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Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 904326-92-7 |
Formula : | C6H7BFNO2 |
M.W : | 154.94 |
SMILES Code : | CC1=CC(B(O)O)=CN=C1F |
MDL No. : | MFCD03411562 |
InChI Key : | XCWIMBMPJGQNHG-UHFFFAOYSA-N |
Pubchem ID : | 17750247 |
GHS Pictogram: | ![]() |
Signal Word: | Warning |
Hazard Statements: | H319 |
Precautionary Statements: | P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.17 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 38.99 |
TPSA ? Topological Polar Surface Area: Calculated from | 53.35 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 | 0.55 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from | -0.37 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from | -0.57 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by | -0.33 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions | -0.14 |
Log S (ESOL):? ESOL: Topological method implemented from | -1.48 |
Solubility | 5.07 mg/ml ; 0.0328 mol/l |
Class? Solubility class: Log S scale | Very soluble |
Log S (Ali)? Ali: Topological method implemented from | -1.24 |
Solubility | 8.87 mg/ml ; 0.0572 mol/l |
Class? Solubility class: Log S scale | Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by | -1.57 |
Solubility | 4.2 mg/ml ; 0.0271 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 | -6.85 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) | 2.18 |
* 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% | With sodium carbonate;trans-bis(triphenylphosphine)palladium dichloride; In 1,2-dimethoxyethane; ethanol; water; at 100℃; for 0.25h;Microwave irradiation; | Example 3 Synthesis of 2-ethyl-4-(6-fluoro-5-methylpyridin-3-yl)-6,7-dimethoxyisoquinolin-1(2H)-one A glass microwave reaction vessel was charged with 4-bromo-2-ethyl-6,7-dimethoxyisoquinolin-1(2H)-one (0.1066 g, 0.34 mmol), <strong>[904326-92-7]6-fluoro-5-methylpyridin-3-ylboronic acid</strong> (0.1099 g, 0.43 mmol), sodium carbonate (0.2012 g, 1.5 mmol), and trans-dichlorobis(triphenyl-phosphine)palladium (ii) (0.0228 g, 0.027 mmol) in a solution of DME: water: ethanol (4.2 mL: 1.8 mL: 1.2 mL). The reaction mixture was stirred and heated in a Discover model microwave reactor (CEM, Matthews, N.C.) at 100 C. for 15 min (80 watts, 1 minute ramp time). The reaction mixture was filtered through Celite and concentrated. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Biotage pre-packed silica gel column (25M), eluding with a gradient of 1% to 5% methanol in dichloromethane, to provide 2-ethyl-4-(6-fluoro-5-methylpyridin-3-yl)-6,7-dimethoxyisoquinolin-1(2H)-one (0.0524 g, 45% yield; M+1=343.2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate;trans-bis(triphenylphosphine)palladium dichloride; In 1,2-dimethoxyethane; water; at 80℃; | To 100 mL round-bottomed flask was added 4-chloro-6,7-dimethoxyquinoline (0.1125 g, 0.503 mmol), <strong>[904326-92-7]6-fluoro-5-methylpyridin-3-ylboronic acid</strong> (0.1075 g, 0.629 mmol), and trans-dichlorobis(triphenyl-phosphine)palladium (II) (0.0321 g, 0.0402 mmol) in 1,2-dimethoxyethane. An aqueous solution of sodium carbonate (27 g, 257 mmol) was added and the temperature was brought to 80 C. stir overnight. Upon completion, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic extract was washed with water, saturated sodium chloride solution, dried with magnesium sulfate, filtered, and concentrated. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Biotage pre-packed silica gel column (25M), eluding with a gradient of 10% to 70% ethyl acetate in hexane, to provide 4-(6-fluoro-5-methylpyridin-3-yl)-6,7-dimethoxyquinoline (0.059 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate;trans-bis(triphenylphosphine)palladium dichloride; In 1,2-dimethoxyethane; water; at 80℃; | To 100 mL round-bottomed flask was added 4-bromo-6,7-dimethoxycinnoline (15.4 g, 57 mmol), <strong>[904326-92-7]6-fluoro-5-methylpyridin-3-ylboronic acid</strong> (10.1 g, 71 mmol), and trans-dichlorobis(triphenyl-phosphine)palladium (II) (3.4 g, 4.6 mmol) in 1,2-dimethoxyethane. An aqueous solution of sodium carbonate (27 g, 257 mmol) was added and the temperature was brought to 80 C. stir overnight. Upon completion, the reaction mixture was diluted with water (10 mL) and extracted with ethyl acetate. The organic extract was washed with water, saturated sodium chloride solution, dried with magnesium sulfate, filtered, and concentrated. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Biotage pre-packed silica gel column eluding with a gradient of 1% to 5% methanol in dichloromethane, to provide 4-(6-fluoro-5-methylpyridin-3-yl)-6,7-dimethoxycinnoline. | |
With sodium carbonate;trans-bis(triphenylphosphine)palladium dichloride; In 1,2-dimethoxyethane; water; at 80℃; | To 100 mL round-bottomed flask was added 4-bromo-6,7-dimethoxycinnoline (15.3809 g, 57 mmol), <strong>[904326-92-7]6-fluoro-5-methylpyridin-3-ylboronic acid</strong> (10.9899 g, 71 mmol), and trans-dichlorobis(triphenyl-phosphine)palladium (II) (3.3834 g, 4.6 mmol) in 1,2-dimethoxyethane. An aqueous solution of sodium carbonate (27 g, 257 mmol) was added and the temperature was brought to 80 C. stir overnight. Upon completion, the reaction mixture was diluted with water (10 mL) and extracted with ethyl acetate. The organic extract was washed with water, saturated sodium chloride solution, dried with magnesium sulfate, filtered, and concentrated. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Biotage pre-packed silica gel column eluting with a gradient of 1% to 5% methanol in dichloromethane, to provide 4-(6-fluoro-5-methylpyridin-3-yl)-6,7-dimethoxycinnoline. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate;trans-bis(triphenylphosphine)palladium dichloride; In 1,2-dimethoxyethane; water; at 80℃; for 5.0h; | To a solution of 6-(4-methoxybenzyloxy)-4-bromo-7-methoxycinnoline (0.58 g, 1.5 mmol), <strong>[904326-92-7]6-fluoro-5-methylpyridin-3-ylboronic acid</strong> (0.24 g, 1.5 mmol), sodium carbonate (3.1 mmol, 2M solution in water), and dimethoxyethane (5 mL) under an atmosphere of nitrogen was added trans-dichlorobis(triphenyl-phosphine)palladium (0.11 g, 0.15 mmol). The resulting mixture was heated to 80 C. for 5 hr. The mixture was cooled to room temperature and azeotroped with acetonitrile to remove water. The remaining residue was purified by Biotage (elution 0-10% MeOH/DCM) to isolate 6-(benzyloxy)-4-(6-fluoro-5-methylpyridin-3-yl)-7-methoxycinnoline. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With dihydrogen peroxide; In tetrahydrofuran; water; at 20℃; | Hydrogen peroxide water (4.37 ml, 42.8 mmol) was added to a tetrahydrofuran solution (50 ml) of <strong>[904326-92-7]2-fluoro-3-methylpyridine-5-boronic acid</strong> (5.1 g, 32.9 mmol), and stirred overnight at room temperature. Water was added to the reaction solution, and extracted with ethyl acetate. The organic layer was washed with aqueous 5 % sodium thiosulfate solution and saturated saline water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 6-fluoro-5-methylpyridin-3-ol (4.03 g, yield: 96 %) as a pale yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With bis(di-tert-?butyl(4-?dimethylaminophenyl)?phosphine)?dichloropalladium(II); cesium fluoride; In methanol; 1,2-dimethoxyethane; at 20 - 110℃; under 1500.15 Torr; for 0.65h;Inert atmosphere; Microwave irradiation; | General procedure: To a solution of 3-substituted-2-iodo imidazo[4,5-b] pyridine derivative (1 equiv) in dimethoxyethane/MeOH (4:1), was added (A-taphos)2PdCl2 (5mol%). The solution was purged with nitrogen and stirred at room temperature for 0.15 h, at which time the boronic acid (1.8equiv), and cesium fluoride (2 equiv) were added. The reaction solution was purged again with nitrogen and then placed in the microwave and heated for 10 to 30 mts at 110 C. When TLC and LCMS showed full consumption of starting materials, the reaction mixture was diluted with ethyl acetate, separated the ethyl acetate layer, given water wash, brine wash and was dried over anhydrous sodium sulphate and concentrated to get the crude material. The crude product was directly purified by column chromatography (0-20% hexane/EtOAc) to isolate the 3-substituted-2-aryl/heteroarylimidao[4,5-b] pyridine derivatives. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; toluene; at 120℃; for 1.0h;Inert atmosphere; Microwave irradiation; | The product from Example 261B (0.792 g, 3.0 mmol), <strong>[904326-92-7]2-fluoro-3-methylpyridine-5-boronic acid</strong> (Combi-Blocks 0.604 g, 3.9 mmol), tetrakis(triphenylphosphune)palladium(0) (0.173 g, 0.15 mmol) and sodium carbonate (4.50 mL, 9.0 mmol) were combined in toluene (10 mL), ethanol (2.5 mL) and water (2.5 mL), sparged with nitrogen for 10 minutes and heated by microwave at 120 C for 60 minutes. The reaction mixture was partitioned between ethyl acetate and brine. The organic layer was separated, dried (Na2S04), filtered and concentrated. Purification by chromatography (silica gel, 0-60% ethyl acetate in hexane) afforded the title compound (0.742 g, 84%). |
84% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; toluene; at 120℃; for 1.0h;Microwave irradiation; Inert atmosphere; | Example 262A 3-(6-fluoro-5-methylpyridin-3-yl)-4-phenoxyaniline [1092] The product from Example 261B (0.792 g, 3.0 mmol), <strong>[904326-92-7]2-fluoro-3-methylpyridine-5-boronic acid</strong> (Combi-Blocks 0.604 g, 3.9 mmol), tetrakis(triphenylphosphune)palladium(0) (0.173 g, 0.15 mmol) and sodium carbonate (4.50 mL, 9.0 mmol) were combined in toluene (10 mL), ethanol (2.5 mL) and water (2.5 mL), sparged with nitrogen for 10 minutes and heated by microwave at 120 C. for 60 minutes. The reaction mixture was partitioned between ethyl acetate and brine. The organic layer was separated, dried (Na2SO4), filtered and concentrated. Purification by chromatography (silica gel, 0-60% ethyl acetate in hexane) afforded the title compound (0.742 g, 84%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; toluene; at 110℃; for 0.5h;Microwave irradiation; | Example 261D N-(3-(6-fluoro-5-methylpyridin-3-yl)-4-phenoxyphenyl)methanesulfonamide [1090] A mixture of <strong>[904326-92-7]2-fluoro-3-methylpyridine-5-boronic acid</strong> (Combi-Blocks 0.088 g, 0.566 mmol), the product from Example 261C (0.149 g, 0.435 mmol), tetrakis(tiriphenylphosphine)palladium(0) (0.025 g, 0.022 mmol) and sodium carbonate (0.435 mL, 0.871 mmol) in toluene (2.4 mL), ethanol (0.62 mL) and water (1.24 mL) was heated by microwave at 110 C. for 30 minutes. The reaction mixture was filtered through a 0.45 um Nylon filter disk to remove solids and the filtrate was partitioned between ethyl acetate and brine. The organic layer was separated and concentrated. Purification by chromatography (silica gel, 0-60% ethyl acetate in hexane) afforded the title compound (0.133 g, 82%). MS (ESI+) m/z 373 (M+H)+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; toluene; at 110℃; for 0.5h;Microwave irradiation; | A mixture of <strong>[904326-92-7]2-fluoro-3-methylpyridine-5-boronic acid</strong> (Combi-Blocks 0.088 g, 0.566 mmol), the product from Example 261C (0.149 g, 0.435 mmol), tetrakis(tiriphenylphosphine) palladium(O) (0.025 g, 0.022 mmol) and sodium carbonate (0.435 mL, 0.871 mmol) in toluene (2.4 mL), ethanol (0.62 mL) and water (1.24 mL) was heated by microwave at 110 °C for 30 minutes. The reaction mixture was filtered through a 0.45um Nylon filter disk to remove solids and the filtrate was partitioned between ethyl acetate and brine. The organic layer was separated and concentrated. Purification by chromatography (silica gel, 0-60percent ethyl acetate in hexane) afforded the title compound (0.133 g, 82percent). MS (ESI+) m/z 373 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In water; toluene; at 90℃;Inert atmosphere; | General procedure: Example 1 A (0.145 g, 1 mmol), 2-fluoro-5-nitrophenylboronic acid (0.294 g, 1.1 mmol), Pd(PPh3)4 (0.058 g, 0.05 mmol) and sodium carbonate (0.212 g, 2.0 mmol) were combined in toluene (4 mL), ethanol (1 mL), and water (1 mL) and the mixture was degassed and left under nitrogen. The reaction mixture was heated at 90 C overnight, and then cooled to room temperature. The mixture was partitioned between ethyl acetate and water. The organic layer was washed with brine, dried (MgS04), filtered and concentrated. The crude product was purified by flash chromatography (silica gel, 20-50% ethyl acetate in hexanes) to provide 0.19 g (76%) of the title compound. Example 266C was prepared according to the procedure used for the preparation of Example 9A, substituting Example 266B for Example 1 A, and substituting 6-fluoro-5-methylpyridin-3- ylboronic acid for 2-fluoro-5-nitrophenylboronic acid, respectively, to provide the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With bis(1,5-cyclooctadiene)nickel (0); potassium phosphate; In 1,4-dioxane; at 80℃; for 6.0h;Inert atmosphere; | General procedure: In a N2-atmosphere glovebox, Ni(cod)2 (either 1.6 mg, 0.006 mmol, 3 mol% or 5.5mg, 0.020 mmol, 10 mol%) and K3PO4 (64.0 mg, 0.30 mmol, 1.5 equiv) were weighed into a 1-dram vial. Benzyl ammonium triflate 1 (0.20 mmol, 1.0 equiv) and boronic acid (0.30 mmol, 1.5 equiv) were added, followed by dioxane (0.6 mL, 0.33 M). The vial was capped with a Teflon-lined cap and removed from the glovebox. The mixture was stirred for 6 h at 80C. After cooling to room temperature, the reaction mixture was then diluted with Et2O (1.5 mL) and filtered through a short plug of silica gel, which was rinsed with Et2O (10 mL). The filtrate was concentrated and purified by silica gel chromatography to give the cross-coupled product. 4.2.3 (R)-2-Fluoro-3-methyl-5-(1-(naphthalen-2-yl)ethyl)pyridine (4) General procedure was followed using 3 mol % Ni(cod)2 and benzylic ammonium triflate 1a prepared in 99.6% ee. The crude material was purified by silica gel chromatography (5% EtOAc/1% Et3N/hexanes) to give compound 4 (37 mg, 70%) as a pale yellow oil. The enantiomeric excess was determined to be 75% ee by chiral HPLC analysis (CHIRALPAK IB, 1.0 mL/min, 5.0% i-PrOH/hexane, lambda=254 nm); tR (minor)=5.99 min, tR (major)=7.18 min. [alpha]D24 -89.6 (c 0.73, CHCl3): 1H NMR (400 MHz, CDCl3) delta 8.30-8.11 (m, 1H), 7.86-7.70 (m, 3H), 7.61-7.51 (m, 1H), 7.52-7.37 (m, 2H), 7.33-7.22 (m, 1H), 6.79-6.67 (m, 1H), 4.39 (q, J=7.1 Hz, 1H), 2.21 (s, 3H), 1.74 (d, J=7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3) delta 162.7 (d, JC-F=238.4 Hz), 151.8 (d, JC-F=8.1 Hz), 145.7 (d, JC-F=15.15 Hz), 142.3, 136.9 (d, JC-F=5.1 Hz), 133.6, 132.2, 128.5, 127.7 (d, JC-F=4.0 Hz), 126.3, 125.8, 125.6, 110.7, 110.4, 39.6, 22.0, 19.8 (d, JC-F=3.0 Hz); 13C NMR (101 MHz, (CD3)2CO) delta 162.6 (d, JC-F=232.3 Hz), 151.9 (d, JC-F=8.1 Hz), 145.6 (d, JC-F=16.2 Hz), 142.6, 137.4 (d, JC-F=4.0 Hz), 133.7, 132.3, 128.2, 127.7, 127.5, 126.4, 126.1, 125.6, 125.5, 109.9 (d, JC-F=19.2 Hz), 39.0, 21.2, 18.6 (d, JC-F=3.0 Hz); FTIR (NaCl/thin film) 3053, 2968, 1608, 1485, 1373, 962 cm-1; HRMS (EI+) [M]+ calculated for C18H16FN: 265.1267, found:265.1252. Please note: Although two 13C NMR peaks are coincident when CDCl3 is used as solvent, all 18 13C NMR peaks are seen when (CD3)2CO is used as solvent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,2-dimethoxyethane; water; at 90℃; | 9 (74 mg, 0.33 mmol) was mixed with Pd(PPh3)4 (38 mg, 0.033 mmol) and 2-fluoro-3-methyl pyridine-5-boronic acid ( 62 mg, 0.4 mmol) in 1, 2 -dimethoxy-ethane (2 mL). A solution of cesium carbonate (271 mg, 0.83 mmol) in 2 mL water was added to the reaction mixture which was stirred overnight at 90 C. After the reaction was complete, the mixture was diluted with water (10mL) and extracted with ethyl acetate (3 × 15 mL). The combined organic layers were dried over anhydrous Na2SO4. The crude product was purified by flash chromatography using hexane/DCM/acetone (from 10/1/1, v/v/v) to yield 19 as a gray solid (80 mg, 81%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,2-dimethoxyethane; water; at 100℃; | 10 (100 mg, 0.33 mmol) was mixed with Pd(PPh3)4 (38 mg, 0.033 mmol) and 2-fluoro-3-methyl pyridine-5-boronic acid ( 62 mg, 0.4 mmol) in 1, 2 -dimethoxy-ethane (2 mL). A solution of cesium carbonate (271 mg, 0.83 mmol) in 2 mL water was added to the reaction mixture which was stirred overnight at 100 C. After the reaction was complete, the reaction mixture was diluted with water (10 mL) and extracted with ethyl acetate (3 × 15 mL). The combined organic layers were dried over anhydrous Na2SO4. The crude product was purified by flash chromatography using hexane/DCM/acetone (15/1/1, v/v/v) to yield 22 as a white solid (87 mg, 70%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42% | With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,2-dimethoxyethane; water; at 90℃; for 12.0h; | 15 (90 mg, 0.26 mmol) was mixed with Pd(PPh3)4 (30 mg, 0.03 mmol) and <strong>[904326-92-7]2-fluoro-3-methylpyridine-5-boronic acid</strong> (48 mg, 0.31 mmol) in 1,2-dimethoxyethane (2 mL). A solution of cesium carbonate (208 mg, 0.65 mmol) and 2 mL water was added and the reaction mixture was stirred at 90C for 12 h. After the reaction was complete, the mixture was diluted with water (5 mL) and extracted with ethyl acetate (3 × 15 mL). The combined organic layers were dried over anhydrous Na2SO4 and concentrated in vacuo. The crude product was purified by flash chromatography using hexane /DCM /acetone (15/1/1, v/v/v) to yield 23 as a white solid (46 mg, 42%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,2-dimethoxyethane; water; at 100℃; for 12.0h; | 16 (70 mg, 0.26 mmol) was mixed with Pd(PPh3)4 (30 mg, 0.03 mmol) and <strong>[904326-92-7]2-fluoro-3-methylpyridine-5-boronic acid</strong> (48 mg, 0.31mmol) in 2 mL 1,2-dimethoxyethane. A solution of cesium carbonate (208 mg, 0.65 mmol) and 2 mL water was added to the reaction mixture which was heated to 100C and stirred for 12 h. After the reaction was complete, the mixture was diluted with water (10 mL), and extracted with ethyl acetate (3 × 15 mL). The combined organic layers were dried over anhydrous Na2SO4 and concentrated in vacuo. The crude product was purified by flash chromatography using hexane /DCM /acetone(15/1/1, v/v/v) to yield 24 as a white solid (36 mg, 40%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,2-dimethoxyethane; water; at 90℃; | Commercially available 4-chloro-[1,3]dioxolo[4,5-g]cinnoline, 17 (125 mg, 0.6 mmol) was mixed with Pd(PPh3)4 (104 mg, 0.09 mmol) and 2-fluoro-3-methyl pyridine-5-boronic acid (121 mg, 0.8 mmol) in 1, 2-dimethoxyethane (2 mL). A solution of cesium carbonate (430 mg, 1.32 mmol) in 2 mL water was added and the reaction mixture was stirred at 90C overnight. After the reaction was complete, the mixture was diluted with water (10 mL) and extracted with ethyl acetate (3 × 15 mL). The combined organic layers were dried over anhydrous Na2SO4. The crude product was purified by flash chromatography using hexane/DCM/acetone (10/1/1, v/v/v) to yield 20 as a white solid (127 mg, 75%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,2-dimethoxyethane; water; at 90℃; | Commercially available 4-chlorocinnoline (18) (250 mg, 1.5 mmol) was mixed with Pd(PPh3)4 (176 mg, 0.15 mmol) and 2-fluoro-3-methyl pyridine-5-boronic acid (282 mg, 1.8 mmol) in 1, 2-dimethoxyethane (2 mL). A solution of cesium carbonate (1.24 g, 3.8 mmol) and 2 mL water was added and the reaction mixture was stirred at 90C overnight. After the reaction was complete, the mixture was diluted with water (10 mL) and extracted with ethyl acetate (3 × 15 mL). The combined organic layers were dried over anhydrous Na2SO4 and concentrated in vacuo. The crude product was purified by flash chromatography using hexane/DCM/acetone (12/1/1, v/v/v) to yield 21 as a white solid (266 mg, 73%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In water; at 100℃; for 3.0h;Inert atmosphere; Microwave irradiation; | STEP 1 : 4-(6-FLUORO-5-METHYLPYRIDIN-3-YL)-3-METHOXY-N- (METHYLSULFONYL)BENZAMIDE[00280] A microwave vial was charged with (6-fluoro-5 -methylpyridin-3 -yl)boronic acid (0.084 g, 0.542 mmol, FSSI), 4-bromo-3-methoxy-N-(methylsulfonyl)benzamide (0.152 g, 0.493 mmol, Method XI, Step 1), and Pd(PPh3)4(0.040 g, 0.035 mmol). The vial was sealed with septum cap and cyclopentylmethylether (CPME) (1.2 mL) was added followed by an aqueous solution of sodium carbonate (0.789 ml, 1.577 mmol, 2 N). The mixture was sparged with N2and heated in a microwave at 100 C for 3 h. The mixture was cooled to rt and the organic and aqueous layers were separated. The aqueous layer was acidified with 6 N HC1 (dropwise) and extracted with EtOAc (2x10 mL). The combined EtOAc extracts were concentrated to provide 4-(6-fluoro-5-methylpyridin-3-yl)-3-methoxy-N- (methylsulfonyl)benzamide, which was of sufficient purity for use in the subsequent reaction. MS m/z: [M-l]~= 337.2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
20% | Intermediate-b (0.075 g, 0.14 mmol) was solubilised in dioxane (3.2 ml). (6-Fluoro-5-methylpyridin-3-yl)boronic acid (44 mg, 0.28 mmol) was added in one portion followed byaddition of caesium carbonate (0.19 g, 0.59 mmol) and PdCI2(dppf) in complex with dichloromethane (11 mg, 0.014 mmol). The reaction was heated for 4 hours in a sealed tube at 110C. The reaction was then cooled to rt and filtered. The filtrate was concentrated under reduced pressure. The crude material was purified by flash column chromatography(hexane/ethyl acetate mixture). The combined fractions were concentrated under reducedpressure, solubilised in methanol (1.5 ml) and 3N hydrochloric acid (1.6 ml) was added. Themixture was stirred overnight at rt and then basified with a 3M sodium hydroxide solution. Thesuspension was filtered and washed with water. The solid was purified by preparative HPLC(acetonitrile/water/formic acid mixture). The title compound was obtained in 20% yield (11 mg).?H-NMR (400MHz, DMSO-d5): 6 [ppm]= 1.30 (dd, 3H), 2.12 (s, 3H), 3.36 - 3.39 (m, 1H), 3.52 - 3.63(m, 1H), 3.68 -3.76 (m, 1H), 3.78 - 3.85 (m, 1H), 4.01 -4.09 (m, 1H), 4.18 -4.27 (m, 1H), 4.57 -4.66(m, 1H), 7.00 (dd, 1H), 7.33 (s, 1H), 7.40- 7.45 (m, 1H), 7.51 (d, 1H), 7.65 (d, 1H), 8.17 (d, 1H), 8.29(d, 1H), 13.42 (br. s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
49% | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 6.0h;Inert atmosphere; | A mixture of methyl (4-chloropyrimidin-2-yl)carbamate (prepared as described in Example 304) (65 mg, 0.347 mmol), 2-fluoro-3-methylpyridine-5- boronic acid (53.7 mg, 0.347 mmol), PdCl2(dppf)-CH2Cl2 adduct (14.15 mg, 0.017 mmol) and CS2CO3 (339 mg, 1.040 mmol) in 1,4-dioxane (3 mL)-water (0.3 mL) was purged with nitrogen and heated at 100 C for 6 h. The reaction mixture was diluted with ethyl acetate (25 mL). The black suspension was filtered through diatomaceous earth (Celite) and the bed was washed with ethyl acetate (50 mL). The filtrate was concentrated under reduced pressure to afford a black residue which was purified via silica gel chromatography (pet ether: ethyl acetate) to afford methyl (4-(6-fluoro-5- methylpyridin-3-yl)pyrimidin-2-yl)carbamate (60 mg, 0.169 mmol, 49% yield) as a brown solid. LCMS (ESI) m/e 263.0 [(M+H)+, calcd for C12H12FN4O2 263.1] ; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
28% | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate; In 1,4-dioxane; at 80℃; for 3.0h; | A mixture of <strong>[904326-92-7]2-fluoro-3-methylpyridine-5-boronic acid</strong> (0.033 g, 0.213 mmol), methyl (6-chloropyrimidin-4-yl)carbamate (prepared as described in Example 432) (0.04 g, 0.213 mmol), PdCl2(dppf)-CH2Cl2 adduct (0.017 g, 0.021 mmol) and CS2CO3 (0.208 g, 0.640 mmol) in 1 ,4-dioxane (3 mL) was heated at 80 C for 3 h. The reaction mixture was cooled to room temperature and filtered through diatomaceous earth (Celite). The bed was washed with ethyl acetate and the filtrate was concentrated under reduced pressure to afford methyl (6-(6-fluoro-5- methylpyridin-3-yl)pyrimidin-4-yl)carbamate (0.03 g, 0.059 mmol, 28% yield) as an off-white solid which was carried forward without further purification. LCMS (ESI) m/e 263.2 [(M+H)+, calcd for C12H12FN4O2 263.1] ; LC/MS retention time (method H): fe = 2.00 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate; In 1,4-dioxane; at 80℃; for 3.0h; | To a solution of <strong>[904326-92-7]2-fluoro-3-methylpyridine-5-boronic acid</strong> (0.048 g, 0.311 mmol) in 1,4-dioxane (3 mL), 4-chloro-6-methylpyrimidine (0.04 g, 0.311 mmol) was added PdCl2(dppf)-CH2Cl2 adduct (0.025 g, 0.031 mmol) and CS2CO3 (0.304 g, 0.933 mmol). The reaction mixture was heated at 80 C for 3 h. The reaction mixture was cooled to room temperature then filtered through diatomaceous earth (Celite), washing the bed with ethyl acetate (100 mL). The filtrate was concentrated under reduced pressure to afford 4-(6-fluoro-5-methylpyridin-3-yl)-6- methylpyrimidine (0.04 g, 0.160 mmol, 52% yield) as a brown solid. LCMS (ESI) m/e 204.2 [(M+H) +, calcd for C11H11FN3 204.1]; LC/MS retention time (Method Al): to = 2.30 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With chloro(2-dicyclohexylphosphino-2?,4?,6?-triisopropyl-1,1?-biphenyl)[2-(2?-amino-1,1?-biphenyl)]palladium(II); caesium carbonate; In 1,4-dioxane; water; at 80℃; for 1.0h;Inert atmosphere; | A stirred solution of 4-chloro-2-methylpyrimidine (100 mg, 0.778 mmol), CS2CO3 (507 mg, 1.556 mmol), <strong>[904326-92-7](6-fluoro-5-methylpyridin-3-yl)boronic acid</strong> (121 mg, 0.778 mmol) in a mixture of 1 ,4-dioxane (6 mL) and water (0.5 mL) was purged with nitrogen for 3 min. XPhos 2nd generation precatalyst (61.2 mg, 0.078 mmol) was added in one portion and the reaction mixture was heated to 80 C and stirred for 1 h. The reaction mixture was allowed to cool to room temperature. Water (20 mL) was added and the solution was extracted with EtOAc (2 x 30 mL). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (EtOAc in hexanes) to afford 4-(6-fluoro-5-methylpyridin-3-yl)-2-methylpyrimidine (115 mg, 0.521 mmol, 67% yield) as an off-white solid. LCMS (ESI) m/e 204.2 [(M+H)+, calcd for C11H11FN3, 204.1]; LC/MS retention time (method Al) to = 1.90 min. |
Tags: 904326-92-7 synthesis path| 904326-92-7 SDS| 904326-92-7 COA| 904326-92-7 purity| 904326-92-7 application| 904326-92-7 NMR| 904326-92-7 COA| 904326-92-7 structure
A142326 [351019-18-6]
2-Fluoro-5-pyridylboronic acid
Similarity: 0.89
A167917 [1072944-18-3]
2-Fluoro-4-methyl-5-pyridineboronic acid
Similarity: 0.83
A255322 [904326-91-6]
(6-Fluoro-2-methylpyridin-3-yl)boronic acid
Similarity: 0.76
A416748 [401815-98-3]
(2-Fluoropyridin-4-yl)boronic acid
Similarity: 0.76
A197554 [444120-95-0]
2-Fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine
Similarity: 0.69
A142326 [351019-18-6]
2-Fluoro-5-pyridylboronic acid
Similarity: 0.89
A167917 [1072944-18-3]
2-Fluoro-4-methyl-5-pyridineboronic acid
Similarity: 0.83
A255322 [904326-91-6]
(6-Fluoro-2-methylpyridin-3-yl)boronic acid
Similarity: 0.76
A416748 [401815-98-3]
(2-Fluoropyridin-4-yl)boronic acid
Similarity: 0.76
A197554 [444120-95-0]
2-Fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine
Similarity: 0.69
A142326 [351019-18-6]
2-Fluoro-5-pyridylboronic acid
Similarity: 0.89
A167917 [1072944-18-3]
2-Fluoro-4-methyl-5-pyridineboronic acid
Similarity: 0.83
A255322 [904326-91-6]
(6-Fluoro-2-methylpyridin-3-yl)boronic acid
Similarity: 0.76
A416748 [401815-98-3]
(2-Fluoropyridin-4-yl)boronic acid
Similarity: 0.76
A197554 [444120-95-0]
2-Fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine
Similarity: 0.69
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