Structure of 13534-98-0
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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. : | 13534-98-0 |
Formula : | C5H5BrN2 |
M.W : | 173.01 |
SMILES Code : | C1=C(Br)C(=CC=N1)N |
MDL No. : | MFCD02068297 |
InChI Key : | DDQYSZWFFXOXER-UHFFFAOYSA-N |
Pubchem ID : | 26095 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 8 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 36.34 |
TPSA ? Topological Polar Surface Area: Calculated from |
38.91 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.28 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.86 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.43 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.58 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.41 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.11 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.01 |
Solubility | 1.69 mg/ml ; 0.00978 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.26 |
Solubility | 9.49 mg/ml ; 0.0549 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.51 |
Solubility | 0.531 mg/ml ; 0.00307 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 |
-6.74 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) |
1.33 |
* 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 |
---|---|---|
70% | With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 20℃; for 48h; | tert-Butyl 3-bromopyridin-4-ylcarbamate To a solution of 4-amino-3-bromopyridine (1.0 g, 5.78 mmol) in THF (10 mL), DIPEA (1.1 mL, 6.36 mmol) and (Boc)20 (1.39 g, 6.36 mmol) were added. The reaction mixture was stirred at rt. for two days. It was then quenched with 1N HCl solution and extracted with ethyl acetate (2*50 mL). The organic layers were combined, dried (MgSO4), filtered and concentrated to give tert-butyl 3-bromopyridin-4-ylcarbamate as a yellowish thick oil, (1.1 g, 70% yield). MS m/z 273,275(MH+); 1H NMR (300 MHz, CDCl3)delta ppm 1.51 (s, 9 H) 7.14 (s, 1 H) 8.12 (d, J=5.49 Hz, 1 H) 8.34 (d, J=5.86 Hz, 1 H) 8.55 (s, 1 H). |
37 g | With triethylamine; In tetrahydrofuran; for 2h; | To stirred a solution of 4-amino 3-bromo pyridine (10.0 g, 57.803 mmol) in THF (500 ml) were added triethylamine (8.8 g, 86.705 mmol) and Boc anhydride (37.89 g, 173.410 mmol). The reaction mixture was stirred for 2 h, before pouring into water (700 ml) and extracted with EtOAc (500 ml x 2), yielding ie/f-butyl (3- bromopyridin-4-yl)carbamate (37.0 g, 136.029 mmol). MS: 274.95 (M+2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | With potassium fluoride; tris-(dibenzylideneacetone)dipalladium(0); tri tert-butylphosphoniumtetrafluoroborate; In tetrahydrofuran; water; at 110℃; | 3-Bromopyridin-4-amine, 2.00 g (11.6 mmol), 2,3-dichlorophenylboronic acid, 3.30 g (17.3 mmol), tris(dibenzylideneacetone)dipalladium, 530 mg (0.6 mmol), tri-tert-butylphosphine tetrafluoroborate, 335 mg (1.2 mmol), and potassium fluoride, 2.00 g (34.7 mmol), were dissolved in 40 mL of tetrahydrofuran and 10 mL of water. The mixture was stirred at 110 C overnight. The solvent was removed in vacuo. Water was added, the mixture was extracted with ethyl acetate and the combined organic phase was dried over anhydrous sodium sulfate. The solvent was removed in vacuo and the residue was purified with silica gel column chromatography (dichloromethane / methanol = 20: 1) to give 1.90 g (59%) of the product as a yellow solid. LC-MS (Method M33): Rt = 1.22 min; m/z = 239 (M+l)+. |
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