Structure of 1H-Pyrazolo[3,4-c]pyridine
CAS No.: 271-47-6
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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. : | 271-47-6 |
Formula : | C6H5N3 |
M.W : | 119.12 |
SMILES Code : | C1(NN=C2)=C2C=CN=C1 |
MDL No. : | MFCD00661308 |
InChI Key : | KNYHISBJRQVMAZ-UHFFFAOYSA-N |
Pubchem ID : | 6451441 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 9 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 33.89 |
TPSA ? Topological Polar Surface Area: Calculated from |
41.57 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.57 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.48 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.96 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.11 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.67 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.71 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.62 |
Solubility | 2.85 mg/ml ; 0.0239 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.92 |
Solubility | 14.2 mg/ml ; 0.12 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.49 |
Solubility | 0.387 mg/ml ; 0.00325 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 |
-6.69 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) |
1.42 |
* 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 |
---|---|---|
84% | With iodine; potassium hydroxide; In N,N-dimethyl-formamide; at 20.0℃; | A suspension of 1H-pyrazolo[3,4-c]pyridine (300 mg, 2.52 mmol, 1.00 equiv), KOH (500 mg,8.91 mmol, 3.50 equiv), and diiodane (1.28 g, 5.04 mmol, 2.00 equiv) in DMF (10 mL) was stirredovernight at room temperature. The reaction was quenched by water, extracted with ethyl acetate,dried over anhydrous sodium sulfate, and concentrated under vacuum. The residue was purified bya silica gel column with ethyl acetate/petroleum ether (1:1) to give the title compound (577 mg,84%) as a yellow solid. LC-MS (ES, mlz): 246 [M+H]. |
73% | With iodine; potassium hydroxide; In N,N-dimethyl-formamide; at 20.0℃; for 3.0h; | To a solution of 1H-pyrazolo[3,4-c]pyridine (4.0 g, 33.6 mmol, 1.0 eq.) in DMF(40 mL) were added K2C03 (9.3 g, 100.8 mmol, 3.0 eq.), ?2 (7.9 g, 33.6 mmol, 1.0 eq.). Theresulting mixture was stirred at r.t. for 3 hr, then diluted by H20 and filtered. The collectedsolid was dried to give 3-iodo-1H-pyrazolo[3,4-c]pyridine (6.0 g, 73.0 %). |
73% | With iodine; potassium carbonate; In N,N-dimethyl-formamide; at 20.0℃; for 3.0h; | To a solution of 1H-pyrazolo[3,4-c]pyridine (4.0 g, 33.6 mmol, 1.0 eq.) in DMF (40 mL) were added K2C03 (9.3 g, 100.8 mmol, 3.0 eq.) and ?2 (7.9 g, 33.6 mmol, 1.0 eq.). The resulting mixture was stirred at rt for 3 h, then diluted by H20 and filtered. The solid was collected and dried to give 3-iodo-1H-pyrazolo[3,4-c]pyridine (6.0 g, 73.0 % yield). |
73% | With iodine; potassium carbonate; In N,N-dimethyl-formamide; at 20.0℃; for 3.0h; | To a solution of lH-pyrazolo[3,4-c]pyridine (4.0 g, 33.6 mmol, 1.0 eq.) in DMF (40 mL) were added K2C03 (9.3 g, 100.8 mmol, 3.0 eq.), I2 (7.9 g, 33.6 mmol, 1.0 eq.). The resulting mixture was stirred at r.t. for 3 hr, then diluted by H20 and filtered. The collected solid was dried to give 3-iodo-lH- pyrazolo[3,4-c]pyridine (6.0 g, 73.0 % yield). |
With iodine; potassium hydroxide; In N,N-dimethyl-formamide; at 20.0℃; for 16.0h; | To a solution of 1 H-pyrazolo[3,4-c]pyridine [271-47-6 ] (4.00 g, 33.6 mmol) in DMF (50 mL) were added iodine (12.8 g, 50.4 mmol) and potassium hydroxide (4.70 g, 84.0 mmol). The reaction mixture was stirred at RT for 16 h. The mixture was diluted with 10% sodium thiosulfate and water, then extracted (3x) with EtOAc. The combined organic extracts were washed with brine, then dried (Phase separator) and concentrated under vacuum. MS (LC/MS): 246.0 [M+H]+; tR (HPLC conditions k): 0.48 min. | |
With iodine; potassium hydroxide; In N,N-dimethyl-formamide; at 20.0℃; for 16.0h; | A. 3-Iodo-I H-pyrazolo[3,4-c]pyridineTo a solution of 1 H-pyrazolo[3,4-c]pyridine [27 1-47-6 1(4.00 g, 33.6 mmol) in DMF (50 mL) were added iodine (12.8 g, 50.4 mmol) and potassium hydroxide (4.70 g, 84.0 mmol). The reaction mixture was stirred at RT for 16 h. The mixture was diluted with 10% sodium thiosulfate and water, then extracted (3x) with EtOAc. The combined organic extracts were washed with brine, dried (Phase separator) and concentrated under vacuum. MS (LCMS): 246.0 [M+H]+; tR (HPLC conditions d): 0.48 mm. | |
With iodine; potassium hydroxide; In N,N-dimethyl-formamide; at 20.0℃; for 16.0h; | A. 3-lodo-1 H-pyrazolo[3,4-c]pyridineTo a solution of IH-pyrazolo[3,4-c]pyridine [271-47-6 ] (4.00 g, 33.6 mmol) in DMF (50 mL) were added iodine (12.8 g, 50.4 mmol) and potassium hydroxide (4.70 g, 84.0 mmol). The reaction mixture was stirred at RT for 16 h. The mixture was diluted with 10% sodium thiosulfate and water, then extracted (3x) with EtOAc. The combined organic extracts were washed with brine, dried (phase separator) and concentrated. MS (LC/MS): 246.0 [M+H]+; tR (H PLC conditions d): 0.48 mm. | |
With iodine; potassium hydroxide; In N,N-dimethyl-formamide; at 20.0℃; for 16.0h; | To a solution of 1 H-pyrazolo[3,4-c]pyridine [271-47-6 ] (4.00 g, 33.6 mmol) in DMF (50 mL) were added iodine (12.8 g, 50.4 mmol) and potassium hydroxide (4.70 g, 84.0 mmol). The reaction mixture was stirred at RT for 16 h. The mixture was diluted with 10% sodium thiosulfate and water, then extracted (3x) with EtOAc. The combined organic extracts were washed with brine, dried (Phase separator) and concentrated under vacuum. MS (LC/MS): 246.0 [M+H]+; tR (HPLC conditions d): 0.48 min. | |
With iodine; potassium hydroxide; In N,N-dimethyl-formamide; at 20.0℃; for 16.0h; | To a solution of 1H-pyrazolo[3,4-c]pyridine [271-47-6] (4.00 g, 33.6 mmol) in DMF (50 mL) were added iodine (12.8 g, 50.4 mmol) and potassium hydroxide (4.70 g, 84.0 mmol). The reaction mixture was stirred at RT for 16 h. The mixture was diluted with 10% sodium thiosulfate and water and extracted with EtOAc (3x). The combined organic extracts were washed with brine, dried (phase separator) and concentrated to afford the title compound. MS (LCMS): 246.0 [M+H]+; tR (H PLC conditions d): 0.48 mm. | |
With iodine; potassium hydroxide; In N,N-dimethyl-formamide; at 20.0℃; for 16.0h;Inert atmosphere; | To a solution of 1H-pyrazolo[3,4-c]pyridine [271-47-6 1(4.00 g, 33.6 mmol) in DMF (50 mL) were added iodine (12.8 g, 50.4 mmol) and potassium hydroxide (4.70 g, 84.0 mmol). The reaction mixture was stirred at RT for 16 h. The mixture was diluted with 10% sodium thiosulfate and water, then extracted (3x) with EtOAc. The combined organic extracts were washed with brine, dried (Phase separator) and concentrated under vacuum. MS (LCMS):246.0 [M+H]+; tR (H PLC conditions b): 0.48 mm. | |
With iodine; potassium hydroxide; In N,N-dimethyl-formamide; at 20.0℃; for 16.0h; | To a solution of 1H-pyrazolo[3,4-c]pyridine [271-47-61(4.00 g, 33.6 mmol) in DMF (50 mL) were added iodine (12.8 g, 50.4 mmol) and potassium hydroxide (4.70 g, 84.0 mmol). The reaction mixture was stirred at RT for 16 h. The mixture was diluted with 10% sodium thiosulfate and water, then extracted with EtOAc (3x). The combined organic extracts were washed with brine, dried (phase separator) and concentrated. MS (LCMS): 246.0 [M+H]+; tR (H PLC conditions d):0.48 mm. |
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