Structure of 17518-98-8
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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. : | 17518-98-8 |
Formula : | C8H4BrClN2O |
M.W : | 259.49 |
SMILES Code : | O=C1NC=NC2=C1C=C(Cl)C(Br)=C2 |
MDL No. : | MFCD10000555 |
InChI Key : | RFCXXKWROOFQSI-UHFFFAOYSA-N |
Pubchem ID : | 135711216 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 10 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 55.07 |
TPSA ? Topological Polar Surface Area: Calculated from |
45.75 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.61 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.09 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.34 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.43 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.37 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.37 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.33 |
Solubility | 0.12 mg/ml ; 0.000463 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.68 |
Solubility | 0.541 mg/ml ; 0.00209 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.71 |
Solubility | 0.00509 mg/ml ; 0.0000196 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) |
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 |
-6.4 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 |
0.0 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) |
1.71 |
* 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 |
---|---|---|
100% | In ethanol; for 16h;Reflux; | To a solution of <strong>[150812-32-1]2-amino-4-bromo-5-chlorobenzoic acid</strong> (500 mg,2mmol) in EtOH (20 mL) at RT, formamidine acetate (620 mg, 6 mmol) was added. The mixture was reflux for 16 hour. The mixture was concentrated in vacuo, and the residue was washed by saturated NaHCO3 aqueous solution, and a mixture of ethylacetate/petroleum ether = 1:2. The solid was dried in vacuo to get the product (520 mg, 100% yield) which was used directly in next step without further purification. ESI-MSm/z: 259.0 [M+H]. |
In ethanol; for 16h;Reflux; | 7-Bromo-6-chloroquinazolin-4-ol To a solution of <strong>[150812-32-1]2-amino-4-bromo-5-chlorobenzoic acid</strong> (500 mg, 2mmol) in EtOH (20 mL) at RT, formamidine acetate (620 mg, 6 mmol) was added. The mixture was reflux for 16 hour. The mixture was concentrated in vacuo, and the residue was washed by saturated NaHCO3 aqueous solution, and a mixture of ethyl acetate/petroleum ether = 1:2. The solid was dried in vacuo to get the product (520 mg, 100% yield) which was used directly in next step without further purification. ESI-MS m/z: 259.0 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | at 150 - 170℃; for 5h; | To a mixture of 3-chlorotoluene (200 g, 1.58 mol), FeCl3 (9.4 g, 0.06 mol) and CH2Cl2 (1000 mL)stirred at 0~10 C, Br2 (500 g, 3.12 mol) was added slowly, during which the produced gas wasabsorbed by 15% NaOH aqueous solution (2000 mL). After 1 h of continued vigorous stirring, water(100 mL) was added and the mixture was adjusted to pH 8.0~10.0 with 10% aqueous NaOH (200 mL).The organic layer was separated and concentrated to dryness under vacuum to give a solid (95.7%, m.p.95~96 C), 426 g of which was added to a mixture of water (2000 mL), pyridine (200 mL) and KOH(112 g, 2.0 mol) and heated. When the interior temperature reached 80 C, KMnO4 (800 g, 5.0 mol) wasadded in portions, and the mixture was refluxed until complete consumption of the KMnO4. Then thesolution was filtered, the precipitate was washed with 10% KOH a.q. (1000 mL). The filtrates werecombined, and then vacuum evaporated to remove the pyridine and form a turbid solution, whichneeded to be filtered again. The fresh filtrate was acidified with concentrated HCl (360 mL) to pH 3~4.Then the precipitate was filtered, dried and crushed (80%, m.p. 170~171 C). A portion (340 g) wasdissolved in 25% NH3-H2O (1700 mL). To the solution, Cu2O was added in batches at 30~40 C. Afterabout 5 h of stirring, the solution without NH3 gas was diluted and acidified. Then the solid was filtered, washed, dried (yield 96%, m.p. 248~249 C) and 250 g was dissolved in 1500 mL of formamide,maintained at 150~170 C for 5 h. The solution was allowed to cool to R.T., and the precipitate wasfiltered and washed to give a white solid (92%, m.p. 306~307 C). Thus, 2 was succesfully obtained inan overall yield of 67%. IR (KBr), (cm1): 3188.6, 1643.4 (NH), 1680.3 (C=O); ESI-MS (m/z): 256.9[M - H]-, 258.9 [M + 2 - H]; 1H-NMR (300 MHz, DMSO-d6), delta (ppm): 12.50 (br, 1H), 8.15 (s, 1H),8.14 (s, 1H), 8.05 (s, 1H). |
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