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Chemical Structure| 123858-51-5

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Product Details of [ 123858-51-5 ]

CAS No. :123858-51-5
Formula : C8H8BrNO
M.W : 214.06
SMILES Code : CC(C1=CC=C(Br)C=C1N)=O
MDL No. :MFCD16659002
Boiling Point : No data available
InChI Key :RCGAXUAOILUCAA-UHFFFAOYSA-N
Pubchem ID :14503614

Safety of [ 123858-51-5 ]

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

Computational Chemistry of [ 123858-51-5 ] 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 1.0
Molar Refractivity 48.74
TPSA ?

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

43.09 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.7
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

2.48
Log Po/w (WLOGP)?

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

2.24
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.

1.86
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

2.11
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.08

Water Solubility

Log S (ESOL):?

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

-3.07
Solubility 0.183 mg/ml ; 0.000857 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.

-3.03
Solubility 0.2 mg/ml ; 0.000934 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

-3.23
Solubility 0.125 mg/ml ; 0.000585 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.

-5.84 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

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)

1.29

Application In Synthesis of [ 123858-51-5 ]

* 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.

  • Upstream synthesis route of [ 123858-51-5 ]

[ 123858-51-5 ] Synthesis Path-Upstream   1~6

  • 1
  • [ 591-19-5 ]
  • [ 123858-51-5 ]
YieldReaction ConditionsOperation in experiment
25% With hydrogenchloride; boron trichloride In toluene; acetonitrile Step A
Preparation of 1-(2-amino-4-bromophenyl)ethanone (162a)
Under an argon atmosphere a solution of 3-bromoaniline (31.3 g, 181.8 mmol) and acetonitrile (75 g, 1.818 mol) in anhydrous toluene (120 ml) was added dropwise to boron trichloride (23.4 g, 200 mmol) in (200 ml) hexanes under cooling in an ice bath and stirring over 2.5 hours.
After the addition was completed, aluminum chloride (26.6 g, 200 mmol) was added portion wise over 30 minutes.
The mixture was allowed to warm to ambient temperature and then heated at reflux for 16 hours with stirring.
A 3N HCl solution (100 ml) was added dropwise to the reaction mixture under stirring at 10° C.
After the addition was complete, the mixture was heated at reflux for 3.5 hours.
The reaction mixture was then cooled to room temperature, and the layers separated.
The aqueous layer was extracted with chloroform (3*250 ml).
Organic layers were combined, dried over magnesium sulfate, filtered, and the filtrate concentrated to give the title compound 162a (9.58 g, 25percent).
1H NMR (CDCl3, 300 MHz): δ 7.54 (d, 1H, J=8.8 Hz), 6.83 (d, 1H, J=1.9 Hz), 6.75 (dd, 1H, J=8.4, 1.8 Hz), 2.54 (s, 3H) ppm.
25% With hydrogenchloride; boron trichloride In toluene; acetonitrile Step A
Preparation of 1-(2-amino-4-bromophenyl)ethanone (162a)
Under an argon atmosphere a solution of 3-bromoaniline (31.3 g, 181.8 mmol) and acetonitrile (75 g, 1.818 mol) in anhydrous toluene (120 ml) was added dropwise to boron trichloride (23.4 g, 200 mmol) in (200 ml) hexanes under cooling in an ice bath and stirring over 2.5 hours.
After the addition was completed, aluminum chloride (26.6 g, 200 mmol) was added portion wise over 30 minutes.
The mixture was allowed to warm to ambient temperature and then heated at reflux for 16 hours with stirring.
A 3N HCl solution (100 ml) was added dropwise to the reaction mixture under stirring at 10° C.
After the addition was complete, the mixture was heated at reflux for 3.5 hours.
The reaction mixture was then cooled to room temperature, and the layers separated.
The aqueous layer was extracted with chloroform (3*250 ml).
Organic layers were combined, dried over magnesium sulfate, filtered, and the filtrate concentrated to give the title compound 162a (9.58 g, 25 percent). 1H NMR (CDCl3, 300 MHz): δ7.54 (d, 1H, J=8.8 Hz), 6.83 (d, 1H, J=1.9 Hz), 6.75 (dd, 1H, J=8.4, 1.8 Hz), 2.54 (s, 3H) ppm.
25% With hydrogenchloride; boron trichloride In toluene; acetonitrile Step 1
Preparation of 1-(2-amino-4-bromophenyl)ethanone
Under an argon atmosphere a solution of 3-bromoaniline (31.3 g, 181.8 mmol) and acetonitrile (75 g, 1.818 mol) in anhydrous toluene (120 ml) was added dropwise over 2.5 hours to a stirred solution of boron trichloride (23.4 g, 200 mmol) in (200 ml) hexanes cooled in an ice bath.
After the addition was completed, aluminum chloride (26.6 g, 200 mmol) was added portion wise over 30 minutes.
The mixture was allowed to warm to ambient temperature and then heated at reflux for 16 hours with stirring.
The reaction mixture was then cooled to 10° C. and 100 ml of a 3N HCl solution was added dropwise with continued stirring.
After the addition was complete, the mixture was heated at reflux for 3.5 hours, then cooled to room temperature, and the layers separated.
The aqueous layer was extracted with chloroform (3*250 ml).
Organic layers were combined, dried over magnesium sulfate, filtered, and concentrated to give the title compound (9.58 g, 25percent).
1H NMR (CDCl3, 300 MHz): δ 7.54 (d, 1H, J=8.8 Hz), 6.83 (d, 1H, J=1.9 Hz), 6.75 (dd, 1H, J=8.4, 1.8 Hz), 2.54 (s, 3H) ppm.
25% With hydrogenchloride; boron trichloride In toluene; acetonitrile Step A
Preparation of 1-(2-Amino-4-bromophenyl)ethanone (162a)
Under an argon atmosphere a solution of 3-bromoaniline (31.3 g, 181.8 mmol) and acetonitrile (75 g, 1.818 mol) in anhydrous toluene (120 ml) was added dropwise to boron trichloride (23.4 g, 200 mmol) in (200 ml) hexanes under cooling in an ice bath and stirring over 2.5 hours.
After the addition was completed, aluminum chloride (26.6g, 200 mmol) was added portion wise over 30 minutes.
The mixture was allowed to warm to ambient temperature and then heated at reflux for 16 hours with stirring.
A 3N HCl solution (100 ml) was added dropwise to the reaction mixture under stirring at 10 ° C.
After the addition was complete, the mixture was heated at reflux for 3.5 hours.
The reaction mixture was then cooled to room temperature, and the layers separated.
The aqueous layer was extracted with chloroform (3*250 ml).
Organic layers were combined, dried over magnesium sulfate, filtered, and the filtrate concentrated to give the title compound 162a (9.58 g, 25percent).
1H NMR (CDCl3, 300 MHz): δ 7.54 (d, 1H, J=8.8 Hz), 6.83 (d, 1H, J=1.9 Hz), 6.75 (dd, 1H, J=8.4, 1.8 Hz), 2.54 (s, 3H) ppm.

References: [1] Patent: US2003/166636, 2003, A1, .
[2] Patent: US2002/52360, 2002, A1, .
[3] Patent: US2002/137737, 2002, A1, .
[4] Patent: US6503902, 2003, B2, .
[5] Patent: US5061800, 1991, A, .
  • 2
  • [ 90004-94-7 ]
  • [ 123858-51-5 ]
YieldReaction ConditionsOperation in experiment
85% at 90℃; for 1 h; Iron powder (5.69 g, 102.0 mmol) was added to a solution of l-(4-bromo-2- nitropheny ethanone (62, 4.16 g, 17.0 mmol) in 30 mL of acetic acid and the resulting suspension was heated to 90 °C for 1 hour. After cooling to room temperature the reaction mixture was diluted with brine and EtOAc and adjusted to pH 10 by the addition of 3N aqueous NaOH. The mixture was filtered and the filtrate was extracted 3x with EtOAc. The combined organic phases were dried with Na2S04, filtered and the filtrate concentrated under vacuum to give of 1 -(2-amino-4- bromophenyl)ethanone (63, 3.1 g, 14.4 mmol, 85percent). MS: 214.0 m/z (M+H)+.
References: [1] Liebigs Annalen der Chemie, 1990, # 2, p. 205 - 206.
[2] Patent: WO2012/162254, 2012, A1, . Location in patent: Page/Page column 152.
  • 3
  • [ 30186-18-6 ]
  • [ 123858-51-5 ]
YieldReaction ConditionsOperation in experiment
56% With ammonia In N,N-dimethyl-formamide at 60℃; for 9 h; Inert atmosphere 2-Acetyl-5-bromophenol (322 mg, 1.5 mmol) was dissolved in N, N-dimethylformamide (3 mL)Ammonia (1.7 mL, 45 mmol) was added dropwise thereto, reacted at 60 ° C under nitrogen for 9 hours, and allowed to cool to room temperature. The reaction solution was poured into 16 mL of water and extracted with dichloromethane (3 x 5 mL). The organic phase was washed with saturated brine (2 x 5 mL), dried over anhydrous sodium sulfate, filtered, sonicated and purified by flash column chromatography The product was dichloromethane: methanol = 50: 1 V / V)2-acetyl-5-bromoaniline as a yellow oil in a yield of 56percent.
References: [1] Patent: CN106631820, 2017, A, . Location in patent: Paragraph 0143; 0144; 0145; 0146.
  • 4
  • [ 75-05-8 ]
  • [ 591-19-5 ]
  • [ 123858-51-5 ]
YieldReaction ConditionsOperation in experiment
4 g
Stage #1: With aluminum (III) chloride; boron trichloride In dichloromethane; toluene at 0 - 90℃; for 5 h;
Stage #2: With hydrogenchloride; water In dichloromethane; toluene at 50℃; for 1 h;
Acetonitrile (23.7 g, 580 mmol) was added to 3-Bromoaniline (10 g, 58 mmol) in toluene (70 mL). The mixture was cooled to 0°C and BC13 (1 M in CH2C12, 64 mL, 64 mmol) was added drop wise, while keeping the temperature below 10°C. Next, A1C13 (11.6 g, 87 mmol) was added in small portions at 0°C. The reaction mixture was heated to 90°C for 5 hours. The reaction mixture was cooled to room temperature and quenched with aqueous HCl (2N, 100 mL). The mixture was heated to 50°C for 1 hour, cooled to room temperature and separated. The organic layer was separated and washed with water and brine. The organic layer was collected, dried and concentrated, resulting in l-(2-amino-4-bromophenyl)ethanone (4 g). Method A2; Rt: 0.98 min. m/z=: 215.7 (M+H)+ Exact mass: 215.0
References: [1] Journal of Medicinal Chemistry, 2015, vol. 58, # 14, p. 5522 - 5537.
[2] Patent: WO2012/13643, 2012, A1, . Location in patent: Page/Page column 86.
[3] Patent: WO2013/98313, 2013, A1, . Location in patent: Page/Page column 41.
[4] Patent: WO2014/152738, 2014, A1, . Location in patent: Page/Page column 72; 73.
  • 5
  • [ 20776-50-5 ]
  • [ 917-54-4 ]
  • [ 123858-51-5 ]
YieldReaction ConditionsOperation in experiment
33% at -78℃; for 1 h; To a -78 °C solution of 2-amino-4-bromobenzoic acid (2.16 g, 10 mmol) in THF (20 mL) was added MeLi (13.3 mL, 3M, 0.04 mmol). The resulting reaction was allowed to stir at -78 °C for 1 hour, then was quenched with water and extracted with EtOAc. The organic extract was dried over anhydrous Na2S04, filtered and concentrated in vacuo and the resulting residue was purified using flash chromatography on silica gel to provide Int-21 (700 mg, 33 percent). 1H NM (CDC13): δ 7.51 - 7.58 (m, 1 H), 6.72 - 6.84 (m, 2 H), 6.37 (s, 2 H), 7.73 (s, 2 H). MS (ESI) m/e (M+H*): 214.
References: [1] Patent: WO2012/50848, 2012, A1, . Location in patent: Page/Page column 121.
  • 6
  • [ 1438400-32-8 ]
  • [ 123858-51-5 ]
References: [1] Chemical Communications, 2013, vol. 49, # 45, p. 5225 - 5227.
 

Historical Records

Technical Information

• Alkyl Halide Occurrence • Baeyer-Villiger Oxidation • Barbier Coupling Reaction • Baylis-Hillman Reaction • Bucherer-Bergs Reaction • Buchwald-Hartwig C-N Bond and C-O Bond Formation Reactions • Chan-Lam Coupling Reaction • Clemmensen Reduction • Corey-Bakshi-Shibata (CBS) Reduction • Corey-Chaykovsky Reaction • Fischer Indole Synthesis • General Reactivity • Grignard Reaction • Henry Nitroaldol Reaction • Hiyama Cross-Coupling Reaction • Horner-Wadsworth-Emmons Reaction • Hydride Reductions • Kinetics of Alkyl Halides • Kumada Cross-Coupling Reaction • Lawesson's Reagent • Leuckart-Wallach Reaction • Mannich Reaction • McMurry Coupling • Meerwein-Ponndorf-Verley Reduction • Passerini Reaction • Paternò-Büchi Reaction • Petasis Reaction • Peterson Olefination • Pictet-Spengler Tetrahydroisoquinoline Synthesis • Preparation of Aldehydes and Ketones • Preparation of Amines • Prins Reaction • Reactions of Aldehydes and Ketones • Reactions of Alkyl Halides with Reducing Metals • Reactions of Amines • Reactions of Benzene and Substituted Benzenes • Reactions of Dihalides • Reformatsky Reaction • Robinson Annulation • Schlosser Modification of the Wittig Reaction • Schmidt Reaction • Specialized Acylation Reagents-Ketenes • Specialized Acylation Reagents-Vilsmeier Reagent • Stille Coupling • Stobbe Condensation • Substitution and Elimination Reactions of Alkyl Halides • Suzuki Coupling • Tebbe Olefination • Ugi Reaction • Wittig Reaction • Wolff-Kishner Reduction

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