Structure of 304693-70-7
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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. : | 304693-70-7 |
Formula : | C7H10N2O2 |
M.W : | 154.17 |
SMILES Code : | O=CC1=CN(CCOC)N=C1 |
MDL No. : | MFCD13248693 |
InChI Key : | OZCYWOQGSFDUNP-UHFFFAOYSA-N |
Pubchem ID : | 23033398 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.43 |
Num. rotatable bonds | 4 |
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 |
1.42 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-0.52 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.34 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.75 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.63 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.22 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.54 |
Solubility | 44.4 mg/ml ; 0.288 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
0.06 |
Solubility | 178.0 mg/ml ; 1.15 mol/l |
Class? Solubility class: Log S scale |
Highly soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.28 |
Solubility | 8.09 mg/ml ; 0.0525 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 |
-7.61 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 |
1.0 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) |
1.79 |
* 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 trichlorophosphate; In N,N-dimethyl-formamide; at 90 - 100℃; for 3.0h; | Intermediate B6-1-(2-Methoxyethyl)pyrazole carboxaldehyde A solution of 1-(2-methoxyethyl)pyrazole (7.27 g) in dry DMF (11.4 ml) was heated to 90 C., then phosphorus oxychloride (5.4 ml) was added dropwise over 1 hour, maintaining the temperature between 95-100 C. After heating for a further 2 hours, the mixture was cooled and poured onto ice.Sodium hydroxide was added to adjust the mixture to PH 4, then the product was extracted into dichloromethane.Drying and evaporation of the organic extracts yielded a brown oil (7.19 g).1H-NMR (CDCl3) delta 3.34 (3H,s), 3.75 (2H,m), 4.32 (2H,m), 7.98 (1H,s), 8.02 (1H,s), 9.85 (1H,s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
26% | In a sealed tube, under N2, intermediate 35 (211 mg; 1.37 mmol) and Ti(OiPr)4 (436 jiL; 1.83 mmol) were added to a solution of intermediate 11(300mg; 0.914 mmol) in THF(6 mL). The solution was stirred at 50C for 5 hours then at rt overnight. The reaction mixture was cooled to 5C and isopropyl magnesium chloride 2M in THF (2.28 mL; 4.57 mmol) was added dropwise. The reaction mixture was allowed to rise slowly to rt and stirred overnight. The reaction mixture was diluted with EtOAc and poured onto a 10% aqueous solution of K2C03. The precipitate was removed by filtration over Celite. Theorganic layer was decanted, washed with brine, dried over MgSO4, filtered and evaporated to dryness. The residue was purified by chromatography over silica gel (irregular SiOH, 40g; mobile phase: gradient from 0% MeOH, 100% DCM to 10% MeOH, 90% DCM). The fractions containing the product were collected and evaporated to dryness to give 0.337 g of an intermediate residue which was purified again bychromatography via reverse phase (stationary phase: YMC-actus Triart C18 lOjim30*150mm, mobile phase: gradient from 55% NH4HCO3 0.2%, 45% ACN to 0%NH4HCO3 0.2%, 100% ACN). The pure fractions were collected and evaporated todryness. The residue was freeze-dried with acetonitrile/water 20/80 to afford 120 mg(26%) of compound 71. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With caesium carbonate; In N,N-dimethyl-formamide; at 60℃; | To a solution of lH-pyrazole-4-carbaldehyde (500 mg, 5.20 mmol) in DMF (20 mL) was added l-bromo-2-methoxyethane (713 mg, 5.2 mmol) and CS2CO3 (3.40 g, 10.4 mmol). After stirring at 60 °C overnight, water (20 mL) was added to the mixture and the mixture was extracted with EtOAc (50 ml x 3). The organic phase was washed with brine, dried over Na2S04 and concentrated to yield intermediate 50 (520 mg, 65percent> yield). |
55% | With caesium carbonate; In acetonitrile; for 2h;Reflux; | 1H-pyrazole-4-carbaldehyde (0.5 g; 5.2 mmol) and cesium carbonate (3.39 g; 10.4mmol) were diluted in ACN (10 mL). Then, 2-bromoethyl methyl ether (0.636 mL; 6.77 mmol) was added and the reaction mixture was refluxed for 2 hours. The reaction mixture was partitionned between a saturated solution of NaHCO3 and EtOAc. The organic layer was separated, dried over MgSO4, filtered and concentrated.The residue was purified by silica gel chromatography (irregular Si02, 120 g, DCM/MeOH: 100/0 to 95/5). The fractions containing the product were mixed andconcentrated to afford 439 mg (55percent) of intermediate 35. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
24.6% | With sodium tris(acetoxy)borohydride; In dichloromethane; at 20℃; | To a solution of Intermediate 47 (300 mg, 0.44 mmol) in dichloromethane (5 mL) was added intermediate 50 (80.0 mg, 0.530 mmol) and NaBH(OAc)3 (186 mg, (0941) 0.880 mmol). After stirring at room temperature overnight, the mixture was concentrated to give a residue which was purified by prep-HPLC (Waters 2767/Qda, Column: Waters Xbridge 19* 150mm lOum, Mobile Phase A: H20 (0.1%NH4OH), B: ACN) to yield Compound 97 (53.0 mg, 24.6% yield) as yellow oil. (0942) NMR CDCI3 (400 MHz): delta 8.42 (s, 1H), 7.42 (s, 1H), 7.38 (s, 2H), 4.26 (t, J= 5.2 Hz, 2H), 3.91-3.83 (m, 3H), 3.75-3.73 (m, 3H), 3.64 (q, J= 10.4 Hz, 2H), 3.43 (s, 2H), 3.33 (s, 3H), 2.54-2.49 (m, 4H), 2.37-2.32 (m, 2H), 1.86-1.80 (m, 1H), 1.70-1.63 (s, 1H). |
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