Structure of 175883-62-2
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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. : | 175883-62-2 |
Formula : | C8H11BO3 |
M.W : | 165.98 |
SMILES Code : | COC1=C(C)C=C(C=C1)B(O)O |
MDL No. : | MFCD02179464 |
InChI Key : | PXVDQGVAZBTFIB-UHFFFAOYSA-N |
Pubchem ID : | 2773487 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.25 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 47.73 |
TPSA ? Topological Polar Surface Area: Calculated from |
49.69 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 |
1.16 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-0.32 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.33 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.3 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.17 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.84 |
Solubility | 2.41 mg/ml ; 0.0145 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.8 |
Solubility | 2.64 mg/ml ; 0.0159 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.79 |
Solubility | 2.66 mg/ml ; 0.016 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 |
No |
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 |
-6.49 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 |
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) |
1.58 |
* 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 |
---|---|---|
62% | Dissolve f [2-(4-bromo-2-isobutylphenoxy)ethyl]-methylamino}-acetic acid tert- butyl ester (2 g, 4.99 mmol) in dry tetrahydrofuran (20 mL). Deliver an aliquot of this stock solution (4 mL, 0.999 mmol) under nitrogen to a solution in tetrahydrofuran (5 mL) of the appropriate arylboronic acid (1.5 eq), palladium acetate (22 mg, 0.1 eq; 0.099 mmol), tricyclohexylphosphine (34 mg, 0.12 eq; 0.1198 mmol) and potassium fluoride (180 mg, 3.1 eq; 3.098 mmol). Stir at reflux for 66 h. Monitor the progress of the reactions after 66 h and treat each reaction then individually as described. Deliver an aliquot of [2-(4-bromo-2-isobutylphenoxy)ethyl]-methylamino)-acetic acid tert-butyl ester (0.999 mmol of the stock solution), along with (4-methoxy-3-methyl) boronic acid (248 mg, 1.4939 mmol, 95% pure), palladium acetate (22 mg), tricyclohexylphosphine (34 mg, 0.12 eq; 0.1214 mmol) and potassium fluoride (180 mg, 3.098 mrnol). Add a second aliquot of reagents after 66 h (4-methoxy-3-methyl) boronic acid (248 mg, 1.4939 mmol), tricyclohexylphosphine (37 mg, 0.1319 mmol), palladium acetate (24 mg) and potassium fluoride (186 mg, 3.20 mmol). Stir for another 24 h. Dilute with tetrahydrofuran (dry, 4 mL) and treat with [1,1'-bis(diphenylphosphino)-ferrocene)- dichloropalladium (II) complex (DPPF) (76 mg, 0.093 eq), 2 N aqueous potassium carbonateaq (5 eq, 2.5 mL) and (4-methoxy-3-methyl) boronic acid (166 mg) and stir at reflux for 24 h until total consumption of the starting material as indicated by thin layer chromatography and LC-MS. Filter the crude reaction mixture through a -wet CeliteNo. pad, dilute with ethyl acetate (50 mL), wash the organic, phase with water (50 mL), dry (magnesium sulfate), filter, concentrate and purify (HPLC, eluting with 10:90 ethyl acetate: hexanes) to give the title compound (302.8 mg, 62%). ¹H NMR (400 MHz, CDC13) 8 7.36-7.32 (m, 3H), 7.28-7.27 (m, 1H), 6.8 8 (d, J = 8.3 Hz, 2H), 4.13 (m, 2H), 3.87 (s, 3H), 3.36 (s, 2H), 3.05 (t, J =.5.7 Hz, 2H), 2.55-2.53 (m, 5H), 2.29 (s, 3H), 1.96 (q, J = 6.6 Hz, 1H, ), 1.49 (s, 9H), 0.94 (d, J = 6.6 Hz, 6H,); LC-MS: mz = 442.0 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30% | With caesium carbonate;tetrakis(triphenylphosphine)palladium (0); In water; ethyl acetate; toluene; | Step 1: 3-Methyl-4-methoxyphenylboronic acid (542 mg) was combined with 4-iodobenzoic acid (810 mg), cesium carbonate (5.32 g), toluene (16 mL), water (8 mL) and n-butanol (4 mL). The mixture was degassed under vacuum with argon purging after which, tetrakis-triphenylphosphine palladium (38 mg) was added. The reaction was heated to 80 C. for 20 hours after which, it was cooled to room temperature and diluted with ethyl acetate (16 mL). The layers were separated and the organics were concentrated to dryness. The residue was purified on silica gel (50% to 100% ethyl acetate/hexane over 40 minutes) giving 3'-methyl-4'-methoxy-4-biphenylcarboxylic acid (240 mg). Yield=30% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.56 g (73%) | 6-(4-Methoxy-2-methylphenyl)-2-naphthol The title compound was prepared by reacting 6-bromo-2-naphthol (1.8 g, 5.4 mmol) with <strong>[175883-62-2]4-methoxy-3-methylphenylboronic acid</strong> (1.74 g, 7.0 mmol) according to method A to yield 1.56 g (73%) of yellowish solid: mp 124-126 C.; 1H NMR (DMDO-d6): delta 2.25(3H,s), 3.78 (3H, s), 6.85 (1H, dd, J=8.35 Hz, J=2.56 Hz), 6.90 (1H, d, J=2.37 Hz), 7.09 (1H, dd, J=8.75 Hz, J=2.25 Hz), 7.13 (1H, s), 7.20 (1H, d, J=8.33 Hz), 7.35 (1H, dd, J=8.39 Hz, J=1.37 Hz), 7.67 (1H,s), 7.70 (1H, d, J=8.53 Hz), 7.78 (1H, d, J=8.78 Hz), 9.74 (1H, s); MS (ESI) m/z263 (M-H)-. Anal. for C18H16O2: Calc'd: C: 81.79H: 6.10 Found: C: 81.43H: 6.01 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; for 2h;Heating / reflux; | To a solution of 6~chloro-pyrido[3,2-d]pyrimidin-4(3H)one (1.94 mmole) in 1 ,4- dioxane (40 ml) and water (20 ml) was added 4-methoxy-3-methylphenyl boronic acid (2.33 mmole), potassium carbonate (4.85 mmole) and tetrakis(tri- phenylphosphine)palladium(O) (0.097 mmole). The reaction mixture was refluxed for two hours, cooled to room temperature and the solvents were evaporated in vacuo. The residue was adsorbed on silica and purified by silica gel column chromatography (the mobile phase being a methanol/dichloromethane mixture in a ratio of 3:97), affording the title compound as a pure white powder (398 mg, yield 77 %) which was characterized by its mass spectrum as follows: MS (m/z) : 268 ([M+H]+, 100). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridine;copper diacetate; In dichloromethane; for 41h;Molecular sieve; | Description 34; 1 -[3-Methyl-4-(methyloxy)phenyl]-4-[(phenylmethyl)oxy]-1 H-indazole (D34)The 4-[(phenylmethyl)oxy]-1 H-indazole (D1) (500 mg, 2.23 mmol), the [3-methyl-4- (methyloxy)phenyl]boronic acid (740 mg, 4.46 mmol), copper (II) acetate (608 mg, 3.345 mmol), pyridine (0.36 mL, 4.46 mmol) and powdered molecular sieves (400 mg) in DCM (75 mL) were stirred at room temperature in the presence of air. After 41 hours the mixture <n="34"/>was filtered through a pad of celite and washed with water. The aqueous was re-extracted with DCM and the combined organics were washed with brine and dried over MgSO4. The crude (1.17 g) was purified by flash chromatography (Biotage SP4) with a gradient of EtOAc 0 to 30% in hexane to afford 562 mg of title compound (D34) containing an impurity. LC-MS: MH+ = 345 (C22H20N2O2 = 344) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
17% | With sodium hydroxide;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; for 24h;Heating / reflux; | Example 24; 8-(4-methoxy-3-methyl phenyl)H-imidazo[1,5-a]pyridine8-bromo-H-imidazo[1,5-a]pyridine (0.1 g, 0.5 mmol, 1 eq) was dissolved in 10 mL of DME and kept under an argon atmosphere. To that solution [Pd(PPh3)4] (0.025 mmol, 0.05 eq), 4-methoxy-3-methylphenyl boronic acid (0.124 g, 0.75 mmol, 1.5 eq) and an aqueous NaOH solution (0.2M, 5 mL) were added under stirring. The resulting mixture was refluxed for 24 h. After cooling, the mixture was diluted with water and the aqueous layer was extracted with CHCl3. The organic layers were dried (Na2SO4), filtered and evaporated under reduced pressure. Semi-preparative HPLC-chromatography afforded the pure product.Yield: 0.020 g (17%), 1H-NMR, 500 MHz, CDCl3: delta 2.29 (s, 3H); 3.90 (s, 3H); 6.94-6.96 (m, 1H); 7.08-7.10 (m, 2H); 7.35 (s, 1H); 7.39-7.41) m, 1H); 7.88 (s, 1H); 8.29 (bs, 1H); 9.52 (bs, 1H), MS: m/z 239.2 [M+H]+; HPLC: Method [B], (214 nm), rt: 6.68 min (88.3%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | EXAMPLE 73 4-amino-8-(4-methoxy-3-methyl-phenyl)-N-propyl-cinnoline-3-carboxamide Using method A, 4-amino-8-bromo-N-propyl-cinnoline-3-carboxamide (125 mg, 0.40 mmol) and <strong>[175883-62-2](4-methoxy-3-methylphenyl)boronic acid</strong> (133 mg, 0.80 mmol) were reacted to afford the title compound (105 mg, 75% yield) as a white solid. 1H NMR (300 MHz, CDCl3) delta 8.59 (bs, 1H), 7.76-7.82 (m, 2H), 7.67-7.72 (m, 1H), 7.53 (dd, J=8.2, 2.2 Hz, 1H), 7.46 (m, 1H), 6.96 (d, J=8.2, 1H), 3.89 (s, 3H), 3.46 (apparent q, J=6.7 Hz, 2H), 2.30 (s, 3H), 1.67 (apparent sextet, J=7.2 Hz, 2H), 1.00 (t, J=7.4 Hz, 3H). MS APCI, m/z=351 (M+H) HPLC 1.88 min. |
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