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Chemical Structure| 706791-83-5 Chemical Structure| 706791-83-5

Structure of 706791-83-5

Chemical Structure| 706791-83-5

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Product Details of [ 706791-83-5 ]

CAS No. :706791-83-5
Formula : C8H8BrNO2
M.W : 230.06
SMILES Code : O=C(OC)C1=CC(Br)=CC(N)=C1
MDL No. :MFCD07786958
InChI Key :MNXLJDUZJCMJCI-UHFFFAOYSA-N
Pubchem ID :18763420

Safety of [ 706791-83-5 ]

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

Computational Chemistry of [ 706791-83-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.12
Num. rotatable bonds 2
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 49.83
TPSA ?

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

52.32 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.93
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

2.19
Log Po/w (WLOGP)?

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

1.83
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.

2.06
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

1.65
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.93

Water Solubility

Log S (ESOL):?

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

-2.88
Solubility 0.3 mg/ml ; 0.00131 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.

-2.92
Solubility 0.275 mg/ml ; 0.0012 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

-2.97
Solubility 0.244 mg/ml ; 0.00106 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

No
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.

-6.15 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)

1.69

Application In Synthesis of [ 706791-83-5 ]

* 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.

  • Downstream synthetic route of [ 706791-83-5 ]

[ 706791-83-5 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 67-56-1 ]
  • [ 42237-85-4 ]
  • [ 706791-83-5 ]
YieldReaction ConditionsOperation in experiment
98% With thionyl chloride; at 20℃;Cooling with ice; 3-Bromo-5-aminobenzoic acid 12 (1.0 g, 4.62 mmol) was stirred in methanol (15mL) with ice cooling, and the yellow solution was treated with thionyl chloride (4.00 mL, 55.0 mmol) dropwise over 20 mm. The resulting mixture was allowed to warm up to room temperature and left stirring overnight. The reaction mixture was quenched with aqueous saturated NaHCO3 solution at 0 C. The solvent was then removed under vacuum, and the residue was suspended in ethyl acetate (200 mL). The organic phase was washed with brine (100 mL), dried (Na2504) and concentrated to afford the title compound as a yellow solid (1.08 g, 98%). ?H NMR (400 MHz, Methanol-d) oe 7.10 (t, J 1.6 Hz, 1H), 6.83 (t, J 1.6 Hz, 1H), 6.57 (t, J= 1.6 Hz, 1H), 3.46 (s, 3H). 13C NMR (100 MHz, CDC13) oe: 52.3, 114.6, 121.6, 122.3, 122.9, 132.6, 147.7, 166.0. m/z (ESI, MH) 231. ESI-HRMS (MH) calcd. for C8H8BrNO2 229.9817, found 229.9818. HPLC purity 98.8 % (R= 12.3 mm).
98% With thionyl chloride; at 20℃; for 15h;Cooling with ice; 3-Bromo-5-aminobenzoic acid (61a, 1.01 g, 4.62 mmol) was stirred in methanol ( 15 mL) with ice cooling, and the yellow solution was treated with thionyl chloride (4.00 mL, 55.0 mmol) dropwise over 20 min. The resulting mixture was warm up to room temperature and left stirring for 15 h. The reaction mixture was quenched with aqueous saturated (0564) NaHCOs solution at 0 C. The solvent was then removed under vacuum, and the residue was suspended in ethyl acetate (200 mL). The organic phase was washed with brine (100 mL), dried (Na2SOi) and concentrated in vacuo to afford the title compound 61b (1.08 g, 98%) as a yellow solid; NMR (400 MHz, DMS0 ) d 7.16 (dd, J =1.48, 2.12 Hz, 1H), 7.13 (t, J =1.64 Hz, 1H), 6.96 (t, J =2.00 Hz, 1H), 5.74 (s, 2H), 3.81 (s, 3H); MS (ESI, m/z) 231 (0565) [M+l]+; ESI-HRMS calcd. m/z for C8H8BrN02 229.9817, found 229.9818 [M+l]+
91% With thionyl chloride; at 0℃; for 24h;Reflux; General procedure: A solution of the appropriate 2-aminobenzoic acid (1equiv) in MeOH was cooled to 0C followed by a dropwise addition of thionyl chloride (2.5equiv). The mixture was refluxed for 24h. After evaporation of the solvent and neutralization by addition of a saturated aqueous NaHCO3 solution, the mixture was extracted with EtOAc and the combined organic layers were dried over MgSO4. Purification by CC (n-hexane/EtOAc) provided the title compounds.
 

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Technical Information

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