Structure of 960370-97-2
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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. : | 960370-97-2 |
Formula : | C10H13NO |
M.W : | 163.22 |
SMILES Code : | N#CC1(C2CC2)CCC(CC1)=O |
MDL No. : | MFCD17013941 |
InChI Key : | PHPMGMPLWGFZKK-UHFFFAOYSA-N |
Pubchem ID : | 53407212 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.8 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 45.64 |
TPSA ? Topological Polar Surface Area: Calculated from |
40.86 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.56 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.06 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.99 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.27 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.63 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.7 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.45 |
Solubility | 5.74 mg/ml ; 0.0352 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.51 |
Solubility | 5.05 mg/ml ; 0.031 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.1 |
Solubility | 1.3 mg/ml ; 0.00794 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 |
-6.54 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) |
1.85 |
* 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 |
---|---|---|
92.8% | With trifluoroacetic acid; In dichloromethane; at 0℃; | The solution of the compound represented by the formula 3 (8-cyclopropyl-1,4-dioxaspiro [4.5] decane-8-carbonitrile) in dichloromethane is contacted with the compound represented by the formula Dichloromethane solution was added trifluoroacetic acid, stirring to the thin layer chromatography without raw materials,And the molar ratio of the compound represented by the formula 3 to trifluoroacetic acid is 0.5: 1,The reaction temperature of the reaction system is 0 C,At 0 ,To a solution of compound 3 (103.5 g, 0.5 mol) in dichloromethane (1000 mL) was added trifluoroacetic acid (100 mL)Stirring to the thin layer chromatography without raw materials,The system is poured into a saturated solution of sodium bicarbonate,Extracted with dichloromethane,Spin dry,Petroleum ether was beaten to give colorless needles 4 (75.6 g, 92.8%), |
With trifluoroacetic acid; In water; for 1.0h; | d). To the cyclopropylcyano acetal prepared above (7.28 g, 35.1 mmol) was added trifluoroacetic acid (100 mL) and water (4 mL). The solution was stirred for 1 h then poured into saturated NaHCO3 (1500 mL). The aqueous was extracted with ethyl acetate (3*300 mL). The combined organics were washed with brine, dried with MgSO4, and concentrated in vacuo to afford the ketone. This material was carried on to the next step without further purification. 1H NMR (500 Hz, CDCl3): delta 0.62-0.69 (m, 4H), 0.88-0.94 (m, 1H), 1.88-1.94 (m, 2H), 2.35-2.39 (m, 2H), 2.47-2.51 (m, 2H), 2.68-2.74 (m, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
e). To the ketone prepared in step d (6.0 g, 37 mmol) in dichloroethane (110 mL) was added cyclopropylamine (3.1 mL, 44 mmol). The solution was cooled to 0 C. (ice bath), and NaBH(OAc)3 (12 g, 55 mmol) and AcOH (2.8 mL, 48 mmol) were added. After 5 minutes the ice bath was removed. The reaction was stirred at room temperature for 4 h. The contents were diluted with CH2Cl2 (100 mL) poured in water (100 mL). The aqueous layer was brought to pH 2 with 5 N HCl. Following removal of the organic layer, the aqueous layer was brought to pH 12 with 5 N NaOH and extracted with 10% MeOH in CH2Cl2 (3×35 mL). The combined organics were dried with Na2SO4 and concentrated in vacuo. Silica gel chromatography (gradient of 5 to 10% ethyl acetate in hexanes with 2.5% triethylamine additive) gave the cis amine followed by the trans amine. 1H NMR (500 Hz, CDCl3, trans isomer): delta 0.15-0.17 (m, 2H), 0.25-0.29 (m, 2H), 0.34-0.37 (m, 4H), 0.58-0.63 (m, 1H), 1.22-1.31 (m, 4H), 1.84-1.90 (m, 4H), 1.96-2.00 (m, 1H), 2.38-2.40 (m, 1H). |
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