Structure of 5182-44-5
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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. : | 5182-44-5 |
Formula : | C8H9ClO |
M.W : | 156.61 |
SMILES Code : | C1=C(C=CC=C1Cl)CCO |
MDL No. : | MFCD00002892 |
Boiling Point : | No data available |
InChI Key : | NDWAVJKRSASRPH-UHFFFAOYSA-N |
Pubchem ID : | 78856 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.25 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 42.39 |
TPSA ? Topological Polar Surface Area: Calculated from |
20.23 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.03 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.73 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.87 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.46 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.64 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.15 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.21 |
Solubility | 0.959 mg/ml ; 0.00613 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.77 |
Solubility | 2.65 mg/ml ; 0.0169 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.23 |
Solubility | 0.0916 mg/ml ; 0.000585 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) |
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 |
-6.03 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 |
2.0 |
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) |
1.12 |
* 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 |
---|---|---|
71% | With carbon tetrabromide; triphenylphosphine; In dichloromethane; at 20℃; for 5h; | Add triphenylphoshpine (3.90 g, 14.9 mmol) to a stirred solution of 3- chlorophenethyl alcohol (2.0 mL, 14.8 mmol), carbon tetrabromide (4.91 g, 14.8 mmol) and anhydrous dichloromethane (100 mL). Stir for 5 h under nitrogen at room temperature, and then wash with water (100 mL) and brine (100 mL). Dry the dichloromethane layer over magnesium sulfate, filter, and concentrate on a rotary evaporator to give the crude product. The crude product is purified by flash chromatography on silica gel eluting with 100% hexanes to yield 2. 30 g (71%) of 1- (2- bromo-ethyl) -3-chloro-benzene: TLC: Rf in 100% hexanes : 0.27 ; LH NMR (CDC13) : 7.26-7. 11 (m, 3H), 7.09-7. 07 (m, 1H), 3.54 (t, 2H), 3.12 (t, 2H). |
64.6% | Production Example 5 Synthesis of 3-chlorophenethyl bromide 3-Chlorophenethyl alcohol (1.0 ml) was treated as in Production Example 1 to give the title compound (1.417 g) as a pale yellow oil (yield: 64.6%). 1H-NMR (400 MHz, CDCl3): delta(ppm) 3.14(2H, t, J=8.6Hz), 3.56(2H, t, J=8.6Hz), 7.11(1H, m), 7.21(1H, s), 7.45(2H, m). | |
With bromotriphenylphosphonium bromide; In acetonitrile; for 24h; | According to Scheme 11, a solution of 3-chlorophenethyl alcohol (5 g, 32 mmol) in 50 mL of dry MeCN was treated with dibromotriphenylphosphorane (13.54 g, 32 mmol) for 24 h. The reaction mixture was filtered and the solvent was removed in vacuo. The residue was triturated with hexane and filtered. Evaporation of the solvent provided 6.5 g of 3-chlorophenethyl bromide |
22.4 g | With phosphorus tribromide; at 0 - 80℃; for 2.16667h; | Specific operations are as follows: 20g of m-chlorophenylacetic acid was added to 200ml of tetrahydrofuran, cooled to 0 C with stirring,At the beginning of batch addition of 8.9g of lithium aluminum hydride, the temperature was raised to 25 ~ 30 after the addition, the reaction 4h after the addition of water 300ml, dichloromethane400 ml of the mixture was separated, and the organic phase was added with 20 g of anhydrous sodium sulfate and dried under reduced pressure at 30-35 C. to obtain a pale yellow oil (S1-1): 18.3 g; Dropping phosphorus tribromide, the dropping temperature during the control at 0 ~ 10 C, dropping completed,After stirring for 10min, the temperature was raised to 75-80 C,After stirring for 2h, 30ml of saturated sodium bicarbonate solution, 200ml of ethyl acetate,The mixture was stirred for 20 minutes, and the filtrate was concentrated under reduced pressure at 40-45 C. to give a yellow liquid (intermediate S2): 22.4 g. Yield: 87.0%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57% | With carbon tetrabromide; triphenylphosphine; In dichloromethane; at 20℃; for 18h;Product distribution / selectivity; | To a solution of 2- (3-chlorophenyl) ethanol (1.06 g, 6.0 mmol) in CH2CL2 (50 mL) at RT under nitrogen was added CBr4 (1.98 g, 5.8 mmol) and PPh3 (1.57 g, 5.8 mmol). After stirring at RT for 18 h the reaction mixture was concentrated and the residue diluted with ETZO (30 mL) resulting in precipitation of triphenylphosphine oxide. The ethereal solution was decanted, evaporated and purified via flash chromatography (silica, hexane) to provide 2- (3-CHLORO) phenylethyl bromide as a clear oil (57%). 1H NMR (400 MHz, DMSO-d6) 8 7.39-7. 22 (m, 3 H), 7.18-7. 09 (m, 1 H), 3.63-3. 51 (m, 2 H), 3.25-3. 17 (m, 2 H); 13C NMR (100.6 MHz, DMSO-d6) B 141.2, 134.6, 130.7, 129.3, 127.6, 127.3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65.5% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 0 - 20℃; for 5h; | General procedure: 2.5mmol thiazole-4-carboxyli acid and 2.0mmol alcohol were dissolved in 25mL dichloromethane (DCM) in a dry flask with continuous stirring, followed by the addition of 2.5mmol 3-(3-dimethylaminopropyl) -1-ethylcarbodiimide hydrochloride. When the temperature of the reaction system cooled to 0°C, 0.2mmol 4-dimethylaminopyridine was added dropwise and reacted for 1hat 0°C. Then the temperature was elevated to room temperature for another 4h reaction. The reaction was stopped by adding 25mL saturated NaHCO3 solution and extracted twice with 20mL dichloromethane (2×20mL). The extracted organic layers were first dried by anhydrous Na2SO4, and then filtered and concentrated under vacuum distillation, obtaining the crude products. Finally, the crude products were further purified using column chromatography (ethy lacetate:petroleum ether, 1:5). |
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