Structure of 34916-10-4
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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. : | 34916-10-4 |
Formula : | C7H9NO |
M.W : | 123.15 |
SMILES Code : | N#CC1CCC(CC1)=O |
MDL No. : | MFCD11847831 |
InChI Key : | QIWQJGMBIABGRX-UHFFFAOYSA-N |
Pubchem ID : | 12235639 |
GHS Pictogram: |
![]() |
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 | 0.71 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 33.6 |
TPSA ? Topological Polar Surface Area: Calculated from |
40.86 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.17 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.12 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.27 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.31 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.62 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.9 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.68 |
Solubility | 25.8 mg/ml ; 0.209 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.53 |
Solubility | 36.0 mg/ml ; 0.293 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.25 |
Solubility | 6.99 mg/ml ; 0.0568 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 |
-6.97 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) |
1.56 |
* 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 |
---|---|---|
95% | With hydrogenchloride; boric acid In tetrahydrofuran; water at 60℃; for 2 h; | Add 1,4-dioxaspiro[4,5]nonane-8-carbonitrile 200.6 g (1.2 mol), boric acid 72 g (1.2 mol), water 2000 mL (10 V), hydrochloric acid in a 5000 mL three-necked flask. 1000 mL (5 V), tetrahydrofuran 500 mL (2.5 V), heated to 60 ° C,The reaction was carried out for two hours, sampled, and sent to the GC for detection. The remaining amount of the raw material was <2percent, and the reaction was completed.Decrease to room temperature, add dichloromethane, extract three times, combine the dichloromethane layer, distill off the dichloromethane under reduced pressure, and rectify the product under the condition of 100 ° C 2 mmHg.4-cyanocyclohexanone 140.4 g, GC purity 98percent, yield 95percent. |
87% | With trifluoroacetic acid In dichloromethane at 20℃; for 16 h; | A solution of R-06i-2 (7.00 g, 41.87 mmol) in TFA (50 mL) and DCM (50 mL) was stirred at 20 °C for 16 hours. Then, the mixture was concentrated to give the crude product. The crude product was purify by column chromatography (Si02, Petroleum ether/Ethyl acetate = 10/1 to 5/1 ) to obtain R-06i-3 (4.50 g, 87percent) as yellow oil. This compound was used in the next step without further characterization. |
75% | With ammonium cerium(IV) nitrate In water; acetonitrile at 70℃; for 0.75 h; | 4-OxocyclohexanecarbonitriIeA solution of ammonium cerium (IV) nitrate (3.70 g, 6.75 mmol) in water (100 mL) was added to a solution of l,4-dioxaspiro[4.5]decane-8-carbonitrile (11.3 g, 67.5 mmol) in MeCN (200 mL) and water (100 mL) at 700C. The reaction mixture was stirred for 45 minutes at 7O0C and cooled to ambient temperature where 100 mL of water were added. The product was extracted with ether (4 x 200 mL). The combined organics were EPO <DP n="10"/>washed with brine and dried over MgSO4. The product was purified by flash chromatography on silica gel using EtOAc 50percent in hexane as eluent to afford the title compound as a colorless liquid. Yield: 6.30 g (75percent). 1H NMR (400 MHz, CHLOROFORM-D): δ 2.07 - 2.31 (m, 4 H), 2.34 - 2.53 (m, 2 H), 2.54 - 2.72 (m, 2 H), 2.95 - 3.14 (m, I H). |
68% | With hydrogenchloride In water at 20℃; for 2 h; | Step 2: A mixture of compound 116-1 (3 g, 18 mmol) in conc. hydrochloric acid / H2O (v/v = 1:1, 20 mL) wasstirred at room temperature for 2h. The reaction mixture was adjusted to pH = 8 with NaOH, and extracted with EtOAc.The combined extraction liquid was washed with brines, dried over sodium sulfate and concentrated to dry, finally purifiedby column chromatography (PE:EtOAc = 1:1) to deliver compound 116-3 (1.5 g, yield 68percent) as colorless oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | at 0 - 20℃; for 1 h; Inert atmosphere | Into a 250-mL 4-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed 119.1 (10 g, 81.20 mmol, 1.00 equiv), methanol (100 mL). This was followed by the addition of NaBH4 (1.52 g, 40.18 mmol, 0.50 equiv) at 0° C. in a water/ice bath. The resulting solution was stirred for 1 h at room temperature. The reaction was then quenched by the addition of 20 mL of NH4Cl (aq). The resulting solution was extracted with 2×100 mL of ethyl acetate and the organic layers combined and dried over anhydrous sodium sulfate and concentrated under vacuum. This resulted in 10.02 g (99percent) of 119.2 as colorless oil. |
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