Structure of 26218-78-0
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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. : | 26218-78-0 |
Formula : | C7H6BrNO2 |
M.W : | 216.03 |
SMILES Code : | C1=NC(=CC=C1C(=O)OC)Br |
MDL No. : | MFCD04972371 |
InChI Key : | NFLROFLPSNZIAH-UHFFFAOYSA-N |
Pubchem ID : | 13349623 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 43.22 |
TPSA ? Topological Polar Surface Area: Calculated from |
39.19 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.04 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.73 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.63 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.09 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.87 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.67 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.54 |
Solubility | 0.622 mg/ml ; 0.00288 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.17 |
Solubility | 1.46 mg/ml ; 0.00677 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.96 |
Solubility | 0.237 mg/ml ; 0.0011 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 |
-6.39 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<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.67 |
* 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 |
---|---|---|
10% | With 3,3-dimethyl-butan-2-one; palladium diacetate; potassium carbonate; tri tert-butylphosphoniumtetrafluoroborate; In N,N-dimethyl-formamide; at 110℃; for 6.0h;Inert atmosphere; | j0235] Procedure:10236] Pd(OAc)2 (15.7 mg, 0.070 mmoles), [P(t-13u)3H] HF4 (60.7 mg, 0.21 mmoles), pivalic acid (28.5 mg, 0.28 mmoles), K2C03 (386 mg, 2.8 mmoles), methyl thiazole-4- carboxylate (200 mg, 1.4 mmoles), and methyl 6-bromoni- cotinate (603 mg, 2.8 mmoles) were added to a dried flask. The flask was fitted with a reflux condenser capped with a septum, evacuated, and purged with nitrogen (.-5 times). Dry DMF (7 mE) was added via syringe, and the reaction was stirred at 1100 C. for 6 h. The reaction mixture was cooled and filtered through Celite, and the filtrate was concentrated under reduced pressure. The crude product was then purified by chromatography on silica (1% acetone in DCM) to afford the title compound (39 mg, 10%) as a white solid. ?H NMR (400 MHz, CDC13) oe 9.18 (dd, J=0.8, 2.0 Hz, 1H), 8.41 (dd, J=2.0, 8.4 Hz, 1H), 8.38 (dd, J=0.8, 8.4 Hz, 1H),8.33 (s, 1H), 3.99 (s, 3H), 3.98 (s, 3H); ?3C NMR (100 MHz, CDC13) oe 168.7, 165.1, 161.7, 153.3, 150.7, 148.3, 138.3, 130.7, 126.9, 119.6, 52.6, 52.6; HRMS (ESI) mlz 279.0423 [calc?d for C,2H,,N204S (M+H) 279.0435]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
29% | With 1-Adamantanecarboxylic acid; palladium diacetate; potassium carbonate; tri tert-butylphosphoniumtetrafluoroborate; In toluene; at 110℃; for 8h;Inert atmosphere; | j0238] Procedure:10239] Pd(OAc)2 (31.8 mg, 0.14 mmoles), [P(t-13u)3H] HF4 (123.2 mg, 0.42 mmoles), 1-adamantanecarboxylic acid (153 mg, 0.85 mmoles), K2C03 (782 mg, 5.7 mmoles), and methyl 6-bromonicotinate (918mg, 4.3 mmoles) were added to a dried flask. The flask was fitted with a reflux condenser capped with a septum, evacuated, and purged with nitrogen (.-5 times). A degassed solution of ethyl oxazole-5-carboxy- late (400 mg, 2.8 mmoles) in dry toluene (7 mE) was added via syringe, and the reaction was stirred at 1100 C. for 8 h. The reaction mixture was cooled and filtered through Celite, and the filtrate was concentrated under reduced pressure. The crude product was then purified by chromatography on silica (30% EtOAc in hexanes followed by 2% acetone in 1:1 DCM:hexanes) to afford the title compound (183 mg, 23%) as a white solid. ?H NMR (400 MHz, CDC13) oe 9.37 (dd, J=0.8, 2.0 Hz, 1H), 8.47 (dd, J=2.0, 8.0 Hz, 1H), 8.30 (dd, J=0.8, 8 Hz, 1H), 7.96 (s, 1H), 4.46 (q, J=7.2 Hz, 2H), 4.00 (s, 3H), 1.43 (t, J=7.2 Hz, 3H); ?3C NMR (100 MHz, CDC13) oe 164.9, 161.6, 157.5, 151.5, 148.0, 143.8, 138.3, 135.5, 127.3, 122.5, 61.9, 52.7, 14.3; HRMS (ESI) mlz 277.0823 [calc?d for C,3H,3N205 (M+H) 279.0819]. For experiments with mammalian cells, this compound was recrystallized from EtOAc to afford a white crystalline solid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
29% | With 3,3-dimethyl-butan-2-one; palladium diacetate; potassium carbonate; tri tert-butylphosphoniumtetrafluoroborate; In toluene; at 110℃; for 24h;Inert atmosphere; | j0241] Procedure:j0242] Pd(OAc)2 (15.9 mg, 0.071 mmoles), [P(t-Hu)3H] HF4 (61.8 mg, 0.21 mmoles), pivalic acid (29.0 mg, 0.28 mmoles), K2C03 (391 mg, 2.8 mmoles), ethyl oxazole-4- carboxylate (200 mg, 1.4 mmoles), and methyl 6-bromoni- cotinate (612 mg, 2.8 mmoles) were added to a dried flask. The flask was fitted with a reflux condenser capped with a septum, evacuated, and purged with nitrogen (.-5 times). Drytoluene (7 mE) was added via syringe, and the reaction was stirred at 1100 C. for 24 h. The reaction mixture was cooled and filtered through Celite, and the filtrate was concentrated under reduced pressure. The crude product was then purified via chromatography on silica (2% acetone in DCM followed by 10% acetone 1:1 DCM:hexanes) to afford the title compound (113 mg, 29%) as a white solid. ?H NMR (400 MHz, CDC13) oe 9.31 (dd, J=0.8, 2.0 Hz, 1H), 8.46 (dd, J=2.0, 8.4 Hz, 1H), 8.42 (s, 1H), 8.38 (dd, J=0.8, 8.4 Hz, 1H), 4.45 (q, J=7.2 Hz, 2H), 4.00 (s, 3H), 1.42 (t, J=7.2 Hz, 3H); ?3C NMR (100 MHz, CDC13) oe 164.9, 160.8, 160.2,151.1, 148.0, 145.2, 138.3, 135.3, 127.1, 122.3, 61.6, 52.7, 14.3; HRMS (ESI) mlz 277.0815 [calc?d for C,3H,3N205 (M+H) 277.0823]. |
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