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Chemical Structure| 460-00-4 Chemical Structure| 460-00-4

Structure of 460-00-4

Chemical Structure| 460-00-4

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Product Citations

Product Citations

Lim, Taeho ; Ryoo, Jeong Yup ; Han, Min Su ;

Abstract: In this study, we developed a simple transition-metal-free borylation reaction of aryl bromides. Bis-boronic acid (BBA), was used, and the borylation reaction was performed using a simple procedure at a mild temperature. Under mild conditions, aryl bromides were converted to arylboronic acids directly without any deprotection steps and purified by conversion to trifluoroborate salts. The functional group tolerance was considerably high. The mechanism study suggested that this borylation reaction proceeds via a radical pathway.

Alternative Products

Product Details of [ 460-00-4 ]

CAS No. :460-00-4
Formula : C6H4BrF
M.W : 175.00
SMILES Code : FC1=CC=C(Br)C=C1
MDL No. :MFCD00000342
InChI Key :AITNMTXHTIIIBB-UHFFFAOYSA-N
Pubchem ID :9993

Safety of [ 460-00-4 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H225-H315-H319-H332-H335
Precautionary Statements:P261-P305+P351+P338
Class:3
UN#:1993
Packing Group:

Computational Chemistry of [ 460-00-4 ] 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 34.1
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.

2.09
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

3.08
Log Po/w (WLOGP)?

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

3.01
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.

3.48
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

3.0
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.

-3.42
Solubility 0.0665 mg/ml ; 0.00038 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.

-2.75
Solubility 0.313 mg/ml ; 0.00179 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

-3.52
Solubility 0.0522 mg/ml ; 0.000299 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.

-5.18 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

2.0
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<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)

1.29

Application In Synthesis of [ 460-00-4 ]

* 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 [ 460-00-4 ]

[ 460-00-4 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 34636-92-5 ]
  • [ 13031-62-4 ]
  • [ 460-00-4 ]
  • [ 72082-64-5 ]
  • 2
  • [ 72551-53-2 ]
  • [ 460-00-4 ]
  • [ 117022-68-1 ]
  • 3
  • [ 540-38-5 ]
  • [ 460-00-4 ]
  • [ 324-94-7 ]
  • [ 398-23-2 ]
  • 4
  • [ 460-00-4 ]
  • potassium-<4-fluoro-phenolate> [ No CAS ]
  • [ 330-93-8 ]
  • 5
  • [ 4747-15-3 ]
  • [ 460-00-4 ]
  • [ 347-84-2 ]
  • 6
  • [ 460-00-4 ]
  • [ 344790-96-1 ]
  • 7
  • [ 82104-74-3 ]
  • [ 142-82-5 ]
  • [ 352-13-6 ]
  • [ 460-00-4 ]
  • [ 207680-98-6 ]
YieldReaction ConditionsOperation in experiment
With sodium tetrahydroborate; magnesium; In tetrahydrofuran; ethanol; water; ethyl acetate; Example 1 (4-Cyano-2-hydroxymethylphenyl)(4-fluorophenyl)methanol A solution of 4-fluorophenylmagnesium bromide, prepared from 4-fluorobromobenzene (605 g, 3.45 mole) and magnesium turnings (107 g, 4.4 mole) in dry THF (1200 mL), is added dropwise to a suspension of 5-cyanophthalid (500 g, 3.14 mole) in dry THF (3000 mL). The temperature is kept below 5° C. After the addition is complete, the reaction mixture is stirred the night over at room temperature. Ethanol (4500 mL) is added to the reaction mixture and NaBH4 (238 g, 6.30 mole) is added to the mixture in portions of 50 grams and is stirred the night over at room temperature. About 2/3 of the solvents is removed in vacuo and water (4000 mL) is added to the reaction mixture. The resulting solution is extracted with EtOAc (2*500 mL). Evaporation of the solvents leaves a crude title compound (780 g) as an oil which is deemed pure enough for further reaction. A pure sample is obtained after column chromatography on silica gel using EtOAc/n-Heptane (1/1) as eluent. The title compound is obtained as crystals after evaporation of the eluent. DSC onset: 116.5° C. 1H NMR (DMSO-db, 500 MHz): 4.42 (1H, dd J=13 Hz, J=5 Hz), 4.53 (1H, dd J=13 Hz, J=5 Hz), 5.45 (1H, t J=5 Hz), 5.98 (1H, d J=3 Hz), 6.14 (1H, d J=3 Hz), 7.15 (2H, J=10 Hz), 7.35 (2H, m), 7.74 (1H, d J=8.5 Hz), 7.77 (1H, d J=8.5 Hz), 7.83 (1H, s). Anal. calcd. for C15H12N1F1O2; C, 70.02; H, 4.71; N, 5.45. Found C, 70.01; H, 4.71; N, 5.51.
  • 8
  • [ 1006-68-4 ]
  • [ 460-00-4 ]
  • [ 324-80-1 ]
  • 9
  • [ 82104-74-3 ]
  • [ 7439-95-4 ]
  • [ 460-00-4 ]
  • [ 64169-67-1 ]
YieldReaction ConditionsOperation in experiment
86% A solution of 4-fluorophenyl magnesium bromide prepared from 153.33g 4-fluoro bromobenzene (0.876 moles), 25.33g magnesium turnings (1.055 moles) and 0.05g iodine in dry 300ml tetrahydrofuran, is added to a suspension of 100g 5-cyanophthalide (0.628 moles) in 1000ml methylene dichloride at-6 to-2 C and worked up according to the method of Example 1, resulting in a thick semi-solid. This is triturated with 500ml of isopropyl alcohol (IPA) and cooled to0-5 C to provide 5-cyano-1- (4-fluorophenyl)-1, 3-dihydroisobenzofuran (2b) as a solid. This solid is filtered and washed with cold 50ml of IPA. Yield: 130-140g HPLC purity: 99.32percent
A solution of 4-fluorophenyl magnesium bromide prepared from 153.33g 4-fluoro bromobenzene (0.876 moles), 25.33g magnesium turnings (1.055 moles) and 0.05g iodine in dry 300ml tetrahydrofuran, is added to a suspension of 100g 5-cyanophthalide (0.628 moles) in 1000 ml toluene at-6to-2 C and worked-up as explained in Example 4 to provide a thick semi-solid. This is triturated with 500mi of isopropyl alcohol (IPA) and cooled to0-5 C to provide 2b as a solid. The solid is filtered and washed with 50ml of cold IPA. Dry weight :105-110g Purity by HPLC: 97.5percent
  • 10
  • [ 82104-74-3 ]
  • [ 7439-95-4 ]
  • [ 460-00-4 ]
  • [ 207680-98-6 ]
YieldReaction ConditionsOperation in experiment
A solution of 4-fluorophenyl magnesium bromide prepared from 153.33g 4-fluoro bromobenzene (0.876 moles), 25.33g magnesium turnings (1.055 moles) and 0.05g iodine in dry300moi tetrahydrofuran, is added to a suspension of 100g 5-cyanophthalide (0.628 moles) in1000ml methylene dichloride at-6to-2 C. After the reaction is completed, the reaction mass is quenched with100ml 20percent aqueous ammonium chloride solution. The organic layer is separated and diluted with100ml of methanol. Slowly, 12g of sodium borohydride (0.324moles) added over a period of one hour at below25 C, and the same temperature is maintained for 4-6 hours. The mixture is then cooled to 5-10 C, maintained for 2 hours and then the precipitated solid is filtered. The solid is washed with cold water and dried under vacuum below40 C to provide pure4-cyano-2-hydroxymethylphenyl- (4-fluorophenyl) methanol (5b). Yield: 115-120g HPLC purity: 99.2percent
  • 11
  • [ 1455-20-5 ]
  • [ 460-00-4 ]
  • [ 1042318-38-6 ]
  • 12
  • [ 19070-16-7 ]
  • [ 82104-74-3 ]
  • [ 460-00-4 ]
  • [ 103146-25-4 ]
YieldReaction ConditionsOperation in experiment
A solution of 4-fluorophenyl magnesium bromide (prepared from 153.3g 4- flouro bromobenzene, 25.3g magnesium turnings and Iodine (0.05gm) in dry 300ml tetrahydrofuran), was added to a suspension of lOOg 5-cyanophthalide in 900ml dichloromethane at -4 to -2°C. After the completion of the reaction a solution of 3- (N,N-dimethylamino)propyl magnesium chloride in toluene/THF mixture [generated in situ by reacting 175g 3-(N,N-dimethylamino)propyl chloride in 350ml toluene with 41.6gm magnesium turnings, 6.0 gin 4-bromofluorobenzene and Iodine in dry tetrahydrofuran] was added between 0 to -50C. The reaction mass was stirred for 3-4 hours. After completion of the reaction, the reaction mass was quenched with 20percent aqueous ammonium chloride solution. The organic layer was separated and washed with water. Organic layer was then extracted with 20percent acetic acid. The aqueous acid extract was cooled and pH was adjusted to 8.5 to 9.0 using liquor ammonia, and extracted with toluene 3 x 600ml. The toluene layer was washed with water, dried and then treated with carbon. Reaction mixture was filtered and subjected to salt formation to get Diol acid addition salts.
  • 13
  • [ 35852-81-4 ]
  • [ 460-00-4 ]
  • [ 1252831-20-1 ]
  • 14
  • [ 1569-16-0 ]
  • [ 460-00-4 ]
  • [ 1256347-61-1 ]
  • 15
  • [ 460-00-4 ]
  • [ 42595-26-6 ]
  • [ 54-60-4 ]
  • 16
  • [ 201230-82-2 ]
  • [ 460-00-4 ]
  • [ 865-48-5 ]
  • [ 58656-98-7 ]
  • 17
  • [ 82104-74-3 ]
  • [ 460-00-4 ]
  • [ 260371-16-2 ]
  • 19
  • [ 460-00-4 ]
  • [ 1030825-20-7 ]
  • 20
  • [ 3282-99-3 ]
  • [ 460-00-4 ]
  • C30H28F2N2 [ No CAS ]
  • 21
  • [ 201230-82-2 ]
  • [ 6638-79-5 ]
  • [ 460-00-4 ]
  • [ 116332-54-8 ]
  • 22
  • [ 381-98-6 ]
  • [ 460-00-4 ]
  • [ 659-21-2 ]
  • 23
  • [ 15226-74-1 ]
  • [ 6638-79-5 ]
  • [ 460-00-4 ]
  • [ 116332-54-8 ]
YieldReaction ConditionsOperation in experiment
80% With palladium diacetate; triethylamine; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 90℃; for 1h;Sealed tube; General procedure: A mixture of arylhalide (I, Br) (1 mmol), Weinreb amine hydrochloride(1.5 mmol), Pd(OAc)2 (5 mol %), xantphos (6 mol %), triethylamine (3 mmol), and cobalt carbonyl (0.3 mmol) in 1,4-dioxane was heated at 90 C for 1h in a septum-closed sealed tube. After cooling, the reaction mixture was concentrated in vacuum and the residue was extracted with ethylacetate and water. The ethylacetate layer was concentrated and the residue obtained was purified by flash column chromatography to get the desired product. Note: Carbon monoxide gas is highly toxic and should be handled by trained professionals in a well-ventilated fumehood with appropriate ventilation. In all the reactions, Co2(CO)8 was handled carefully in fumehoods using appropriate personal protective clothing and equipment.
  • 24
  • [ 6638-79-5 ]
  • [ 460-00-4 ]
  • [ 13939-06-5 ]
  • [ 701-49-5 ]
  • [ 116332-54-8 ]
  • 25
  • [ 568577-88-8 ]
  • [ 460-00-4 ]
  • 4-(N-morpholinyl)-4'-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)biphenyl [ No CAS ]
  • 26
  • [ 568577-88-8 ]
  • [ 460-00-4 ]
  • 4-fluoro-4'-(4-morpholinyl)biphenyl [ No CAS ]
  • 28
  • [ 120-72-9 ]
  • [ 460-00-4 ]
  • [ 101125-32-0 ]
  • 29
  • [ 20485-41-0 ]
  • [ 460-00-4 ]
  • [ 623577-48-0 ]
  • 30
  • [ 145901-11-7 ]
  • [ 460-00-4 ]
  • [ 1342811-68-0 ]
YieldReaction ConditionsOperation in experiment
47.6% With palladium diacetate; sodium t-butanolate; XPhos; In 1,4-dioxane; at 110℃; for 2h;Schlenk technique; Inert atmosphere; An oven dried schlenk flask was evacuated and back filled with argon gas. The procedure was repeated for 3-4 times and cooled to room temperature. The dioxane (8 ml) was introduced with syringe and degassed for 20min with argon gas balloon. Then, the XPhos (267mg, 0.563mmol), Pd(OAc)2 (41mg, 0.187mmol) were added together and heated at 110 C for 1min. The reaction mixtures become clear red color solution. Then, the amine derivative 5 (250 mg, 1.87 mmol), 4-fluoro-bromobenzene (325mg, 1.87mmol) and sodium tert butoxide (540 mg, 5.63 mmol) were added together under argon atmosphere and the reaction mixture was heated at 110 C for 2h. The reaction mixture was poured in ethyl acetate (150 ml). The organic phase was washed with water, brine, and dried over Na2SO4. The solvent was removed and the residue was purified on silica gel column chromatography (100% EtOAc) to give the compound 33 (203 mg, 47.6%). 1H-NMR (400 MHz, CDCl3): delta = 8.63 (brs, 1H), 7.42 (dd, J = 4.8Hz, J = 13.6Hz, 2H), 7.06 (m, 2H), 6.58 (d, J = 8.4Hz, 1H), 6.41(brs, 2H).
  • 31
  • [ 70199-60-9 ]
  • [ 460-00-4 ]
  • 4-(bis(4-fluorophenyl)(methoxy)methyl)pyridine [ No CAS ]
  • 32
  • [ 460-00-4 ]
  • [ 182482-25-3 ]
  • 2,4,6,4'-tetrafluoro-biphenyl [ No CAS ]
  • 33
  • [ 460-00-4 ]
  • [ 511295-00-4 ]
  • 2,3,4,6-tetrafluoro-4’-fluorobiphenyl [ No CAS ]
  • 34
  • [ 460-00-4 ]
  • [ 193217-39-9 ]
  • tert-butyl 4-[(4-fluorophenyl)hydroxyphenylmethyl]piperidine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
29% To a solution of 4-bromofluorobenzene (2 g, 11.4 mmol) in THF (20 mL) cooled to - 78 C, was added n-butyllithium dropwise (5.81 mL, 14.51 mmol) and the reaction mixture was stirred for 30 min. Then, a solution of tert- butyl 4-benzoylpiperidine-l- carboxylate (3 g, 10.37 mmol) in THF (15 mL) was added to the mixture which was stirred at -78 C for 2 hours. The mixture was allowed to warm up to room temperature, poured into a solution of sat. NH4C1 aqueous solution (50 mL) and extracted with EtOAc. The combined organic layers were dried over Na2S04, filtered and concentrated in vacuo. The residue was purified peparative HPLC (Gemini NX column) to give the title compound (1.18 g, 29%) as colorless solid; MS: 312.1 (M-tBu-H20)+.
  • 35
  • [ 460-00-4 ]
  • [ 154258-82-9 ]
 

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Technical Information

Categories

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[ 460-00-4 ]

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