Structure of 16499-57-3
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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. : | 16499-57-3 |
Formula : | C8H5FN2O |
M.W : | 164.14 |
SMILES Code : | O=C1NC=NC2=C1C=CC(F)=C2 |
MDL No. : | MFCD07689443 |
InChI Key : | KCORZHJVTZIZFD-UHFFFAOYSA-N |
Pubchem ID : | 135398496 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 10 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 42.32 |
TPSA ? Topological Polar Surface Area: Calculated from |
45.75 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.22 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.87 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.48 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.55 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.5 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.53 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.02 |
Solubility | 1.56 mg/ml ; 0.0095 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.41 |
Solubility | 6.32 mg/ml ; 0.0385 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.5 |
Solubility | 0.0513 mg/ml ; 0.000313 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 |
-6.68 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) |
1.69 |
* 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% | With thionyl chloride;Heating / reflux; | 7-Fluoro-3H-quinazolin-4-one (8.2 g, 50 mmol) is heated at reflux in thionyl chloride (80 mL). Concentration affords the expected 4-Chloro-7-fluoro-quinazoline (9.1 g, quant). |
With thionyl chloride; N,N-dimethyl-formamide; for 8h;Reflux; | General procedure: A mixture of 4-quinazolone analogues 2a-2j (8.0 mmol) in SOCI2 (27.4 mL) containing DMF (2 drops) was refluxed for 8 h. SOCI2 was removed under reduced pressure and the residue was dissolved in DCM. The solution was washed with saturated NaHCO3 solution and brine, respectively, dried over anhydrous Na2S04 and then concentrated under reduced pressure to yield the compounds 3a-3j (65.1-88.9percent yield) as white or off-white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With thionyl chloride; In N,N-dimethyl-formamide; toluene; for 10h;Reflux; | To a suspension of 7-fluoroquinazolin-4-ol compound A (6.32 g, 38.5 mmol) in dry PhMe (30 mL), SOCk (22 mL, 7.7 eq.) and DMF (2.6 mL) were added. The resulting mixture was refluxed for 10 h. The mixture was then cooled to room temperature, quenched with water (200 mL), and extracted with ethyl acetate (EtOAc; 170 mL). The combined organic extracts were washed with water (300 mL) and brine (30 mL), dried over sodium sulfate (Na2S04), and concentrated to afford compound B (6.08 g, 86%) as a yellow solid. LCMS (ESI) m/z calculated for C8H4CIFN2: 182, 184; found: 183, 185 [M+H]+.1H-NMR (400 MHz, CDCl3) d 9.04 (s, 1H), 8.33 (dd, J = 9.2 Hz,4JF,H= 6.0 Hz, 1H), 7.71 (dd,3JF,H= 9.2 Hz, J= 2.4 Hz, 1H), 7.52 (ddd, J = 9.2, 2.4 Hz,3JF,H= 8.4 Hz, 1H). |
With thionyl chloride; N,N-dimethyl-formamide; for 5h;Reflux; | To the crude product SP-0011321-021 (0.82 g, 5 mmol) was added thionyl dichloride (12.0 g, 0.1 mol) and catalytic amount of anhydrous DMF (0.5 mL). The reaction mixture was heated to reflux for 5 h. After the reaction was completed, the mixture was cooled down and excess thionyl dichloride was removed by rotary evaporation. The resulting crude product SP-0011321-023 (950 mg) was used in the next step of reaction without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With thionyl chloride; In N,N-dimethyl-formamide; at 0℃;Reflux; | A General/Typical Procedure includes: A solution of 18.2 g of CAS: 446-32-2 (100 mmol) in 76.5 g (64 ml) of formamide (1.7 mol) was heated under reflux for 4 hrs at 120- 125C. Solvent was removed under reduced pressure and the crude solid was recrystallized from ethyl alcohol to give 12.7 g of compound CAS: 16499-57-3 (yield, 87 %). To 7.3 g of compound CAS: 16499-57-3 (50 mmol) was added dropwise 230 ml of thionyl chloride (2 mol) at 0C. with stirring. To the mixture was added 2-3 drops of N,N-dimethylformamide and the reaction heated under reflux for 3-4 hrs. Thionyl chloride was removed under reduced pressure and the resulting residue was washed with sodium carbonate. The product was extracted with ethyl acetate and the organic layer was dried over Mg504, filtered and concentrated under reduced pressure. The crude product was purified by 5i02 column chromatography to give 4-chloro-7-fluoroquinazoline (CAS: 16499-62-0). |
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