Structure of 3-Furanboronic acid
CAS No.: 55552-70-0
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CAS No. : | 55552-70-0 |
Formula : | C4H5BO3 |
M.W : | 111.89 |
SMILES Code : | OB(C1=COC=C1)O |
MDL No. : | MFCD01319007 |
InChI Key : | CYEFKCRAAGLNHW-UHFFFAOYSA-N |
Pubchem ID : | 2734358 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 8 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 28.53 |
TPSA ? Topological Polar Surface Area: Calculated from |
53.6 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 |
-0.11 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-1.04 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-1.76 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-1.17 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
-0.81 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.86 |
Solubility | 15.4 mg/ml ; 0.138 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.56 |
Solubility | 30.6 mg/ml ; 0.274 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.44 |
Solubility | 40.5 mg/ml ; 0.362 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 |
-7.06 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 |
2.0 |
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) |
2.73 |
* 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 |
---|---|---|
2-[1-(3-Nitrophenyl)ethylamino]-4-[benzimidazol-1-yl]-6-(furan-3-yl)pyrimidine The title compound was prepared from 2-[1-(3-nitrophenyl)ethylamino]-4-[benzimidazol-1-yl]-6-chloropyrimidine and furan-3-boronic acid according to the precedure described in EXAMPLE 306, Step C and using [1,1'-bis(diphenylphosphino)ferrocene]-dichloropalladium(H) as catalyst. Mass spectrum (CH3CN/TFA/NH4O2CH/ESI) 427.0 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 150℃; for 0.333333h;Inert atmosphere; Microwave irradiation; | (step 2) To a mixed solution of the compound (0.300 g) obtained in step 1, 3-furylboronic acid (0.187 g) and potassium carbonate (0.154 g) in DME/water (6 mL)/0.6 mL) was added under an argon atmosphere tetrakis(triphenylphosphine)palladium (0) (Pd(PPh3)4) (0.129 g), and the reaction vessel was irradiated in a microwave reaction apparatus at 150C for 20 min. To the reaction solution was added water, and the resulting product was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated. The obtained residue was purified by silica gel column chromatography (solvent gradient: 0?30% ethyl acetate/hexane) to give tert-butyl 2-(3-furyl)-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylate (0.310 g, 92%) as an oil. 1H-NMR(CDCl3):delta1.50(9H,s), 2.95-3.05(2H,m), 3.73-3.77(2H,m), 4.58(2H,s), 6.87(1H,dd,J=1.7Hz,0.7Hz), 7.29(1H,d,J=8.2Hz), 7.39(1H,d,J=8.2Hz), 7.47(1H,dd,J=1.7Hz,1.7Hz), 7.99(1H,s) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 100℃;Inert atmosphere; | Step 1: 3-(4-Bromo-3,5-dimethylphenyl)furan A mixture of <strong>[100189-84-2]2,5-dibromo-1,3-dimethylbenzene</strong> (2.00 g), 1-furan-3-ylboronic acid (856 mg), and 2 M aqueous Na2CO3 solution (11 mL) in 1,4-dioxane (40 mL) is purged with argon for 5 min. Tetrakis-triphenylphosphine-palladium-(0) (270 mg) is added and the mixture is stirred at 100 C. over night. More tetrakis-triphenylphosphine-palladium-(0) (50 mg) is added and the mixture is stirred for another 5 h at 100 C. After cooling to room temperature the mixture is diluted with ethyl acetate and aqueous NH4Cl solution. The aqueous phase is extracted with ethyl acetate and the combined extracts are washed with brine, dried over MgSO4 and concentrated in vacuo. The residue is chromatographed on silica gel (cyclohexane/ethyl acetate 100:0?90:10) to give the title compound. LC (method 7): tR=1.22 min; Mass spectrum (EI+): m/z=250 [M]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87.8% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate; In 1,4-dioxane; at 80℃; for 6h;Inert atmosphere; | A solution of fert-butyl 4-bromo-lH-indole-l-carboxylate (LXXI) (10 g, 33.8 mmol), 3-furylboronic acid (LXXII) (5.29 g, 47.3 mmol), K3P04 (14.3 g, 67.5 mmol) and Pd(dppf)Cl2 (1.24 g, 1.69 mmol) in dioxane (150 mL) was heated to 80C for 6 hours under N2. The mixture was filtered and the filtrate was concentrated, the residue was purified by MPLC (PE:EtOAc = 10: 1) to give fert-butyl 4-(furan-3-yl)-lH-indole-l-carboxylate (LXXIII) (8.4 g, 29.6 mmol, 87.8% yield) as yellow oil. NMR (CDC13, 400 MHz) delta ppm 1.70 (s, 9H), 6.7 - 6.81 (m, 2H), 7.28 - 7.38 (m, 2H), 7.56 (d, J=1.6Hz, 1H), 7.66 (d, J=4Hz, 1H), 7.79 (s, 1H), 8.13 (d, J=8Hz, 1H); ESIMS found for Ci7Hi7N03 mlz 284.1 (M+H). |
87.8% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate; In 1,4-dioxane; at 80℃; for 6h;Inert atmosphere; | A solution of fert-butyl 4-bromo-lH-indole-l-carboxylate (LXXXVIII) (10 g, 33.8 mmol), 3-furylboronic acid (LXXXIX) (5.29 g, 47.3 mmol), K3P04 (14.3 g, 67.5 mmol) and Pd(dppf)Cl2 (1.24 g, 1.69 mmol) in dioxane (150 mL) was heated to 80C for 6 h under N2. The mixture was filtered and the filtrate was concentrated, the residue was purified by MPLC (PE:EtOAc = 10: 1) to give fert-butyl 4-(furan-3-yl)-lH-indole-l-carboxylate (XC) (8.4 g, 29.6 mmol, 87.8% yield) as yellow oil. NMR (CDC13, 400 MHz) delta ppm 1.70 (s, 9H), 6.7 - 6.81 (m, 2H), 7.28 - 7.38 (m, 2H), 7.56 (d, J=1.6Hz, 1H), 7.66 (d, J=4Hz, 1H), 7.79 (s, 1H), 8.13 (d, J=8Hz, 1H); ESIMS found for Ci7Hi7N03 mlz 284.1 (M+H). |
87.8% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate; In 1,4-dioxane; at 80℃; for 6h;Inert atmosphere; | A solution of <strong>[676448-17-2]tert-butyl 4-bromo-1H-indole-1-carboxylate</strong> (LXXI) (10 g, 33.8 mmol), 3-furylboronic acid (LXXII) (5.29 g, 47.3 mmol), K3PO4 (14.3 g, 67.5 mmol) and Pd(dppf)Cl2 (1.24 g, 1.69 mmol) in dioxane (150 mL) was heated to 80C for 6 h under N2. The mixture was filtered and the filtrate was concentrated, the residue was purified by MPLC (PE:EtOAc = 10: 1) to give tert-butyl 4-(furan-3-yl)-1H-indole-1-carboxylate (LXXIII) (8.4 g, 29.6 mmol, 87.8% yield) as yellow oil. 1H NMR (CDCI3, 400 MHz) delta ppm 1.70 (s, 9H), 6.7 - 6.81 (m, 2H), 7.28 - 7.38 (m, 2H), 7.56 (d, J=1.6Hz, 1H), 7.66 (d, J=4Hz, 1H), 7.79 (s, 1H), 8.13 (d, J=8Hz, 1H); ESIMS found for C17H17NO3 m/z 284.1 (M+H). |
87.8% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate; In 1,4-dioxane; at 80℃; for 6h;Inert atmosphere; | A solution of <strong>[676448-17-2]tert-butyl 4-bromo-1H-indole-1-carboxylate</strong> (LXXI) (10 g, 33.8 mmol), 3-furylboronic acid (LXXII) (5.29 g, 47.3 mmol), K3P04 (14.3 g, 67.5 mmol) and Pd(dppf)C12 (1.24 g, 1.69 mmol) in dioxane (150 mL) was heated to 80C for 6 h under N2. The mixture was filtered and the filtrate was concentrated, the residue was purified by MPLC (PE:EtOAc = 10:1) to give tert-butyl 4-(furan-3-yl)-1H-indole-1-carboxylate (LXXIII) (8.4 g, 29.6 mmol, 87.8% yield) as yellow oil. ?H NMR (CDC13, 400 MHz) ppm 1.70 (s, 9H), 6.7 - 6.81 (m, 2H), 7.28-7.38 (m, 2H), 7.56 (d,J1.6Hz, 1H), 7.66 (d,J=4Hz, 1H), 7.79 (s, 1H), 8.13 (d,J=8Hz, 1H); ESIMS found for C,7H,7N03 mlz 284.1 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In toluene; at 110.0℃; for 3.0h; | General procedure: To an argon degassed solution of 6-halogeno-2,4-dichloropyrido[2,3-d]pyrimidine 6 or 7 (0.5 mmol) in toluene (6mL) the desired (Het)aryl boronic acid was added then (1.5 equiv)potassium carbonate and (0.05 equiv) Pd(PPh3)4 were also added.The reaction was stirred at 110C for the desired time. After completion of the reaction, 10 mL of water was added, and then extracted with dichloromethane (3 10 mL), the organic layers were combined and dried using magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained material was purified on silica gel by column chromatography (CH2Cl2/PE: 90/10)to afford compounds 8-12. 2,4-Dichloro-6-(4-methoxyphenyl)pyrido[2,3-d]pyrimidine (8) (C14H9Cl2N3O): Compound 8 was obtained from 2,4,6-trichloropyrido[2,3-d]pyrimidine 6 using 4-methoxyphenyl boronic acid (1.05 equiv), as a white solid in 83%yield. |
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