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Structure of Ethyl 6-Bromohexanoate
CAS No.: 25542-62-5
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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. : | 25542-62-5 |
Formula : | C8H15BrO2 |
M.W : | 223.11 |
SMILES Code : | CCOC(=O)CCCCCBr |
MDL No. : | MFCD00000270 |
InChI Key : | DXBULVYHTICWKT-UHFFFAOYSA-N |
Pubchem ID : | 117544 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H225-H315-H319 |
Precautionary Statements: | P501-P240-P210-P233-P243-P241-P242-P264-P280-P370+P378-P337+P313-P305+P351+P338-P362+P364-P303+P361+P353-P332+P313-P403+P235 |
Class: | 3 |
UN#: | 3272 |
Packing Group: | Ⅲ |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.88 |
Num. rotatable bonds | 7 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 49.72 |
TPSA ? Topological Polar Surface Area: Calculated from |
26.3 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.8 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.53 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.5 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.43 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.55 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.56 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.36 |
Solubility | 0.985 mg/ml ; 0.00441 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.73 |
Solubility | 0.417 mg/ml ; 0.00187 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.25 |
Solubility | 0.127 mg/ml ; 0.000569 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 |
-5.86 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 |
1.0 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) |
2.34 |
* 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 |
---|---|---|
100% | Step 9b: Ethyl 4-(benzyloxy)-3-(6-ethoxy-6-oxohexyloxy)benzoate (Compound 503-16) The title compound 503-16 (6.7 g, 100%) was prepared as a yellowish oil from 502 (4.43 g, 16.3 mmol), ethyl 6-bromohexanoate (4.36 g, 19.5 mmol) using a procedure similar to that described for compound 307-9 (Example 3): LCMS: 437 [M+23]+; 1H NMR (DMSO-d6): delta 7.53 (d, J=8.4 Hz, 1H), 7.44-7.31 (m, 6H), 7.14 (d, J=8.4 Hz, 1H), 5.17 (s, 2H), 4.25 (q, J=7.2 Hz, 2H), 4.04-3.98 (m, 4H), 2.26 (t, J=6.9 Hz, 2H), 1.74-1.65 (m, 2H), 1.59-1.52 (m, 2H), 1.46-1.36 (m, 2H), 1.28 (t, J=6.9 Hz, 3H), 1.14 (t, J=7.2 Hz, 3H). | |
100% | Step 11a: Ethyl 4-(benzyloxy)-3-(6-ethoxy-6-oxohexyloxy)benzoate (compound 503-19) The title compound 503-19 (6.7 g, 100%) was prepared as a yellow oil from compound 502 (4.43 g, 16.3 mmol) and ethyl 6-bromohexanoate (4.36 g, 19.5 mmol) using a procedure similar to that described for compound 503-18 (Example 10): LCMS: 437 [M+23]+; 1H NMR (DMSO-d6): delta 7.53 (d, J=8.4 Hz, 1H), 7.44-7.31 (m, 6H), 7.14 (d, J=8.4 Hz, 1H), 5.17 (s, 2H), 4.25 (q, J=7.2 Hz, 2H), 4.04-3.98 (m, 4H), 2.26 (t, J=6.9 Hz, 2H), 1.74-1.65 (m, 2H), 1.59-1.52 (m, 2H), 1.46-1.36 (m, 2H), 1.28 (t, J=6.9 Hz, 3H), 1.14 (t, J=7.2 Hz, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.75 g | To sodium hydride (300 mg) in DMF at 0 C. was added 5,6-dichloro-2-methylbenzoimidazole (500 mg) in one portion. The mixture was stirred at 0 C. for 15 minutes, followed by addition of ethyl 6-bromohexanoate (0.66 mL). The mixture was stirred at 0 C. for another 15 minutes and then at room temperature for 1 hour. The solution was concentrated to dryness under vacuum and the residue was purified by column chromatography on silica gel to give pale brown solid (0.75 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With potassium carbonate; In N,N-dimethyl-formamide; at 100℃; for 18.0h; | 7-bromo-l, 2,3,4-tetrahydroquinoline (5. 0 g, 23.6 mmol) was dissolved in DMF (10 mL). Potassium carbonate (6.4 g) and 6-bromohexanoate ethyl ester (10.0 g, 47.2 mmol) were added into the solution. The mixture was heated to 100 C for 18 hours. After the reaction was cooled down, 50 niL of dichloromethane was added and washed with 10 niL of water three times. The organic layer was dried over sodium sulfate and concentrated. It was purified by flash chromatography in silica gel with hexanes-ethyl acetate to afford ethyl 6-(7-bromo-3,4- dihydroquinolin-l(2H)-yl)hexanoates as a clear oil (yield : 70%). H NMR (CDC13): delta 6.79 (d, 1H), 6.64 (d, 2H), 4.15 (t, 2H), 3.29 (t, 2H), 3.21 (t, 2H), 2.32 (t, 2H), 1.92 (m, 2H), 1.72 (m, 2H), 1.65 (m, 2H), 1.43 (m, 2H), 1.31 (t, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
14%Spectr. | General procedure: To a suspension of the DA 12- sodium salt, butyl chloride or cyclohexyl bromide (1 equiv.) was added dropwise at -40 C and the reaction mixture was kept at the same conditions for 40÷60 min. Afterwards required alkyl bromide (1.1÷1.4 equiv.) was added (Table 1, entries 2÷5) and reaction mixture was treated as described above for dienone 2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With potassium carbonate; In N,N-dimethyl-formamide; at 20℃;Inert atmosphere; Schlenk technique; | A mixture of <strong>[617-05-0]ethyl 4-hydroxy-3-methoxybenzoate</strong> 9 (5.0 g,25.51 mmol), potassium carbonate (10.5 g, 76.5 mmol) and ethyl 6-bromohexanoate (6.8 g, 30.6 mmol) in DMF (20 mL) was stirred overnightat rt. The reaction mixture was filtered and concentrated in vacuum.The residue was dissolved in dichloromethane, and washed withbrine. The organic layer was dried over magnesium sulfate, filtered andconcentrated to yield derivative 10. Yield 8.6 g, 99%; 1H NMR(400 MHz, DMSO-d6) delta 1.18 (t, 3H, J=7.0 Hz), 1.31 (t, 3H,J=7.0 Hz), 1.44-1.40 (m, 2H), 1.63-1.56 (m, 2H), 1.78-1.71 (m, 2H),2.31 (t, 3H, J=7.4 Hz), 3.82 (s, 3H), 4.08-4.00 (m, 4H), 4.28 (q, 2H,J=7.2 Hz), 7.04 (d, 1H, J=8.4 Hz), 7.44 (d, 1H, J=1.8), 7.56 (dd,1H, J1=8.5 Hz, J2=2.0 Hz); 13C NMR (100 MHz, DMSO-d6) delta 172.8,165.4, 152.3, 148.5, 123.0, 121.9, 111.9 (2C), 68.1, 60.3, 59.6, 55.5,33.4, 28.2, 25.0, 24.2, 14.2, 14.0; HR-MS m/z 339.1797 (calcd forC18H27O6 [M+H]+, 339.1802). |