Structure of 855793-63-4
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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. : | 855793-63-4 |
Formula : | C16H17NO4 |
M.W : | 287.31 |
SMILES Code : | O=C(OC)C1=CC(OCC2=CC=CC=C2)=C(OC)C=C1N |
MDL No. : | MFCD17168884 |
InChI Key : | JWLWWDOXMYIBAM-UHFFFAOYSA-N |
Pubchem ID : | 22667093 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319 |
Precautionary Statements: | P264-P280-P302+P352-P305+P351+P338-P321-P332+P313-P337+P313-P362 |
Num. heavy atoms | 21 |
Num. arom. heavy atoms | 12 |
Fraction Csp3 | 0.19 |
Num. rotatable bonds | 6 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 79.6 |
TPSA ? Topological Polar Surface Area: Calculated from |
70.78 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.88 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.08 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.5 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.16 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.63 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.65 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.59 |
Solubility | 0.0741 mg/ml ; 0.000258 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-4.23 |
Solubility | 0.0168 mg/ml ; 0.0000584 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.9 |
Solubility | 0.00363 mg/ml ; 0.0000126 mol/l |
Class? Solubility class: Log S scale |
Moderately 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) |
Yes |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
Yes |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
Yes |
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 |
-5.87 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 |
0.0 |
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<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.41 |
* 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 |
---|---|---|
With hydrogenchloride; sodium hydroxide; sodium methylate; iron; formamide; In methanol; chloroform; water; acetic acid; N,N-dimethyl-formamide; | Production Example 29: 6-(Benzyloxy)-7-methoxy-3,4-dihydro-4-quinazolinone Methyl 5-(benzyloxy)-4-methoxy-2-nitrobenzoate (15.8 g) was dissolved in acetic acid (200 ml) at room temperature. Iron (powder) (13.9 g) was then added to the solution. The mixture was heated to 90C and was stirred for one hr. The resultant gray solid was filtered through Celite and was washed with acetic acid. Concentrated hydrochloric acid was added to the mother liquor, and the solvent was then removed by distillation under the reduced pressure to precipitate a solid. The solid was collected by filtration, was washed with ethyl acetate and ether, and was dried through a vacuum pump. Subsequently, chloroform and methanol were added to the solid to prepare a suspension, and a 10% aqueous sodium hydroxide solution was then added to the suspension to dissolve the solid, followed by extraction with chloroform. The extract was washed with water, and the organic layer was then dried over sodium sulfate. Next, the organic layer was filtered, and the solvent was then removed by distillation under the reduced pressure. The residue was dried through a vacuum pump to give 10.4 g (yield 73%) of a crude product of methyl 2-amino-5-(benzyloxy)-4-methoxybenzoate. Methyl 2-amino-5-(benzyloxy)-4-methoxybenzoate (5.0 g) was dissolved in N,N-dimethylformamide (150 ml) and methanol (30 ml). Formamide (3.5 ml) and sodium methoxide (2.8 g) were added to the solution. The mixture was heated to 100C and was then stirred overnight. The reaction solution was then cooled to room temperature, and 10 ml of water was then added. The reaction solution was neutralized with a 1 M aqueous hydrochloric acid solution to precipitate a solid. The solid was collected by filtration, was washed with waterand ether, and was then dried through a vacuum pump to give 3.7 g (yield 76%) of the title compound. 1H-NMR (DMSO-d6, 400 MHz): delta 3.92 (s, 3H), 5.21 (s, 2H), 7.16 (s, 1H), 7.33 - 7.49 (m, 5H), 7.55 (s, 1H), 7.99 (s, 1H), 12.06 (br, 1H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
38.4 g | In ethyl acetate; for 12.0h;Reflux; | A mixture of iron powder (29 g, 0.527 mol) and acetic acid 270 mL was stirred and heated to 50-60C till a grey white suspension was formed. The suspension was diluted with 150 mL methanol. Methyl 4-methoxy-3-benzyloxy-6-nitrobenzoate 7 (50g, 0.1575 mol) was added portion wise at regular intervals. The reaction was maintained at the same temperature for 5-6 hr. The mixture was filtered hot and the filtrate was evaporated to a residue mass under reduced pressure. The residue was extracted with ethyl acetate 2 × 300 mL. The combined organic layers were washed with water* and formamidine acetate 28.6 g (0.2747 mol) was added to the organic layer and refluxed for 12 hr. Reaction mass was cooled to 25-30C and stirred for 1 hr and precipitated solid was collected by filtration. Isolated solid was slurry washed with 250 mL methanol and dried to get the off white powder 9, 38.4 g (yield 91%, purity 98%); m.p. 258-60C; 1HNMR (DMSO-d6, 300 MHz): 12.076 (s, 1H), 7.986 (s, 1H), 7.342-7.545 (m, 6H), 7.152 (s, 1H), 5.206 (s, 2H), 3.913 (s, 3H); MS (EI): m/z 283 (M + 1). |
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