Structure of 695-87-4
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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. : | 695-87-4 |
Formula : | C5H6N2O2 |
M.W : | 126.11 |
SMILES Code : | COC1C=NC=NC1=O |
MDL No. : | MFCD02685611 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.4 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 39.34 |
TPSA ? Topological Polar Surface Area: Calculated from |
51.02 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.08 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-0.66 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-1.12 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.62 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.28 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
-0.01 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.14 |
Solubility | 91.3 mg/ml ; 0.724 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
0.06 |
Solubility | 146.0 mg/ml ; 1.15 mol/l |
Class? Solubility class: Log S scale |
Highly soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.36 |
Solubility | 54.8 mg/ml ; 0.435 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 |
-7.54 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) |
3.42 |
* 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 |
---|---|---|
69% | With water; nickel; for 8h;Heating / reflux; | 3.9 g of Raney nickel (slurry) are added to a hot solution of 4.1 g (0.026 mol) of 2-mercapto- 5-methoxy-3H-pyrimidin-4-one (Example P1) in 60 ml of water. After vigorous stirring for 8 hours at reflux temperature, the reaction mixture is filtered and the combined filtrates and washing fractions are concentrated by evaporation on a hot water bath. The residue obtained is recrystallised from ethanol in the presence of activated carbon. The desired target compound is obtained in a yield of 1.9 g (69 % of theory) in the form of needles having a melting point of 206-208C. 1 H NMR (300 MHz, DMSO-d6) : 7.828 ppm (s, 1H) ; 7.527 ppm (s, 1H) ; 3.728 ppm (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With N,N-diethylaniline; trichlorophosphate; at 115℃; for 3h; | A suspension of 1.9 g (0.015 mol) of <strong>[695-87-4]5-methoxy-3H-pyrimidin-4-one</strong> (Example P2) in 4.2 ml (0.046 mol) of phosphorus oxychloride and 5.0 mi (0.031 mol) of N, N-diethylaniline is heated at 115C for 3 hours. The dark, homogeneous mixture obtained is hydrolyse by adding crushed ice, the temperature being kept below 30C. Extraction with diethyl ether, drying of the combined organic ethereal phases over sodium sulfate, and purification on a silica gel column (eluant : ethyl acetate/n-hexane 1/9) yields the desired target compound in a yield of 1.3 g (58 % of theory). Further purification by means of sublimation at 80-85C/15 Torr yields the desired title compound, having a melting point of 63-64C. oh NMR (300 MHz, Ceci3) : 8.635 ppm (s, 1H) ; 8.321 ppm (s, 1H) ; 4.025 ppm (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81.2% | With caesium carbonate; In dimethyl sulfoxide; at 25℃; for 1h; | To a solution of <strong>[695-87-4]5-methoxypyrimidin-4(3H)-one</strong>, 1 (2 g, 0.0158 mol) in DMSO (10 mL), Cs2CO3 (15.4 g, 0.0475 mol) was added followed by ethyl bromoacetate (3.97 g, 0.0237 mol) and stirred at 25C for lh. After completion of the reaction, the reaction mixture was diluted with water and extracted with EtOAc. The aqueous layer was extracted with EtOAc (2X100 mL). The combined organic layers were washed with brine and organic layer was dried over anhydrous Na2 SO4, filtered and concentrated under reduced pressure to get (2.6 g, 81.2%) of 2. This was taken to the next step without further purification.UPLC = Calculated for C9H12N2O4 is 212.21, Observed = 213.2 [M+H] |
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