Structure of 51105-90-9
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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. : | 51105-90-9 |
Formula : | C5H6N2O2 |
M.W : | 126.11 |
SMILES Code : | O=C(C1=CNN=C1)OC |
MDL No. : | MFCD00297363 |
Boiling Point : | No data available |
InChI Key : | VFTZKSMAJVLWOV-UHFFFAOYSA-N |
Pubchem ID : | 9793760 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.2 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 29.87 |
TPSA ? Topological Polar Surface Area: Calculated from |
54.98 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.82 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.07 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.2 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.4 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.8 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.3 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.95 |
Solubility | 14.3 mg/ml ; 0.113 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.78 |
Solubility | 21.0 mg/ml ; 0.167 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.27 |
Solubility | 6.77 mg/ml ; 0.0537 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 |
No |
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 |
-7.02 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) |
1.18 |
* 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 |
---|---|---|
79.6% | With hydrogenchloride; In methanol; water; | 3. Preparation of 4-carbomethoxypyrazole (5): To an ice cold saturated solution of HCl in methanol (500 ml), <strong>[37718-11-9]pyrazole-4-carboxylic acid</strong> (4) (19.2 g, 0.17 m) was added and the solution stirred at 0° C. for 3 hours and at ambient temperature overnight. The solvent was distilled off and the brown residue was dissolved in water. The aqueous solution was neutralized with NaHCO3 and the product was repeatedly extracted with ether (25*100 ml). The ether extract was dried over Mg SO4 and concentrated to give the methyl ester (5) as a pale yellow solid (13.59 g, 79.6percent). |
With sulfuric acid; sodium methylate; In methanol; chloroform; | PREPARATIVE EXAMPLE 6 Synthesis of methyl pyrazole-4-carboxylate <strong>[37718-11-9]4-Pyrazolecarboxylic acid</strong> (514 mg) was dissolved in methanol (10 ml) and sulfuric acid (0.25 ml), and the mixture was stirred at room temperature for 2 hours, followed by refluxing under heating for 4 hours. After cooling, a 28percent solution (0.95 ml) of sodium methylate in methanol was added to the reaction mixture for neutralization and the solvent was distilled away. Chloroform was added to the residue, and the residue was washed with water and brine and dried over anhydrous magnesium sulfate. The solvent was distilled away to give 433 mg of the title compound. 1 H-NMR(CDCl3 /ppm) delta3.92(3H, s), 8.08(2H, s), 8.26(1H, br s) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93.32% | With sulfuric acid; at 0 - 80℃; for 16h; | To the stirred solution of lH-pyrazole-4-carboxylic add 19-1 (20 g, 178.43 mmol) in methanol (100 niL) was added H2SO4 (17.50 g, 178.43 mmol, 9.51 rnL) at 0C and the reaction mixture was refluxed for 16 hours at 80C. Solvent was evaporated and the crude material was neutralized by saturated sodium bicarbonate solution. The aqueous layer was extracted with ethyl acetate and washed with brine. After separation, the organic layer was dried over sodium sulfate and evaporated to obtain methyl lH-pyrazole-4-earboxylate 19-2 (21 g, 166.52 mmol, 93.32% yield) as white solid. LC MS: ES+127.0. |
78% | With sulfuric acid; at 70℃; for 20h; | 1 H-<strong>[37718-11-9]pyrazole-4-carboxylic acid</strong> (20 g, 178.4 mmol) and sulfuric acid (39.65 ml)in MeOH (200 ml) were heated at 70C for 20 h. The reactbn mixture was cooled to room temperature and concentrated in vacuo. Aqueous NaOH solution was added to adjust the pH to ~6. The aqueous layer was extracted with EtOAc (3 x 200 ml) and the combined organic extracts were dried (MgSQ;), filtered and evaporated in vacuo to afford the title compound (18.5 g , 78%) as a white solid. 1 H-NMR (CDCI3, 500 MHz): d[ppm]= 8.10 (s, 2H), 3.87 (s, 3H) HPLCMS (Method A): [m/z]: 126.85 [M+H]+ |
5 g | With hydrogenchloride; at 10 - 35℃; | A) methyl 1H-pyrazol-4-carboxylate A mixture of <strong>[37718-11-9]1H-pyrazol-4-carboxylic acid</strong> (4.00 g) and 4 M hydrogen chloride/methanol solution (150 mL) was stirred overnight at room temperature, and the solvent was evaporated under reduced pressure to give the title compound (5.0 g). 1H NMR (400 MHz, DMSO-d6) delta 3.72 (3H, s), 8.09 (2H, s), 11.62 (1H, s). |
4.5 g | With sulfuric acid; at 0℃;Reflux; | To a mixture of lH-<strong>[37718-11-9]pyrazole-4-carboxylic acid</strong> (5.00 g, 44.6 mmol) in dry CH3OH (100 mL) was added drop-wise H2S04 (874 mg, 8.92 mmol) at 0C. The mixture was stirred at reflux overnight. A solution of NaOH (3.83 g, 95.7 mmol, 10 N) was added drop- wise to the reaction mixture. The mixture was poured into ice-water and diluted with ethyl acetate. The organic layer was washed with saturated aqueous lithium chloride solution and brine successively, dried over anhydrous Na2SC>4 and concentrated. The residue was purified by silica gel chromatography (petroleum ether : ethyl acetate = 10 : 1) to give methyl 1H- pyrazole-4-carboxylate (4.50 g) as a white solid. LC-MS (ESI) found: 127 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71.1% | With caesium carbonate; In N,N-dimethyl-formamide; | To a mixture of methyl 1H-pyrazole-4-carboxylate (800 mg, 6.34 mmol, 1 eq) and 3- iodotetrahydrofuran (1.51 g, 7.61 mmol, 1.2 eq) in DMF (8 mL) was added cesium carbonate (4.13 g, 12.7 mmol, 2 eq) at 20 C under nitrogen. The mixture was stirred at 20 C for 4 h. The residue was poured into ice-water (w/w = 1/1) (100 mL). The aqueous phase was extracted with EA (30 mLx3). The combined organic phase was washed with brine (30 mLx3), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography to give methyl 1-cyclopentylpyrazole-4-carboxylate as a white solid in 71.1% yield. LC-MS (ES+, m/z): 198.0 [(M+H)+]. |
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