* 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.
Reference：
[1] Synlett, 2011, # 17, p. 2517 - 2520
6
[ 5720-07-0 ]
[ 626-02-8 ]
Reference：
[1] Journal of Organic Chemistry, 2013, vol. 78, # 23, p. 12154 - 12160
[2] Patent: KR101572521, 2015, B1,
7
[ 5720-07-0 ]
[ 7511-49-1 ]
Reference：
[1] Patent: CN107915753, 2018, A,
8
[ 619-58-9 ]
[ 5720-07-0 ]
[ 725-14-4 ]
Yield
Reaction Conditions
Operation in experiment
95%
With caesium carbonate In 1,2-dimethoxyethane; water at 80℃; for 6 h; Inert atmosphere
Method B.A solution of 4-methoxyphenyl boronic acid (1 g, 6.58 mmol), 4-iodobenzoic acid (1.63 g, 6.58 mmol) and cesium carbonate (5.36 g, 16.45 mmol) in 3:1 1,2- dimethoxyethane/water was deoxygenated with nitrogen for 15 minutes. Pd(PPtLs)4 (380 mg, 0.329 mmol) was then added and the solution was heated to 80° C for 6h. The reaction was allowed to cool and acidified with 2M HCl which caused a precipitate to form. The precipitate was filtered and the filtrate was extracted twice with dichloromethane. The organic layer was then dried over magnesium sulfate, filtered through diatomaceous earth filter aid (CELITE.(R).) and evaporated under reduced pressure to yield a combined 1.5O g (95percent). 1HNMR (DMSO): δ 7.99 (d, J=8.4 Hz, 2H), 7.74 (d, J=8.4 Hz, 2H), 7.69 (d, J=8.7 Hz, 2H), 7.04 (d, J=8.7 Hz, 2H), 3.80 (s, 3H). 13CNMR (DMSO): δ 167.17, 159.49, 143.90, 131.16, 129.91, 128.77, 128.09, 126.08, 114.45, 55.17.
89%
With Pd/C; potassium carbonate In water at 110℃; for 1 h;
General procedure: The Ni and Pd carbon aerogels were always sinked in water 24 h before their use as catalysts and kept in the same solvent.Catalytic reactions: In a 100 mL three necked round-bottom flask, arylboronic acid (15 mmol), aryl halide (10 mmol) and K2CO3 (2.76 g, 20 mmol) were dissolved in 20 mL of H2O. Then, Ni or Pd carbon aerogel (0.1 mmol, 1 mol percent) was added to the mixture and the reaction was carried out under reflux (110 °C), in the presence of air and mechanical stirring. Periodic sampling of the reaction media was made to analyze the reaction evolution by GC and 1H NMR measurements. The liquid phase was decanted and the carbon aerogel was washed with water. This water extracts and the reactive solution were mixed together and acidified until pH 1 to cause the precipitation of the final product. The solid was filtrated, washed with water and dried. The pieces of aerogel were washed with AcOEt, with water and were kept submerged in this solvent before reused.
Reference：
[1] Russian Chemical Bulletin, 2007, vol. 56, # 2, p. 369 - 370
[2] Green Chemistry, 2010, vol. 12, # 1, p. 150 - 158
[3] Patent: WO2009/146013, 2009, A1, . Location in patent: Page/Page column 52
[4] Green Chemistry, 2009, vol. 11, # 12, p. 1929 - 1932
[5] Tetrahedron, 2012, vol. 68, # 32, p. 6517 - 6520
[6] Green Chemistry, 2013, vol. 15, # 12, p. 3468 - 3473
[7] Tetrahedron Letters, 2006, vol. 47, # 25, p. 4225 - 4229
9
[ 586-76-5 ]
[ 5720-07-0 ]
[ 725-14-4 ]
Yield
Reaction Conditions
Operation in experiment
99%
With potassium carbonate; palladium dichloride In PEG400; water at 20℃; for 0.133333 h; Air atmosphere
General procedure: A mixture of arylboronic acid (0.5 mmol), aryl bromides/iodides (0.6 mmol), PdCl2 (0.0025 mmol), K2CO3 (1.75 mmol), PEG400 1.5 mL, and H2O 1.5 mL were added to a 50 mL round-flask, and stirred at room temperature for the desired time until complete consumption of starting material as judged by TLC. Then, the reaction mixture was extracted with ether (10 mL.x.4) and the combined organic layers were dried over anhydrous MgSO4 (acidification was needed for carboxyl substituted substrates before extraction). The solvent was removed by evaporation under reduced pressure to afford the crude products, which were further purified by column chromatography on silica gel using petroleum ether and ethyl acetate as the eluent.
Reference：
[1] Tetrahedron, 2011, vol. 67, # 26, p. 4914 - 4918
[2] Asian Journal of Chemistry, 2014, vol. 26, # 7, p. 2077 - 2082
[3] Organic and Biomolecular Chemistry, 2014, vol. 12, # 25, p. 4511 - 4516
[4] Applied Organometallic Chemistry, 2014, vol. 28, # 12, p. 861 - 867
[5] Green Chemistry, 2010, vol. 12, # 1, p. 150 - 158
[6] Journal of the American Chemical Society, 2009, vol. 131, # 23, p. 8262 - 8270
[7] Green Chemistry, 2009, vol. 11, # 12, p. 1929 - 1932
[8] Journal of Medicinal Chemistry, 1997, vol. 40, # 20, p. 3144 - 3150
[9] Tetrahedron Letters, 2004, vol. 45, # 29, p. 5661 - 5663
10
[ 5720-07-0 ]
[ 74-11-3 ]
[ 725-14-4 ]
Reference：
[1] Synthesis (Germany), 2013, vol. 45, # 9, p. 1201 - 1206
[2] RSC Advances, 2017, vol. 7, # 74, p. 47104 - 47110
[3] Organic and Biomolecular Chemistry, 2014, vol. 12, # 25, p. 4511 - 4516
11
[ 5720-07-0 ]
[ 556809-46-2 ]
[ 725-14-4 ]
Reference：
[1] Journal of Organic Chemistry, 2003, vol. 68, # 11, p. 4189 - 4194
12
[ 5720-07-0 ]
[ 96898-10-1 ]
[ 710-18-9 ]
Reference：
[1] Journal of the American Chemical Society, 2011, vol. 133, # 34, p. 13308 - 13310
13
[ 100-66-3 ]
[ 73183-34-3 ]
[ 10365-98-7 ]
[ 5720-07-0 ]
Reference：
[1] Journal of Organometallic Chemistry, 2007, vol. 692, # 20, p. 4244 - 4250
[2] Journal of Organometallic Chemistry, 2007, vol. 692, # 20, p. 4244 - 4250
[3] Journal of Organometallic Chemistry, 2007, vol. 692, # 20, p. 4244 - 4250
14
[ 100-66-3 ]
[ 10365-98-7 ]
[ 5720-07-0 ]
Reference：
[1] Journal of Organometallic Chemistry, 2007, vol. 692, # 20, p. 4244 - 4250
With palladium diacetate; sodium carbonate; triphenylphosphine In tetrahydrofuran; water at 60℃; for 6 h;
[00234] To a solution of 2,4,6-trichloropyrimidine (5.5 mL, 48 mmol) in THF (70 mL) were added palladium acetate (0.147 g, 0.64 mmol), triphenylphosphine (0.353 g, 1.28 mmol), 4-methoxybenzeneboronic acid (5 g, 31.9 mmol) and aqueous sodium carbonate solution (1 M, 64 mL, 64 mmol). The mixture was stirred at 60 °C for 6 h. After the reaction was completed, the mixture was cooled to rt, and concentrated in vacuo to remove the solvent. To the residue was added H20 (100 mL), and the mixture was extracted with ethyl acetate (100 mL x 3). The combined organic layers were washed with saturated brine (100 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated in vacuo. The residue was purified by silica gel column chromatography (PE) to give the title compound as a white solid (5.58 g, 68percent).MS (ESI, pos.ion) m/z: 255.0 [M+H]+1H NMR (400 MHz, CDC13) (ppm): 8.07 (dd, J = 9.4, 2.4 Hz, 2H), 7.60 (s, 1H), 7.08-6.99 (m,2H), 3.91 (s, 3H).
68%
With palladium diacetate; sodium carbonate; triphenylphosphine In tetrahydrofuran; water at 60℃;
To a solution of 2,4,6-trichloropyrimidine (5.5 mL, 48.0 mmol) in tetrahydrofuran (70 mL) were added palladium acetate (0.147 g, 0.64 mmol), triphenylphosphine (353 mg, 1.28 mmol), 4-methoxyphenylboronic acid (5 g, 31.9 mmol) and an aqueous sodium carbonate soltuion (1 M, 64 mL, 64 mmol). The mixture was heated to 60 °C and stirred overnight. After the reaction, the reaction mixture was cooled to rt and concentrated to remove the organic solvent. To the residue was added H20 (100 mL), and the mixture was extracted with EtOAc (100 mL x 3). The combined organic layers were washed with saturated brine (100 mL), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated in vacuoto dry,and the residue was purified by silica gel column chromatography (PE) to give the title compound as a white solid (5.58 g, 68percent).MS (ESI, pos.ion) m/z: 255.0 [M+Hfb;‘H NIVIR (400 IVIFIz, CDC13) (ppm): 8.07 (dd, J = 9.4, 2.4 Hz, 2H), 7.60 (s, 1H), 7.08 — 6.99 (m, 2H), 3.91 (s, 3H).
68%
With palladium diacetate; sodium carbonate; triphenylphosphine In tetrahydrofuran; water at 60℃; for 6 h; Inert atmosphere
2,4,6-Trichloropyrimidine (5.5 mL, 48.0 mmol) was dissolved in tetrahydrofuran (70 mL).Then, palladium acetate (0.147 g, 0.64 mmol) was sequentially added thereto.Triphenylphosphine (353 mg, 1.28 mmol),p-Methoxybenzeneboronic acid (5.01 g, 31.9 mmol)And aqueous sodium carbonate (1M, 64 mL, 64 mmol),The resulting mixture was heated to 60 ° C under a nitrogen atmosphere and stirred for 6 hours.Cool to room temperature, concentrate under reduced pressure to remove organic solvent.Water (100 mL) was added to the residue.The resulting mixture was extracted with ethyl acetate (100 mL×3).The combined organic phases were washed with brine (100 mL).Dry anhydrous sodium sulfate, filter, and concentrate the filtrate to dryness.The residue was purified by EtOAc EtOAc EtOAc(5.58g, 68percent).
68%
With palladium diacetate; sodium carbonate; triphenylphosphine In tetrahydrofuran; water at 60℃; for 6 h; Inert atmosphere
To a solution of 2,4,6-trichloropyrimidine (5.5 mL, 48.0 mmol) in THF (70 mL) were added palladium acetate (0.147 g, 0.64 mmol), triphenylphosphine (353 mg, 1.28 mmol), 4-methoxybenzeneboronic acid (5.01 g, 31.9 mmol) and aqueous sodium carbonate solution (1 M, 64 mL, 64 mmol). The mixture was stirred at 60 °C for 6 h under nitrogen protection. The reaction mixture was cooled to rt and concentrated in vacuo to remove the solvent. To the residue was added water (100 mL), and the resulting mixture was extracted with ethyl acetate (100 mL x3). The combined organic layers were washed with saturated brine (100 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo and the residue was purified by silica gel column chromatography (PE) to give the title compound as a white solid (5.58 g, 68percent). MS (ESI, pos.ion) m/z: 255.0 [M+H]‘H NMR (400 IVIFIz, CDC13) (ppm): 8.07 (dd, J= 9.4, 2.4 Hz, 2H), 7.60 (s, 1H), 7.08 — 6.99 (m, 2H), 3.91 (s, 3H).
68%
With palladium diacetate; sodium carbonate; triphenylphosphine In tetrahydrofuran; water at 60℃; for 5 h;
To a solution of 2, 4, 6-trichloropyrimidine (5.5 mL, 48.0 mmol) in THF (70 mL) were added palladium acetate (0.147 g, 0.64 mmol) , triphenylphosphine (353 mg, 1.28 mmol) , p-methoxybenzeneboronic acid (5 g, 31.9 mmol) and aqueous sodium carbonate solution (1 M, 64 mL, 64 mmol) . The mixture was stirred at 60 for 5 h. The reaction mixture was cooled to rt and concentrated in vacuo to remove organic solvent. To the residue was added water (100 mL) , and the resulting mixture was extracted with ethyl acetate (100 mL × 3) . The combined organic layers were washed with saturated brine (100 mL) , dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo and the residue was purified by silica gel column chromatography (PE) to give the title compound as a white solid (5.58 g, 68percent) .[0757]MS-ESI: (ESI, pos. ion) m/z: 255.0 [M+H]+;[0758]1H NMR (400 MHz, CDCl3) δ (ppm) : 8.07 (dd, J = 9.4, 2.4 Hz, 2H) , 7.60 (s, 1H) , 7.08–6.99 (m, 2H) , 3.91 (s, 3H) .
Reference：
[1] Organic Letters, 2006, vol. 8, # 3, p. 395 - 398
[2] Patent: WO2017/97234, 2017, A1, . Location in patent: Paragraph 00234
[3] Patent: WO2018/33082, 2018, A1, . Location in patent: Paragraph 00441
[4] Patent: CN108276401, 2018, A, . Location in patent: Paragraph 0595; 0597; 0598
[5] Patent: WO2018/127096, 2018, A1, . Location in patent: Paragraph 00284
[6] Patent: WO2018/157830, 2018, A1, . Location in patent: Paragraph 00298
20
[ 5720-07-0 ]
[ 914348-82-6 ]
Reference：
[1] Patent: EP2308838, 2011, A1,
21
[ 109-04-6 ]
[ 5720-07-0 ]
[ 168823-65-2 ]
Reference：
[1] Angewandte Chemie - International Edition, 2015, vol. 54, # 50, p. 15284 - 15288[2] Angew. Chem., 2015, vol. 127, # 50, p. 15499 - 15503,5
22
[ 5350-93-6 ]
[ 5720-07-0 ]
[ 52057-98-4 ]
Reference：
[1] Journal of Organic Chemistry, 2013, vol. 78, # 22, p. 11513 - 11524
23
[ 13534-97-9 ]
[ 5720-07-0 ]
[ 52057-98-4 ]
Reference：
[1] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 15, p. 3057 - 3061
Example 58 3-(4.6-Diamino-[1,3,5]triazin-2-yl)-biphenyl-4,4'-diol One equivalent of 5-bromo-2-methoxy-benznitrile (1 mmol) was reacted with 4-methoxyphenylboronic acid (1.05 mmol), following General Procedure G, to give 4,4'-dimethoxy-3-cyanobiphenol in 90percent yield.
bis(dibenzylideneacetone)-palladium(0); In 1,4-dioxane;
Reference Example 31 tert-Butyl {(3R)-1-[5-(2-chlorobenzyl)-7-(4-methoxyphenyl)-1,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl]piperidin-3-yl}carbamate Bis(dibenzylideneacetone)palladium (18 mg), tri-tert-butylphosphonium tetrafluoroborate (22 mg), potassium phosphate (329 mg) and 4-methoxyphenylboronic acid (236 mg) were added to a solution of tert-butyl {(3R)-1-[7-bromo-5-(2-chlorobenzyl)-1,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl]piperidin-3-yl}carbamate (90 mg) in dioxane (4 ml), and the resulting mixture was stirred with heating at 50°C for 15 hours. The reaction solution was filtered through Celite and washed with tetrahydrofuran and the filtrate was concentrated under reduced pressure. A 10percent aqueous potassium carbonate solution was added to the residue, followed by two runs of extraction with chloroform (50 ml). The organic layer was dried over sodium sulfate and filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel column chromatography (hexane / ethyl acetate = 2/1) to obtain the title compound (10 mg). 1H NMR (300 MHz, CDCl3) delta 7.41-7.37 (m, 1H), 7.26-7.10 (m, 4H), 6.92 (d, J = 8.8 Hz, 1H), 6.52-6.50 (m, 1H), 5.80 (d, J = 16.7 Hz, 1H), 5.66 (d, J = 16.7 Hz, 1H), 3.87 (s, 3H), 3.52-3.50 (m, 1H), 3.37 (s, 3H), 3.07 (s, 3H), 2.80-2.40 (m, 4H), 1.62-1.39 (m, 4H), 1.38 (s, 9H). MS (ESI+) 608 (M++1, 76percent).
With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,2-dimethoxyethane; water; at 90℃; for 2h;Inert atmosphere;
4-Chloro-6-(4-methoxy-phenyl)-pyrimidine-2,5-diamine (Intermediate compound 7)To a solution of commercially available 4,6-dichloro-pyhmidine-2,5-diamine (2.500 g, 13.9657 mmol) in DME (20 ml) and water (10 ml), 4-methoxy phenyl boronic acid (2.122 g, 13.9657 mmol) and sodium carbonate (2.960 g, 27.9314 mmol) were added. The reaction mixture was degassed and kept under nitrogen atmosphere during the entire course of the reaction. Palladium (II) (bistriphenylphosphine)dichloride <n="24"/>(0.490 g, 0.6983 mmol) was added and the resulting reaction mixture, heated at 9O0C for 2 hrs, was worked up by addition of water and extraction with AcOEt. The organic phase, dried over anhydrous MgSO4, afforded upon evaporation a dark solid residue (-3.5 g), which eluted through silica gel with 15% AcOEt in hexane gave 2.501 g 5 (-60% yield) of the pure title compound as a yellow solid.
With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In tetrahydrofuran; water;Inert atmosphere; Reflux;
General Procedure I-AAThe mixture of <strong>[63279-58-3]1-bromo-4-iodonaphthalene</strong> (I-IVb) (6.00 g, 18.01 mmol), 4-methoxyphenylboronic acid (2.74 g, 18.01 mmol), Na2CO3 (3.82 g, 36.02 mmol) and Pd(dppf)Cl2 (658 mg, 0.90 mmol) in 50 mL of THF and 10 mL of H2O was heated to reflux under argon overnight. The mixture was concentrated, the residue was partitioned between H2O and DCM, the aqueous phase was extracted with DCM. The combined organic layer was washed with brine, dried over Na2SO4, and concentrated. The residue was purified by chromatography on silica gel to afford 1-bromo-4-(4-methoxyphenyl)naphthalene (I-IVd) (4.50 g, yield 63percent).
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In water; acetonitrile; at 150℃; for 0.333333h;Inert atmosphere; Microwave irradiation;
4.3.20 3,5-Bis-(4-methoxyphenyl)-1H-pyrazin-2-one 57 A solution of 56 (50.6 mg, 0.242 mmol), sodium carbonate (35.6 mg, 0.336 mmol), 4-methoxyphenylboronic acid (182 mg, 1.20 mmol) and tetrakis(triphenylphosphine)palladium (0) (17 mg, 0.015 mmol) in water (0.7 mL) and acetonitrile (2.7 mL) was heated in a microwave reactor using variable wattage to 150 C for 20 min. The mixture was partitioned between ethyl acetate (50 mL) and water (40 mL). The organic layer was filtered through a plug of silica gel (6 g). The filtrate was concentrated and purified by flash column chromatography on silica, eluting with ethyl acetate to give 57 (73 mg, 47%). Mp >300 C; Rf (EtOAc) 0.16; numax (thin film/cm-1) 3019 (Ar CH), 1653 (C=O), 972 (C-O), 929 (C--O); deltaH (500 MHz; CD3OD) 3.85 (3H, s, OCH3), 3.88 (3H, s, OCH3), 7.01 (2H, d, J 8.0 Hz, ArH), 7.02 (2H, d, J 9.0 Hz, ArH), 7.66 (1H, s, 6-H), 7.86 (2H, d, J 8.0 Hz, ArH), 8.46 (2H, d, J 9.0 Hz, ArH); LC-MS (6 min) m/z 309 (MH+); HPLC tR 4.11 min; purity 99%; HRMS (found: m/z 309.1243; C18H17N2O3 requires 309.1234).
With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 75℃; for 4.0h;Inert atmosphere;
General procedure: A 1,4-Dioxane solution (8 mL) of 10 (1.0 mmol), arylboronic acid 2 (1.0 equiv.), K3PO4, and Pd(PPh3)4 (5 molpercent) was heated at 75 C for 4 h. After cooling to room temperature, H2O was added and the reaction mixture was extracted with CH2Cl2. The organic layer was dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (pure n-heptane).#10;#10;#10;#10;#10;#10;#10;
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 80℃; for 6h;Inert atmosphere;
General procedure: A 1,4-dioxane solution (3 mL) of 1, arylboronic acid (1.2 equiv), aqueous K2CO3 (2.0 M, 1.0 mL) and Pd(PPh3)4 (3 mol percent) was heated at 80 °C for 6 h under argon atmosphere. After cooling to 20 °C, H2O was added and the reaction mixture was extracted with CH2Cl2 (3×25 mL). The organic layers were dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (silica gel, heptane/EtOAc).#10;
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 120℃; for 8h;Inert atmosphere;
General procedure: A 1,4-dioxane solution (3 mL) of 1, arylboronic acid (2.2 equiv), aqueous K2CO3 (2.0 M, 1.0 mL) and Pd(PPh3)4 (6 mol percent) was heated at 120 °C for 8 h under argon atmosphere. After cooling to 20 °C, H2O was added and the reaction mixture was extracted with CH2Cl2 (3×25 mL). The organic layers were dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (silica gel, heptane/EtAOc).#10;
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 120℃; for 1h;Microwave irradiation;
General procedure: <strong>[290368-00-2]ter<strong>[290368-00-2]t-butyl 3-iodo-1H-indazole-1-carboxylate</strong></strong> (S2, 100 mg, 0.29 mmol) was placed in a microwave vial and dissolved in 1,4-dioxane (11.5 mL). 3-Methoxyphenylboronic acid (88 mg, 0.58 mmol, 2.0 equiv) and tetrakis(triphenylphosphine)palladium (20 mg, 0.017 mmol, 0.06 equiv) were added, and the resulting mixture was sparged thoroughly with nitrogen. An aqueous solution of sodium carbonate (2.0 M, 0.65 mL, 1.3 mmol, 4.5 equiv) was then added. The biphasic mixture was microwaved for 1 hour at a reaction temperature of 120 C. After cooling to room temperature, the reaction was diluted with ethyl acetate (2 mL), and then filtered through a celite pad with additional ethyl acetate. The filtrate was concentrated under reduced pressure to give an oil. The crude material was purified by column chromatography over silica gel (hexanes/ethyl acetate: 100/0 to 30/70) to give the title compound as an oil (58.0 mg, 89%).
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; at 60℃; for 2h;Inert atmosphere;
(2-1) In a nitrogen atmosphere, 20.00 g of 4-propylbromobenzene, 0.58 g of tetrakis-triphenylphosphine palladium, and 55 mL of an aqueous potassium carbonate solution (2 mol/L) were dissolved in 100 mL of ethanol, and the resultant solution was heated to 60° C. Then, a solution prepared by suspending 15.27 g of 4-methoxyphenylboronic acid in 60 mL of ethanol was added dropwise to the solution. After stirring at 60° C. for 2 hours, the mixture was allowed to cool to room temperature, and toluene was added to separate the mixture into layers. An aqueous layer was subjected to extraction with toluene, and the toluene extract was combined with an organic layer. The resultant mixture was washed with saturated brine and dried by adding sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography and recrystallized from ethanol to yield 21.60 g of 4-(4-propylphenyl)anisole.
4-[6-(4-Methoxy-phenyl)-pyridin-2-yl]-benzaldehyde[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
81%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; at 70.0℃; for 12h;Inert atmosphere;
General procedure: 4-Formylphenylboronic acid (0.7 g, 4.64 mmol) was treated with 1 (1 g, 4.2 mmol) in THF:water (5:1) solvents mixture, Pd[PPh3]4 (0.24 g, 0.21 mmol), K2CO3 (1.72 g, 12.6 mmol) and stirred at 70 C for 12 h. The completion of the reaction was monitored by TLC. The mixture is extracted with DCM and dried over Na2SO4. The compound was purified by column chromatography (silica gel 60-120 mesh, hexane/EtOAc) (4:1 v/v) as an eluent to afford the compound 7 as a solid [29].
With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate; In 1,2-dimethoxyethane; water; at 80℃;
Step 1: 5-(4-Methoxyphenyl)thiazole[00375] A mixture of (4-methoxyphenyl)boronic acid (7 g, 45.7 mmol), <strong>[3034-55-7]<strong>[3034-55-7]5-bromothiazol</strong>e</strong> (5g, 30.5 mmol), potassium carbonate (8.4 g, 61 mmol), and PdCl2(PPh3)2(2.1 g, 3 mmol) in DME/water (5:1, 60 mL) was heated to 80C overnight. After cooling, ethyl acetate and brine were added to the reaction mixture and the two layers were separated. The organic layer was washed with more brine, dried over sodium sulfate, and filtered. The organic layer was evaporated to dryness. The residue was purified by flash chromatography on silica gel to afford 5.1g of 5-(4-methoxyphenyl)thiazole as a yellow solid. 1H NMR (400 MHz, DMSO-d6): delta 9.00 (s, 1H), 8.18 (s, 1H), 7.60 (d, 2H), 7.00 (d, 2H), 3.79 (s, 3H).
With bis-triphenylphosphine-palladium(II) chloride; caesium carbonate; In 1,4-dioxane; water; at 90℃;Inert atmosphere;
Step 1: preparation of 5-(4-methoxyphenyl)thiazole To a 100mL single-neck flask were added 2.2g p-methoxyphenylboronic acid(0.014mol), 2g <strong>[3034-55-7]<strong>[3034-55-7]5-bromothiazol</strong>e</strong>(0.012mol), 7.8g cesium carbonate(0.024mol) and 0.4g bis(triphenylphosphine)palladium dichloride(0.6mmol), then added 30mL 1,4-dioxane and 8mL water. The mixture was heated to 90C under nitrogen protection, and was reacted overnight. The reaction was stopped after the starting materials were almost reacted completely. The mixture was cooled to room temperature, concentrated, and extracted with water and ethyl acetate. The organic phases were combined, dried, concentrated, and separated by silica gel column chromatography to give a pale yellow solid product. 1HNMR(300MHz,CDCl3)delta:8.74(s,1H,Ar-H), 8.00(s,1H,Ar-H),7.51-7.54(m,2H, Ar-H), 6.95-6.99 (m,2H, Ar-H),3.87(s,3H,OCH3). ESI-MS m/z: [M+H]+ =192.2.
General procedure: A one dram vial equipped with a stir bar was charged with <strong>[54198-88-8]2-(chloromethyl)pyrimidine</strong> (12.mg,0.070 mmol), 4-bromothiophenol (13.06 mg, 0.070 mmol), and cesium carbonate (95.37 mg, 0.290 mmol). The solids were then dissolved in 1,4-Dioxane (0.327 mL) and stirred at 90 °C for 20 min before the vial was removed from the heat. At this time pyridine-3-boronic acid (11.62 mg, 0.090 mmol), water (36 lL), and [1,10-bis(diphenylphosphino)ferrocene]dichloropalladium (II) (5.34 mg, 0.010 mmol) were added to the reaction mixture followed by a thirty second purge with argon. The reaction vessel was allowed to stir at 90 °C for anadditional two hours. After being allowed to cool to room temperature the crude reaction mixture was filtered over a thin celite plug in a phase separator with EtOAc (10 mL) and the resulting organics concentrated before crude product was purified using Gilson reverse phase automated system (30 50 mm column, 5?50percent MeCN in 0.1percent Aq. TFA, 5 min gradient). Fractions containing product by LC/MS were pooled and quenched with sat. sodium bicarbonate before being extracted with DCM (5 mL) and dried to afford 2-[[4-(3-pyridyl)phenyl]sulfanylmethyl]pyrimidine (12d,17.6 mg,0.063 mmol, 87percent) as a yellow solid.
With potassium phosphate; (NC5H3(N2C7H4(CH2)3CH3)2)NiBr(1+)*Br(1-)=Ni(NC5H3(N2C7H4(CH2)3CH3)2)Br2; triphenylphosphine; In 1,4-dioxane; at 80℃; for 24h;Schlenk technique;
General procedure: To a 50mL Schlenk tube containing benzylic ammonium iodide (0.5mmol), arylboronic acid (2.0mmol), K3PO4 (2.25mmol), castalyst (5molpercent) and PPh3 (20molpercent) were added and the tube was purged with N2 for 3 times. Then 1,4-dioxane (2.0mL), subsequently, was introduced to the tube. The resulted mixture was allowed to stir for 24h at 80°C under atmosphere of N2. After the completion of the reaction, the resulting mixture was filtered through a Celite pad and concentrated under the vacuum and directly purified by flash chromatography to give the desired product.
82%
With potassium phosphate; palladium diacetate; XPhos; In tetrahydrofuran; at 50℃; for 14h;Sealed tube; Inert atmosphere;
General procedure: The desired amount of substrate, boronic acid (3 equiv), base (3equiv), Pd(OAc)2 (2.5 molpercent) and ligand (5 molpercent) were weighed out as solids, the vial was sealed and purged with argon, then solvent was added and the vial was purged again. The reactions were run for 14 h at the specified temperature. The crude material was filtered through a pad of Celite and washed three times with CHCl3. The solvent was removed under reduced pressure, an internal standard was added and the reaction was analysed by 1H NMR spectroscopy. For purification, the analysed mixture was concentrated, the product extracted with Et2O and filtered through anhydrous MgSO4 and further purified by flash column chromatography.
4-(4-methoxyphenyl)-1-methyl-2-(5-methylthiophen-2-yl)-5-nitro-1H-imidazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
61%
General procedure: A solution of 2,4-dibromo-1-methyl-5-nitro-1H-imidazole (2, 0.1 g, 0.35 mmol),4-methoxy-phenylboronic acid (72 mg, 0.46 mmol, 1.3 equiv.), Pd(OAc)2 (3 mg, 0.014 mmol,0.04 equiv.), Na2CO3 (0.11 g, 1.05 mmol, 3 equiv.), in a DME/EtOH/H2O mixture (3/1/1, 5 mL)was heated at 60 °C under microwave irradiation for 2 h. After cooling, boronic acid (0.45 mmol,1.3 equiv.), PPh3 (9 mg, 0.035 mmol, 0.1 equiv.), Na2CO3 (0.11 g, 1.05 mmol, 3 equiv.), were introduced under argon. The mixture was heated at 110 °C for 1 h under microwave irradiation. After cooling, 60 mL of water were added and the solution was extracted with dichloromethane (3 x 50 mL). The organic layer was washed with water (3 x 100 mL), dried over Na2SO4 and evaporated. The crude product was purified by column chromatography [silica gel, petroleum ether/ethyl acetate (9/1), (7/3for 6e), (5/5 for 6j)] and recrystallized from propan-2-ol.
4-methoxy-N-(4-methoxyphenyl)-3-(trifluoromethyl)aniline[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
44%
With triethylphosphine; In m-xylene; at 120℃; for 16h;Inert atmosphere; Schlenk technique; Sealed tube;
General procedure: A glass culture tube containing a magnetic stir bar was charged with a nitroarene substrate and boronic acid, then fitted with a PTFE-lined silicone septum within a phenolic screw-thread open-top cap after wrapping the reaction tube thread once with Teflon tape. The vessel was evacuated and backfilled with nitrogen on a Schlenk line. Dry m-xylene (2 mL, 0.5 M) was added via syringe, followed by triethylphosphine (0.44 mL, 3 equivalents) and the reaction mixturewas heated 120 C with stirring. Upon completion, the reaction mixture was cooled to ambient temperature then diluted with 10 mL of distilled water. With the aid of ethyl acetate (ca. 3 x 10 mL), the reaction mixture was transferred to a separatory funnel. After mixing and separating the phases, the organic layer was washed with 10 mL of a 1M NaOH aqueous solution, and 10 mL of brine. Each aqueous phase was back-extracted with one 10 mL portion of ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated by rotary evaporation. The crude residues were purified via column chromatography to yield pure coupling products. Columns were primarily slurry packed with hexanes and mobile phase polarity was increased gradually to the mixture indicated. Note: hexanes = Hex, dichloromethane = DCM, ethyl acetate = EA.
With tetrakis(triphenylphosphine) palladium(0); tetrabutylammomium bromide; potassium carbonate; In toluene; at 80℃; for 16h;Inert atmosphere;
Step 2, under nitrogen protection, in a 100 mL three-necked flask was added 0.60 g of compound A, 0.72 g of 4-methoxybenzeneboronic acid, 0.60g TauBetaAlphaBeta,3.6 mL of a 2 mol aqueous solution of potassium carbonate, 0.60 g of tetrakistriphenylphosphine palladium and 25 mL of toluene, stirred at 80 ° C for 16 h, extracted with CH2CI2 (40 mL X 3 ) Rotary steaming, column chromatography:PE: EA = 50:1 gave compound B.
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