Structure of 1352717-91-9
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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. : | 1352717-91-9 |
Formula : | C9H6BrFN2O |
M.W : | 257.06 |
SMILES Code : | O=C1NC(C)=NC2=C1C=C(F)C=C2Br |
MDL No. : | MFCD27996279 |
InChI Key : | JAUJGOMEEXESRV-UHFFFAOYSA-N |
Pubchem ID : | 135742242 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 10 |
Fraction Csp3 | 0.11 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 54.99 |
TPSA ? Topological Polar Surface Area: Calculated from |
45.75 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.85 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.48 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.55 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.57 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.59 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.41 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.89 |
Solubility | 0.328 mg/ml ; 0.00127 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.05 |
Solubility | 2.3 mg/ml ; 0.00896 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.76 |
Solubility | 0.00449 mg/ml ; 0.0000175 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 |
-6.82 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) |
1.89 |
* 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 |
---|---|---|
76% | With tris-(dibenzylideneacetone)dipalladium(0); N,N,N,N,-tetramethylethylenediamine; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In N,N-dimethyl-formamide; at 160.0℃; for 0.055555600000000004h;Microwave irradiation; Inert atmosphere; | To a solution of 8-bromo-6-fluoro-2-methyl-quinazolin-4(3H)-one (13, 100 mg, 0.39 mmol) in DMF (1 ml), was successively added N1,N1,N2,N2-tetramethylethane-1,2-diamine (0.012 ml, 0.08 mmol), dicyanozinc (0.015 ml, 0.23 mmol), tris(dibenzylideneacetone)dipalladium (17.81 mg, 0.02 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis-(diphenylphosphine) (2.251 mg, 3.89 mumol). The reaction tube was sealed, sparged with argon and heated to 160 C over a period of 200 s in the microwave reactor. The resulting suspension was filtered and the filtrate was concentrated to dryness. The resulting liquid was diluted with water (we obtain a suspension) and triturated with diethyl ether to give a solid, which was collected by filtration and dried under vacuum to give 6-fluoro-2-methyl-4-oxo-3,4-dihydroquinazoline-8-carbo-nitrile (18, 60 mg, 76%) as a clear beige solid, which was used without further purification; LCMS (tR=1.53 min, purity=98%), ESI-m/z, 202.0 (M-H)-; 1H NMR (DMSO-d6), delta (ppm) 2.41 (s, 3H), 8.08 (dd, J=3.0 Hz, JH-F=8.2 Hz, 1H), 8.37 (dd, J=3.0 Hz, JH-F=8.2 Hz, 1H); 12.70 (br s, 1H); 13C NMR (DMSO-d6) 22.5, 102.0, 114.8, 115.2, 115.3, 138.9, 159.0, 162.9, 166.3; HRMS m/z (ESI+) calculated for C10H6ON3F: 204.05677; found: 204.05670. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73.7% | With ammonia; In water; at 100.0℃; for 1.5h; | A suspension of 8-bromo-6-fluoro-2-methyl-4H-benzo[d][1,3]oxazin-4-one (12, 466 mg, 1.81 mmol) in concd aqueous NH3 (28% v/v, 8 ml) was stirred at reflux (100 C) for 1.5 h. The reaction mixture was concentrated. The resulting precipitate was collected by filtration, washed with water (20 ml) and dried to a constant weight to afford 8-bromo-6-fluoro-2-methylquinazolin-4(3H)-one (14, 342 mg, 73.7%) as a pale white solid, which was used without further purification: (tR=2.40 min, purity=100%), ESI+m/z, no ion detected; 1H NMR (DMSO-d6), delta (ppm) 2.39 (s, 3H), 7.80 (dd, J=3.0 Hz, JH-F=8.2 Hz, 1H), 8.13 (dd, J=2.7 Hz, JH-F=8.2 Hz, 1H), 12.54 (br s, 1H); 13C NMR (DMSO-d6) delta (ppm) 21.6, 110.7 (d, JC-F=23.0 Hz), 122.9 (d, JC-F=9.7 Hz), 123.0 (d, JC-F=8.8 Hz), 126.5 (d, JC-F=26.6 Hz), 143.9 (d, JC-F=2.7 Hz), 155.3 (d, JC-F=1.8 Hz), 159.0 (d, JC-F=247.7 Hz), 161.1 (d, JC-F=3.5 Hz); HRMS m/z (ESI+) calculated for C9H7N2BrF: 256.97203; found: 256.97205. |
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