Structure of 89-54-3
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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| 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 |
| 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 |
63.32 Ų |
| Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.91 |
| Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.33 |
| Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.63 |
| Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.48 |
| Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.14 |
| Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.1 |
| Log S (ESOL):? ESOL: Topological method implemented from |
-2.08 |
| Solubility | 1.43 mg/ml ; 0.00833 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| Log S (Ali)? Ali: Topological method implemented from |
-2.26 |
| Solubility | 0.941 mg/ml ; 0.00548 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.02 |
| Solubility | 1.63 mg/ml ; 0.00948 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| 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) |
No |
| CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
| CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
| CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
| CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
| CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
| Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.4 cm/s |
| Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
| Ghose? Ghose filter: implemented from |
None |
| Veber? Veber (GSK) filter: implemented from |
0.0 |
| Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
| Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
| Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.56 |
| PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
| Brenk? Structural Alert: implemented from |
1.0 alert: heavy_metal |
| Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
| Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.18 |
* 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.

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With hydrogenchloride at 150 - 160℃; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With sodium carbonate |
| Yield | Reaction Conditions | Operation 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%). |
| Yield | Reaction Conditions | Operation 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. |
| Yield | Reaction Conditions | Operation 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 |
| Yield | Reaction Conditions | Operation 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 |
| Yield | Reaction Conditions | Operation 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 |
| Yield | Reaction Conditions | Operation 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) |
| Yield | Reaction Conditions | Operation 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. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 62% | With triethylamine In dichloromethane at 20℃; for 18.5h; |

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