Structure of 53014-84-9
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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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Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 53014-84-9 |
Formula : | C7H7NO |
M.W : | 121.14 |
SMILES Code : | O=CC1=CN=C(C)C=C1 |
MDL No. : | MFCD08272279 |
InChI Key : | IMWMEIWYPWVABQ-UHFFFAOYSA-N |
Pubchem ID : | 10192566 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 34.59 |
TPSA ? Topological Polar Surface Area: Calculated from |
29.96 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.28 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.71 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.2 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.13 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.96 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.05 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.47 |
Solubility | 4.15 mg/ml ; 0.0342 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.92 |
Solubility | 14.7 mg/ml ; 0.121 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.31 |
Solubility | 0.589 mg/ml ; 0.00486 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 |
-6.53 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) |
1.08 |
* 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% | B. Preparation of 6-methylnicotinaldehyde To a solution of oxalyl chloride (2 M in dichloromethane, 9.34 mL, 18.68 mmol) in 30 mL dichloromethane at -60 C. under argon, dimethyl sulfoxide (3.1 g, 2.81 mL, 39.63 mmol) was added over 20 min. The mixture was stirred at -60 C. for 20 min before a solution of (6-methylpyridin-3-yl)methanol in 8 mL dichloromethane was added over 20 min. The reaction mixture was stirred for 20 min, and then triethylamine (8.02 g, 11.05 mL, 79.25 mmol) was added over 10 min. The reaction mixture was allowed to warm up to room temperature and 48 mL water was added. The mixture was extracted with dichloromethane and the combined extracts were dried (Na2SO4), filtered and concentrated. The crude product was purified by automated silica gel chromatography (eluted with ethyl acetate-hexanes) to isolate 1.67 g (85%) of the title compound as a light brown oil. HPLC: retention time=0.19 min. | |
85% | With oxalyl dichloride; dimethyl sulfoxide; triethylamine; In dichloromethane; at -60℃; for 1.5h; | B. Preparation of 6-methylnicotinaldehyde To a solution of oxalyl chloride (2 M in dichloromethane, 9.34 mL, 18.68 mmol) in 30 mL dichloromethane at -60 C. under argon, dimethyl sulfoxide (3.1 g, 2.81 mL, 39.63 mmol) was added over 20 min. The mixture was stirred at -60 C. for 20 min before a solution of (6-methylpyridin-3-yl)methanol in 8 mL dichloromethane was added over 20 min. The reaction mixture was stirred for 20 min, and then triethylamine (8.02 g, 11.05 mL, 79.25 mmol) was added over 10 min. The reaction mixture was allowed to warm up to room temperature and 48 mL water was added. The mixture was extracted with dichloromethane and the combined extracts were dried (Na2SO4), filtered and concentrated. The crude product was purified by automated silica gel chromatography (eluted with ethyl acetate-hexanes) to isolate 1.67 g (85%) of the title compound as a light brown oil. HPLC: retention time=0.19 min. |
In pyridine; water; | Chromium trioxide (11.5 g) is slowly added to 170 ml of pyridine at 20 C., and 10 g of the crude 5-hydroxymethyl-2-methylpyridine in 70 ml of pyridine is added in one portion to the complex. The temperature is raised to reflux temperature for 2 hours, and the mixture is refluxed for 1.5 hours. After cooling, 250 ml of water is added, and the mixture is extracted with five 150-ml portions of diethyl ether. The combined extracts are dried over magnesium sulfate and concentrated to give 4.2 g of crude 6-methyl-3-pyridinecarbaldehyde. |
With manganese(IV) oxide; In dichloromethane; at 25℃; for 68h; | A solution of methyl 6-methylnicotinate (0.5 g, 3.3 mmol) in THF (16 mL) at 0 C. was treated dropwise with lithium aluminum hydride in THF (6.6 mL, 1 M), stirred at 0 C. for 1.5 hours, treated with ethyl acetate (3 mL), stirred at 25 C. The reaction was partitioned between ethyl acetate and saturated NaHCO3, and the organic phase was washed with brine and dried over MgSO4, filtered and concentrated. A solution of the residue (0.395 g) in dichloromethane (16 mL) was treated with MnO2 (2 g), stirred at 25 C. for 68 hours, filtered through celite to give the title compound (0.326 g, 80% yield), which was used without further purification. | |
In pyridine; water; | Chromium trioxide (11.5 g) is slowly added to 170 ml of pyridine at 20C, and 10 g of the crude 5-hydroxy-methyl-2-methylpyridine in 70 ml of pyridine is added in one portion to the complex. The temperature is raised to reflux temperature for 2 hours, and the mixture is refluxed for 1.5 hours. After cooling, 250 ml of water is added, and the mixture is extracted with five 150-ml portions of diethyl ether. The combined extracts are dried over magnesium sulfate and concentrated to give 4.2 g of crude 6-methyl-3-pyridinecarbaldehyde. | |
With manganese(IV) oxide; In dichloromethane; at 0 - 20℃; for 1.25h; | Stage 2 - Preparation of 6-methylnicotinaldehyde; To a cooled (ice bath) solution of stage 1 product (14.85g, 120.6mmol) in DCM (100OmL) was added manganese oxide (10Og) in 1Og portions over a period of 30 minutes. The mixture was warmed to RT and stirred for 45 minutes and was then filtered through Celite. The residues were washed with DCM (50OmL), and the combined DCM portions were concentrated to yield the desired product. 1 H NMR (300MHz, CDCI3) delta: 10.00 (1H, s), 8.88 (1 H, d, J=1.8Hz), 8.00 (1 H, dd, J=2.4, 8.1 Hz), 7.26 (1 H, d, J=8.1 Hz), 2.60 (3H, s). | |
To a stirred solution of dimethyl sulfoxide (25.3 mL, 0.357 mol) and CH2Cl2 (600 mL) under nitrogen at -78 0C was slowly added oxalyl chloride (16 mL, 0.19 mol). After completion of the addition, the mixture was stirred for additional 10 min. To the resulting solution was added dropwise a solution of (6-methyl-3-pyridyl)methanol (20 g, 0.162 mol) in CH2Cl2 (10 mL), and then the mixture was stirred at -78 0C for 2.5 hr. Triethylamine (110 mL, 0.82 mol) was slowly added at -78 0C and then the mixture was slowly warmed to room temperature and stirred for another 1 hr. The mixture was treated with water and the aqueous phase was extracted with CH2Cl2 (3 x 500 mL). The combined organic layers were washed with brine, dried over anhydrous MgSO4, filtered and concentrated. The residue was purified by silica gel column to afford the title compound. |