Structure of 1069-72-3
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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. : | 1069-72-3 |
| Formula : | C6H15Br2N |
| M.W : | 261.00 |
| SMILES Code : | CCN(CC)CCBr.[H]Br |
| English Name : | 2-Bromo-N,N-diethylethylamine Hydrobromide |
| MDL No. : | MFCD00040376 |
| InChI Key : | HLMHCDKXKXBKQK-UHFFFAOYSA-N |
| Pubchem ID : | 70607 |
| Num. heavy atoms | 9 |
| Num. arom. heavy atoms | 0 |
| Fraction Csp3 | 1.0 |
| Num. rotatable bonds | 4 |
| Num. H-bond acceptors | 1.0 |
| Num. H-bond donors | 0.0 |
| Molar Refractivity | 51.76 |
| TPSA ? Topological Polar Surface Area: Calculated from |
3.24 Ų |
| Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.0 |
| Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.73 |
| Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.68 |
| Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.54 |
| Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.32 |
| Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.85 |
| Log S (ESOL):? ESOL: Topological method implemented from |
-2.91 |
| Solubility | 0.318 mg/ml ; 0.00122 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| Log S (Ali)? Ali: Topological method implemented from |
-2.45 |
| Solubility | 0.921 mg/ml ; 0.00353 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.46 |
| Solubility | 0.903 mg/ml ; 0.00346 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) |
No |
| 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 |
-5.95 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 |
1.0 alert: heavy_metal |
| Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<0.0 |
| Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.18 |
* 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 |
|---|---|---|
| 87% | Stage #1: 7-hydroxy-2,2-dimethyl-4H-benzo[d][1,3]dioxin-4-one With tetrabutyl-ammonium chloride; potassium carbonate In acetone for 0.333333h; Stage #2: 2-bromo-N,N-diethylethanamine hydrobromide In acetone for 4h; Reflux; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 66% | Stage #1: 5-bromo-1H-pyrrolo[2,3-c]pyridine With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.25h; Stage #2: 2-bromo-N,N-diethylethanamine hydrobromide In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 16h; | 9 2-(5-Bromo-1H-pyrrolo[2,3-c]pyridin-1-yl)-N,N-diethylethanamine To a stirred suspension of 60% NaH (0.21 g, 8.88 mmol) in DMF (5 mL), 5-bromo-1H-pyrrolo[2,3-c]pyridine (0.7 g, 3.55 mmol) was added at °0 C and stirred for 15 min. Then, 2-bromo-N,N-diethylethylamine hydrobromide (1.1 g, 4.26 mmol) was added at °0 C. The reaction mixture was stirred at RT for 16 h and poured into ice cold water (50 mL), and extracted with EtOAc. The organic layer was dried over anhydrous Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude compound was purified by flash column chromatography using 60% ethyl acetate in pet ether as an eluent to afford the title compound (0.7 g, 66%) as brown liquid. LC-MS (method 1): Rt =1.22 min; m/z = 296.24 (M+H+) |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 81% | Stage #1: [(1R)-1-cyclohexylethyl]amine; 2-bromo-N,N-diethylethanamine hydrobromide With triethylamine In toluene for 72h; Reflux; Stage #2: With zinc(II) chloride In methanol; toluene for 12h; Stage #3: With sodium cyanide In dichloromethane at 20℃; for 4h; | 2.3.2 Synthesis of LB 2-(Diethylamino)-ethylbromide hydrobromide (4.00g 15.32mmol) was refluxed with 2equiv. Et3N (3.10g 30.64mmol) and 1equiv. (R)-1-cyclohexylethanamine (1.94g 15.32mmol) in toluene (50mL) for 3days. After cooling ZnCl2 (2.27g, 15.32mmol) dissolving in MeOH 10mL was added to the solution and stirred for 12h. The white solid, Zn(II) complex, was filtered and dried in oven (70°C, 1h). Zn(II) complex (2.60g 7.17mmol) was dissolved in CH2Cl2 (20mL) and treated with 6equiv. NaCN (aq.) (2.11g, 43.0mmol) for 4h at the room temperature. The organic phase was dried with MgSO4. The solvent was eliminated by evaporation to get LB as a yellow oil (1.31g, 81%). Anal. Calc. for C14H30N2 (%): C, 74.27; H, 13.36; N, 12.37. Found: C, 73.90; H, 13.20; N, 12.40. 1H NMR (500MHz, CDCl3): δ 2.65-2.59 (m, 1H, CHCyH), 2.50-2.35 (m, 8H, NCH2), 1.63-1.51 (m, 6H, CyH), 1.26-1.20 (m, 1H, CyH), 1.14-0.97 (m, 4H, CyH), 0.95 (d, J=2.44Hz, 3H, CH3CHCyH), 0.92 (t, J=3.05Hz, 6H, NCH2CH3). 13C NMR (125MHz, CDCl3): δ 58.32 (1C, CHCyC), 52.98, 46.95 (2C, NCH2CH3), 45.40 (1C, CyC), 42.92, 29.96, 28.11, 26.65 (3C, CyC), 16.87 (1C, CH3CHCyC), 11.86 (2C, NCH2CH3). IR (oily liquid neat; cm-1): 2965 (w), 2922 (w), 2851 (w), 2805 (w), 1448 (m), 1371 (m), 1293 (m), 1202 (m), 1067 (m), 889 (m), 798 (m), 730 (m). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With sodium hydride In tetrahydrofuran at 0 - 20℃; for 16h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 54% | With triethylamine In tetrahydrofuran for 24h; Reflux; | VI.1 N,N-diethyl-2-(6-nitro-3,4-dihydroisoquinolin-2(1H)-yl)ethan-1-amine, (271). 6-nitro- 1,2,3,4-tetrahydroisoquinoline, 270 (300 mg, 1.68 mmols) and 2-(diethylamino)ethyl Bromide Hydrobromide (2.24 g, 8.42 mmols) were suspended in 25 ml of THF. Triethylamine (1.7 g, 16.84 mmols) was added in one portion. The mixture was stirred and heated under reflux conditions for 24 h. The solvent was evaporated under vacuum, the residue was dissolved in water (50 ml) and extracted with CH2CI2 (3 x 50 ml). The organic layer was dried over Na2S04, filtered, and the solvent removed under reduced pressure. The crude mixture was separated by flash column chromatography on basic alumina using CH2CI2, CH2Cl2:MeOH 98:2 for elution. Yield 250 mg (54 %). lH NMR (400 MHz, CDCl3) d 7.92 (d, J = 6.9 Hz, 2H), 7.16 (d, J = 9.1Hz, 1H), 3.80 (s, 2H), 3.14 - 3.07 (m, 4H), 2.97 (t, J = 5.8 Hz, 2H), 2.84 (t, J = 5.7 Hz, 2H), 1.37 (dd, J = 7.3, 3.9 Hz, 6H). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 1.6 g | With potassium hydroxide In water; acetonitrile at 85℃; | 5.V Example 5: Step V & VI: Preparation of Tilorone dihydrochloride (Formula g) 250-mL round bottom flask equipped with a stir bar was charged with 2,7-dihydoxy-9H- fluorenone (1g), 2-bromo-N, N-diethylethylamine hydrobromide (4.55 g) and KOH (2.26g), followed by the addition of 15mL acetonitrile and 3.2mL distilled water. The reaction was then stirred vigorously and heated to reflux for 20 h. After cooling to room temperature, the reaction mixture was poured into water and extracted with lfoO. The combined organic layers were dried over Na2SC>4, and the solvent evaporated under reduced pressure. The resulting residue was dried thoroughly to get the desired product as an orange gummy solid (1.6 g, 83 %). Which was dissolved in dry ether and added 2M ethereal HC1 solution drop by drop to obtain Tilorone dihydrochloride salt with >99% yield (1.88 g) and the orange product was recrystallized with anhydrous ethanol. |
| 1.6 g | With potassium hydroxide In water; acetonitrile at 85℃; | 5.V Example 5: Step V & VI: Preparation of Tilorone dihydrochloride (Formula g) 250-mL round bottom flask equipped with a stir bar was charged with 2,7-dihydoxy-9H- fluorenone (1g), 2-bromo-N, N-diethylethylamine hydrobromide (4.55 g) and KOH (2.26g), followed by the addition of 15mL acetonitrile and 3.2mL distilled water. The reaction was then stirred vigorously and heated to reflux for 20 h. After cooling to room temperature, the reaction mixture was poured into water and extracted with lfoO. The combined organic layers were dried over Na2SC>4, and the solvent evaporated under reduced pressure. The resulting residue was dried thoroughly to get the desired product as an orange gummy solid (1.6 g, 83 %). Which was dissolved in dry ether and added 2M ethereal HC1 solution drop by drop to obtain Tilorone dihydrochloride salt with >99% yield (1.88 g) and the orange product was recrystallized with anhydrous ethanol. |

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