Structure of 1,4-Diazabicyclo[3.2.2]nonane
CAS No.: 283-38-5
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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. : | 283-38-5 |
Formula : | C7H14N2 |
M.W : | 126.20 |
SMILES Code : | N1(CC2)CCNC2CC1 |
MDL No. : | MFCD14581694 |
InChI Key : | XJKNACDCUAFDHD-UHFFFAOYSA-N |
Pubchem ID : | 398407 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 1.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 45.06 |
TPSA ? Topological Polar Surface Area: Calculated from |
15.27 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.76 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.16 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-0.71 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.57 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.92 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.54 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.72 |
Solubility | 23.9 mg/ml ; 0.189 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.04 |
Solubility | 116.0 mg/ml ; 0.916 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.94 |
Solubility | 14.7 mg/ml ; 0.116 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
Low |
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 |
-6.96 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) |
2.9 |
* 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 |
---|---|---|
68.4% | EXAMPLE 19 1-Cyclopropyl-6-fluoro-7-(1,4-diazabicyclo-[3.2.2]-non-4-yl)-1,4-dihydro-4-oxo-3-quinoline carboxylic acid (R1 =H; Y=cyclopropyl; A=CH; R2 =d; n=2; p=1) The title compound was prepared in 68.4percent yield according to example 9 by reacting 6,7-difluoro-1-cyclopropyl-1,4-dihydro-4-oxo-3-quinoline carboxylic acid with 1,4-diazabicyclo[3,2,2]nonane, m.p. 296°-297° C. | |
68.4% | EXAMPLE 19 1-Cyclopropyl-6-fluoro-7-(1,4-diazabicyclo[3.2.2]-non-4-yl)-1,4-dihydro-4-oxo-3-quinoline carboxylic acid R1 =H; Y=cyclopropyl; A=CH; R2 =d; n=2; p=1) The title compound was prepared in 68.4percent yield according to example 9 by reacting 6,7-difluoro-1-cyclopropyl-1,4-dihydro-4-oxo-3-quinoline carboxylic acid with 1,4-diazabicyclo[3,2,2]nonane, m.p. 296°-297° C. | |
68.4% | EXAMPLE 19 1-Cyclopropyl-6-fluoro-7-(1,4-diazabicyclo[3.2.2]-non-4-yl)-1,4-dihydro-4-oxo-3-quinoline carboxylic acid (R1 =H; Y=cyclopropyl; A=CH; R2 =d; n=2; p=1) The title compound was prepared in 68.4percent yield according to example 9 by reacting 6,7-difluoro-1-cyclopropyl-1,4-dihydro-4-oxo-3-quinoline carboxylic acid with 1,4-diazabicyclo[3,2,2]nonane, m.p. 296°-297° C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
104 mg (34%) | With ammonium hydroxide; sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); In chloroform; toluene; | 2-Chloro-benzoimidazole-1-carboxylic acid tert-butyl ester (333 mg, 1.32 mmol), 1,4-diazabicyclo[3.2.2]nonane (57%, 195 mg, 0.88 mmol), tris(dibenzylideneacetone)dipalladium (28 mg, 0.031 mmol), racemic-2,2'-bis(diphenylphosphino)-1,1 '-binaphthyl (58 mg, 0.093 mmol), sodium tert-butoxide (208 mg, 2.17 mmol) and toluene (1.55 mL) were added to a flame dried round bottom flask purged with nitrogen. The mixture was placed in an oil bath at 80 C. for 18 h and then cooled to RT. The mixture was filtered through a pad of celite and washed with chloroform and methanol. The filtrate was concentrated and the residue was purified by chromatography (Biotage, 12M) eluding with 8% methanol in chloroform with 20 drops of NH4OH per liter of eluent to afford 104 mg (34%) of 2-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-benzoimidazole-1-carboxylic acid tert-butyl ester: MS (Cl) m/z 343.1 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
4.2 N-[2-(1,4-Diazabicyclo[3.2.2]non-4-yl)-2-oxoethyl]-4-methoxybenzamide 0.42 g (2 mmol) of <strong>[13214-64-7]N-(4-methoxybenzoyl)_glycine</strong> dissolved in 20 ml of dioxane is placed in a 50 ml round-bottomed flask, 0.45 g (2.2 mmol) of dicyclohexylcarbodiimide is added, the mixture is stirred at room temperature for 30 minutes, 0.25 g (2 mmol) of 1,4-diazabicyclo[3.2.2]nonane is added and the mixture is stirred for a further one hour. 20 ml of water are added, the precipitate formed is filtered off, the filtrate is extracted with chloroform, the organic phase is extracted with aqueous 0.1N hydrochloric acid solution and the aqueous extraction phase is basified to pH 10 by addition of concentrated aqueous sodium hydroxide solution and extracted with chloroform. The organic phase is dried over sodium sulfate and concentrated under reduced pressure. 0.49 g of product is obtained in the form of an amorphous solid. |
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