Structure of 201733-56-4
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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. : | 201733-56-4 |
Formula : | C10H20B2O4 |
M.W : | 225.89 |
SMILES Code : | CC1(C)COB(B2OCC(C)(C)CO2)OC1 |
MDL No. : | MFCD02093062 |
InChI Key : | MDNDJMCSXOXBFZ-UHFFFAOYSA-N |
Pubchem ID : | 2734316 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 16 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 1.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 63.4 |
TPSA ? Topological Polar Surface Area: Calculated from |
36.92 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 |
2.18 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.19 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.21 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.36 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.56 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.55 |
Solubility | 0.64 mg/ml ; 0.00283 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.59 |
Solubility | 0.582 mg/ml ; 0.00258 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.12 |
Solubility | 1.72 mg/ml ; 0.00762 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) |
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) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
Yes |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.13 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<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
3.42 |
* 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 |
---|---|---|
With potassium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In ethanol; for 20h;Heating / reflux; | [306] 4-Iodo-7-Azaindole (1.0Og, 4.12mmol), bis(neopentylglycolato)diboron (1.49g, 6.59mmol), potassium acetate (0.65g, 6.59mmol), and l,r-bis(diphenylphosphino)ferrocene dichloro palladium (II) dichloromethane complex (0.09g, 0.12mmol) were added to a round bottom flask. The flask was evacuated and backfilled with N2 (3 x). Anhydrous ethanol (2OmL) was added and the mixture was heated to reflux for 2Oh. After cooling to rt, the reaction mixture was diluted with diethyl ether (35mL) and then filtered through celite. The resulting filtrate was concentrated in vacuo and dissolved in ethyl acetate (5OmL). The solution was washed with water (15mL), brine (15mL), and dried over MgSO4. The filtrate was concentrated to a brown solid which was recrystallized with ethyl acetate to yield the title compound as a tan solid. The mother liquor was concentrated in vacuo and purified by column chromatography (HexanesrEtOAc = 80:20 ? 60:40) to yield the title compound. 1H NMR (400 MHz, DMSO-d6) delta 0.99 (s, 6H), 3.83 (s, 4H), 6.69 (dd, IH3 J= 1.8, 1.0 Hz), 7.30 (d, IH, J = 2.4 Hz), 7.45 (dd, IH3 J= 2.8, 2.4 Hz), 8.18 (d, IH, J= 2.2 Hz), 11.52 (bs, IH). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 110℃; for 2h;Inert atmosphere; | A mixture of 5,5,5',5'-tetramethyl-2,2'-bi(1,3,2-dioxaborinane) (16.50 g, 48.33 mmol), oven dried potassium acetate (20.03 g, 204.1 mmol), and <strong>[19936-14-2]1-(4-bromophenyl)cyclobutanol</strong> (10.00 g, 44.03 mmol) in 1,4-dioxane (120 mL) was degassed with N2 for 15 min, then treated with [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (2.44 g, 2.99 mmol). The reaction mixture was heated to 110 C. and stirred for 2 hours under N2. The reaction mixture was cooled to room temperature and filtered through celite, eluting with EtOAc. The filtrate was evaporated to give a black oil, which was purified by flash chromatography (0-50% EtOAc/Heptane) three times to afford the title compound (8.68 g, 76%) as a white solid. GC/MS: 259. 1H NMR (400 MHz, CD3Cl) delta 7.83 (d, J=8.05 Hz, 2H), 7.50 (d, J=8.29 Hz, 2H), 3.78 (s, 4H), 2.65-2.52 (m, 2H), 2.38-2.42 (m, 2H), 1.98-2.03 (m, 1H), 1.72-1.80 (m, 1H), 1.03 (s, 6H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | Step 1 : To a degassed solution of compound 35 (350 mg, 0.99 mmol), bis(neopentylglycolato)diboron (289 mg, 1.3 mmol) and KOAc (339 mg, 3.4 mmol) in DMSO (10 mL) was added Pd(dppf)CI2 (80 mg, 0.1 mmol). The resulting mixture was stirred at 75 C for 1 h. LCMS analysis indicated that the boronic acid intermediate was formed. After cooling to RT, compound 59 (31 1 mg, 1.03 mmol) and NaHC03 (aq) (1 M solution, 3.0 mL, 3.0 mmol) and dioxane (10 mL) were added. The mixture was degassed, followed by the addition of Pd(dppf)CI2 (80 mg, 0.1 mmol). The resulting mixture was stirred at 80 C for 2 hours and concentrated in vacuo, ethyl acetate (100 mL) and water (150 mL) were added and then partitioned. The aqueous was extracted with EtOAc (2 x 100 mL), and the combined organic layers were washed with brine (400 mL), dried over MgS04, and then concentrated in vacuo. Purification by flash column chromatography over silica gel, which was eluted with 1 % MeOH and 10% heptane in DCM, gave compound 355 as a yellow solid (260 mg, 53% yield). 1 H NMR (400 MHz, CDCI3) δ 8.06 (dd, 1 H), 7.66 (s, 1 H), 7.16 - 7.30 (m, 5 H), 7.05 (ddd, 1 H), 6.86 (d, 1 H), 5.53 (s, 2 H), 4.80 (br s, 2H), 4.33 (br s, 2 H), 3.96 (s, 3 H), 2.63 (br d, 3 H), 1.42 (br d, 9 H). LCMS ES m/z 440 [M-'Bu]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | Under nitrogen protection, 550 mL of dioxane and <strong>[52092-47-4]2-nitro-5-chloropyridine</strong> (15.8 g, were added to the reaction flask in turn. 0.10 mol), neopentyl glycol diborate (22.6 g, 0.10 mol), potassium acetate (14.7 g, 0.15 mol), after stirring uniformly, finally adding catalyst PdCl2dppf (0.74 g, 0.001 mol), slowly heating to 80 -90 ° C, Stir the reaction for 2-3 h. After the end of the GC reaction, the reaction was stopped by cooling, and the reaction solution was filtered through celite to obtain a dark-black reaction solution. After charging at 3 atm of hydrogen, the reaction was carried out at room temperature overnight. After the reaction was completed, the activated carbon was decolorized, and the filtrate was distilled under reduced pressure until no liquid was poured. / heptane mixed solvent was cooled and beaten for half an hour, filtered to obtain an off-white product, heated again with ethanol, and then cooled down, and the filter cake was rinsed with -20 ° C anhydrous ethanol, and dried to obtain an off-white solid 14.0 g. 68percent, HPLC purity 98.9percent |
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