Structure of 866319-00-8
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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. : | 866319-00-8 |
Formula : | C7H5FN2 |
M.W : | 136.13 |
SMILES Code : | FC1=CN=C2C(=C1)C=C[NH]2 |
MDL No. : | MFCD06659678 |
InChI Key : | BALBNSFYMXBWNM-UHFFFAOYSA-N |
Pubchem ID : | 20784462 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H319 |
Precautionary Statements: | P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 9 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 36.05 |
TPSA ? Topological Polar Surface Area: Calculated from |
28.68 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.43 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.41 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.12 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.42 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.5 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.77 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.24 |
Solubility | 0.786 mg/ml ; 0.00578 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.62 |
Solubility | 3.29 mg/ml ; 0.0242 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.16 |
Solubility | 0.0944 mg/ml ; 0.000693 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 |
-6.13 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) |
1.55 |
* 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 |
---|---|---|
81.56% | With N-Bromosuccinimide; In N,N-dimethyl-formamide; at -10℃; for 1h; | At -10 C., to a solution of the compound BB-3-4 (7.40 g, 54.36 mmol) in DMF (100.00 mL) was added N-bromo-succinimide (9.67 g, 54.36 mmol). The mixture was stirred at -10 C. for one hour. Water (100 mL) was added dropwise into the reaction liquid, the mixture was filtered, and the soiled was spun to dry to give the compound BB-3-5 (11.50 g, 44.34 mmol, yield 81.56%). MS (ESI) m/z=217.0 [M+1]. |
64% | With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 0℃; for 2h; | To a stirred solution of 5-fluoro-1H-pyrrolo[2,3-b]pyridine (4.5 g, 33 mmol) in DMF (50 mL) was added NBS (6.4 g, 36 mmol) in portions at 0 C and left it for 2 h. After completion of the reaction as indicated by TLC, the reaction mixture was poured into ice cold water (100 mL), filtered the precipitated solid and dried under vacuum to afford 3-bromo-5-fluoro-1H-pyrrolo[2,3-b]pyridine (5) (4.6 g, 21 mmol, 64%) as pale brown solid. TLC system: 20% EtOAc in hexanes Rf : 0.5 LCMS (ESI): m/z 215 [M+H]+. |
64% | With N-Bromosuccinimide; In N,N-dimethyl-d6-formamide; at 0℃; for 2h; | To a stirred solution of 5-fluoro-1H-pyrrolo[2,3-b]pyridine (4.5 g, 33 mmol) in DMF (50 mL) was added NBS (6.4 g, 36 mmol) in portions at 0 C and left it for 2 h. After completion of the reaction as indicated by TLC, the reaction mixture was poured into ice cold water (100 mL), filtered the precipitated solid and dried under vacuum to afford 3-bromo-5- fluoro-1H-pyrrolo[2,3-b]pyridine (5) (4.6 g, 21 mmol, 64%) as pale brown solid. TLC system: 20% EtOAc in hexanes Rf : 0.5 LCMS (ESI): m/z 215 [M+H]+ |
40% | With bromine; In N,N-dimethyl-formamide; at 20℃; for 4h; | To the solution of 5-fluoro-1H-pyrrolo[2,3-b]pyridine (1 g, 7.34 mmol) in DMF (10 mL) was added bromine (0.75 mL, 14.5 mmol). The mixture was stirred at it for 4 hours. The reaction mixture was quenched with saturated aqueous sodium thiosulfate (100 mL). The resulting mixture was extracted with ethyl acetate (100 mL x 2). The combined organic layers were washed with saturated brine (100 mL x 3), dried over ahydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo, and the residue was purified by silica gel column chromatography (PE/EtOAc (v/v) = 4/1) to give the title compound as yellow powder (0.6 g, 40%).MS (ESI, pos. ion) m/z: 216.9 [M+H]+1H NMR (400 MHz, DMSO-d6) ö (ppm): 12.23 (s, 1H), 8.35-8.21 (m, 1H), 7.81 (d, J = 2.7 Hz, 1H), 7.71 (dd, J = 8.9, 2.6 Hz, 1H). |
40% | With bromine; In N,N-dimethyl-formamide; at 20℃; for 4h; | To a solution of 5-fluoro-1H-pyrrolo[2,3-b]pyridine (1.0 g, 7.34 mmol) in DMF (10 mL) was added bromine (0.75 mL, 14.5 mmol) . The reaction mixture was stirred at r. t. for 4 h. A saturated aqueous Na2S2O3 solution (100 mL) was added to quench the reaction, and the resulting mixture was extracted with EtOAc (100 mL × 2) . The combined organic phases were washed with saturated brine (100 mL × 3) , dried over anhydrous Na2SO4, filtered, and the filtrate was concentrated in vacuo. The residue was purified by silica gel chromatograph (PE/EtOAc (v/v) 4/1) to give the tilte compound as a yellow solid (0.6 g, 40 %). MS (ESI, pos. ion) m/z: 216.9 [M+H]+ 1H NMR (400 MHz, DMSO-d6) δ (ppm) : 12.23 (s, 1H) , 8.35-8.21 (m, 1H) , 7.81 (d, J 2.7 Hz, 1H) , 7.71 (dd, J 8.9, 2.6 Hz, 1H). |
40% | With bromine; at 20℃; for 4h; | 5-Fluoro-1H-pyrrolo[2,3-b]pyridine (1 g, 7.34 mmol) was dissolved in DMF (10 mL)Then, bromine (0.75 mL, 14.5 mmol) was added dropwise thereto, and the reaction was stirred at room temperature for 4 hours.Quenched with saturated aqueous sodium thiosulfate solution (100 mL)The reaction mixture was extracted with ethyl acetate (100 mL×2).The combined organic phases were washed with brine (100 mL×3)Filtered, concentrated under reduced pressure,The residue was subjected to silica gel column chromatography(PE/EtOAc (v/v) = 4/1) purified,The title compound was obtained as a yellow powder (0.6 g, 40%). |
40% | With bromine; In N,N-dimethyl-formamide; at 20℃; for 4h; | 5-Fluoro-1H-pyrrolo[2,3-b]pyridine (1 g, 7.34 mmol) was dissolved in DMF (10 mL)Then bromine (0.75 mL, 14.5 mmol) was added dropwise thereto.The reaction was stirred at room temperature for 4 hours.The reaction was quenched by the addition of saturated aqueous sodium thiosulfate (100 mL).The resulting mixture was extracted with ethyl acetate (100 mL X 2).The combined organic phases were washed with saturated brine (100 mL×3).Dry over anhydrous sodium sulfate, filter,Concentrated under reduced pressure, and the residue was applied to silica gel column chromatography(Petroleum ether / ethyl acetate (ν / ν) = 4 / 1) purification,The title compound was obtained as a yellow powder (0.6 g, 40%). |
With N-Bromosuccinimide; In dichloromethane; at 20℃; for 19h; | Preparation of compound 2: N-bromosuccinimide (NBS, 5 · 29 g, 29 · 7 mmol) was added to a solution of compound 1 (4.50 g, 33 mmol) in dichloromethane (100 mL) and react at room temperature 19 hour,After the reaction, a saturated sodium hydrogen sulfite solution (200 ml) was added, and the mixture was separated.The organic layer was washed with 20% sodium hydroxide solution.Dry over anhydrous sodium sulfate, filter,The filtrate was concentrated in vacuo to give a crude product4.62g. | |
With N-Bromosuccinimide; In dichloromethane; at 20℃; for 19h; | N-bromosuccinimide (NBS, 5.29 g, 29.7 mmol) was added to Compound 6(4.50 g, 33 mmol) in dichloromethane (100 mL) and reacted at room temperature for 19 hours,After the reaction was completed, a saturated sodium bisulfite solution (200 mL) was added.The layers were separated, and the organic layer was washed with 20% sodium hydroxide solution and dried over anhydrous sodium sulfate.Filtration and concentration of the filtrate in vacuo gave the crude product4.62g. |
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