Structure of 114897-91-5
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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. : | 114897-91-5 |
Formula : | C8H5BrFN |
M.W : | 214.03 |
SMILES Code : | N#CCC1=CC=C(Br)C=C1F |
MDL No. : | MFCD07368653 |
InChI Key : | QLASQEZPJFNZQC-UHFFFAOYSA-N |
Pubchem ID : | 7172308 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.12 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 43.62 |
TPSA ? Topological Polar Surface Area: Calculated from |
23.79 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.97 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.37 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.07 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.94 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.22 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.71 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.0 |
Solubility | 0.215 mg/ml ; 0.00101 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.51 |
Solubility | 0.661 mg/ml ; 0.00309 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.03 |
Solubility | 0.0202 mg/ml ; 0.0000942 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) |
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 |
-5.92 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) |
1.45 |
* 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 |
---|---|---|
70% | (2) Production of ethyl (4-bromo-2-fluorophenyl)acetate: Hydrochloric acid (10 mL) was added to an ethanol solution (20 mL) of (4-bromo-2-fluorophenyl)acetonitrile (2.11 g, 9.86 mmol), and heated under reflux for 15 hours. Next, with cooling with ice, aqueous saturated sodium hydrogencarbonate solution was gradually added to the reaction liquid for neutralization. After extracted with ethyl acetate, the obtained organic layer was washed with saturated saline, then dried with anhydrous sodium sulfate, and filtered. The obtained filtrate was concentrated under reduced pressure, then the residue was purified by silica gel column chromatography (hexane:ethyl acetate = 10:0 to 9:1) to obtain the entitled compound (1.81 g, 70 %). 1H-NMR (400 MHz, DMSO-d6, δ ppm): 1.26 (3H, t, J=7.2 Hz), 3.62 (2H, s), 4.17 (2H, q, J=7.2 Hz), 7.12-7.18 (1H, m), 7.23-7.28 (2H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | Step 1. 1-(4-Bromo-2-fluorophenyl)cyclopropanecarboxylic acid Sodium hydroxide, 50% aqueous solution (5.71 mL, 0.149 mol), was added to a mixture of (4-bromo-2-fluorophenyl)acetonitrile (3.16 g, 0.0145 mol), benzyltriethylammonium chloride (0.26 g, 0.0011 mol), and 1-bromo-2-chloro-ethane (2.51 mL, 0.0302 mol) at 50 C. for 10 h. The mixture was poured into ice-water (50 mL) and was extracted with ethyl ether (2*50 mL). The combined organic phase was washed with brine (30 mL), dried over MgSO4, filtered, and concentrated under reduced pressure to give 2.88 g of brown solid. 1H-NMR confirmed that desired nitrile intermediate was isolated. To the resulting residue was added 50% NaOH aqueous solution (3.8 mL) and ethylene glycol (20 mL) and the solution was heated to 100 C. and stirred overnight. The reaction mixture was poured into 50 mL of water and washed with ether (2*50 mL). The aqueous layer was cooled with an ice bath and then acidified by the slow addition of 6 N HCl. to pH=2. The product was extracted with EtOAc (2*100 mL), dried over MgSO4 and concentrated to give 1.634 g. (70%) of the desired product. 1H NMR confirmed that the desired product was isolated. | |
To a stirred mixture of the (4-bromo-2-fluorophenyl)acetonitrile (12.53 g, 0.05854 mol), benzyltriethylammonium chloride (0.9 g, 0.004 mol), and l-bromo-2-chloro-ethane (9.70 mL, 0.117 mol) was added dropwise sodium hydroxide, 50% aqueous solution (21.00 mL, 0.5484 mol) at 50 C. After stirring for 16 h, the reaction mixture was diluted with water, 1,2-ethanediol (65.00 mL, 1.166 mol), and sodium hydroxide, 50% aqueous solution (5 mL). The resulting mixture was heated at 100C for 16 h. The reaction mixture was extracted with diethyl ether and the aqueous layer was acidified to pH~2 and the product precipitated out and was collected by filtration and used in the subsequent reaction without further purification. |
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