Structure of 7089-68-1
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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. : | 7089-68-1 |
| Formula : | C12H7ClN2 |
| M.W : | 214.65 |
| SMILES Code : | ClC1=CC=C2C=CC3=CC=CN=C3C2=N1 |
| MDL No. : | MFCD00185678 |
| InChI Key : | JHRMQHFRVPVGHL-UHFFFAOYSA-N |
| Pubchem ID : | 355193 |
| GHS Pictogram: |
|
| Signal Word: | Warning |
| Hazard Statements: | H302-H315-H319-H335 |
| Precautionary Statements: | P261-P305+P351+P338 |
| Num. heavy atoms | 15 |
| Num. arom. heavy atoms | 14 |
| Fraction Csp3 | 0.0 |
| Num. rotatable bonds | 0 |
| Num. H-bond acceptors | 2.0 |
| Num. H-bond donors | 0.0 |
| Molar Refractivity | 62.05 |
| TPSA ? Topological Polar Surface Area: Calculated from |
25.78 Ų |
| Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.98 |
| Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.74 |
| Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.44 |
| Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.4 |
| Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.58 |
| Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.83 |
| Log S (ESOL):? ESOL: Topological method implemented from |
-3.59 |
| Solubility | 0.0555 mg/ml ; 0.000258 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| Log S (Ali)? Ali: Topological method implemented from |
-2.94 |
| Solubility | 0.249 mg/ml ; 0.00116 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-5.63 |
| Solubility | 0.000507 mg/ml ; 0.00000236 mol/l |
| Class? Solubility class: Log S scale |
Moderately 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) |
Yes |
| 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) |
Yes |
| Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-5.66 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 |
2.0 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) |
1.77 |
* 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 |
|---|---|---|
| 75% | Reference Example 32-Chloro-1,10-phenanthroline (3) [0113] [Chem. 20] [0114] Under a stream of argon, to compound (2) (8 g; 38 mmol), phosphorus oxychloride (72 mL) and phosphorus pentachloride (9.8 g; 47.6 mmol) were added in an ice bath. The resulting reaction mixture was stirred and refluxed for 8 hours, and excess phosphorus oxychloride was removed under reduced pressure. To the resulting reaction concentrate, ice water and concentrated aqueous ammonia were added and the resulting mixture was made alkaline to precipitate crude crystals. The crude crystals were separated by filtration and washed with water, and then dried under reduced pressure to give 6.1 g (yield: 75percent) of the title compound (3). [0115] 1H NMR (DMSO-d6) d: 7.80-7.88 (m, 2 H), 8.07 (s, 2 H), 8.54 (d, J = 8.5 Hz, 1 H), 8.60 (d, J = 8.5 Hz, 1 H), 9.14 (d, J = 7 Hz, 1 H) | |
| 75% | Production Example 32-Chloro-1,10-phenanthroline (3)[0149] [Chem. 26] [0150] Under a stream of argon, to compound (2) (8 g; 38 mmol), phosphorus oxychloride (72 mL) and phosphorus pentachloride (9.8 g; 47.6 mmol) were added in an ice bath. The resulting reaction mixture was stirred and refluxed for 8 hours, and excess phosphorus oxychloride was removed under reduced pressure. To the resulting reaction concentrate, ice water and concentrated aqueous ammonia were added and the resulting mixture was made alkaline to precipitate crude crystals. The crude crystals were separated by filtration and washed with water, and then dried under reduced pressure to give 6.1 g (yield: 75percent) of the title compound (3).[0151] 1H NMR (DMSO-d6)d: 7.80-7.88 (m, 2H), 8.07 (s, 2H), 8.54 (d, J=8.5 Hz, 1H), 8.60 (d, J=8.5 Hz, 1H), 9.14 (d, J=7 Hz, 1H) |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 94% | With acetamide; potassium carbonate; at 200℃; for 5h; | <strong>[7089-68-1]2-Chloro-1,10-phenanthroline</strong> (100 mg, 0.5 mmol) and potassiumcarbonate (451 mg, 3.3 mmol) and acetamide (688 mg,11.7 mmol) were stirred at 200 C for 5 h. The reaction mixturewas cooled to room temperature, and poured into water. The aqueouslayer was extracted with chloroform (40 mL) twice. The combinedorganic layers were washed with brine and dried overmagnesium sulfate. The crude product was purified by silica gelchromatography eluted with chloroform/methanol = 100:1 to give2 (85 mg, 94%) as white solids. |
| 52.5% | With acetamide; potassium carbonate; at 200℃; for 1h; | <strong>[7089-68-1]2-chloro-1,10-phenanthroline</strong> (859 mg, 4 mmol), acetamide (4.73 g, 80 mmol), potassium carbonate (3.87 g, 28 mmol), and heated to 200 C, stirred for 1 hour, dropped to room temperature, add water (30 mL) to the reaction and extract with dichloromethane. The organic phase was collected, dried over anhydrous sodium sulfate and filtered. The organic phase was removed by concentration under reduced pressure. The residue was subjected to silica gel column chromatography to afford 2-amino-1,10-phenanthroline 409 mg (2.1 mmol, 52.5%). |
[ 7089-68-1 ]
[ 556082-02-1 ]
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 57% | With N,N-dimethyl-formamide; trichlorophosphate; In dichloromethane; at 0 - 25℃;Inert atmosphere; | General procedure: The procedure is identical to general procedure I, except that reactions were conducted at 0.2 M concentration with N-oxide (1.00 equiv), POBr3 (3.00 equiv), DMF (1.50 equiv) at rt. 4.2 General procedure I for the bromination of azine N-oxides (0013) To a stirred solution of the appropriate azine N-oxides in anhydrous CH2Cl2 (0.1 M) at 0 C is added POBr3 (1.2 equiv) followed by dropwise addition of DMF (0.5 equiv) under argon. The resulting reaction mixture was warmed to 25 C and stirred for several hours until the reaction is complete as indicated by TLC. Saturated aqueous sodium carbonate solution is added to the reaction mixture slowly to adjust the pH to 7-8. The resulting mixture is separated and the aqueous phase is extracted with CH2Cl2 thoroughly. The organic phase is combined and washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure to afford the crude product, which is purified by flash column chromatography using PE/EA (100:1) as eluent. |
| 48% | With sodium chloride; trichlorophosphate; In N,N-dimethyl-formamide; at 100℃; for 6h; | 1,10-phenanthroline-N-oxide (1.96 g, 10 mmol), NaCl (11.7 g, 0.2 mol) was added to DMF (40 mL). Slowly add POCl3 (30 mmol) to the solution. The reaction solution was heated at 100 C for 6 h and allowed to cool to room temperature. Ammonia water (50 mL) was added to the reaction mixture, and extracted with chloroform. The organic phase was collected, dried over anhydrous sodium sulfate and filtered. The organic phase was removed by concentration under reduced pressure. The residue was subjected to silica gel column chromatography to give 2-chloro-1,10-phenanthroline 1.03 g (4.8 mmol, 48.0%). |
| 44% | With sodium chloride; trichlorophosphate; In N,N-dimethyl-formamide; at 0 - 100℃; for 6h;Inert atmosphere; Schlenk technique; Sealed tube; | To the mixture of 1,10-phenanthroline-N-oxide (196.1 mg, 1 mmol, 1.0 eq.),sodium chloride in anhydrous DMF, a neat POCl3 (3 mmol, 3.0 eq.) was added slowly after cooling to 0 C. Then, the mixture was heated to 100 C for 6 hours. After cooling to room temperature, water was added, and the mixture was quenched with saturated ammonium chloride (aqueous) and saturated with NaCl (20 mmol, 20.0 eq.), solids were filtered, and the solution was extracted with chloroform.The combined extracts were washed with brine, dried over MgSO4, and evaporated, and then purified by column chromatography using eluent EA/PE (3:2) to get the target product as a light yellow solid, (94.2 mg, 0.44 mmol, yield = 44%). The spectral data were in accordance with the literature [55]. 1H-NMR(400MHz, CDCl3) 9.12 (dd, J = 1.7, 4.1 Hz, 1H), 8.57 (d, J = 9.4 Hz, 1H), 8.53 (dd, J = 1.7, 8.0 Hz, 1H),8.07-8.03 (m, 2H), 7.84 (d, J = 8.4 Hz, 1H), 7.81 (dd, J = 4.3, 8.2 Hz, 1H); 13C-NMR (400MHz, CDCl3) 151.3, 150.7, 146.0, 145.0, 138.7, 136.0, 129.0, 127.2, 126.9, 125.7, 124.2, 123.4. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 2-Chloro-1,10-Phenanthroline, (1) 2-Chloro-1,10-phenanthroline was prepared from 1,10-phenanthroline following the procedure of B. E. Halcrow, Wm. O. Kermack; Journal of the Chemical Society (1946), 155-7 and was isolated in satisfactory yield. |