Structure of 37435-12-4
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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. : | 37435-12-4 |
Formula : | C7H5ClN2 |
M.W : | 152.58 |
SMILES Code : | ClC1=C2NN=CC2=CC=C1 |
MDL No. : | MFCD07368214 |
InChI Key : | WIYOYUQVNPTVQG-UHFFFAOYSA-N |
Pubchem ID : | 11116249 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P280-P305+P351+P338-P310 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 9 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 41.1 |
TPSA ? Topological Polar Surface Area: Calculated from |
28.68 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.31 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.18 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.22 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.72 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.71 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.03 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.83 |
Solubility | 0.228 mg/ml ; 0.00149 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.42 |
Solubility | 0.586 mg/ml ; 0.00384 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.51 |
Solubility | 0.0472 mg/ml ; 0.000309 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) |
Yes |
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 |
-5.68 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 |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
0.0 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) |
1.44 |
* 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 hydrazine hydro-chloride; In ethanol; for 3h;Reflux; | General procedure: To a solution of 2-hydroxy-3-methylbenzaldehyde (5 g, 36.7 mmol) inEtOH (30 mL) was added hydrazine hydrochloride (in excess) in a 250 mL flask. The solution was refluxed for 3 h and the solvent was distilled under reduced pressure. Purification of the residue by column chromatography (EtOAc:PE=10:1) on silica gel was performed to give 3.5 g of 7-methyl-1H-indazole, yellow crystals (73% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
34% | General procedure: Sodium hydride (0.53 g, 6.6 mmol, 60% oil dispresion) was added to the stirred solution of the corresponding azole (3.3 mmol) in anhydrous THF (2 mL) at room temperature. After 15 min, freshly prepared 2-(chloromethyl)-4,5-dihydro-1H-imidazole 2 (0.47 g, 4.0 mmol) was added and the reaction mixture was stirred at ambient temperature for 6 h. The N-alkylation products 3, 5, 7 and 8 were isolated upon quenching the reaction mixture with water (5 mL) followed by extraction with dichloromethane (3 × 5 mL). The combined organic layers were dried over anhydrous sodium sulfate and evaporated under reduced pressure. The oily residue thus obtained was purified on silica with use of chromatotron (Et3N/MeOH/AcOEt 1:5:100). All products were very polar with Rf values close to 0.05.The N-alkylation reaction of indazoles (1) provided the desired N1 substituted products (3) along with the N2 substituted side product. The latter compounds demonstrated considerably lower Rf than 3 and were not isolated in pure form. The alkylation reactions of benzotriazoles 6a and 6c allowed the isolation of N1 substituted products 7a-b (higher Rf) and N2 isomer 8b (lower Rf). However, in the case of 4-methyl-benzotriazole 6b only the N2 substituted isomer 8a was isolated as a pure product.The products 3, 5, 7 and 8 were then converted into water-soluble hydrochloride salts suitable for biological tests with use of methanolic hydrochloric acid solution or by passing gaseous hydrogen chloride through dichloromethane solution of the corresponding free base. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87.8% | With iodine; potassium hydroxide; In N,N-dimethyl-formamide; at 20℃; | To a mixture of 7-chloro-lH-indazole (0.6 g, 3.93mmol, 1.0 eq.), KOH (0.55 g, 9.8 mmol) in DMF was added I2 (1.02g, 4.01 mmol, 1.02 eq.). The mixture was stirred at r.t. overnight, then quenched by aqueous Na2S204 solution. The mixture was extracted with EtOAc (2 x 50 mL). The combined organic layers were dried over anhydrous Na2S04 and concentrated. The resulting residue was purified by column chromatography (PE/EA =10: 1) to provide 7-chloro-3-iodo-lH-indazole (0.96 g, 87.8%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With copper(l) iodide; hexamethylenetetramine; caesium carbonate; In N,N-dimethyl-formamide; for 26h;Reflux; | General procedure: In a 250 mL flask, 1-chloro-2-nitrobenzene (3.5 g, 22.3 mmol), 4-methyl-1H-indazole (3.0 g, 23 mmol), cesium carbonate (7.4 g, 23 mmol), HMTA (0.1 g) and CuI (0.1g) were dissolved in DMF (100 mL). The mixture was heated to reflux for 26 h. After the complete disappearance of the substrates, the reaction was stopped and the mixture was cooled to room temperature. The reaction mixture was passed through a plug of celite and the filtrate was slowly added to the same volume of water, extracted three times with EtOAc and the organic phase was combined. The combinedorganic layer was dried over anhydrous magnesium sulfate and evaporated under reduced pressure to givea crude product. After the organic layer was concentrated, the residue was purified by column chromatography (EtOAc:PE=8:1) on silica gel to give 4-methyl-1-(2-nitrophenyl)-1H-indazole (3.8 g,yellow crystals. yield 68%). |