Structure of 105807-83-8
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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. : | 105807-83-8 |
Formula : | C10H12N2O2 |
M.W : | 192.21 |
SMILES Code : | NC1=CC2=C(C=C1)NC(C(O2)(C)C)=O |
MDL No. : | MFCD11048439 |
InChI Key : | UXMAGPQBCODAEJ-UHFFFAOYSA-N |
Pubchem ID : | 13665546 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.3 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 57.32 |
TPSA ? Topological Polar Surface Area: Calculated from |
64.35 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.6 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.78 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.81 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.56 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.24 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.0 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.84 |
Solubility | 2.78 mg/ml ; 0.0144 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.71 |
Solubility | 3.73 mg/ml ; 0.0194 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.04 |
Solubility | 0.177 mg/ml ; 0.00092 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 |
-6.92 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 |
1.0 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) |
2.16 |
* 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 |
---|---|---|
73.4% | With iron; ammonium chloride; In ethanol; water; at 90℃; | 30 mM 2,2-dimethyl-7-nitro-2H-1,4-benzoxazol-3 (4H) -one was added100 mL of solvent (EtOH: H20 = 3: 1)Under stirring at room temperature, 10 mM ammonium chloride and 30 mM iron powder were further added, and the mixture was heated to 90 C. and refluxed for 1-2 hours.After the TLC detection of the reaction is over, the excess iron powder is filtered while hot, after the reaction solution is cooled and the solvent is distilled off under reduced pressure,The residual solid was adjusted to pH 10 with an aqueous solution of potassium carbonate, precipitated with a solid, filtered,The filter cake was washed with cooling water and dried in vacuo to give pure intermediate product as 4.23 g of a yellow powder,Yield 73.4%. This intermediate was used directly in the next reaction without further purification |
66% | With 20% palladium hydroxide-activated charcoal; hydrogen; In methanol; at 40℃; under 750.075 Torr; for 4h; | (2) Preparation of 7-amino-2,2-dimethyl-2H-1,4-benzoxazin-3(4H)-one A mixture of the compound (wet material: 384.6 g) obtained in the above step (1), methanol (2880 mL), and 20% palladium hydroxide carbon (13.8 g) was stirred under hydrogen pressure (0.1 MPa) at 40C until hydrogen absorption terminated (about 4 hours). The reaction mixture was filtered, and the unfiltered residue was washed with methanol (300 mL). The filtrate and the washings were combined, then concentrated under reduced pressure at 50C or lower, to the residue were added methanol (288 mL) and water (1440 mL), and the mixture was stirred at 50C for about 1 hour. The mixture was cooled to 25C, then stirred for 30 minutes, the precipitated crystals were collected by filtration, washed with water (1440 mL), and then dried to obtain the title compound (163.94 g) as red-brown crystals (yield: 66%, purity: 100%). MS: ESI-MS m/Z: 193 [M+H]+ 1 H-NMR (CDCl3): delta 1.51 (6H, s), 3.56 (2H, brs), 6.29 (1H, dd), 6.32, 6.33 (1H, m), 6.59 (1H, d), 8.34 (1H, brs) |
With hydrogen;palladium 10% on activated carbon; In tetrahydrofuran; methanol; at 20℃; | To a solution of the compound obtained in Reference Example 1(1) (500 mg) in tetrahydrofuran (7 mL)-methanol (5 mL) was added 10% palladium-carbon (100 mg, water content: ca. 50%), and the mixture was stirred overnight at room temperature <n="76"/>under atmospheric pressure of hydrogen. The insolubles were removed by filtration, and the filtrate was concentrated in vacuo to give 7-amino-2,2-dimethyl~2H-l,4- benzoxazin- 3(4H)-one (429 mg) as a pale pink solid. MS(APCI) m/z: 193 [M+H]+ |
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