Structure of 4138-26-5
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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. : | 4138-26-5 |
Formula : | C6H12N2O |
M.W : | 128.17 |
SMILES Code : | O=C(C1CNCCC1)N |
MDL No. : | MFCD00005993 |
InChI Key : | BVOCPVIXARZNQN-UHFFFAOYSA-N |
Pubchem ID : | 92980 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.83 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 38.47 |
TPSA ? Topological Polar Surface Area: Calculated from |
55.12 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.06 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-1.26 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-0.91 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.41 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.23 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
-0.26 |
Log S (ESOL):? ESOL: Topological method implemented from |
0.23 |
Solubility | 215.0 mg/ml ; 1.68 mol/l |
Class? Solubility class: Log S scale |
Highly soluble |
Log S (Ali)? Ali: Topological method implemented from |
0.6 |
Solubility | 509.0 mg/ml ; 3.97 mol/l |
Class? Solubility class: Log S scale |
Highly soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.64 |
Solubility | 29.4 mg/ml ; 0.229 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 |
No |
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 |
-7.98 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 |
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) |
1.67 |
* 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 |
---|---|---|
98.4% | With hydrogen;palladium 10% on activated carbon; In isopropyl alcohol; at 75℃; under 3750.38 Torr; for 4h; | 122.12 g (1.00 mol) of nicotinamide was dissolved in 500 mL of 2-propanol. To the resulting solution was charged 14.4 g of palladium-carbon (10percent), and the solution was stirred for 4 hours at 75° C. under hydrogen pressure of 0.5 MPa. After the reaction was completed, the palladium-carbon was filtered and separated. The filtered palladium-carbon was washed with 100 mL of 2-propanol. The filtrate and the washing liquid were combined and condensed, and 126.08 g of white crystals of nipecotamide in a racemic form was obtained. The yield was 98.4percent. The resultant was confirmed to be the target object by NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
List B-Amines:1. dimethylamine...12. methyl-prop-2-ynyl-amine13. methylamino-acetonitrile hydrochloride14. 1-(4-fluoro-phenyl)-piperazine15. furan-2-ylmethyl-methyl-amine16. piperidine-3-carboxylic acid amide17. methyl-phenethyl-amine18. methyl-(2-pyridin-2-yl-ethyl)-amine20. methyl-(1-methyl-piperidin-4-yl)-amine... | ||
1. dimethylamine...12. methyl-prop-2-ynyl-amine13. methylamino-acetonitrile hydrochloride14.1-(4-fluoro-phenyl)-piperazine15. furan-2-ylmethyl-methyl-amine16. piperidine-3-carboxylic acid amide17. methyl-phenethyl-amine18. methyl-(2-pyridin-2-yl-ethyl)-amine19. N,N,N'-trimethyl-propane-1,3-diamine... |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | In chloroform; at 20℃; | To a solution of amine 15.1 (10.7 g, 83.6 mmol) in CHC13 (150 mL) was added (Boc)20 (19 g, 87 mmol). The mixture was stirred at RT overnight. The reaction mixture was concentrated in vacuo to give a white solid, which was recrystallized with hexane to afford compound 15.2 (17g, 95percent yield). |
79% | To a stirred solution of piperidine-3-carboxylic acid amide (1.28 g, 10 mmol) in methanol (50 ml) triethylamine (1.4 ml, 10 mmol) was added and the mixture was cooled to 0-5 0C. A solution of di-tert-butyl dicarbonate (2.4 g, 11 mmol) in methanol (30 ml) was added and the reaction mixture was kept at room temperature overnight. The mixture was EPO <DP n="38"/>concentrated in vacuo, then the residue was suspended in 5percent sodium hydrogencarbonate solution (30 ml), filtered and washed with water to yield 1.8 g (79 percent) of the title compound. Melting point: 174-175 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | Referring to Scheme 2, compound 9 is obtained by reacting compound 2 with <strong>[4138-26-5]nipecotamide</strong>. Compound 9 was isolated in 90percent yield. Compound 9 then is reacted with lithium aluminum hydride to give compound 10 as a yellow oil. Compound 10 then is reacted with m-CF3-PhCOCl and triethylamine in methylene chloride to produce compound 11 (Table 2). Alternatively, compound 10 is reacted either with p-fluorophenyl isocynate to produce compound 12 or with p-fluorobenzylisocyanate to produce compound 13 (Table 2) under the same conditions used for compounds 5-8. |
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