Structure of 17012-21-4
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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. : | 17012-21-4 |
Formula : | C13H17NO2 |
M.W : | 219.28 |
SMILES Code : | O=C(C1CN(CC2=CC=CC=C2)CC1)OC |
MDL No. : | MFCD04038678 |
InChI Key : | GDWFCUOFVSNTTG-UHFFFAOYSA-N |
Pubchem ID : | 4610751 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 16 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.46 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 66.23 |
TPSA ? Topological Polar Surface Area: Calculated from |
29.54 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.7 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.75 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.15 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.86 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.11 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.91 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.32 |
Solubility | 1.06 mg/ml ; 0.00484 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.99 |
Solubility | 2.26 mg/ml ; 0.0103 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.1 |
Solubility | 0.174 mg/ml ; 0.000794 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 |
-6.4 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 |
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) |
2.02 |
* 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 |
---|---|---|
88.7% | 2-Pyrrolidin-3-ylmethyl-1H-pyrrolo[2,3-b]pyridine. (Compound 66); 8.83 g (91 mmol) methoxymethylamine. (HCl salt) was stirred in 200 ml anhydrous benzene (0 C., under N2). 46.2 ml trimethylaluminium/toluene (2.5M) was added and the mixture was stirred for 2.5 hours at 0 C. Compound 62 (6.73 g, 30.7 mmol) dissolved in 100 ml benzene was added and the resulting mixture was stirred for 1 hour at room temperature. To the mixture was added subsequently saturated NaHCO3 (0 C.) and ethyl acetate. The organic layer was washed three times with a 5% NaHCO3 solution, dried (Na2SO4), filtered and concentrated. The resulting residue was purified by flash chromatography (MeOH/ethyl acetate (1/9)) to give 1-benzyl-pyrrolidine-3-carboxylic acid methoxy-methyl-amide (compound 63, 6.76 g, 88.7%).1H-NMR (400 MHz, CDCl3): δ 7.38-7.22 (m, 5H), 3.69-3.62 (m, 5H), 3.45-3.35 (m, 1H), 3.19-3.18 (2×s, 3H), 3.06-2.99 (m, 1H), 2.88-2.81 (m, 1H), 2.56-2.41 (m, 2H), 2.14-2.03 (m, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In dichloromethane; at 20℃; for 0.5h;Heating / reflux; | [0151] Following general procedure 5, to a cold (0 C.), stirred solution of amide (20) (32.7 g, 1 equiv.) in THF (70 mL) was added, dropwise, a solution of BH3-Me2S in THF (2 M, 140 mL, 2 equiv.). The resultant mixture was then heated to reflux for 2 h. The reaction was cooled to 0 C. and MeOH was added (25 mL). This mixture was stirred under reflux for 3 h and then cooled to rt. The solution was concentrated under reduced pressure and to the resultant residue was added ice (30 g) and 10 N NaOH until the pH of the mixture was adjusted to pH 9. The mixture was then extracted with CH2Cl2 (2×), dried (MgSO4) and concentrated under reduced pressure to afford the desired benzyl amine which was purified by distillation (bp 125-135 C., 1-2 mm Hg) of the benzyl amine. To a solution of the benzyl amine (219 mg, 1 equiv.) in CH2Cl2 (5 mL) was added a solution of BrCN in CH2Cl2 (1 M, 1.5 mL, 1.5 equiv.). The mixture was refluxed for 30 min, cooled to rt and concentrated under reduced pressure. The resultant residue was purified by flash chromatography (gradient elution 20% EtOAc in hexane to 50% EtOAc in hexane) to afford the desired methyl 1-cyano-3-pyrrolidinecarboxylate (21). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97.5% | With hydrogenchloride; palladium 10% on activated carbon; hydrogen; In 1,4-dioxane; methanol; at 50℃; for 5h; | A solution of 4a (5g, 22.80mmol) in MeOH (150 mL) and 4M HCl in dioxane (5.7mL, 22.80mmol) were treated with 10% Pd/C (500mg) of hydrogen at 50oC for 5h. The solid was filtered off and the filtrate was concentrated to give the compound 5a (3.68g, 97.5%). |
94% | With hydrogenchloride; palladium 10% on activated carbon; hydrogen; In 1,4-dioxane; methanol; at 50℃; for 5h; | A solution of B1_4(19.50 g, 88.99 mmol), HCl dioxane solution (22.3 mL, 88.99 mmol) in methanol (150 mL) was treatedwith 10% Pd/C (1.95 g) and stirred at 50 C under hydrogen atmosphere for 5 h. The solid was filteredo and the filtrate was concentrated to give the title compound (13.85 g, 94%). |
With hydrogenchloride; hydrogen;palladium 10% on activated carbon; In methanol; water; | Reference Example 134 To a solution of <strong>[17012-21-4]methyl 1-benzylpyrrolidine-3-carboxylate</strong> in methanol (50 ml) and 1 N hydrochloric acid (16.9 ml) was added palladium carbon (10%, 1.8 g), and the mixture was stirred overnight under a hydrogen atmosphere. The insolubles were removed by filtration, and then the solvent was distilled off under reduced pressure. Toluene was added thereto, and then the solvent was again distilled off under reduced pressure to give methyl pyrrolidine-3-carboxylate hydrochloride (2.71 g) as a yellow oily material. 1H-NMR (300 MHz, DMSO-d6) δ 1.95-2.25 (2H, m), 3.11-3.45 (5H, m), 3.66 (3H, s), 9.23 (2H, br). |
Tags: 17012-21-4 synthesis path| 17012-21-4 SDS| 17012-21-4 COA| 17012-21-4 purity| 17012-21-4 application| 17012-21-4 NMR| 17012-21-4 COA| 17012-21-4 structure
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