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Structure of 14401-72-0

Chemical Structure| 14401-72-0

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Product Details of [ 14401-72-0 ]

CAS No. :14401-72-0
Formula : C8H6Cl2O
M.W : 189.04
SMILES Code : CC(C1=CC(Cl)=CC(Cl)=C1)=O
MDL No. :MFCD00045189
InChI Key :JGMBBKVZFUHCJC-UHFFFAOYSA-N
Pubchem ID :2758058

Safety of [ 14401-72-0 ]

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

Computational Chemistry of [ 14401-72-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.12
Num. rotatable bonds 1
Num. H-bond acceptors 1.0
Num. H-bond donors 0.0
Molar Refractivity 46.66
TPSA ?

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

17.07 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.1
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

2.86
Log Po/w (WLOGP)?

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

3.2
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.

2.94
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

3.43
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.9

Water Solubility

Log S (ESOL):?

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

-3.15
Solubility 0.133 mg/ml ; 0.000706 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.

-2.88
Solubility 0.251 mg/ml ; 0.00133 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

-3.97
Solubility 0.0204 mg/ml ; 0.000108 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.

-5.42 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)

1.18

Application In Synthesis of [ 14401-72-0 ]

* 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 [ 14401-72-0 ]

[ 14401-72-0 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 184970-30-7 ]
  • [ 14401-72-0 ]
  • 2
  • [ 37148-48-4 ]
  • [ 14401-72-0 ]
  • 3
  • [ 917-64-6 ]
  • [ 6575-00-4 ]
  • [ 14401-72-0 ]
  • 4
  • [ 14401-72-0 ]
  • [ 56041-58-8 ]
  • 5
  • [ 383-63-1 ]
  • [ 14401-72-0 ]
  • 4,4,4-trifluoro-1-(3,5-dichlorophenyl)-1-hydroxybut-1-en-3-one sodium salt [ No CAS ]
  • 6
  • [ 337-82-6 ]
  • [ 14401-72-0 ]
  • 4,4,5,5-tetrafluoro-1-(3,5-dichlorophenyl)-1-hydroxypent-1-en-3-one sodium salt [ No CAS ]
  • 7
  • [ 426-65-3 ]
  • [ 14401-72-0 ]
  • 4,4,5,5,5-pentafluoro-1-(3,5-dichlorophenyl)-1-hydroxypent-1-en-3-one sodium salt [ No CAS ]
  • 8
  • [ 356-27-4 ]
  • [ 14401-72-0 ]
  • 4,4,5,5,6,6,6-heptafluoro-1-(3,5-dichlorophenyl)-1-hydroxyhex-1-en-3-one sodium salt [ No CAS ]
  • 9
  • [ 51-36-5 ]
  • [ 917-54-4 ]
  • [ 14401-72-0 ]
  • [ 184970-30-7 ]
  • 10
  • [ 14401-72-0 ]
  • [ 84499-83-2 ]
  • 11
  • [ 485-47-2 ]
  • [ 14401-72-0 ]
  • 2-[2-(3,5-Dichloro-phenyl)-2-oxo-ethyl]-2-hydroxy-indan-1,3-dione [ No CAS ]
  • 12
  • [ 27607-77-8 ]
  • [ 14401-72-0 ]
  • [1-(3,5-Dichloro-phenyl)-vinyloxy]-trimethyl-silane [ No CAS ]
  • 14
  • [ 14401-72-0 ]
  • aqueous KOH-solution [ No CAS ]
  • [ 51-36-5 ]
  • 15
  • [ 14401-72-0 ]
  • [ 4637-24-5 ]
  • [ 96604-27-2 ]
YieldReaction ConditionsOperation in experiment
12.3 g for 3h;Reflux; 3?,S?-Dichloroacetophenone (9.7 g, 51 mmol) was heated at reflux in N,N-dimethylformamide dimethylacetal (50 mL) for 3 h. After cooling to ambient temperature, the reaction mixture was concentrated and dried under vacuum to give of anorange solid (12.3 g) that was used without further purification.1HNMRoe 7.82 (d, 1H), 7.74 (s, 2H), 7.42 (s, 1H), 5.58 (d, 1H), 3.18 (bs, 3H), 2.95 (bs, 3H).
  • 16
  • [ 14401-72-0 ]
  • [ 154257-66-6 ]
  • 17
  • [ 14401-72-0 ]
  • [ 154257-73-5 ]
  • 18
  • [ 14401-72-0 ]
  • 6-(3,5-Dichlorophenyl)-4-hydroxy-3-[(2-isopropylphenyl)thio]-2H-pyran-2-one [ No CAS ]
  • 19
  • [ 14401-72-0 ]
  • 3-(3,5-Dichloro-phenyl)-indeno[1,2-c]pyridazin-5-one [ No CAS ]
  • 20
  • [ 14401-72-0 ]
  • [ 84580-08-5 ]
  • 21
  • [ 10203-08-4 ]
  • [ 14401-72-0 ]
  • 22
  • [ 99-92-3 ]
  • [ 14401-72-0 ]
  • 23
  • [ 14401-72-0 ]
  • [ 74-89-5 ]
  • [ 499780-69-7 ]
YieldReaction ConditionsOperation in experiment
Methylamine (2M solution in [MEOH-13] mL) was added to a solution of 3,5-di- [CHLOROACETOPHENONE] (500 mg) in MeOH (26 mL) under a Nitrogen atmosphere. The mixture was stirred at r. t. for 18 hours, then it was cooled to [0C] and sodium borohydride (98 mg) was added. The mixture was stirred at [0C] for 2 hours, then it was quenched with water and extracted with DCM. The organic layer was dried and concentrated in vacuo to give the title compound (340 mg) as an yellow oil. T. I. c. : CH/AcOEt 1: 1, Rf=0.15. NMR [(CDCI3)] : [5] (ppm) 7.3 (m, 3H); 3.6 (q, [1 H)] ; 2.3 (s, 3H); 1.35 (d, 3H). MS (ES/+): [M/Z=204] [M+H] +.
  • 24
  • [ 14401-72-0 ]
  • [ 74-89-5 ]
  • [ 1225838-76-5 ]
YieldReaction ConditionsOperation in experiment
Methylamine (2M solution in [MEOH-13] mL) was added to a solution of intermediate 14 (500 mg) in MeOH (26 mL) under a Nitrogen atmosphere. The mixture was stirred at r. t. for 18 hours, then it was cooled to [0C] and sodium borohydride (98 mg) was added. The mixture was stirred at [0C] for 2 hours, then it was quenched with water and extracted with DCM. The organic layer was dried and concentrated in vacuo to give the title compound (340 mg) as yellow oil. T. [I.] c.: CH/AcOEt 1: [1,] Rf=0.15. NMR [(CDCI3)] : 8 (ppm) 7.3 (m, 3H); 3.6 (q, [1 H)] ; 2.3 (s, 3H); 1.35 (d, 3H). MS (ES/+): m/z=204 [[M+HL+.]
  • 25
  • [ 14401-72-0 ]
  • [ 52334-81-3 ]
  • [ 372122-75-3 ]
YieldReaction ConditionsOperation in experiment
[0159] A reaction vessel was charged with sodium hydride (as a 60% oil dispersion, 5.52 g, 1 38 mmol), DME (23 ml) and 2-chloro-5-trifluoromethylpyridine (7.06 g, 42 mmol). 3,5-Dichloroacetophenone (8.3 g, 44 mmol) in DME (23 ml) was added in portions to the mixture under nitrogen at room temperature. The mixture was stirred at ambient temperature for one hour then at 40-45 C. overnight. Upon completion of the reaction, the mixture was cooled to 5 C. and 10% aqueous sodium hydroxide solution (23 ml) was slowly added to the reaction mixture followed by methanol (46 ml) then hydroxylamine hydrochloride (14.5 g, 210 mmol). The mixture was heated to 72 C. for 4 hours then cooled and diluted with water (1500 ml) with stirring. The resulting solid was removed by filtration and dried under vacuum. It was then slurried in cyclohexane (100 ml) then filtered, washing with further cyclohexane. The crude solid 13.30 g (86%) was used in subsequent reactions without further purification. [0160] Mass Spectrum: Found: (M-H)-348 [0161] HPLC (?,=220-230 nm) RT 3.83 min
  • 26
  • [ 5780-37-0 ]
  • copper(ll) sulfate pentahydrate [ No CAS ]
  • [ 626-43-7 ]
  • [ 7757-83-7 ]
  • 5'-dicholoroacetophenone [ No CAS ]
  • [ 14401-72-0 ]
YieldReaction ConditionsOperation in experiment
30% With hydrogenchloride; sodium nitrite; In water; sodium acetate; EXAMPLE 1 3',5'-dichloroacetophenone. 300 ml of water and 70 ml of concentrated hydrochloric acid are added to 48.6 g (0.30 mol) of 3,5-dichloroaniline. Then, after 30 minutes, 27.5 g (0.40 mol) of sodium nitrite in 32 ml of water are run in dropwise while maintaining the temperature between 0 C. and 5 C. 16.2 g (0.2 mol) of sodium acetate are added to the filtered reaction mixture. This solution is run in dropwise into a solution of 28.5 g (0.48 mol) of acetaldoxime, 25.0 g (0.10 mol) of copper sulphate pentahydrate, 20.5 g (0.018 mol) of anhydrous sodium sulphite and 121 g (1.50 mol) of sodium acetate in 250 ml of water maintained at 15 C. After stirring for 1 hour, the mixture is acidified by addition of concentrated hydrochloric acid. After steam distillation and chromatography of the crude product on a silica column (eluent 90/10 heptane/ethyl acetate), 16.6 g (yield 30 %) of 3', 5'-dicholoroacetophenone (compound 1) are recovered in the form of a colourless liquid.
  • 27
  • [ 5780-37-0 ]
  • copper(ll) sulfate pentahydrate [ No CAS ]
  • [ 626-43-7 ]
  • [ 7757-83-7 ]
  • [ 14401-72-0 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; sodium nitrite; In water; sodium acetate; a) preparation of (3,5-dichlorophenyl)ethanone (compound 90) from 3,5-dichloroaniline (passing from IV to V): 300 ml of water and 70 ml of concentrated hydrochloric acid are added to 48.6 g (0.30 mol) of 3,5-dichloroaniline. 30 minutes after, 27.5 g (0.40 mol) of sodium nitrite in 32 ml of water are run in dropwise while maintaining the temperature between 0 and 5 C. 16.2 g (0.2 mol) of sodium acetate are added to the filtered reaction mixture. This solution is run in dropwise onto a solution of 28.5 g (0.48 mol) of acetaldoxime, 25.0 g (0.10 mol) of copper sulphate pentahydrate, 20.5 g (0.018 mol) of anhydrous sodium sulphite and 121 g (1.50 mol) of sodium acetate in 250 ml of water maintained at 15 C. After stirring for 1 h, the mixture is acidified by addition of concentrated hydrochloric acid. After steam distillation and chromatography of the crude product on a silica column (heptane 90, ethyl acetate 10), there are recovered 16.6 g (30%) of (3,5-dichlorophenyl)-ethanone in the form of a colourless liquid.
  • 28
  • [ 14401-72-0 ]
  • [ 53631-13-3 ]
YieldReaction ConditionsOperation in experiment
81% With bromine; In acetic acid; i) 2-Bromo-1-(3,5-dichlorophenyl)-1-ethanone: 1.03 ml (0.02 mol) of bromine are added, at room temperature, to 3.77 g (0.019 mol) of (3,5-dichlorophenyl)ethanone in solution in 50 ml of acetic acid. After stirring for 12 hours, evaporation of the acetic acid leads to the production of a yellow precipitate: 2-bromo-1-(3,5-dichlorophenyl)-1-ethanone (yield 81%).
With N-Bromosuccinimide; toluene-4-sulfonic acid; In ethyl acetate; at 20℃; for 12h; 0.27g (1.5mmol) 3,5- dichloro-acetophenone, 0.27g (1.5mmol) N- bromosuccinimide and 0.03g (0.15mmol) of p-toluenesulfonic acid dissolved in 15mL ethyl acetate , the reaction was stirred for 12 hours at room temperature, TLC tracking, completion of the reaction, deionized water (3 × 10mL) and washed, the organic solvent was removed under reduced pressure to give the crude product alpha- bromo-4- (3,5-dichloro) acetophenone ketone, 95% yield, was used directly without purification in the next reaction.
  • 29
  • [ 6575-00-4 ]
  • [ 74-88-4 ]
  • [ 14401-72-0 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; magnesium; In water; benzene; 3',5'-Dichloroacetophenone To a suspension of magnesium turnings (2 g.) in dry ether (20 ml.), under nitrogen was added iodomethane (12 g.), in dry ether (50 ml.), at such a rate that the reaction refluxed. The addition took 1 hour. Dry benzene (150 ml.) was added and the ether blown off under a strong stream of nitrogen. 3,5-Dichlorobenzonitrile (5 g.) was dissolved in dry benzene (60 ml.) and then added dropwise over 10 minutes and the resulting mixture refluxed for 3 hrs. After cooling to 0 6N hydrochloric acid (100 ml.), was added slowly over 10 minutes. The resulting mixture was refluxed for 6 hours. After cooling water (50 ml.) and ether (50 ml.) were added and the mixture filtered. The aqueous phase was washed with ether (2*50 ml.), and the combined organic layers washed with sodium hydrogen carbonate solution (50 ml.), brine (50 ml.) and dried over magnesium sulphate. Evaporation yielded the title compound. Nuclear Magnetic Resonance spectrum (NMR) was as follows: 2.6, 3H, s; 7.4, 1H, m; 7.6, 2H, d.
A solution of methyl iodide (4 mL) in anhydrous Et20 (40 mL) was dropped into a suspension of magnesium (1.6 g) in anhydrous [ET20] (16 mL) under a Nitrogen atmosphere. At the end of the dropping, benzene (120 mL) was added and the [ET20] eliminated with a Nitrogen flux. Then, a solution of 3, 5-dichlorobenzonitrile (4 g) in benzene (48 mL) was added and the mixture was heated to reflux for 3 hours. The solution was cooled to [0C] and a 6N hydrochloric acid solution was added and the mixture was stirred overnight at r. t.. Water and [ET20] were added and the layers were separated. The organic phase was washed with a saturated sodium hydrogen carbonate solution and brine, dried and concentrated in vacuo. The residue was purified by flash chromatography (CH/AcOEt 95: 5) to give the title compound (2.55 g) as an orange oil. T. [I.] c.: CH/AcOEt 8: 2, Rf=0.64. NMR [(CDCI3)] : 8 (ppm) 7.75 (s, 2H); 7.6 (s, [1 H)] ; 2.55 (s, 3H).
  • 30
  • [ 75-16-1 ]
  • [ 259796-12-8 ]
  • [ 14401-72-0 ]
YieldReaction ConditionsOperation in experiment
To the product from step A (5.42 g, 23.2 mmol) in 100 mL of tetrahydrofuran was added methylmagnesium bromide (11.6 mL, 34.8 mmol) drop-wise. After stirring at ambient temperature for 25 min, IN hydrochloric acid was added and the mixture extracted with two portions of ethyl acetate. The combined organic layers were dried over magnesium sulfate and concentrated in vacuo to provide the title compound which was used without further purification. 1H NMR (500 MHz, CDCl3) delta: 7.84 (d, J = 1.9 Hz, 2H); 7.58 (d, J = 1.8 Hz, IH); 2.63 (s, 3H)
  • 31
  • [ 2033-24-1 ]
  • [ 14401-72-0 ]
  • [ 1194065-53-6 ]
  • 32
  • [ 14401-72-0 ]
  • 3,5-dichlorobenzoylformic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% With selenium(IV) oxide; In 1,4-dioxane; for 4h;Reflux; Selenium dioxide (30.0 g 270 mmol) was dissolved in dioxane (450 mL) and warmed to 50C. 3,5-Dichloroacetophenone (30. Og, 158 mmol) was added at at this temperature and the resulting mixture was refluxed for 4 h. After completion of the reaction, the mixture was filtered through celite and concentrated in vacuo. (3,5- Dichlorophenyl)(oxo)acetic acid was isolated and purified by column chromatography, eluting with ethyl acetate/hexane mixtures(28 g, 80%).Mass spectroscopy: (ESI -ve) 217 [M-H]~
  • 33
  • [ 14401-72-0 ]
  • [ 1321518-26-6 ]
  • 34
  • [ 14401-72-0 ]
  • [ 1321518-27-7 ]
  • 35
  • [ 14401-72-0 ]
  • [ 1321518-28-8 ]
 

Historical Records

Technical Information

Categories

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[ 14401-72-0 ]

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