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Structure of 10160-87-9
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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. : | 10160-87-9 |
Formula : | C7H12O2 |
M.W : | 128.17 |
SMILES Code : | C#CC(OCC)OCC |
MDL No. : | MFCD00009237 |
Boiling Point : | No data available |
InChI Key : | RGUXEWWHSQGVRZ-UHFFFAOYSA-N |
Pubchem ID : | 66285 |
GHS Pictogram: |
![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H225-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Class: | 3 |
UN#: | 1993 |
Packing Group: | Ⅲ |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.71 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 36.1 |
TPSA ? Topological Polar Surface Area: Calculated from |
18.46 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.28 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.91 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.1 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.22 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.15 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.33 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.94 |
Solubility | 14.6 mg/ml ; 0.114 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.88 |
Solubility | 16.8 mg/ml ; 0.131 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.04 |
Solubility | 11.8 mg/ml ; 0.0918 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 |
-6.44 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 |
2.0 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) |
3.28 |
* 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 |
---|---|---|
82% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; In tetrahydrofuran; at 70℃; for 14h;Inert atmosphere; | A mixture of <strong>[40263-57-8]2-iodo-3-hydroxypyridine</strong> (1 g, 4.5 mmol, 1.0 eq), 3,3-diethoxyprop-1-yne (754.0 mg, 5.9 mmol,1.3 eq), TEA (4.1 g, 41 mmol, 9.0 eq), CuT (172 mg, 905 imol, 0.2 eq) and Pd(PPh3)2C12 (318mg, 453 imol, 0.1 eq) in 10 mL of THF was degassed and purged with N2 three times. The mixture was stirred at 70 C for 14 hours under N2 atmosphere. The reaction mixture was concentrated in vacuo. The residue was purified by column chromatography (Si02, eluting with petroleum ether: ethyl acetate = 100:1 to 2:1) to afford 820 mg of 2-(diethoxymethyl)furo[3,2- bjpyridine (3.7 mmol, 82% yield) as yellow oil. |
With copper(l) iodide; triethylamine;bis-triphenylphosphine-palladium(II) chloride; In N,N-dimethyl-formamide; for 17h; | 2-Iodo-3-pyridinol (24 mmol), triethylamine (1.0 eq), 3,3-diethoxy-1-propyne (1.0 eq), bis(triphenylphosphine)palladium (II) chloride (0.02 eq), and copper(I) iodide (0.04 eq) were combined in DMF (14 mL) and allowed to stir for 17 hours. The mixture was diluted with ethyl acetate (100 mL) and filtered through a Celite pad. The filtrate was washed with saturated sodium bicarbonate (2*50 mls), dried over anhydrous magnesium sulfate, filtered, and the filtrate concentrated under reduced pressure to provide the title compound which was used in the next step without further purification. 1H NMR (CDCl3, 400 MHz) δ 1.28 (t, J=7.1 Hz, 6H), 3.70 (q, J=7.1 Hz, 4H), 5.68 (s, 1H), 7.05 (s, 1H), 7.23 (dd, J=8.5, 4.8 Hz, 1H), 7.77 (d, J=8.5 Hz, 1H), 8.57 (br, 1H). MS (DCI/NH3) m/z 222 (M+H)+. | |
With copper(l) iodide;bis-triphenylphosphine-palladium(II) chloride; for 17h; | [2-IODO-3-PYRIDINOL] (24 mmol), triethylamine (1.0 [EQ),] 3, [3-DIETHOXY-1-PROPYNE] (1.0 eq), bis (triphenylphosphine) palladium [(II)] chloride (0.02 [EQ),] and copper [(I)] iodide (0.04 eq) were combined in DMF (14 mL) and allowed to stir for 17 hours. The mixture was diluted with ethyl acetate (100 mL) and filtered through a Celite pad. The filtrate was washed with saturated sodium bicarbonate (2x50mls), dried over anhydrous magnesium sulfate, filtered, and the filtrate concentrated under reduced pressure to provide the title compound which was used in the next step without further [PURIFICATION.'H] NMR [(CDC13,] [400MHZ)] [5] 1.28 (t, J=7. [1HZ,] 6H), 3.70 (q, J=7. [1HZ,] 4H), 5.68 (s, 1H), 7.05 (s, [1H),] 7.23 (dd, J=8.5, 4.8Hz, [1H),] 7.77 (d, J=8. 5Hz, 1H), 8.57 (br, 1H). MS (DCI/NH3) [M/Z] 222 (M+H) [+.] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
2-(Diethoxymethyl)-1H-pyrrolo[3,2-c]pyridine-1-carboxylic acid 1,1-dimethylethyl ester, 8b-1 (Scheme 3, step h) Heat a solution of (3-iodo-pyridin-4-yl)carbamic acid 1,1-dimethylethyl ester (13.3 g, 41.56 mmol, Darnbrough, Shelley; Mervic, Miljenko; Condon, Stephen M.; Burns, Christopher J. Synthetic Communications (2001) 31(21), 3273-3280), 3,3-diethoxy-1-propyne (5.96 ml, 41.56 mmole), triethylamine (23 ml, 166 mmol), dichlorobis(triphenyl-phospine)palladium(II) (1.46 g, 2.08 mmol) and copper iodide (237 mg, 1.25 mmol) in dry DMF under argon to 90 C. for 3 h. Allow the reaction mixture to cool to 70 C. and add DBU (12.5 ml, 83.12 mmol). Stir the reaction at 70 C. for 3 h and then stir at room temperature overnight. Pour the reaction mixture into EtOAc, wash with water (2*) and brine, dry over MgSO4, filter and concentrate to give the title compound as an oil. Purify the oil by flash chromatography (silica, elute with 10-20% EtOAc/n-heptane) to provide 9.8 g of the title compound as a clear oil, tlc (silica, 30% EtOAc/heptane, Rf=0.30). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine;copper(I) iodide; In N,N-dimethyl-formamide; | EXAMPLE 35a 2-(diethoxymethyl)furo[3,2-b]pyridine 2-Iodo-3-pyridinol (24 mmol), triethylamine (1.0 eq), 3,3-diethoxy-1-propyne (1.0 eq), bis(triphenylphosphine)palladium (II) chloride (0.02 eq), and copper(I) iodide (0.04 eq) were combined in DMF (14 mL) and allowed to stir for 17 hours. The mixture was diluted with ethyl acetate (100 mL) and filtered through a Celite pad. The filtrate was washed with saturated sodium bicarbonate (2*50 mls), dried over anhydrous magnesium sulfate, filtered, and the filtrate concentrated under reduced pressure to provide the title compound which was used in the next step without further purification. 1H NMR (CDCl3, 400 MHz) δ1.28 (t, J=7.1 Hz, 6H), 3.70 (q, J=7.1 Hz, 4H), 5.68 (s, 1H), 7.05 (s, 1H), 7.23 (dd, J=8.5, 4.8 Hz, 1H), 7.77 (d, J=8.5 Hz, 1H), 8.57 (br, 1H). MS (DCI/NH3) m/z 222 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With copper(l) iodide; palladium 10% on activated carbon; triethylamine; triphenylphosphine; In 1,4-dioxane; at 25 - 80℃; for 3.5h;Inert atmosphere; | General procedure: (a) The reaction was performed in a bigger scale using 100 mg of 10% Pd/C (0.092 mmol), PPh3 (0.37 mmol), CuI (0.184 mmol), Et3N (10.68 mmol), compound 1a (3.56 mmol), and acetylenic compound 2a (5.32 mmol) in 1,4-dioxane (20.0 mL). After stirring at 80 C for 3 h under nitrogen the mixture was cooled to room temperature. The Pd/C was filtered off and washed with water (2 10 mL), acetone (2 10 mL), and EtOAc (2 10 mL). Then the catalyst was collected, dried at 100 C in an oven, and reused for the next run. The co-catalyst CuI along with PPh3 was added in every repeated run. (b) General method for the preparation of 3: A mixture of compound 1 (0.89 mmol), 10% Pd/C (0.023 mmol), PPh3 (0.092 mmol), CuI (0.046 mmol), and Et3N (2.67 mmol) in 1,4-dioxane (5.0 mL) was stirred at 25 C for 30 min under nitrogen. The acetylenic compound 2 (1.33 mmol) was added slowly with stirring. The mixture was then stirred at 80 C for 3 h, cooled to room temperature, diluted with EtOAc (30 mL), and filtered through celite. The filtrate was collected and concentrated. The residue was purified by column chromatography (2-15% EtOAc/hexane) to afford the desired product |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; In N,N-dimethyl-formamide; at 20℃; for 16h;Inert atmosphere; | Reference Example 33-1 3-(3,3-Diethoxyprop-1-yn-1-yl)-4-hydroxybenzonitrile In a nitrogen atmosphere, <strong>[2296-23-3]4-hydroxy-3-iodobenzonitrile</strong> (600 mg, 2.5 mmol), 3,3-diethoxypropyne (388 muL, 2.7 mmol), triethylamine (374 muL, 2.7 mmol), copper(I) iodide (19 mg, 0.10 mmol), and bis(triphenylphosphine)palladium (II) dichloride (34 mg, 0.048 mmol) were dissolved in DMF (2.5 mL), and the solution was stirred for 16 hours at room temperature. Water was added to the reaction liquid, the mixture was stirred for a while, and then the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and was dried over anhydrous sodium sulfate. Insoluble materials were filtered, and then the solvent was distilled off under reduced pressure. A residue thus obtained was purified by silica gel column chromatography (hexane:ethyl acetate) (concentration gradient: 29% to 50%), and thus the title compound (brown oily material, 356 mg, 59%) was obtained. 1H NMR(CDCl3, 400MHz):delta=1.28(t, 6H, J=7Hz), 3.6-3.8(m, 4H), 5.67(s, 1H), 6.87(s, 1H), 7.57(s, 2H), 7.9-8.0(m, 1H). |
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