Structure of 19646-07-2
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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. : | 19646-07-2 |
Formula : | C5H4Cl2N2O |
M.W : | 179.00 |
SMILES Code : | ClC1=NC=C(C(=N1)Cl)OC |
MDL No. : | MFCD02685670 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P280-P305+P351+P338-P310 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.2 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 38.54 |
TPSA ? Topological Polar Surface Area: Calculated from |
35.01 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.1 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.79 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.55 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.21 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.73 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.65 |
Solubility | 0.4 mg/ml ; 0.00223 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.47 |
Solubility | 0.613 mg/ml ; 0.00342 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.01 |
Solubility | 0.175 mg/ml ; 0.000975 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) |
Yes |
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 |
-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 |
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) |
2.02 |
* 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 |
---|---|---|
73% | With potassium carbonate; at 20.0℃; for 19.0h; | a. Preparation of Compound 2-Chloro-4,5-dimethoxypyrimidine 2,4-Dichloro-5-methoxypyrimidine (2.37 g, 13.2 mmol) and K2C03 (1.8 g, 13.2 mmol) were dissolved in MeOH (50 mL) and stirred for 19 hours at room temperature. The solvent was removed under reduced pressure. The resulting residue was dissolved in EtOAc and washed with distilled water followed by brine. The organic layer was dried over Na2S04 and concentrated. It was then flash chromatographed on silica gel eluting with 0 to 20% EtOAc/Hexane to give 2-chloro-4,5-dimethoxypyrimidine as a white solid (1.70 g, 73%); m.p.65-67 C; NMR (400 MHz, CDC13) delta 7.84 (s, 1H), 4.03 (s, 3H), 3.88 (s, 3H); 13C NMR (100 MHz, CDC13) delta 161.2, 150.0, 141.7, 138.2, 56.6, 55.0. |
With potassium carbonate; at 20.0℃; for 24.0h; | 2-Chloro-4,5-dimethoxy-pyrimidine To a solution of 10 g (55.9 mmol) 2,4-dich.oro-5-methoxy-pyrimidine in 200 mL MeOH was added 7.7 g (55.9 mmo.) K2CO3. The reaction mixture was stirred at room temperature for 24 h, then the volatiles were removed in vacuo. The residue was diluted with EtOAc (200 mL) and water (100 mL). The organic layer was separated, dried (Na2S04), and evaporated affording 9,0 g (92%) 2-chioro-4,5- dimethoxy-pyrimidine as a fluffy white solid which was used in subsequent steps without further purification. LCMS [M+H]+ =175.0. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With N-ethyl-N,N-diisopropylamine; In isopropyl alcohol; at 20 - 60℃; for 5h; | Dichloro-5-methoxypyrimidine (2.79 mmol, 0.50 g) and the compound prepared in Step 1 (3.07 mmol) were stirred at room temperatureDIPEA (N, N-diisopropylethylamine) was added to isopropanol (30 ml), and the mixture was stirred and heated to 60 C for 5 hours. After the reaction was terminated, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Methanol / dichloromethaneTo give the desired compound in 60% yield. |
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