Structure of 78760-60-8
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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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Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 78760-60-8 |
Formula : | C13H10N2O |
M.W : | 210.23 |
SMILES Code : | N#CC1=CC=C(OCC2=CC=CC=C2)C=N1 |
MDL No. : | MFCD11977436 |
InChI Key : | FCECYLUEYDBZHV-UHFFFAOYSA-N |
Pubchem ID : | 15574701 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H312-H332 |
Precautionary Statements: | P280 |
Num. heavy atoms | 16 |
Num. arom. heavy atoms | 12 |
Fraction Csp3 | 0.08 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 59.93 |
TPSA ? Topological Polar Surface Area: Calculated from |
45.91 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.24 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.37 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.38 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.07 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.84 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.18 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.99 |
Solubility | 0.213 mg/ml ; 0.00101 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.97 |
Solubility | 0.223 mg/ml ; 0.00106 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.78 |
Solubility | 0.00349 mg/ml ; 0.0000166 mol/l |
Class? Solubility class: Log S scale |
Moderately 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) |
Yes |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
Yes |
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 |
-5.9 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 |
0.0 |
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) |
2.23 |
* 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 |
---|---|---|
85% | Step l:5-Benzyloxy-pyridine-2-carbonitrile (3_60_2) [00482] A mixture of 5-hydroxy-pyridine-2-carbonitrile 3_60_1 (14 g, 116 mmol) and potassium carbonate (32.2 g, 233 mmol) in Nu,Nu-dimethylformamide (140 mL) was heated at 60C for 0.5 hours. Benzylbromide (13.9 g, 116 mmol) was added and the mixture was stirred at 66C for 1 hour, and filtered and the filtrate was concentrated, extracted with ethyl acetate, washed with brine, dried over sodium sulfate and concentrated. The residue was triturated with diethyl ether and hexanes to give a precipitate, which was collected to give compound 3_60_2 (21 g, 85 % yield) as a solid. [00483] NMR (400 MHz, DMSO-d6): delta = 5.27 (s, 2H), 7.33-7.50 (m, 5H), 7.65 (dd, J=8.8, 2.9 Hz, 1H), 8.00 (d, J = 8.6 Hz, 1H), 8.50 (d, J = 3.2 Hz, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
10 g | With n-butyllithium; 1,1,1,3,3,3-hexamethyl-disilazane; In tetrahydrofuran; hexane; at 0 - 20℃; for 16h; | Step 2:5-Benzyloxy-pyridine-2-carboxamidine (3_60_3) [00484] Butyllithium (1.6N in hexane, 168 mL, 269 mmol) was added to a solution of hexamethyldisilazane (56.5 mL, 269 mmol) in tetrahydrofuran (250 mL) at 0C, and stirred at 0C for 1 hour to form lithium hexamethyldisilazide (LHMDS). A solution of compound 3_60_2 (22.6 g, 107.6 mmol) in tetrahydrofuran (250 mL) was added slowly at 0C, and the mixture was warmed to room temperature slowly and stirred for 16 hours at room temperature. A IN hydrochloric acid solution (300 mL) was added to the reaction mixture to give a precipitate which was collected to give pure compound 3_60_3 (17 g, 70 % yield). From the mother liquor an additional amount of crude compound 3_60_3 (10 g) was obtained as a gum. [00485] NMR (400 MHz, DMSO-d6): delta = 5.32 (s, 2H), 7.32-7.52 (m, 5H), 7.78 (dd, J = 8.8, 2.9 Hz, 1H), 8.25 (d, J = 8.6 Hz, 1H), 8.54 (d, J = 2.7 Hz, 1H), 9.18 (s, 2H), 9.32 (s, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | In tetrahydrofuran; for 3h;Inert atmosphere; Reflux; | To a reflux condenser 20mL round bottom flask was added 5mL anhydrous tetrahydrofuran solution, 0.5mmol <strong>[78760-60-8]5-benzyloxy-2-cyanopyridine</strong>,The mixture was stirred and replaced with nitrogen for three times. 1.5 mmol of methylmagnesium bromide was slowly added under the protection of nitrogen at room temperature. The whole system was heated to reflux and reacted for 3 hours.The whole reaction was poured into ice-water and extracted three times with dichloromethane, each time 20 mL, concentrated to give a white solid product, 102 mg, yield 90%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80.2% | With sodium hydride; In N,N-dimethyl-formamide; at 0 - 5℃; for 0.416667h; | Step C: at 0 ~ 5 , benzyl alcohol (7.68g, 71.0mmol) was added dropwise 60% sodium hydride (2.84g, 71.0mmol) in DMF (60mL) suspension.After the addition was completed, stirring was continued for 10 minutes, and then 5-bromo-2-cyanopyridine (10.0 g, 54.6 mmol) was added portionwise.The resulting mixture was stirred at this temperature for a further 15 minutes.Add water (180 mL), filter, and filter cake with water (100 mL)5-Benzyloxy-2-cyanopyridine (25) (9.2 g) was obtained. The yield was 80.2%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98.7% | In tetrahydrofuran; at -5 - 0℃; for 1h; | Step D: at -5 ~ 0 , a 2M ethylmagnesium bromide in THF (26.5mL, 53mmol) was added dropwise to compound 25 (8.6g, 40.9mmol) in THF (30 mL) solution. After the addition was completed, the resulting mixture was further stirred at this temperature for 1 hour. Slowly add water (90mL),Adjust the pH to 3~4 with 2M hydrochloric acid.Extracted with ethyl acetate (100 mL × 3),The combined organic phases were washed with water (50 mL) and brine brineThe solvent was evaporated under reduced pressure to give 1-(5-benzyloxypyridin-2-yl)propan-1-one (26) (9.74 g). The yield was 98.7%. |
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