Structure of 627899-90-5
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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. : | 627899-90-5 |
Formula : | C17H28BNO3 |
M.W : | 305.22 |
SMILES Code : | CC1(C)C(C)(C)OB(C2=CC=C(OCCCN(C)C)C=C2)O1 |
MDL No. : | MFCD09702395 |
InChI Key : | ONRJKPSMQGEPHV-UHFFFAOYSA-N |
Pubchem ID : | 24229609 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 22 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.65 |
Num. rotatable bonds | 6 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 91.53 |
TPSA ? Topological Polar Surface Area: Calculated from |
30.93 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.27 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.32 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.57 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.17 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.86 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.6 |
Solubility | 0.077 mg/ml ; 0.000252 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.59 |
Solubility | 0.0777 mg/ml ; 0.000255 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-5.05 |
Solubility | 0.00273 mg/ml ; 0.00000893 mol/l |
Class? Solubility class: Log S scale |
Moderately 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) |
Yes |
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) |
Yes |
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 |
-5.84 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 |
0.0 |
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 |
1.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
3.19 |
* 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 |
---|---|---|
45% | Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1.16667 h; Inert atmosphere Stage #2: at -78 - 20℃; for 24 h; Inert atmosphere |
To a 100-mL flame-dried two necked flask was added M1 (3.0g, 11.6mmol) and freshly distilled THF (80mL). The resulting solution was cooled at−78°C and 8.7mL n-butyllithium (13.9mmol, 1.6M in hexane) was added over 10min under a nitrogen atmosphere. The mixture was stirred at−78°C for 1h. 2-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (2.6g, 13.9mmol) was added rapidly to the solution, and the resulting mixture was slowly warmed to room temperature for 24h. The mixture was poured into 50mL water and extracted with CHCl3 (300mL). The combined organic layers were washed with brine and dried over anhydrous MgSO4. The solvent was removed by rotary evaporation, and the residue purified by column chromatography on silica gel (ethylacetate:dichloromethane as eluent) to obtain the product as a light-yellow oil (1.6g, yield: 45.0percent). 1H NMR (400MHz; CDCl3; Me4Si): δ=7.77 (d, 2H, J=8.8Hz), 6.90 (d, 2H, J=8.8Hz), 3.94 (t, 2H, J=6.4Hz), 2.46 (t, 2H, J=6.8Hz), 2.26 (s, 6H), 1.88 (m, 2H, J=6.8Hz) 1.25 (s, 12H). 13C NMR (100MHz; CDCl3; Me4Si): 161.57; 136.73; 113.41; 83.13; 74.40; 66.02; 54.09; 45.42; 27.43; 25.00. Anal. Calcd for: C17H28BNO3: C, 66.90; H, 9.25; N, 4.59. Found: C, 66.73; H, 9.23; N, 4.63. IR (KBr, cm−1): 2981, 2936, 2816, 2716, 1566, 1463, 1281, 1245. |
45% | Stage #1: With n-butyllithium In tetrahydrofuran at -78℃; for 2 h; Inert atmosphere Stage #2: at -78 - 20℃; for 26 h; Inert atmosphere |
Dissolved in dry 30 Compound A 3g in a nitrogen atmosphere, THF, -78° C after the temperature was reduced to 2.2equivalent of n-butyllithium(nBuLi,Aldrich Co.) was slowly added. The reaction mixture was stirred at -78° C for 2 hours andthen, 2-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane,Aldrich) was added, and the mixture was stirred while the temperature gradually to room temperature after stirring at -78° Cfor 2 hours, the height for 24 hours. After the reaction was completed to extract the organic material with chloroform, to giveafter washing the column with water to obtain the compound B, 1.6 g (yield 45.0percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42.4% | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate In 1,4-dioxane at 90℃; for 16 h; Inert atmosphere | NrV-Dimethyl-3-[4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)phenoxy]propan-l- amine N,N-Dimethyl-3-[4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)phenoxy]propan-l -amine is available commercially from several suppliers including Apollo Scientific Ltd., Whitefield Rd, Bredbury, Stockport, Cheshire, SK6 2QR, UK. CAS number [627899-90- 5], catalogue number OR12268. Alternatively, it can be prepared as follows: A 1 : 1 complex of [l, -bis(diphenylphosphino)ferrocene]dichloropalladium(II) with dichloromethane (8.64 mg, 10.58 μιηο) was added to 3-(4-bromophenoxy)-N,N- dimethylpropan-1 -amine (546 mg, 2.12 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(l,3,2- dioxaborolane) (644 mg, 2.54 mmol) and potassium acetate (830 mg, 8.46 mmol) in 1,4- dioxane (6 mL) warmed to 90°C under nitrogen. The resulting suspension was stirred at 90 °C for 16 h. The reaction mixture was evaporated to dryness and re-dissolved in DCM (25 mL), and washed with water (20 mL). The organic layer was dried with a phase separating cartridge, filtered and evaporated to afford crude product. The crude product was purified by FCC, elution gradient 0 to 10percent MeOH in DCM. Pure fractions were evaporated to dryness to afford the desired material as a brown waxy solid (274 mg, 42.4 percent). NMR Spectrum: NMR (500MHz, CDCls) δ 1.33 (12H, s), 1.89 - 2.08 (2H, m), 2.32 (6H, s), 2.53 (2H, dt), 4.05 (2H, t), 6.86 - 6.91 (2H, m), 7.71 - 7.76 (2H, m). Mass Spectrum: m/z (ES+)[M+H]+ = 258. |
42.3% | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate In 1,4-dioxane at 90℃; for 16 h; Inert atmosphere | Dichloro [1,1 ‘-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct(0.063 g, 0.08 mmol) was added to 3-(4-bromophenoxy)-N,N-dimethylpropan-1-amine(2g, 7.75 mmol), 4,4,4’,4’,5 ,5 ,5’,5 ‘-octamethyl-2,2’-bi(1 ,3 ,2-dioxaborolane) (2.36 g, 9.30 mmol) and potassium acetate (3.04 g, 30.99 mmol) in 1,4-dioxane (35 mL) and the mixture degassed for 15 minutes. The resulting suspension was stirred at 90 °C for 16 hours under an inert atmosphere. The reaction mixture was evaporated to dryness, redissolved in DCM(25 mL), washed with water (20 mL) and the organic layer was dried with a phase separating cartridge, filtered and evaporated. The crude product was purified by flash silica chromatography, elution gradient 0 to 10percent MeOH in DCM, to afford the desired material as a brown oil (1.000 g, 42.3 percent) which solidified on standing. NMR Spectrum: ‘H NMR (400MHz, CDC13) ö 1.33 (12H, s), 1.96 - 2.07 (2H, m), 2.34(6H, s), 2.52 - 2.65 (2H, m), 4.04 (2H, t), 6.83 - 6.94 (2H, m), 7.68 - 7.78 (2H, m).Mass Spectrum: mlz (ES+) [M+H]+ = 306 |
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