Structure of 6342-77-4
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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. : | 6342-77-4 |
Formula : | C10H12O3 |
M.W : | 180.20 |
SMILES Code : | O=C(O)CCC1=CC=CC=C1OC |
MDL No. : | MFCD00002772 |
Boiling Point : | No data available |
InChI Key : | XSZSNLOPIWWFHS-UHFFFAOYSA-N |
Pubchem ID : | 80652 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.3 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 49.29 |
TPSA ? Topological Polar Surface Area: Calculated from |
46.53 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.83 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.14 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.71 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.67 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.91 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.85 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.38 |
Solubility | 0.746 mg/ml ; 0.00414 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.75 |
Solubility | 0.321 mg/ml ; 0.00178 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.71 |
Solubility | 0.354 mg/ml ; 0.00196 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 |
-5.88 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 |
0.56 |
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) |
1.34 |
* 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% | Preparation of 3-(2-methoxyphenyl)propan-l-ol3-(2-methoxyphenyl)propanoic acid (1.0 g, 5.55 mmol) was dissolved in THF (27.7 ml).A solution of borane tetrahydrofuran complex (12.21 ml, 12.21 mmol) was added slowly.The reaction was stirred for about 4 h. Methanol was added and the solvents removed.This process was repeated twice. The solution was passed through a short pad of silica gel with 1 : 1 ethyl acetate/heptane And then rotovapped to give 3-(2-methoxyphenyl)propan-l- ol (0.946 g, 5.69 mmol, 103 % yield) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ ppm <n="129"/>7.19 (dt, IH), 7.15 (dd, IH), 6.90 (dt, IH), 6.86 (d, IH), 3.84 (s, 3H), 3.60 (t, 2H), 2.73 (t, 2H), 1.92-1.79 (m, 2H), 1.76 (s, IH), | |
67% | With lithium aluminium tetrahydride; In diethyl ether; at 20℃;Reflux; | 3-(2-Methoxyphenyl)propanoic acid (11.4 g, 0.0 mol) dissolved in ether (126 mL) was added slowly to a suspension of LiAlH4 (6.0 g, 0.16 mol) in ether (190 mL) at RT. The reaction was headed at reflux overnight, then cooled to RT before the reaction was quenched with water (100 mL). The reaction was filtered through a pad of celite washing with water (20 mL) and EtOAc (200 mL). The EtOAc layer was removed and the aqueous layer was extracted with more EtOAc (100 mL2). The EtOAc layers were washed with brine (100 mL) and dried (Na2SO4). Concentration gave a yellow/brown oil (5.1 g). Rewashing the celite pad with water (100 mL) and DCM (200 mL), and extracting the aqueous layer with more DCM (20 mL3) afforded more product (1.61 g). Total yield (6.71 g, 67%). 1H NMR (CDCl3, 600 MHz) δ 7.18 (1H, t, J 7.8 Hz), 7.14 (1H, d, J 6.6 Hz), 6.89 (1H, t, J 7.2 Hz), 6.85 (1H, d, J 7.8 Hz), 3.82 (3H, s), 3.60 (2H, t, J 6.0 Hz), 2.71 (2H, t, J 7.2 Hz), 1.90 (1H, bs), 1.84 (2H, t, J 6.6 Hz). |
67% | With lithium aluminium tetrahydride; In diethyl ether; at 20℃;Reflux; | 3-(2-Methoxyphenyl)propanoic acid (11.4 g, 0.0 mol) dissolved in ether (126 mL) was added slowly to a suspension of LiAlH4 (6.0 g, 0.16 mol) in ether (190 mL) at RT. The reaction was headed at reflux overnight, then cooled to RT before the reaction was quenched with water (100 mL). The reaction was filtered through a pad of celite washing with water (20 mL) and EtOAc (200 mL). The EtOAc layer was removed and the aqueous layer was extracted with more EtOAc (100 mL2). The EtOAc layers were washed with brine (100 mL) and dried (Na2SO4). Concentration gave a yellow/brown oil (5.1 g). Rewashing the celite pad with water (100 mL) and DCM (200 mL), and extracting the aqueous layer with more DCM (20 mL3) afforded more product (1.61 g). Total yield (6.71 g, 67%). 1H NMR (CDCl3, 600 MHz) δ 7.18 (1H, t, J 7.8 Hz), 7.14 (1H, d, J 6.6 Hz), 6.89 (1H, t, J 7.2 Hz), 6.85 (1H, d, J 7.8 Hz), 3.82 (3H, s), 3.60 (2H, t, J 6.0 Hz), 2.71 (2H, t, J 7.2 Hz), 1.90 (1H, bs), 1.84 (2H, t, J 6.6 Hz). |
With lithium aluminium tetrahydride; | 3-(2-Methoxyphenyl)propan-1-ol 3-(2-Methoxyphenyl)propanoic acid (11.4 g, 0.0 mol) dissolved in ether (126 mL) was added slowly to a suspension of LiAlH4 (6.0 g, 0.16 mol) in ether (190 mL) at RT. The reaction was headed at reflux overnight, then cooled to RT before the reaction was quenched with water (100 mL). The reaction was filtered through a pad of celite washing with water (20 mL) and EtOAc (200 mL). The EtOAc layer was removed and the aqueous layer was extracted with more EtOAc (100 mL*2). The EtOAc layers were washed with brine (100 mL) and dried (Na2SO4). Concentration gave a yellow/brown oil (5.1 g). Rewashing the celite pad with water (100 mL) and DCM (200 mL), and extracting the aqueous layer with more DCM (20 mL*3) afforded more product (1.61 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | N-[2-(1H-Indol-2-yl)-phenyl]-3-(2-methoxy-phenyl)-propionamide Prepared from 2-(2-aminophenyl) indole and 3-(2-methoxyphenyl) propionic acid in 62% yield following procedure 1. The product was crystallized from acetonitrile. 96% Purity by LC/MS (TIC, DAD), Mass-spec [M+H+]=371, 1H NMR (MeOH-d4): 2.62 t, 7.5 Hz (2H), 2.97 t, 7.5 Hz (2H), 3.74 s (3H, OMe), 6.40 s (1H), 6.81 t, 7 Hz (1H), 6.88 d, 8 Hz (1H), 7.03 t, 8 Hz (1H), 7.10-7.14 m (2H), 7.17 t, 8 Hz (1H), 7.27 t, 7 Hz (1H), 7.33 td, 7.5, 1 Hz (1H), 7.40 d, 8 Hz (1H), 7.54 d, 8 Hz (1H), 7.57 dd, 7,1 Hz (1H), 7.76 d, 8 Hz (1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | In tetrahydrofuran; | A. 2-Methoxybenzenepropanol To a solution of 3-(2-methoxyphenyl)propionic acid (2.0 g, 11.1 mmol) in tetrahydrofuran (25 mL) was added dropwise at 0 C. lithium aluminum hydride solution (1M in tetrahydrofuran, 11.1 mL, 11.1 mmol). The reaction was warmed to room temperature and stirring was continued overnight. The reaction was quenched with methanol (5 mL), and 1M potassium sodium tartrate solution (100 mL) was added. The mixture was stirred at room temperature overnight. Ethyl ether (200 mL) was added, and the organic layer was washed with water (2*50 mL), brine (2*50 mL) and dried over magnesium sulfate. Evaporation gave compound A (1.5 g, 81%) as a colorless oil. |
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