Structure of 137628-16-1
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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. : | 137628-16-1 |
Formula : | C5H3BrClNO |
M.W : | 208.44 |
SMILES Code : | OC1=NC=C(Cl)C=C1Br |
MDL No. : | MFCD01764522 |
InChI Key : | IPCVJZRBMDESEV-UHFFFAOYSA-N |
Pubchem ID : | 2726791 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 38.97 |
TPSA ? Topological Polar Surface Area: Calculated from |
33.12 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 |
2.15 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.2 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.6 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.27 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.01 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.98 |
Solubility | 0.218 mg/ml ; 0.00105 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.48 |
Solubility | 0.694 mg/ml ; 0.00333 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.92 |
Solubility | 0.248 mg/ml ; 0.00119 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 |
-6.04 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<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.56 |
* 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 |
---|---|---|
66% | A mixture of 5-CHLORO-2-HYDROXYPYRIDINE (20.1 g, 155.4 MMOL) and bromine (11.9 ml) in acetic acid (250 m) was stirred at r. t. for 2 hours. Then, the solvent was evaporated in vacuo and ethyl acetate (600 ML) and saturated sodium bicarbonate (300 ML) were added. The organic layer was washed with saturated sodium bicarbonate (2X200 ML), brine and was dried (NA2SO4) and concentrated to give a solid that was crystallized from hexane/ diethyl ether. The solid 3-bromo-<strong>[4214-79-3]5-chloro-2-hydroxypyridine</strong> (21.3 g, 66percent) so obtained was used in the subsequent reaction. | |
With bromine; In water; acetic acid; | Step 1: 3-Bromo-<strong>[4214-79-3]5-chloro-2-hydroxypyridine</strong> A mixture of <strong>[4214-79-3]5-chloro-2-hydroxypyridine</strong> (100 g) and bromine (40.1 mL) in acetic acid (400 mL) was stirred at r.t. for 1 h. The mixture was poured into 3 L of water and stirred for 30 min then filtered. The residual solid was washed with 2 L of cold water, air dried and then coevaporated with toluene three times and with benzene two times. The white solid (81 g) so obtained was used in the subsequent reaction. | |
With bromine; In water; acetic acid; | Step 1 3-Bromo-<strong>[4214-79-3]5-chloro-2-hydroxypyridine</strong> A mixture of <strong>[4214-79-3]5-chloro-2-hydroxypyridine</strong> (100 g) and bromine (40.1 mL) in acetic acid (400 mL) was stirred at r.t. for 1 h. The mixture was poured into 3 L of water and stirred for 30 min then filtered. The residual solid was washed with 2 L of cold water, air dried and then coevaporated with toluene three times and with benzene two times. The white solid (81 g) so obtained was used in the subsequent reaction. |
4.4 g | With bromine; acetic acid; at 20℃; | To a stirred solution of <strong>[4214-79-3]5-chloropyridin-2-ol</strong> (4 g, 31 mmol) in acetic acid (35 mL) at room temperature was added bromine (2.55 mL, 49.6 mmol) dropwise. After stirring the reaction mixture for overnight at room temperature, water was added and the mixture was extracted twice with ethyl acetate (2 x 150 mL). The organic layer was washed with water, dried over anhydrous sodium sulfate and was concentrated under reduced pressure to afford crude product. The crude product was purified by column chromatography by using silica (100-200 mesh) using 22percent EtOAc-hexane as eluent to afford the 3-bromo-<strong>[4214-79-3]5-chloropyridin-2-ol</strong> (4.4 g) as yellow solid. |
With bromine; In acetic acid; at 20℃; for 48h; | 5-CHLORO-2-PYRIDINOL (5.18g, 40MMOL) was dissolved in glacial acetic acid (50ml) and bromine (7. 51 G, 2. 41ml, 47mmol) added. The mixture was stirred at room temperature for 48 hours. Ethyl acetate and water were added and the organic layer washed with water (*3), dried (MGS04) and evaporated. The residue was triturated with diethyl ether and the buff solid filtered and dried (5.59g). 1H NMR (CDCI3) 7.52 (1 H, d J=3Hz), 7.87 (1 H, d J=3Hz). | |
With bromine; In acetic acid; at 20℃; | At room temperature, bromine (1.2 mL, 24 mmol) was added dropwise to a solution of <strong>[4214-79-3]5-chloro-2-pyridinol</strong> (2.9 g, 20 mmol) in glacial acetic acid (25 mL). After stirred at room temperature overnight, ethyl acetate and water were added. The organic layer was washed with water, dried and concentrated. The residue was triturated with diethyl ether and the precipitate was filtered and dried to give the title compound (1.5 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81.76 g (89%) | With trichlorophosphate; In N,N-dimethyl-formamide; | EXAMPLE 3 3-Bromo-2,5-dichloropyridine To a solution of 3-bromo-5-chloropyridin-2-one (84.3 g, 0.404 mol) in DMF (100 mL) was added POCl3 (56.5 mL, 0.61 mol) via dropping funnel over 3 hours at room temperature. The resulting black solution was then heated to 70 C. and allowed to stir for 3 days. After cooling to room temperature, the solution was poured into 1 L of ice/water, filtered, and the solid dried in a vacuum oven to provide 81.76 g (89%) of the desired 3-bromo-2,5-dichloropyridine as an off-white solid, m.p. 39-41 C.: IR(CHCl3) 3867, 3663, 2989, 2734, 1812, 1606, 1547, 1400, 1366, 1230, 1155, 1129, 1074, 1027, 894, 658, 563 cm-1; 1 H NMR (300 MHz, CDCl3) delta 8.0 (d, 1H, J=2.2 Hz), 8.35 (d, 1H, J=2.2 Hz); 13 C NMR (CDCl3) delta 120.43, 130.74, 141.46, 146.64, 148.99; exact mass calculated for C5 H2 NBrCl2 =224.8748; high resolution mass spec. 224.8764. |
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