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Chemical Structure| 875664-25-8 Chemical Structure| 875664-25-8

Structure of 875664-25-8

Chemical Structure| 875664-25-8

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Product Details of [ 875664-25-8 ]

CAS No. :875664-25-8
Formula : C13H8BrNO
M.W : 274.11
SMILES Code : N#CC1=CC=C(Br)C=C1OC2=CC=CC=C2
MDL No. :MFCD13193389
InChI Key :WFMNRTXOZNBDSV-UHFFFAOYSA-N
Pubchem ID :57436665

Safety of [ 875664-25-8 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Computational Chemistry of [ 875664-25-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 16
Num. arom. heavy atoms 12
Fraction Csp3 0.0
Num. rotatable bonds 2
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 65.37
TPSA ?

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

33.02 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.77
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

4.28
Log Po/w (WLOGP)?

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

4.11
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.

3.27
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

3.69
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.62

Water Solubility

Log S (ESOL):?

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

-4.66
Solubility 0.00601 mg/ml ; 0.0000219 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-4.69
Solubility 0.00565 mg/ml ; 0.0000206 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately 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

-5.59
Solubility 0.000701 mg/ml ; 0.00000256 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately 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

Yes
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

Yes
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.

-4.93 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

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)

2.21

Application In Synthesis of [ 875664-25-8 ]

* 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 [ 875664-25-8 ]

[ 875664-25-8 ] Synthesis Path-Upstream   1~4

  • 1
  • [ 105942-08-3 ]
  • [ 108-95-2 ]
  • [ 875664-25-8 ]
YieldReaction ConditionsOperation in experiment
91%
Stage #1: With potassium carbonate In N,N-dimethyl-formamide; toluene for 4 h; Dean-Stark; Inert atmosphere; Reflux
Stage #2: for 4 h; Reflux; Inert atmosphere
In a three-neck flask equipped with a Dean-Stark trap, phenol (12.35 g, 131.25 mmol), K2CO3 (34.55 g, 250 mmol), N,N-dimethylformamide (125 mL) and toluene (125 mL) were charged, and refluxed in a nitrogen atmosphere for 4 hours to perform dehydration until no further water was formed from the reaction system. Thereafter, 100 mL of toluene was removed with the Dean-Stark trap. (0176) After returning to room temperature, 4-bromo-2-fluorobenzonitrile (25.0 g, 125 mmol) was added thereto, and the mixture was refluxed in a nitrogen atmosphere for 4 hours. After completing the reaction, the solution was diluted by adding toluene (200 mL) thereto, and then filtered with Celite. The solution was rinsed twice with water with a separating funnel, dried over anhydrous magnesium sulfate, and filtered. The product was purified by silica gel chromatography (mobile phase: toluene/ethyl acetate=9/1), and a specimen deposited through concentration of the solution was rinsed with 200 mL of hexane under application of ultrasonic wave for 5 minutes, and then filtered. The specimen was dried in vacuum (50° C. for 4 hours) to provide a white solid matter (yield amount: 31.2 g, yield: 91percent). The product was identified by 1H-NMR and ESI-MS. (0177) 1H NMR (500 MHz, CDCl3, δ): 6.97 (s, 1H), 7.11 (d, 2H), 7.25-7.31 (m, 2H), 7.42-7.48 (m, 2H), 7.51 (d, 1H) (0178) ESI-MS (m/z) (M+) calcd. 272.98, found 273.09.
References: [1] Patent: US9685615, 2017, B2, . Location in patent: Page/Page column 85-86.
[2] Patent: US2006/135524, 2006, A1, . Location in patent: Page/Page column 23.
[3] Patent: WO2007/30089, 2007, A1, . Location in patent: Page/Page column 85.
[4] Angewandte Chemie - International Edition, 2017, vol. 56, # 44, p. 13809 - 13813[5] Angew. Chem., 2017, vol. 129, # 44, p. 13997 - 14001,5.
[6] Organic Letters, 2019, vol. 21, # 1, p. 10 - 13.
[7] Patent: CN108997299, 2018, A, . Location in patent: Paragraph 0053; 0054.
  • 2
  • [ 139-02-6 ]
  • [ 105942-08-3 ]
  • [ 875664-25-8 ]
References: [1] Patent: US2006/135522, 2006, A1, . Location in patent: Page/Page column 19.
  • 3
  • [ 118-55-8 ]
  • [ 875664-25-8 ]
References: [1] Angewandte Chemie - International Edition, 2017, vol. 56, # 44, p. 13809 - 13813[2] Angew. Chem., 2017, vol. 129, # 44, p. 13997 - 14001,5.
  • 4
  • [ 2243-42-7 ]
  • [ 875664-25-8 ]
References: [1] Angewandte Chemie - International Edition, 2017, vol. 56, # 44, p. 13809 - 13813[2] Angew. Chem., 2017, vol. 129, # 44, p. 13997 - 14001,5.
 

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