Structure of 3528-58-3
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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. : | 3528-58-3 |
Formula : | C5H9N3 |
M.W : | 111.15 |
SMILES Code : | CCN1N=CC=C1N |
MDL No. : | MFCD00010849 |
InChI Key : | FSJOLBAFVKSQQJ-UHFFFAOYSA-N |
Pubchem ID : | 337310 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 8 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.4 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 32.7 |
TPSA ? Topological Polar Surface Area: Calculated from |
43.84 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.05 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.19 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.49 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.14 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.05 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.37 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.05 |
Solubility | 10.0 mg/ml ; 0.0901 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.67 |
Solubility | 23.8 mg/ml ; 0.214 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.78 |
Solubility | 18.4 mg/ml ; 0.166 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 |
-6.84 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) |
1.4 |
* 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 |
---|---|---|
at 150℃; for 5h;Product distribution / selectivity; | Alternative preparation of ethyl 4-chloro-1-ethyl-6-methyl-1H-pyrazolo[3,4-blpvridine-5- carboxylate: A mixture of 5-amino-1-ethylpyrazole (1.614g, 14.5mmol) and diethyl 2-(1- ethoxyethylidene)malonate [e.g. see J. Am. Chem. Soc, 1931, 53, 1836] (3.68g) is heated at 150 0C under Dean Stark conditions for 5 hours. Phosphorous oxychloride (25ml) is carefully added to the mixture and the resulting solution is heated at 130 0C under reflux for 18 hours. The mixture is concentrated in vacuo and the residual oil is carefully added, with cooling, to water (100ml). The resulting mixture is extracted with dichloromethane (3 x 100ml) and the combined organic extracts are dried over anhydrous sodium sulphate and concentrated in vacuo. The residual oil is purified by Biotage chromatography (silica; 9Og) eluting with 5% ethyl acetate in petroleum ether. Fractions containing the desired product are combined and concentrated in vacuo to give ethyl 4-chloro-1 -ethyl-6-methyl-1 /-/-pyrazolo[3,4-]pyridine-5-carboxylate.. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57.17% | A mixture of l-ethyl-lH-pyrazol-5-amine (16 gm, 0.144 moles) (example 2) and 2-(l-ethoxy-ethylidene)-malonic acid diethyl ester (29 gm, 0.12 moles) (example 3) was stirred at 1200C for about 2 hrs. When the reaction was complete on TLC, crude reaction mixture was concentrated in vacuo to remove ethanol, which was formed as byproduct. Crude residue was taken in phosphorous oxychloride (50 ml) and heated at 115 C for about 12-13 hrs. The reaction mixture was poured into ice-cooled water with continuous stirring. Solid which precipitated out was filtered and dried under vacuum to afford title compound as creamy white solid.Yield: 12 gm (57.17%) m/z: (M++l) 268.28 | |
Intermediate 11: Ethyl 4-chloro-1-ethyl-6-methyl-lH-pyrazolo [3, 4-b] pyridine-5- carboxylate; A mixture of 5-amino-1-ethylpyrazole (1.614g, 14. 5mmol) and diethyl 2- (1- ethoxyethylidene) malonate (3.68g, 16. 0mmol, as described by P. P. T. Sah, J. Amer. Chem. Soc., 1931,53, 1836) was heated at 150 C under Dean Stark conditions for 5 hours. Phosphorous oxychloride (25ml) was carefully added to the mixture and the resulting solution was heated at 130 C under reflux for 18 hours. The mixture was concentrated in vacuo, then the residual oil was carefully added, with cooling, to water (100ml). The resulting mixture was extracted with DCM (3xlOOml) and the combined organic extracts were dried over anhydrous sodium sulphate and concentrated in vacuo. The residual oil was purified by Biotage chromatography (silica, 90g) eluting with ethyl acetate-petrol (1: 19). Fractions containing the desired product were combined and concentrated in vacuo to afford Intermediate 58 (1. 15g). LCMS showed MH+ = 268 ; TpBT = 3. 18min | ||
A mixture of 5-amino-1-ethylpyrazole (1.614g, [14.] [5MMOL)] and diethyl [2- (1-] ethoxyethylidene) malonate (3.68g, [16.] [0MMOL,] as described by P. P. T. Sah, [J AMER.] Chem. Soc., 1931,53, 1836) was heated at [150 C] under Dean Stark conditions for 5 hours. Phosphorous oxychloride [(25ML)] was carefully added to the mixture and the resulting solution was heated at [130 C] under reflux for 18 hours. The mixture was concentrated in vacuo, then the residual oil was carefully added, with cooling, to water [(100ML).] The resulting mixture was extracted with DCM [(3XLOOML)] and the combined organic extracts were dried over anhydrous sodium sulphate and concentrated in vacuo. The residual oil was purified by Biotage chromatography (silica, 90g) eluting with ethyl acetate-petrol (1: 19). Fractions containing the desired product were combined and concentrated in vacuo to afford Intermediate 51 (1.15g). LCMS showed MH+ = 268; TRET = 3. [18MIN.] |
A mixture of 5-amino-1-ethylpyrazole (1.614 g, 14.5 mmol) and <strong>[3044-06-2]diethyl 2-(1-ethoxyethylidene)malonate</strong> [J. Am. Chem. Soc., 1931, 53, 1836] (3.68 g) was heated at 150 C. under Dean Stark conditions for 5 hours. Phosphorous oxychloride (25 ml) was carefully added to the mixture and the resulting solution was heated at 130 C. under reflux for 18 hours. The mixture was concentrated in vacuo and the residual oil was carefully added, with cooling, to water (100 ml). The resulting mixture was extracted with dichloromethane (3*100 ml) and the combined organic extracts were dried over anhydrous sodium sulphate and concentrated in vacuo. The residual oil was purified by Biotage chromatography (silica; 90 g) eluding with 5% ethyl acetate in petroleum ether. Fractions containing the desired product were combined and concentrated in vacuo to give Intermediate 17 (1.15 g). LCMS showed MH+=268; TRET=3.18 min. | ||
Intermediate 17: Ethyl 4-chloro-1-ethyl-6-methyl-1H-pyrazolo[3,4-Jb]pyridine-5- carboxylate EPO <DP n="145"/>A mixture of 5-amino-i-ethylpyrazole (1.614g, 14.5mmol) and diethyl 2-(1- ethoxyethylidene)malonate [J. Am. Chem. Soc, 1931, 53, 1836 (3.68g) was heated at 150 0C under Dean Stark conditions for 5 hours. Phosphorous oxychloride (25ml) was carefully added to the mixture and the resulting solution was heated at 130 0C under reflux for 18 hours. The mixture was concentrated in vacuo and the residual oil was carefully added, with cooling, to water (100ml). The resulting mixture was extracted with dichloromethane (3 x 100ml) and the combined organic extracts were dried over anhydrous sodium sulphate and concentrated in vacuo. The residual oil was purified by Biotage chromatography (silica; 9Og) eluting with 5% ethyl acetate in petroleum ether. Fractions containing the desired product were combined and concentrated in vacuo to give Intermediate 17 (1.15q). LCMS showed MH+ = 268; TREtau = 3.18min. |
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