Structure of 3143-02-0
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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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CAS No. : | 3143-02-0 |
Formula : | C5H10O2 |
M.W : | 102.13 |
SMILES Code : | C(C1(COC1)C)O |
MDL No. : | MFCD00010273 |
InChI Key : | NLQMSBJFLQPLIJ-UHFFFAOYSA-N |
Pubchem ID : | 137837 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H317 |
Precautionary Statements: | P280 |
Num. heavy atoms | 7 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 1.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 26.02 |
TPSA ? Topological Polar Surface Area: Calculated from |
29.46 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.42 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-0.18 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.02 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.16 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.1 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.44 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.29 |
Solubility | 51.9 mg/ml ; 0.508 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
0.02 |
Solubility | 106.0 mg/ml ; 1.04 mol/l |
Class? Solubility class: Log S scale |
Highly soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.58 |
Solubility | 26.8 mg/ml ; 0.262 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 |
-7.05 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) |
1.19 |
* 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 |
---|---|---|
95% | With carbon tetrabromide; triphenylphosphine; In dichloromethane; at 0 - 20℃; for 0.333333h;Product distribution / selectivity; | 10 ml (0.1 mol) of 3-methyl-3-(hydroxymethyl)oxetane and 36.58 g (0.11 mol) of carbone tetrabromide were dissolved in 100 ml of CH2Cl2. The solution was cooled to 0C under nitrogen atmosphere, and 31.56 g (0.12 mol) of triphenylphosphine was gradually added thereto. The mixture was heated to room temperature and stirred for 20 minutes. After the reaction terminated, the solvent was removed under reduced pressure. 100 ml of ethylene acetate was added thereto and the mixture was filtered using celite to remove impurities. After the solvent was removed from the mixture, hexane was added thereto. The mixture was filtered using celite, and concentrated under reduced pressure. The resultant product was fractionally distilled to obtain 16 g of 3-methyl-3-(bromomethyl)oxetane (Yield: 95%). NMR spectroscopy of the resulting product was: 1H NMR (CDCl3, 300MHz): delta4.46-4.38 (d+d, 4H), 3.65(s, 2H), 1.44(s, 3H). |
With carbon tetrabromide; triphenylphosphine; In dichloromethane; at 0 - 23℃; for 1.33333h; | 3-Bromomethyl-3-methyl-oxetane; To a dichloromethane (600 ml) solution of (3-Methyl-oxetan-3-yl)-methanol (50 g, 0.4896 mol, prepared as in Corey, E. J., Raju, N., Tetrahedron Lett., 1983, 5571) at about 0 C. was added carbon tetrabromide (165.35 g, 0.4986 mol) followed by the addition of triphenyl phosphine (179 g, 0.683 mol) slowly in portions over about 20 minutes. The reaction was allowed to warm to about 23 C. and was stirred at that temperature for about 1 hour then was concentrated in vacuo. The residue was diluted with diethyl ether and cooled to about 0 C., then was filtered through Celite and the organic layer was concentrated in vacuo. The residue was then diluted with hexanes and filtered then concentrated in vacuo and distilled under vacuum to give 124.3 g of 3-bromomethyl-3-methyl-oxetane as a colorless oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In dichloromethane; | 3-Bromomethyl-3-methyl-oxetane To a dichloromethane (600 ml) solution of (3-Methyl-oxetan-3-yl)-methanol (50 g, 0.4896 mol, prepared as in Corey, E.J., Raju, N., Tetrahedron Lett.,1983, 5571) at about 0C was added carbon tetrabromide (165.35 g, 0.4986 mol) followed by the addition of triphenyl phosphine (179 g, 0.683 mol) slowly in portions over about 20 minutes. The reaction was allowed to warm to about 23C and was stirred at that temperature for about 1 hour then was concentrated in vacuo.The residue was diluted with diethyl ether and cooled to about 0C, then was filtered through Celite and the organic layer was concentrated in vacuo.Theresidue was then diluted with hexanes and filtered then concentrated in vacuoand distilled under vacuum to give 124.3 g of 3-bromomethyl-3-methyl-oxetane as a colorless oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | NaH (60percent in oil, 1.24 g, 30.9 mmol) was washed twice with pentane and dried under vacuum. Dioxane (50 mL) was added, followed by (3-methyloxetan-3-yl)methanol (3.0 mL, 30.9 mmol) dropwise. This was allowed to stir 2 h at room temp before addition of 6-chloropyrazin-2-amine (2.0 g, 15.4 mmol). The reaction was heated to reflux for 16 h, cooled and concentrated. Water was added (50 mL), and the mixture was extracted with EtOAc (3x75 mL), and the combined organics were washed with water and brine, dried with Na2SO4, filtered and concentrated. The crude product was purified by silica gel column chromatography (0-10percent MeOH/CH2 ) to give 6-((3-methyloxetan-3- yl)methoxy)pyrazin-2-amine (3.02 g, quant). MS (ESI) calcd for C9H13N3O2: 195.10; found: 196 [M+H] | |
100% | NaH (60percent in oil, 1.24 g, 30.9 mmol) was washed twice with pentane and dried under vacuum. Dioxane (50 mL) was added, followed by (3-methyloxetan-3-yl)methanol (3.0 mL, 30.9 mmol) dropwise. This was allowed to stir 2 h at room temp before addition of 6-chloropyrazin-2-amine (2.0 g, 15.4 mmol). The reaction was heated to reflux for 16 h, cooled and concentrated. Water was added (50 mL), and the mixture was extracted with EtOAc (3x75 mL), and the combined organics were washed with water and brine, dried with Na2SO4, filtered and concentrated. The crude product was purified by silica gel column chromatography (0-10percent MeOH/CH2Cl2) to give 6-((3-methyloxetan-3-yl)methoxy)pyrazin-2-amine (3.02 g, quant.). MS (ESI) calcd for C9H13N3O2: 195.10; found: 196 [M+H]. |
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