Structure of 956034-07-4
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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. : | 956034-07-4 |
Formula : | C6H2Cl2N2O |
M.W : | 189.00 |
SMILES Code : | ClC1=NC2=C(C(=N1)Cl)OC=C2 |
MDL No. : | MFCD11520866 |
InChI Key : | OTFDNOQBJWBJJM-UHFFFAOYSA-N |
Pubchem ID : | 45789968 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 9 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 41.82 |
TPSA ? Topological Polar Surface Area: Calculated from |
38.92 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.14 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.62 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.53 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.97 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.72 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.2 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.27 |
Solubility | 0.102 mg/ml ; 0.00054 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.09 |
Solubility | 0.155 mg/ml ; 0.000818 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.78 |
Solubility | 0.0317 mg/ml ; 0.000167 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 |
-5.59 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) |
2.33 |
* 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 |
---|---|---|
40 mg | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,4-dioxane; water; at 80℃;Inert atmosphere; | To a reaction flask were added compound 27-c (36 mg, 0.106 mmol), compound 38-b (prepared according to the method disclosed in: WO 2011/079230 A2) (20 mg, 0.106 mmol), PdC12(dppf) (4 mg, 0.005 mmol), 2 N sodium carbonate aqueous solution (0.16 mE, 0.32 mmol, 3.0 equiv.) and 1 ,4-dioxane (1 mE). The mixture was stirred under nitrogen atmosphere at 80 C. overnight. The reaction mixture was concentrated under reduced pressure, and then partitioned between water (15 mE) and dichioromethane (20 mE). The organic phase was separated out, dried over anhydrous sodium sulfate, and concentrated under reduced pressure, to obtain compound 38-a (40 mg). EC-MS (ESI): mlz=354.7 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 100.0℃; for 5.0h; | [0111] A mixture of 2,4-dichlorofuro[3,2-d]pyrimidine (150 mg, 0.79 mmol), 4-(lH- pyrazol-4-yl)aniline (126.3 mg, 0.79 mmol), and diisopropylethylamine (0.28 mL, 1.59 mmol) in DMF (1.59 mL) was heated at 100 C for 5 h. TLC showed the reaction was complete. The mixture was then diluted with water. The resulted yellow precipitate was filtered and washed with water and dried in vacuo to provide 210 mg (85%) title compound which was used directly for next step reaction without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | A mixture of(lr,4r)-4-morpholinocyclohexan-1-ol (0.53 g, 2.9 mmol, 1.1 eq) in 5.0 mL of THF was prepared and 60% NaH (0.56 g, 14 mmol, 5.3 eq) was added. The reaction mixture was stirred at room temperature for 30 mm and 2,4-dichlorofuro[3,2-djpyrimidine (0.50 g, 2.6 mmol, 1.0 eq) was added and the resulting mixture was heated at 60 C for 3 hr. The reaction was cooled to room temperature and quenched with saturated aqueous ammonium chloride. The quenched mixture was rotary evaporated and purified on normal phase Combi-Flash using a 40 g column and eluting with a gradient of 0-20% MeOH/CH2C12 in 10 mm. The product containing fractions were combined and rotary evaporated to give 2-chloro-4-(((lr,4r)-4- morpholinocyclohexyl)oxy)furo[3,2-djpyrimidine (0.59 g, 1.7 mmol, 60% yield) as a white solid. LC-MS:M+H=338.0 |
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