Structure of 27427-89-0
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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. : | 27427-89-0 |
Formula : | C8H10N2O2 |
M.W : | 166.18 |
SMILES Code : | O=C(C1=NC(C)=CC(C)=N1)OC |
MDL No. : | MFCD16660497 |
InChI Key : | OZQKMZUCPKQXSQ-UHFFFAOYSA-N |
Pubchem ID : | 12276698 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.38 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 43.24 |
TPSA ? Topological Polar Surface Area: Calculated from |
52.08 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.1 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.19 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.88 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.22 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.61 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.2 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.86 |
Solubility | 2.3 mg/ml ; 0.0139 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.88 |
Solubility | 2.19 mg/ml ; 0.0132 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.5 |
Solubility | 0.532 mg/ml ; 0.0032 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 |
-6.47 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) |
1.78 |
* 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 |
---|---|---|
285 mg | With sodium tetrahydroborate; ethanol; at 0 - 20℃;Inert atmosphere; | [0589] Synthesis of (4, 6-dimethylpyrimidin-2-yl) methanol: [0590] To a stirred solution of <strong>[27427-89-0]methyl 4,6-dimethylpyrimidine-2-carboxylate</strong> (400 mg, 2.40 mmol) in ethanol (10 mL) under argon atmosphere was added sodium borohydride (137 mg, 3.60 mmol) at 0 C; warmed to room temperature and stirred for 2 h. The reaction was monitored by TLC; after completion of the reaction, the reaction mixture was quenched with water (15 mL) and extracted with CH2CI2 (2 x 30 mL). The combined organic extracts were dried over sodium sulphate, filtered and concentrated in vacuo to obtain the crude (4, 6-dimethylpyrimidin-2-yl) methanol (285 mg, 86%>) as thick syrup. The crude was carried to the next step without any further purification. [0591] 1H-NMR (CDCI3, 400 MHz): delta 6.91 (s, 1H), 4.71 (s, 2H), 2.50 (s, 6H); LC-MS: 96.66%; 139.3 (M++l); (column: Eclipse XDB C-18, 150 4.6 mm, 5 mupiiota); RT 4.03 min. 0.05% TFA: ACN; 1.0 mL/min); TLC: 40% EtOAc/ Hexanes (R 0.5). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With palladium bis[bis(diphenylphosphino)ferrocene] dichloride; triethylamine; In acetonitrile; at 20 - 100℃;Inert atmosphere; | [0586] Synthesis of methyl 4, 6-dimethylpyrimidine-2-carboxylate: [0587] To a stirred solution of 2-chloro-4, 6-dimethylpyrimidine (1 g, 7.05 mmol) in MeOH: CH3CN (4: 1, 20 mL) under argon atmosphere were added triethyl amine (1.98 mL, 14.02 mmol) and Pd(dppf)2Cl2 (1 g, 1.40 mmol) at room temperature; heated to 100 C and stirred for 20 h under CO pressure in steel bomb. The reaction was monitored by TLC; after completion of the reaction, the reaction mixture was filtered through celite and the filtrate was concentrated in vacuo to obtain the crude. The crude was purified through silica gel column chromatography using 30% EtOAc/ Hexanes to afford methyl 4,6-dimethylpyrimidine-2-carboxylate (400 mg, 34%) as an off- white solid. [0588] 1H-NMR (CDCI3, 400 MHz): delta 7.20 (s, 1H), 4.07 (s, 3H), 2.61 (s, 6H); LC-MS: 87.29%; 167.2 (M++l); (column: X-Bridge C-18, 50 3.0 mm, 3.5 mupiiota); RT 1.47 min. 0.05% Aq TFA: ACN; 0.8 mL/min); TLC: 30% EtOAc/ Hexanes (R 0.3). |
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