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Chemical Structure| 89-54-3 Chemical Structure| 89-54-3

Structure of 89-54-3

Chemical Structure| 89-54-3

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Product Details of [ 89-54-3 ]

CAS No. :89-54-3
Formula : C7H6ClNO2
M.W : 171.58
SMILES Code : C1=C(N)C=CC(=C1C(O)=O)Cl
English Name :5-Amino-2-chlorobenzoic acid
MDL No. :MFCD00007845
InChI Key :GVCFFVPEOLCYNN-UHFFFAOYSA-N
Pubchem ID :37879

Safety of [ 89-54-3 ]

Computational Chemistry of [ 89-54-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 2.0
Molar Refractivity 42.82
TPSA ?

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

63.32 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.91
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

1.33
Log Po/w (WLOGP)?

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

1.63
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.

0.48
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

1.14
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.1

Water Solubility

Log S (ESOL):?

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

-2.08
Solubility 1.43 mg/ml ; 0.00833 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.

-2.26
Solubility 0.941 mg/ml ; 0.00548 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

-2.02
Solubility 1.63 mg/ml ; 0.00948 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.

-6.4 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

1.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.56

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)

1.18

Application In Synthesis of [ 89-54-3 ]

* 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 [ 89-54-3 ]

[ 89-54-3 ] Synthesis Path-Downstream   1~10

  • 1
  • [ 719282-11-8 ]
  • [ 89-54-3 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride at 150 - 160℃;
  • 2
  • [ 89-54-3 ]
  • [ 108-24-7 ]
  • [ 719282-11-8 ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate
  • 3
  • [ 207981-46-2 ]
  • [ 89-54-3 ]
  • [ 1001340-15-3 ]
YieldReaction ConditionsOperation in experiment
60% In tetrahydrofuran; for 16h; EXAMPLE 26. Synthesis of 2-ChJoro-5-f2-Fluoro-5-TrifluoromethyI-Benzoylamino)-Benzoic Acid (Intermediate 18)18[0162] 5-Amino-2-chIoro-benzoic acid (0.4 g, 2.32 mmol) was diluted with THF (12 mL), treated with 2-fluoro-5-trifluoromethyl-benzoyl chloride (0.388 g, 2.56 mmol) and stirred for 16h. Solvents were then removed and resulting solids were triturated with DCM. After filtration, the title compound was obtained as a white solid (0.5 g, 60%).
  • 4
  • [ 89-54-3 ]
  • [ 75-36-5 ]
  • [ 719282-11-8 ]
YieldReaction ConditionsOperation in experiment
27% With triethylamine In dichloromethane at 20℃; for 2h; 111 EXAMPLE 111. Synthesis of S-Aeety.amino^-Chloro-Benzoic Acid (Intermediate 57)57[0315] To a solution of 5-amino-2-chloro-benzoic acid (0.50 g, 2.9 mmol) in DCM (15 mL) was added acetyl chloride (0.30 mL, 4.2 mmol) followed by triethylamine (1.2 mL, 8.6 mmol). The mixture was stirred at RT for 2 h and poured into water. The mixture was extracted with ethyl acetate and the combined organic layers washed with water, brine, dried over Na2SO4 and filtered. The filtrate was concentrated and afforded the title compound (0.17 g, 27%) as a brown solid.
  • 5
  • [ 89-54-3 ]
  • [ 914106-36-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: NaNO2; aq. HCl 1.2: KCN 2.1: 94 percent / 1,3-dicyclohexylcarbodiimide / 4-dimethylaminopyridine / CH2Cl2 / 0 - 25 °C
  • 6
  • [ 89-54-3 ]
  • [ 105191-41-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: NaNO2; aq. HCl 1.2: KCN 2.1: 94 percent / 1,3-dicyclohexylcarbodiimide / 4-dimethylaminopyridine / CH2Cl2 / 0 - 25 °C 3.1: 41 percent / pyrrolidine; t-BuOK; Red-Al / toluene; various solvent(s) / 0.25 h / 10 °C
  • 7
  • [ 89-54-3 ]
  • [ 120569-07-5 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 1.) NaNO2, 2N HCl; 2.) cuprous cyanide / 1.) water, 0 deg C, 35 min; 2.) water, 60 deg C, 40 min 2: SOCl2 / toluene / 1 h / 70 °C 3: 2.) H2SO4 / 1.) reflux, 20 min; 2.) AcOH, water, 100 deg C, 3 h
  • 8
  • [ CAS Unavailable ]
  • [ 89-54-3 ]
  • [ 607380-17-6 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; iron(II) sulfate; sodium 3-nitrobenzenesulfonate In water at 95℃; for 1.25h; 4.b (b) 6-chloro-2-methyl-5-quinolinecarboxylic acidm-nitrobenzenesulphonic acid Crotonaldehyde (1.5 mL) was added dropwise over a period of 1 hour to a mixture of 5- AMINO-2-CHLOROBENZOIC acid (1.7 g), ferrous sulphate heptahydrate (0.77 g), sodium M-NITROBENZENESULPHONATE (1.2 g) and concentrated hydrochloric acid (11 mL) at 95°C. The reaction mixture was heated for a further 15 minutes then filtered whilst still hot. The collected solid was extracted with boiling 2M aqueous hydrochloric acid solution (20 mL) and the extract combined with the filtrate. Ammonium acetate was then added to give a solution of pH 4, which was cooled in ice and the resultant precipitate collected by filtration and washed with water. The product was converted to its hydrochloride salt by treatment with hydrochloric acid (4M in 1,4-dioxane) and the solid dried in vacuo to give the sub-title compound (0.5 g) as a solid. MS: APCI (+ve) 222/224 (M+1)
With hydrogenchloride; iron(II) sulfate In water at 95℃; for 0.0208333h; 1.a (a) 6-Chloro-2-methyl-5-quinolinecarboxylic acid Crotonaldehyde (1.50 mL) was added dropwise over a period of 1 hour to a mixture of 5- amino-2-chlorobenzoic acid (1.72 g), ferrous sulphate heptahydrate (0.77 g), sodium nitrobenzenesulphonate (1.23 g) and concentrated hydrochloric acid (11 mL) at 95°C. The reaction mixture was heated for a further 15 minutes then filtered whilst still hot. The resulting solid was extracted with boiling 2M aqueous hydrochloric acid solution (20 mL) and the extract combined with the filtrate. Ammonium acetate was then added to give a solution of pH 4, which was cooled in ice and the resultant precipitate collected by filtration and washed with water. The solid was dried in vacuo to give the sub-title compound (0.5 g) as a solid. MS: APCI (+ve) 222/224 (M+1)
  • 9
  • [ 89-54-3 ]
  • [ 67-68-5 ]
  • [ 88487-25-6 ]
YieldReaction ConditionsOperation in experiment
With hydrogen fluoride In dichloromethane; sodium nitrite (Process variant b) The preparation of the starting compounds of the formula V can, for example, be carried out as follows: 1.8 liters of anhydrous hydrofluoric acid are initially introduced into a 5 liter stirred vessel with a cooler (-10° C.), 726 g of 2-chloro-5-amino-benzoic acid are then introduced in portions at -5° to 0° C., 480 g of NaNO2 are then introduced, likewise in portions, at 0°-5° C., the mixture is stirred for a further 30 minutes and 800 ml of dimethylsulphoxide are then added. The reaction is allowed to continue at 80°-85° C. until splitting off of N2 is complete. The mixture is cooled, and poured onto approx. 5 kg of ice, the precipitate is filtered off under suction, the residue from filtration is dissolved in an alkaline medium, the solution is filtered, the product is again precipitated with HCl, the precipitate is filtered off under suction, the residue from filtration is again dissolved in CH2 Cl2 (in order to free it from residual NaF), and the solution is filtered and again concentrated. Yield: 465 g m.p.: 145°-6° C. 350 g of the above acid are introduced into initially taken, excess thionyl chloride. After the addition and the HCl evolution are complete, the mixture is heated to approx. 100° C., and, after the reaction is complete, is worked up by distillation. Yield: 317 g boiling point 103° C./24 mbar nD20: 1.5487 By reaction with excess approx. 12.5% strength NH3 solution, and after filtration, 258 g of 2-chloro-5-fluoro-benzamide are obtained m.p.: 138° C.
 

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