Structure of 13534-99-1
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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. : | 13534-99-1 |
Formula : | C5H5BrN2 |
M.W : | 173.01 |
SMILES Code : | BrC1=CC=CN=C1N |
MDL No. : | MFCD03095187 |
InChI Key : | RBCARPJOEUEZLS-UHFFFAOYSA-N |
Pubchem ID : | 817700 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | 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 |
1.69 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.2 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.43 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.99 |
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 |
1.34 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.22 |
Solubility | 1.03 mg/ml ; 0.00597 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.61 |
Solubility | 4.21 mg/ml ; 0.0243 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 |
-6.5 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) |
1.42 |
* 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 |
---|---|---|
12.0% | With potassium carbonate; In ethanol; at 75℃; for 4h; | 3-Bromo-2-pyridinamine (0.504 g, 2.9 mmol) and K2CO3 (0.392 g, 2.84 mmol) were added to a solution of 2-bromo-l-(tetrahydro-2H-pyran-4-yl)ethanone (0.784 g, 3.8 mmol) in EtOH (10 ml). The r.m. was stirred at 75 0C for 4 h. and was then cooled to r.t. Subsequently, DCM was added and the solution was washed with a sat. aq. NaHCO3 solution. The organic layer was dried (MgSO4), filtered and the solvent was evaporated in vacuo. The residue was purified by flash chromatography over silicagel (eluent: mixtures of hexane: EtOAc (ratios: 15:1; 10:1; 5:1; 1 :1)). The desired fractions were collected and worked up. Yield 0.096 g of intermediate 7 (12.0 %). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With copper(ll) sulfate pentahydrate; In water; at 150℃; for 0.75h;Microwave irradiation; | 2-Amino-3-bromo-pyridine (200 mg, 1.2 mmol) and copper sulfate pentahydrate (17 mg, 0.069 mmol, 0.06 eq.) was added to microwave vessel with 40% methylamine in H2O (2.14 ml). The reaction mixture was heated at 150 C for 45 min. The crude mixture was filtered through Celite, partitioned between saturated aqueous NaHCO3 and DCM, then extracted with DCM. The organic layer was dried with brine and anhydrous Na2SO4, filtered, evaporated to dryness under vacuum and purified on silica gel by column chromatography using solvent gradient from hexane to EtOAc to give the desired product was yellow solid (86 mg, 70%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
14% | With N-ethyl-N,N-diisopropylamine; In 1,2-dimethoxyethane; at 140℃; for 1.5h;Microwave irradiation; | To a 10-mL microwave reaction container, it is 2-amino-3-bromopyridine (0.10 g). 0.58mmol and tert-butyl 3-bromo-4-oxo piperidine- 1-carboxylate (0.16 g) After measuring 0.58mmol and adding 1,2-dimethoxyethane (2 mL), diisopropylethylamine (following, DIPEA) (75 mg, 0.58mmol) was added, and it agitated for 90 minutes at 140 degrees C using the microwave reaction apparatus. Flash silica gel column chromatography (only n-hexane - n-hexane / ethyl acetate = 34/66) refines the rough product produced by condensing a reaction mixture, tert-butyl 6-bromo-3,4-dihydroimidazo [1,2-a:5,4-c'] **********- 2(1H)-carboxylate (compound of the following and the reference example 2) (29 mg, 81 **mols) was obtained as a light yellow oily matter (14percent of yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | In isopropyl alcohol; at 75℃; for 72h; | To a solution of 3-bromopyridin-2-amine (200 mg, 1.16 mmol) in 2-propanol (2.3 mL) was added 2-bromo- 1 -(2,4-dimethylphenyl)ethanone (315 mg, 1.39 mmol). The mixture wasstirred at 75 C for 72 h. The reaction mixture was then cooled to room temperature and concentrated in vacuo. The crude residue was partitioned between DCM (50 mL) and saturated aqueous NaHCO3 solution (50 mL) and the two phases were separated. The aqueous layer was extracted with DCM (2 X 50 mL). The combined organic layers were dried over anhydrous MgSO4, filtered and concentrated in vacuo. The mixture obtained was purified by silica gelchromatography (iPrOAc / Heptane = 1: 9) to give the title compound (242 mg, 70%) as a pale yellow solid. ‘HNMR (400 IVIFIz, DMSO-d6) 8.12 (dd, J = 6.7, 1.1 Hz, 1H), 7.84-7.77 (m, 1H), 7.74 (s, 1H), 7.43 (dd, J = 7.3, 1.0 Hz, 1H), 7.13 - 7.06 (m, 2H), 6.66 (dd, J = 7.3, 6.7 Hz, 1H), 2.52 (s, 3H), 2.36 (s, 3H). LCMS M/Z (M+H) 301. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | With potassium carbonate; In acetonitrile; at 75℃; for 6h;Schlenk technique; Inert atmosphere; | General procedure: Experimental Procedure: A dried 25 mL Schlenk tube equipped with a magnetic stir bar was charged with Togni?s Reagent 2 (0.25 mmol, 1.0 equiv), free anilines 1 (0.75 mmol, 3.0 equiv), K2CO3 (0.375 mmol, 1.5 equiv) and CH3CN (1.5 mL). The reaction mixture was then stirred at 75 C for 6 h under an argon atmosphere. The reaction progress was monitored by TLC. After cooling to room temperature, the mixture was washed with water and extracted with CH2Cl2 three times, then washed with saturated NaCl solution. The combined organic layer was dried with anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuo. The crude product was purified by flash column chromatography on silica gel (Elutent: petroleum ether-EtOAc) to give the pure product. The products were characterized by 1H NMR, 13C NMR, 19F NMR, GC -MS. |
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