Structure of 1,6-Dibromohexane
CAS No.: 629-03-8
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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. : | 629-03-8 |
Formula : | C6H12Br2 |
M.W : | 243.97 |
SMILES Code : | C(CCCBr)CCBr |
MDL No. : | MFCD00000272 |
InChI Key : | SGRHVVLXEBNBDV-UHFFFAOYSA-N |
Pubchem ID : | 12368 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H302+H332-H317-H318-H411 |
Precautionary Statements: | P273-P280-P305+P351+P338 |
Class: | 9 |
UN#: | 3082 |
Packing Group: | Ⅲ |
Num. heavy atoms | 8 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 1.0 |
Num. rotatable bonds | 5 |
Num. H-bond acceptors | 0.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 46.7 |
TPSA ? Topological Polar Surface Area: Calculated from |
0.0 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.76 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.17 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.34 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.61 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.09 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.19 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.02 |
Solubility | 0.233 mg/ml ; 0.000956 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.84 |
Solubility | 0.352 mg/ml ; 0.00144 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.02 |
Solubility | 0.0234 mg/ml ; 0.0000957 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
Low |
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 |
-5.54 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<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
3.16 |
* 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 |
---|---|---|
94.52% | Weigh 20.36gNa was added to a 250ml three-necked flask containing 25ml of ethanol until Na was completely dissolved.To this, 200 ml of an ethanol solution containing 51.0 g of p-cyanophenol was added dropwise to control the feeding rate so that the reaction temperature was maintained at 25 to 30,After the addition was completed, the mixture was slowly heated to reflux. After 1 hour of reaction, 40.4 g of 1,6-dibromohexane was added dropwise to the reaction system to control the feeding rate. After completion of the addition, the reaction was carried out for 3 hours.After the reaction was completed, the temperature was lowered to below 10 , stirred for 2 hours, filtered and the filter cake was dried to give 55.4g of white powder. Yield: 94.52%. | |
81% | In with stirring, thermometer, a reflux condenser of the dropping funnel and 2L in three-mouth bottle, to which in turn is added to sodium hydroxide 23.3g (0.56mol) and water 240 ml, after stirring to make it dissolve completely, cooling to room temperature; the instillment contains 66.7g (0.56mol) 4-cyano phenol 267 ml ethanol solution, control drop of acceleration, keeping the temperature at the 25-30 C; after dripping slowly increase, 80 C reaction 2h, cooling to room temperature; dropwise 65.3g (0.27mol) 1,6- two hexyl bromides, reflux (80-85 C) 8-10h, cooling to 0 C, stirring 2-3h, filtered, white solid product I shall be intermediate 98g, to the wet product 417 ml in ethanol, heating and stirring to 75 C reflux reaction 2-3h, cooling, about 50 C the left and right filter, drying filter cake, weighing more 70.01g, yield 81%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
A solution of (5R)-5-(2, 2-DIMETHYL4H-1, 3-BENZODIOXIN-6-YL)-1, 3-OXAZOLIDIN-2-ONE (2. 00g) (WO 02/066422) in DMF (60ML) under nitrogen was treated with sodium hydride (60% dispersion in mineral oil, 385mg) and the mixture stirred at 20 for 30min. A solution of 1,6-dibromohexane (4. 94MOI) was added and the mixture was stirred at 20 for 3h. Phosphate buffer solution (pH 6.5, 30MI) and water (150ML) were added and the mixture was extracted with ET20. The extract was washed with water and dried (Na2SO4). The solvent was evaporated in vacuo and the residue purified by flash chromatography on silica gel. Elution with DCM then MEOH-DCM (1: 50) gave the title compound (2. 565G). LCMS RT = 3. 71 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | In acetonitrile; for 24h;Reflux; Inert atmosphere; | 1,6-Dibromohexane (10.00 g, 42 mmol) was dissolved in anhydrous acetonitrile (10 mL) and introduced into a three-neck round-bottom flask. After the solution was heated gently to reflux, a solution of 1 (0.50 g, 2.80 mmol) in anhydrous acetonitrile (5 mL) was added dropwise under N2 atmosphere. The reaction mixture was stirred for 24 h at reflux and then cooled to room temperature. The solvent was removed to give a residue, which was purified by washing with anhydrous diethyl ether (35 mL), and concentrated under reduced pressure. The residue was dried under vacuum to afford 2 as a puce oil (1.01 g,85 percent). deltaH (CDCl3, 400 MHz) 10.32 (1H, s), 7.62 (1H, s), 7.50 (1H, s), 4.40 (2H, t, J 7.2), 4.34 (2H, t, J 7.6), 3.43?3.40 (4H, m), 2.03?1.84 (6H, m), 1.51?1.23 (12H, m), 0.87 (3H, t, J 6.8). deltaC (CDCl3, 100 MHz) 136.3, 122.1, 121.8, 49.9, 49.6, 33.7, 32.3,32.1, 31.5, 30.1, 30.0, 28.9, 27.2, 26.1, 25.1, 22.4, 14.0. m/z (ESI) 345 ([M]+). m/z 345.1733. HRMS (ESI) Anal. Calc. for C17H32BrN2 ([M]+) 345.1728. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With potassium carbonate; In acetonitrile; for 12h;Reflux; | To a solution of amine (2b) (25 g, 110 mmol, 1.0 eq) in acetonitrile(200 mL), were charged K2CO3 (30.40 g, 220 mmol,2.0 eq) and 1,6 dibromo hexane (29.55 g, 121 mmol, 1.1 eq).The reaction mixture was heated to reflux and stirred for12 h. After completion of reaction, it was cooled and filtered.The solvent was evaporated from filtrate under vacuumto get crude material, which was recrystallized byusing acetone (125mL) to get pure 1-((1R,2R)-2-hydroxy-1,2-diphenylethyl)-1-methylazepan-1-ium bromide (2c) as awhite colored solid, (31.81 g, 74%).(2c) - White solid, Yield 31.81 g, 74%, M.p.: morethan 238 C, [alpha]D20 26.23 (c 1.0 in Methanol); 1H NMR(500MHz, DMSO-d6- very less solubility) delta: 1.52-1.94 (m,8H), 3.21 (s, 3H), 3.64-4.16 (m, 4H), 4.62 (d, J = 2.5 Hz,1H), 5.81 (d, J = 2.0 Hz, 1H), 6.58 (s, 1H, D2O exchangeable),6.92-8.17 (m, 10H); 13C NMR (125MHz DMSO-d6very less solubility) delta: 129.1, 128.9, 128.8, 128.4, 128.3,127.4, 127.2, 82.5,74.4, 72.2, 71.8, 71.1, 66.3, 65.6, 64.4,55.6,28.7, 27.1, 23.4, 23.3; IR (ATR), nu /cm-1 3422, 3061,1480, 1492, 730, 707. Anal. calculated for C21H28NOBr: C,64.61; H, 7.23; N, 3.59. Found; C, 64.55; H, 7.21; N, 3.60. |