure 2-(biphenyl-2-yl)benzimidazoles.
  • 23
  • [ 773881-43-9 ]
  • [ 352-34-1 ]
  • 1,3-bis(4-fluorophenyl)-5-octyl-4H-thieno[3,4-c]pyrrole-4,6(5H)-dione [ No CAS ]
  • 24
  • [ 352-34-1 ]
  • 1-(4-methylbenzoyl)piperidine-2,6-dione [ No CAS ]
  • [ 530-46-1 ]
  • 25
  • [ 352-34-1 ]
  • [ 201230-82-2 ]
  • [ 108-88-3 ]
  • [ 68295-42-1 ]
  • [ 530-46-1 ]
YieldReaction ConditionsOperation in experiment
With bis(eta3-allyl-mu-chloropalladium(II)); silver trifluoromethanesulfonate; In 1,2-dichloro-ethane; at 80℃; under 3040.2 Torr; for 24h;Inert atmosphere; Sealed tube; Glovebox; Schlenk technique; Green chemistry; General procedure: Under an inert nitrogen atmosphere, silver triflate (386 mg,1.5 mmol) was transferred to a Teflon sealed thick-walled 50 ml glass reaction vessel equipped with a stir bar, followed by aryl iodide (1.0 mmol), arene (2.0 mmol), DCE (4 ml) and then a freshly prepared stock solution of [Pd(allyl)Cl]2 (0.2 mg, 5 × 10?4 mmol). The vessel was closed, removed from the glovebox, evacuated and backfilled with carbon monoxide three times, and finally pressurized with 4 atm carbon monoxide. After heating at 100 °C for 24 h with stirring, the reaction was cooled to room temperature and carbon monoxide was released. The reaction mixture was filtered through Celite, eluting with dichloromethane. Saturated NaHCO3 was added and the aqueous layer was extracted with dichloromethane. The combined organic layers were concentrated in vacuo and the residue was purified by column chromatography (silica gel, gradient hexane/ethyl acetate 0 to 20percent) to afford the pure ketone product.
  • 26
  • [ 352-34-1 ]
  • [ 5720-05-8 ]
  • [ 13939-06-5 ]
  • [ 530-46-1 ]
 

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