Structure of 1201924-32-4
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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. : | 1201924-32-4 |
Formula : | C7H6ClNO2 |
M.W : | 171.58 |
SMILES Code : | O=C(O)C1=NC(Cl)=CC=C1C |
MDL No. : | MFCD16249840 |
InChI Key : | ODSPBBWQVLWOPG-UHFFFAOYSA-N |
Pubchem ID : | 46941470 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 41.17 |
TPSA ? Topological Polar Surface Area: Calculated from |
50.19 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.17 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.04 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.74 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.18 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.82 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.32 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.53 |
Solubility | 0.51 mg/ml ; 0.00297 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.72 |
Solubility | 0.325 mg/ml ; 0.0019 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.4 |
Solubility | 0.688 mg/ml ; 0.00401 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 |
-5.9 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) |
1.64 |
* 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 methanol; In tetrahydrofuran; at 20℃; for 2h; | Step 4. Methyl 6-chloro-3 -methylpyridine-2-carbox ylate6-Chloro-3-methylpyridine-2-carboxylic acid (3.69 g, 21.51 mmol) was taken up in THF (100 raL)/MeOH (25 mL). A solution of TMS-diazomethane (21.5 mL, 43.0 mmol) was added and the resulting solution stirred at room temperature for 2 hours. The solvent was removed in vacuo and the residue purified by silica gel chromatography (2-20% EtOAc/hexanes) to give the title compound as a white solid.LRMS (APCI) calc'd for (C8H9ClNO2) [M+Hf: 186, 188, Found: 186, 188. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Step 3. 6-Chloro-3 -methylpyridine-2-carboxylic acid6-Chloro-3-methylrhoyridine-2-carbonitrile (2.95 g, 19.3 mmol) and Potassium hydroxide (3.25 g, 58 mmol) were stirred in refluxing water (60 mL) for 2 hours. The mixture was cooled to room temperature, 30 mL of 2 N HCl was added, followed by the addition of water. The resulting mixture was extracted with EtOAc (3x). The combined organic extracts were washed with brine, dried over MgSO4, filtered, and concentrated in vacuo to give the title compound as a white solid.1H NMR (600 MHz, DMSO): delta 13.45 (br s, 1 H), 7.81 (d, J= 8.4 Hz5 1 H), 7.55 (d, J- 8.4 Hz, 1 H), 2.39 (s, 3 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | Scheme 14. step B. To a solution of6-chloro-3-methyl-pyridine-2-carboxylic acid(0.35 g, 0.20 mmol) in CH2Ch (6 ml) at room temperature are added methyl3-amino-3,5-dimethylbenzoate (0.36 g, 0.20 mmol, see preparation 12), and N,N-diisopropylethylamine (0.77 g, 0.60 mmol). After stirring the reaction mixture for 10minutes, 1-propanephosphonic acid cyclic anhydride (50percent solution in ethyl acetate, 2.54g, 0.80 mmol) is added via syringe. After 16 hours at ambient temperature, the reactionmixture is diluted with CH2Ch, washed with water and brine. The organic layers arecombined and dried over anhydrous Na2S04, filtered, and concentrated under reduced pressure to give the title compound as a white powder (0.52 g, 76 percent). Mass spectrum15(m/z): 333.2 (M+ 1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | Scheme 15, step A. To a solution of 6-chloro-3-methyl-pyridine-2-carboxylicacid (0.70 g, 4.093 mmol, see preparation 1) in CH2Ch (6 mL) at 0 oc are added <strong>[3095-48-5]methyl 4-amino-3,5-dimethylbenzoate</strong> (0.74 g, 4.093 mmol, see preparation 12), andtriethylamine (0.83 g, 8.187 mmol). After stirring the reaction mixture for 10 minutes, 1-propanephosphonic acid cyclic anhydride (50percent solution in ethyl acetate, 2.60 g, 8.187mmol) is added via syringe and stirred at ambient temperature. After 12 hours, the solvent is removed under reduced pressure and the residue is diluted with water andextracted with ethyl acetate. The organic layers are combined and dried over anhydrousNa2S04, filtered, and concentrated under reduced pressure. The resulting residue ispurified by flash chromatography (silica gel) using a gradient of0-40percent ethyl acetate inhexanes to give the title compound as an off-white solid (1.10 g, 81 percent). Mass spectrum (m/z): 333.2 (M+ 1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With water; sodium hydroxide; In tetrahydrofuran; at 0 - 50℃; for 2h; | A solution of aqueous 2N NaOH (5 ml) is added to a stirred solution of <strong>[878207-92-2]methyl 6-chloro-3-methyl-pyridine-2-carboxylate</strong> (0.500 g, 2.702 mmol) in THF (10 mL) at 0 C. The mixture is heated at 50C for 2 hours. The reaction mixture is acidified with aqueous citric acid solution and extracted with EtOAc (2 x 10 ml). The combined organic layers are dried over sodium sulfate, filtered, and concentrated under reduced pressure to give the title compound as an off-white solid (0.45 g, 97%). The residue is used in next step without further purification. Mass spectrum (m/z): 172.0 (M+H)+. |
84% | With water; sodium hydroxide; In tetrahydrofuran; methanol; at 20℃; for 3h; | Scheme 1, step A. A solution of aqueous IN NaOH (10 ml) is added to a stirred solution ofmethyl6-chloro-3-methyl-pyridine-2-carboxylate (1.0 g, 5.39 mmoles) inTHF:MeOH (IOml:2 ml). The mixture is stirred at room temperature for 3 hours. Theorganic solvent is removed under reduced pressure and the semi-solid is dissolved inwater and acidified to pH I-2 with aqueous IN HCI. The resulting precipitate is filtered,washed with water, and dried at 40C in a vacuum oven for I2 hours to give the title compound as a white solid (780 mg, 84%). Mass spectrum (m/z): I72.0 (M+I). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With thionyl chloride; at 65℃; for 3h; | Step A: Methyl 6-chloro-3-methylpicolinate. Thionyl chloride (208 g, 1.75 mol) was added to a solution of 6-chloro-3-methylpicolinic acid (200 g, 1.17 mol) in methanol (300 mL) and the reaction mixture was warmed to 65 C. After 3 hours, the reaction mixture was concentrated under reduced pressure, and saturated aqueous NaHCO3 solution (1 L) was added. The aqueous layer was extracted twice with ethyl acetate which resulted in several organic solvent fractions which were combined, dried over Na2SO4, filtered, and concentrated to dryness under reduced pressure to provide the title compound as a dark-brown solid (210 g, 97%). 1H NMR (400 MHz, CDCl3) 7.57 (d, J=8.0 Hz, 1H) 7.36 (d, J=8.0 Hz, 1H) 3.95 (s, 3H) 2.53 (s, 3H). |
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