Structure of 85290-80-8
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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. : | 85290-80-8 |
Formula : | C7H10N2O2 |
M.W : | 154.17 |
SMILES Code : | O=C(C1=CN(C)N=C1)OCC |
MDL No. : | MFCD12180234 |
InChI Key : | GXKQVOXCQOQZED-UHFFFAOYSA-N |
Pubchem ID : | 11116265 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.43 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 39.58 |
TPSA ? Topological Polar Surface Area: Calculated from |
44.12 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.88 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.45 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.6 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.33 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.47 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.75 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.22 |
Solubility | 9.34 mg/ml ; 0.0606 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.94 |
Solubility | 17.5 mg/ml ; 0.114 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.26 |
Solubility | 8.41 mg/ml ; 0.0546 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 |
-6.92 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) |
1.54 |
* 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 |
---|---|---|
99.1% | In ethanol; at 5 - 20℃; | j00324J Step A: ethyl l-methyl-1H-pyrazole-4-carboxylate: To a 3000-mL three- necked flask was added <strong>[80370-42-9]ethyl 2-formyl-3-oxopropanoate</strong> (100 g, 694 mmol), followed by anhydrous 200-proof EtOH (694 mL) to obtain a clear yellowish solution. The reaction was cooled in an ice bath to 5 °C, and then methyihydrazine (35.8 mL, 680 mmol) was added dropwise. A vigorous exotherm was observed during hydrazine addition and the temperature was kept below 12 °C by controlling the addition rate. After the hydrazine addition was complete, the ice bath was removed, and the reaction was allowed to stir at ambient temperature overnight. The reaction was concentrated on a rotary evaporator to a crude orange oil. The crude was taken up in DCM and re-concentrated, then on high vacuum for 2 days to yield tan orange oil. LC/MS and ?H NMR showed essentially pure ethyl 1-methyl- 1 H-pyrazole-4-carboxylate (106 g, 99.1percent). |
99% | In ethanol; at 5 - 20℃; for 16h; | [00352] Step A: ethyl 1 -methyl- 1 H-pyrazole-4-carboxylate: To a 3000-mL three- necked flask was added <strong>[80370-42-9]ethyl 2-formyl-3-oxopropanoate</strong> (100 g, 694 mmol), followed by anhydrous 200-proof EtOH (694 mL). The reaction was cooled in an ice bath to 5 °C, and then methylhydrazine (35.8 mL, 680 mmol) was added dropwise. A vigorous exotherm was observed during hydrazine addition and the temperature was kept below 12 °C by controlling the addition rate. After the hydrazine addition was complete, the ice bath was removed, and the reaction was allowed to stir at ambient temperature for 16 hours. The reaction was concentrated in vacuo and the residue dissolved in DCM and re-concentrated, then dried for 2 days to yield ethyl 1 -methyl- lH-pyrazole-4-carboxylate (106 g, 99percent yield) as a tan orange oil. MS (apci) m/z = 155.1 (M+H). |
99.1% | In ethanol; at 5 - 20℃; | 1006631 Step A: ethyl 1-methyl-1H-pyrazole-4-carboxylate: To a 3000-mL three- necked flask was added <strong>[80370-42-9]ethyl 2-formyl-3-oxopropanoate</strong> (100 g, 694 mmol), followed by anhydrous 200-proof EtOH (694 mE) to obtain a clear yellowish solution. The reaction was cooled in an ice bath to 5 °C, and then methyihydrazine (35.8 mL, 680 mmol) was added dropwise. A vigorous exotherm was observed during hydrazine addition and the temperature was kept below 12 °C by controlling the addition rate. After the hydrazine addition was complete, the ice bath was removed, and the reaction was allowed to stir at ambient temperature overnight. The reaction was concentrated on a rotary evaporator to a crude orange oil. The crude was taken up in DCM and re-concentrated, then on high vacuum for 2 days to yield tan orange oil. LC/MS and ?H NMR showed essentially pure ethyl 1-methyl-1H- pyrazole-4-carboxylate (106 g, 99.1percent). |
99% | In ethanol; at 5 - 20℃; for 16h; | Intermediate 24 1 ',4-dimethyl- 1 -phenyl- 1 H, 1 -3 ,4'-bipyrazol-5-amine [00463] Step A: ethyl 1 -methyl- 1 H-pyrazole-4-carboxylate: To a 3000-mL three-necked flask was added <strong>[80370-42-9]ethyl 2-formyl-3-oxopropanoate</strong> (100 g, 694 mmol), followed by anhydrous 200-proof EtOH (694 mL). The reaction was cooled in an ice bath to 5 °C, and then methylhydrazine (35.8 mL, 680 mmol) was added dropwise. A vigorous exotherm was observed during hydrazine addition and the temperature was kept below 12 °C by controlling the addition rate. After the hydrazine addition was complete, the ice bath was removed, and the reaction was allowed to stir at ambient temperature for 16 hours. The reaction was concentrated under vacuum and the residue dissolved in DCM and re-concentrated, then dried for 2 days to yield ethyl 1 -methyl- lH-pyrazole-4-carboxylate (106 g, 99percent yield) as a tan orange oil. MS (apci) m/z = 155.1 (M+H). |
99% | In ethanol; at 5 - 20℃; | To a 3000-mL three- necked flask was added <strong>[80370-42-9]ethyl 2-formyl-3-oxopropanoate</strong> (100 g, 694 mmol), followed by anhydrous 200-proof EtOH (694 mL). The reaction was cooled in an ice bath to 5 °C, and then methylhydrazine (35.8 mL, 680 mmol) was added dropwise. A vigorous exotherm was observed during hydrazine addition and the temperature was kept below 12 °C by controlling the addition rate. After the hydrazine addition was complete, the ice bath was removed, and the reaction was allowed to stir at ambient temperature for 16 hours. The reaction was concentrated under vacuum and the residue dissolved in DCM and re-concentrated, then dried for 2 days to yield ethyl 1 -methyl- lH-pyrazole-4-carboxy late (106 g, 99percent yield) as a tan orange oil. MS (apci) m/z = 155.1 (M+H). |
99% | In ethanol; at 12 - 20℃; for 16h; | 1006621 Step A: ethyl 1-methyl-1H-pyrazole-4-carboxylate: To a 3000-mL three- necked flask was added <strong>[80370-42-9]ethyl 2-formyl-3-oxopropanoate</strong> (100 g, 694 mmol), followed by anhydrous 200-proof EtOH (694 mL). The reaction was cooled in an ice bath to 5 °C, and then methylhydrazine (35.8 mL, 680 mmol) was added dropwise. A vigorous exotherm was observed during hydrazine addition and the temperature was kept below 12 °C by controlling the addition rate. After the hydrazine addition was complete, the ice bath was removed, and the reaction was allowed to stir at ambient temperature for 16 hours. The reaction was concentrated in vacuo and the residue dissolved in DCM and re-concentrated, then dried for 2 days to yield ethyl 1-methyl-i H-pyrazole-4-carboxylate (106 g, 99percent yield) as a tan orange oil. MS (apci) m/z = 155.1 (M+H). |
99.1% | In ethanol; at 5 - 20℃; | To a 3000-mL three-necked flask was added <strong>[80370-42-9]ethyl 2-formyl-3-oxopropanoate</strong> (100 g, 694 mmol), followed by anhydrous 200-proof EtOH (694 mL) to obtain a clear yellowish solution. The reaction was cooled in an ice bath to 5 °C, and then methylhydrazine (35.8 mL, 680 mmol) was added dropwise. A vigorous exotherm was observed during hydrazine addition and the temperature was kept below 12 °C by controlling the addition rate. After the hydrazine addition was complete, the ice bath was removed, and the reaction was allowed to stir at ambient temperature overnight. The reaction was concentrated on a rotary evaporator to a crude orange oil. The crude was taken up in DCM and re-concentrated, then on high vacuum for 2 days to yield the title compound as a tan orange oil (106 g, 99.1percent yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With lithium aluminium tetrahydride; In tetrahydrofuran; at 0 - 60℃; | A solution of ethyl 1 -methyl- lH-pyrazole-4-carboxylate (1.16 g, 7.52 mmol) in THF (13.3 mL) was added into a solution of lithium aluminiumhydride (1.0 M in THF, 15.05 mL, 15.05 mmol) in THF (53 mL) dropwise at 0 °C. The resulting mixture was allowed to heat at 60 °C for lh. After lh, the reaction was allowed to cool to rt. Sodium sulfate decahydrate (4.0 g) was added portion wise and the resulting mixture was stirred for lh at rt. EtOAc (150mL) was added and the resulting mixture was stirred overnight. The mixture was filtered through a pad of celite and the residual solid was washed with EtOAc several times. The filtrate was concentrated in vacuo to afford the title compound as colorless oil (790 mg, 93percent).1H NMR (400 MHz, CDC13) delta 7.49 (s, 1H), 7.39 (s, 1H), 4.59 (s, 2H), 3.90 (s, 3H). |
62% | With lithium aluminium tetrahydride; In tetrahydrofuran; at 25 - 30℃; for 3h;Inert atmosphere; Cooling; | Lithium aluminium hydride (320 mL, 0.32 mole, 1M in THF) was added to acooled solution of ethyl 1-methyl-1H-pyrazole-4-carboxylate (32.34 g, 0.21 mole) inTHF (300 mL) under stirring in N2 atmosphere. The reaction mixture was warmed toRT and stirred further for 3 hours. The reaction mixture was cooled to 0 °C, dilutedwith ethyl acetate and treated with water (25 mL). The mixture was filtered throughcelite bed and concentrated under vacuum to obtain the crude compound which was further purified by flash chromatography (ethyl acetate: methanol (98:2)) to afford (1- methyl- 1H-pyrazol-4-yl)-methanol.Yield: 14.66 g (62 percent); ?H - NMR (CDC13, 400 MHz) oe ppm: 1.98 (bs, 1H), 3.88 (s,3H), 4.56 (s, 2H), 7.36 (s, 1H), 7.45 (s, 1H); Mass (mlz): 113.1 (M+H). |
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