Structure of 427-49-6
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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. : | 427-49-6 |
Formula : | C13H16O3 |
M.W : | 220.26 |
SMILES Code : | O=C(O)C(O)(C1CCCC1)C2=CC=CC=C2 |
MDL No. : | MFCD00019296 |
InChI Key : | WFLUEQCOAQCQLP-UHFFFAOYSA-N |
Pubchem ID : | 98283 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H315-H318-H335 |
Precautionary Statements: | P261-P264-P271-P280-P302+P352-P304+P340+P312-P305+P351+P338-P310-P332+P313-P362-P403+P233-P405-P501 |
Num. heavy atoms | 16 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.46 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 60.95 |
TPSA ? Topological Polar Surface Area: Calculated from |
57.53 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.8 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.48 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.04 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.86 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.04 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.04 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.85 |
Solubility | 0.313 mg/ml ; 0.00142 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.33 |
Solubility | 0.102 mg/ml ; 0.000465 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.41 |
Solubility | 0.859 mg/ml ; 0.0039 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 |
0.0 |
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) |
2.29 |
* 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 |
---|---|---|
Example 1; Preparation of (3S,2'R)- and (3R,2'S)-3-[(cyclopentyl-hydroxyphenylacetyl)-oxy]-l,l- dimethylpyrrolidinium bromide; 30 g of cyclopentyl mandelic acid, dissolved in 135 g dimethylformamide (DMF), were treated with 27 g carbonyldiimidazole at 180C (in portions) to form the "active amide". After the addition of 16.9 g of l-methyl-pyrrolidin-3-ol, the mixture was heated to 600C within 1 hour and stirred for 18 hours at this temperature. After checking for complete conversion, the mixture was cooled and 200 g water was added. The mixture was extracted with 200 g toluene and the extract was washed with water three times. The organic phase was concentrated to obtain cyclopentyl-hydroxy-phenyl-acetic acid l-methyl-pyrrolidin-3-yl ester as an about 50percent solution in toluene, ready to use for the next step.This solution was diluted with 120 g of n-propanol and cooled to O0C. 16.8 g methyl bromide was introduced and the mixture was stirred for 2 hours and then gradually heated to 60°C to evaporate the excess methyl bromide into a scrubber. The mixture was then cooled to 500C and seed crystals were added to facilitate crystallisation. The temperature was then slowly reduced over 18 hours to 15°C. The solid was then isolated by filtration to obtain 22.7 g after drying. It was composed mainly of one pair of enantiomers, a racemic mixture of (3S,2'R)- and (3R,2'S)-3-[(cyclopentyl-hydroxyphenylacetyl)-oxy]-l,l- dimethylpyrrolidinium bromide, with a purity greater than 90percent (by HPLC). The other pair of diastereoisomers ((3R,2'R)- and (3S,2'S)-3-[(cyclopentyl-hydroxyphenyl-acetyl)-oxy]-l,l- dimethylpyrrolidinium bromide) remains mainly in the filtrate as those compounds are significantly more soluble in n-propanol than the other stereoisomers.The solid obtained is further recrystallised in n-propanol (1:10 wt) to give pure (3S,2'R)- and (3R,2'S)-3-[(cyclopentyl-hydroxyphenylacetyl)-oxy]-l,l-dimethylpyrrolidinium bromide i.e. purity >; 99.9percent as determined by high performance liquid chromatography (HPLC). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 1 : Synthesis of 2-Cyclopentyl-2-hydroxy-lambda/-[2-(lH-imidazol-l-yl)ethyll-2- phenylacetamide (Compound No. 1) <n="36"/>To a solution of the hydrochloride salt of 2-(lH-imidazol-l-yl)ethanamine (0.5 g, 4.50 mmol) in chloroform (10 ml) was added N-methyl morpholine (2.96 ml, 27.02 mmol) and stirred the mixture for 5 to 10 minutes at the room temperature followed by the addition of 2- cyclopentyl-2-hydroxy-2-phenyl acetic acid (0.99 g, 4.5 mmol) and hydroxy benzotriazole (0.60 g, 4.5 mmol) at room temperature. The resulting reaction mixture was stirred for 30-45 minutes followed by the addition of l-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and again stirred for over night. The mixture was diluted with water and stirred for 10-15 minutes followed by the addition of dichloromethane. The mixture was stirred for 15-20 minutes. The organic layer was separated, washed with water and brine, dried over anhydrous sodium sulphate and concentrated under reduced pressure. The residue thus obtained was purified by preparative column chromatography using 10 % methanol in dichloromethane as eluent to furnish the title compound. Yield: 70 mg.1H NMR (CDCl3)delta: 7.60-7.31 (5H, m), 6.99 (IH, s), 6.99 (IH, s), 6.65 (IH, s), 4.01-4.00 (2H, m), 3.99-3.49 (2H, m), 3.11-3.07 (IH, m), 1.64-1.42 (8H, m). |
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