* 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] Angewandte Chemie - International Edition, 2014, vol. 53, # 39, p. 10510 - 10514[2] Angew. Chem., 2014, vol. 126, # 39, p. 10678 - 10682,5
5
[ 16419-60-6 ]
[ 95-52-3 ]
Reference:
[1] Journal of the American Chemical Society, 2013, vol. 135, # 7, p. 2552 - 2559
6
[ 16419-60-6 ]
[ 62-53-3 ]
[ 1205-39-6 ]
Yield
Reaction Conditions
Operation in experiment
95%
With potassium carbonate In water at 20℃;
General procedure: In a typical example, phenylboronic acid 1 (1.22 g, 1 mmol) was charged in the flask containing K2CO3 (2 equiv) in water as solvent (2 mL). To this was added aniline 2 (0.93 g, 1 mmol) and Cu–Mn catalyst, and the reaction mixture was allowed to stir at room temperature. The completion of the reaction was monitored by TLC. After completion, the base was neutralized using 2 N HCl and the catalyst was filtered off, thorough washings of water were given, extracted with ethyl acetate, and the organic layer was separated and dried under reduced vacuum. The crude product obtained was purified on silica gel column chromatography (solvents, ratio?), to obtain white crystalline product diphenylamine 3a (1.60 g) with 95percent yield. All reactions were similarly carried out.
88%
With potassium carbonate In water at 20℃; for 5 h;
General procedure: To a stirred solution of phenylboronic acid (1.0 mmol), aniline (1.0 mmol), and K2CO3 (2.0 mmol) in deionized H2O (10 mL) at room temperature was added an aqueous suspension of FePd nanowires (3.0 mol percent in 3 mL of H2O). The mixture was stirred at room temperature for 5h. After completion of the reaction (as monitored by TLC), 2 M HCl was added and the catalyst was separated by applying an external magnet. The catalyst was washed with EtOAc. The mixture was extracted with EtOAc (2 * 20 mL), dried, and concentrated. The residue was subjected to gel permeation chromatography to afford pure product.
Reference:
[1] Tetrahedron Letters, 2013, vol. 54, # 39, p. 5351 - 5354
[2] RSC Advances, 2014, vol. 4, # 90, p. 49273 - 49279
[3] Bulletin of the Korean Chemical Society, 2012, vol. 33, # 5, p. 1785 - 1787
[4] Journal of Organic Chemistry, 2006, vol. 71, # 25, p. 9522 - 9524
[5] Tetrahedron Letters, 2014, vol. 55, # 17, p. 2813 - 2817
[6] RSC Advances, 2014, vol. 4, # 43, p. 22775 - 22778
[7] Organic Letters, 2012, vol. 14, # 17, p. 4326 - 4329
[8] Organic letters, 2001, vol. 3, # 13, p. 2077 - 2079
7
[ 16419-60-6 ]
[ 149105-19-1 ]
Reference:
[1] Synthesis, 2002, # 8, p. 1043 - 1046
[2] Tetrahedron, 1963, vol. 19, p. 821 - 826
[3] J. Prakt. Chem. (2), 1930, vol. 128, p. 153 - 170
[4] Liebigs Annalen der Chemie, 1901, vol. 315, p. 26 - 40
[5] Arkiv foer Kemi, 1957, vol. 10, p. 473 - 482
[6] Arkiv foer Kemi, 1957, vol. 10, p. 513 - 521
[7] Journal of the American Chemical Society, 1934, vol. 56, p. 1865 - 1870
[8] , Gmelin Handbook: B: B-Verb.13, 4.7.2.5, page 209 - 219,
8
[ 16419-60-6 ]
[ 91983-14-1 ]
Yield
Reaction Conditions
Operation in experiment
84.6%
With bromine In tetrachloromethane for 2 h; Irradiation
Was added to the flask, 500mL of o-tolyl boronic acid 14.8g (0.11 mol), was added 380mL of carbon tetrachloride was heated slightly to dissolve, 85mL of carbon tetrachloride was added a solution of 17.9g of bromine under light irradiation, a portion was added rapidly at the start of a few minutes leg color solution, maintaining the solution yellowish 71/92; after the addition the reaction under light irradiation 2h, the basic solution bleaching, filtration, carbon tetrachloride, washed five times, washed three times with n-hexane, and dried in vacuo to afford a white powdery solid 19.97 g, yield: 84.6percent.
Reference:
[1] Patent: CN103497211, 2016, B, . Location in patent: Paragraph 0242; 0243
[2] Tetrahedron Letters, 2001, vol. 42, # 34, p. 5875 - 5877
[3] Russian Chemical Bulletin, 2005, vol. 54, # 11, p. 2602 - 2611
[4] Russian Chemical Bulletin, 2004, vol. 53, # 2, p. 370 - 375
[5] Chinese Journal of Chemistry, 2011, vol. 29, # 11, p. 2445 - 2450
[6] Journal of the American Chemical Society, 1958, vol. 80, p. 3611,3615
[7] Journal of the American Chemical Society, 1958, vol. 80, p. 835,836
[8] Arkiv foer Kemi, 1957, vol. 10, p. 507,509
[9] Journal of Fluorescence, 2012, vol. 22, # 6, p. 1609 - 1615
9
[ 128-08-5 ]
[ 16419-60-6 ]
[ 91983-14-1 ]
Reference:
[1] Russian Chemical Bulletin, 2005, vol. 54, # 11, p. 2602 - 2611
[2] Russian Chemical Bulletin, 2004, vol. 53, # 2, p. 370 - 375
10
[ 16419-60-6 ]
[ 40138-16-7 ]
Reference:
[1] Arkiv foer Kemi, 1957, vol. 10, p. 507,509
11
[ 16419-60-6 ]
[ 84392-17-6 ]
Reference:
[1] Synthesis, 2002, # 8, p. 1043 - 1046
12
[ 533-58-4 ]
[ 16419-60-6 ]
[ 77897-02-0 ]
Reference:
[1] Chemistry - A European Journal, 2014, vol. 20, # 44, p. 14329 - 14335
[2] Organic Letters, 2011, vol. 13, # 20, p. 5504 - 5507
[3] Organic Letters, 2013, vol. 15, # 15, p. 3962 - 3965
13
[ 95-56-7 ]
[ 16419-60-6 ]
[ 77897-02-0 ]
Reference:
[1] Chemical Communications, 2016, vol. 52, # 69, p. 10529 - 10532
[2] Angewandte Chemie - International Edition, 2013, vol. 52, # 40, p. 10598 - 10601[3] Angew. Chem., 2013, vol. 125, # 40, p. 10792 - 10795,4
14
[ 16419-60-6 ]
[ 251320-86-2 ]
Reference:
[1] Journal of the American Chemical Society, 1999, vol. 121, # 41, p. 9550 - 9561
[2] European Journal of Organic Chemistry, 2012, # 11, p. 2127 - 2131
15
[ 16419-60-6 ]
[ 255837-19-5 ]
Reference:
[1] Chemical Communications, 2014, vol. 50, # 36, p. 4686 - 4689
16
[ 76-09-5 ]
[ 16419-60-6 ]
[ 377780-72-8 ]
Yield
Reaction Conditions
Operation in experiment
80%
Stage #1: for 2 h; Dean-Stark; Reflux; Inert atmosphere Stage #2: With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) In acetonitrile at 90℃; for 2 h; Inert atmosphere
To a three-necked flask equipped with a Dean-Stark trap was added 30 mL of toluene,Then 2-methylbenzeneboronic acid (0.21 g, 1.55 mmol) was added,Pinacol-H2O (0.22 g, 1.86 mmol),The resulting mixture was heated to reflux for two hours.After the reaction,The mixture was washed with water (30 mL x 3)Unreacted pinacol and phenylboronic acid were removed,The separated organic phase was then evaporated under reduced pressure to remove the toluene solvent.The resulting crude product was dissolved with dichloromethane (50 mL)After washing again (30 mL)To the resulting organic phase, anhydrous sodium sulfate was added for drying,The dried solution was evaporated under reduced pressure to give 0.32 g of crude product.The resulting crude product (0.32 g, 1.47 mmol)NBS (N-bromosuccinimide, 0.39 g, 2.2 mmol),AIBN (azobisisobutyronitrile, 0.003 g, 0.018 mmol) dissolved in acetonitrile (10 mL).The resulting reaction solution was refluxed at 90 ° C for two hours.After cooling at room temperature,The solvent was distilled off under reduced pressure,Crude product.The resulting crude product was purified by silica gel column chromatography,With petroleum ether (60 ~ 90 ) / ethyl acetate (v / v) = 1: 1 as eluent,The product was obtained as a white solid (0.53 g, 80percent yield).
Reference:
[1] Patent: CN107383078, 2017, A, . Location in patent: Paragraph 0058; 0063; 0064; 0065; 0066; 0067; 0068
17
[ 16419-60-6 ]
[ 377780-72-8 ]
Reference:
[1] Chemistry - A European Journal, 2013, vol. 19, # 27, p. 9050 - 9058
[2] Chemical Communications, 2017, vol. 53, # 14, p. 2218 - 2221
18
[ 16419-60-6 ]
[ 62336-24-7 ]
[ 402822-72-4 ]
Reference:
[1] Tetrahedron Letters, 2007, vol. 48, # 11, p. 2025 - 2027
[2] Journal of Organometallic Chemistry, 2008, vol. 693, # 19, p. 3135 - 3140
[3] Journal of Organometalic Chemistry, 2002, vol. 645, # 1-2, p. 14 - 26
[4] Tetrahedron Letters, 2009, vol. 50, # 39, p. 5470 - 5473
[5] Angewandte Chemie - International Edition, 2013, vol. 52, # 45, p. 11892 - 11895[6] Angew. Chem., 2013,
19
[ 16419-60-6 ]
[ 402822-72-4 ]
Reference:
[1] Tetrahedron Letters, 2001, vol. 42, # 51, p. 9085 - 9088
[2] Chemical Communications, 2014, vol. 50, # 17, p. 2193 - 2195
[3] Chemical Communications, 2014, vol. 50, # 36, p. 4686 - 4689
With sodium carbonate;palladium diacetate; triphenylphosphine; In propan-1-ol; for 3h;Heating / reflux;
Preparation 52: 2,4-Dimethoxy-5-o-tolyl-pyrimidine (Prep52); 5-lodo-2,4-dimethoxy-pyrimidine (1 g, 3.75 mmol) was dissolved in degassed n-PrOH (25 ml.) and then 2- methylphenyl boronic acid (766 mg, 3.8 mmol), Na2CO3 (865 mg, 8.16 mmol), PPh3 (215 mg, 0.8 mmol) and Pd(OAc)2 (50 mg, 5.67 mmol) were added. The suspension was stirred at reflux for 3 hours. The solvent was evaporated and the crude was partitioned between water and DCM. The organic phase was dried (Na2SO4) and evaporated. The crude was purified by flash chromatography with ethyl acetate-petroleum ether (1-9) to give 400 mg of the title compound (46% yield). MS (ES) m/z 231.2 [M+H]+.
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; toluene; for 3.5h;Heating / reflux;
A mixture of ethyl 6-bromobenzoisoxazole-3-carboxylate (550 mg, 1.39 mmol), o- tolylboronic acid (377 mg, 1.5 [EQ),] Pd (PPh3) 4 (171 mg, 0.08 [EQ),] toluene (10 mL), ethanol (1.5 mL), and 1 M [NA2C03] (1.5 [ML)] is stirred at reflux for 3.5 h. The reaction mixture is diluted with [CHUCK] (0.1 L) and [H2O] (0.1 mL). The [CHZC12] solution is dried [(NA2S04),] filtered, and evaporated. The residue is purified by silica chromatography (heptane/EtOAc) to give Preparation [PA.'H] NMR (300 MHz, CDC) 8 8.14 (1H), 7.61 (2H), 7.42 (1H), 7.35-7. 2 (1H), 4.59 (2H), 2.28 (3H), 1.51 (3H).
With potassium fluoride;palladium diacetate; In tetrahydrofuran;
A. 2-Methyl-2-(4-{2-[5-methyl-2-(2'-methyl-biphenyl-4-yl)-oxazol-4-yl]-ethoxy}-phenoxy)propionic acid ethyl ester A solution of 2-(4-{2-[2-(4-bromophenyl)-5-methyloxazol-4-yl]ethoxy}phenoxy)-2-methylpropionic acid ethyl ester (300 mg, 0.614 mmol) (see Ex. 2, part B), 2-methylphenylboronic acid (0.921 mmol), potassium fluoride (88.6 mg, 1.84 mmol), palladium acetate (1.3 mg, 0.14 mumol), and 2-(dicyclohexylphosphino)biphenyl (4.3 mg, 12.3 mumol) were combined under N2, to which anhydrous THF (1.23 mL) was added. The yellow mixture was heated at reflux for 12 h. After cooling to room temperature, the mixture was partitioned between Et2O (20 mL) and 1M NaOH (10 mL). The layers were separated, and the aqueous phase was back-extracted with Et2O (10 mL). Combined organic phases were dried over Na2SO4, and concentrated. The product was purified by silica gel chromatography (25 g SiO2, 1:4 ethyl acetate:hexanes) to yield the desired product as an oil. Rf=0.44 in 1:4 ethyl acetate:hexanes; 1H NMR (400 MHz, CDCl3) delta7.99 (d, J 8.6 Hz, 2H), 7.36 (d, J 8.6 Hz, 2H), 7.26-7.21 (m, 4H), 6.81-6.74 (m, 4H), 4.20 (t, J=6.6 Hz, 2H), 4.19 (q, J=7.2 Hz, 2H), 2.94 (t, J=6.6 Hz, 2H), 2.35 (s, 3H), 2.26 (s, 3H), 1.50 (s, 6H), 1.25 (t, J=7.2 Hz, 3H); MS (EI) 500.2 (M+H)-.
With sodium carbonate; In 1,2-dimethoxyethane; hexane; ethyl acetate;
Preparation 51 To a suspension of <strong>[89488-29-9]2-bromo-4-methoxypyridine</strong> (1.88 g), 2-methylphenylboronic acid (1.77 g) and tetrakis(triphenylphosphine)-palladium (578 mg) in 1,2-dimethoxyethane (30 ml) was added 2M aqueous solution of sodium carbonate (13 ml). The mixture was stirred at 80 C. for 7 hours under a nitrogen atmosphere, then cooled to room temperature and diluted with ethyl acetate. The organic layer was separated, washed with water and brine and dried over sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by column chromatography (silica gel 50 g, 25% ethyl acetate in n-hexane) to give 2-(4-methoxypyridin-2-yl)toluene (1.98 g). 1H-NMR (CDCl3): delta2.36(3H,s), 3.91(3H,s), 6.79(1H,dd,J=5.8 Hz,2.5 Hz), 6.91(1H,d,J=1.3 Hz), 7.2-7.5(4H,m), 8.50(1H,d,J=5.8 Hz)
[1,1'-Bis(diphenylphosphino)ferrocene]dichloro-pallidium[ No CAS ]
[ 16419-60-6 ]
[ 317826-93-0 ]
Yield
Reaction Conditions
Operation in experiment
Step C: 2-[1-(3-Nitrophenyl)ethylamino]-4-[benzimidazol-1-yl]-6-(2-methylphenyl)pyrimidine The title compound was prepared from 2-[1-(3-nitrophenyl)ethylamino]-4-[benzimidazol-1-yl]-6-chloropyrimidine and 2-methylphenylboronic acid according to the precedure described in EXAMPLE 306, Step C and using [1,1'-bis(diphenylphosphino)-ferrocene]dichloropalladium(II) as catalyst. Mass spectrum (CH3CN/TFA/NH4O2CH/ESI) 451.3 (M+1).
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; for 5h;Heating / reflux;
A mixture of <strong>[458-50-4]<strong>[458-50-4]4-bromo-3-fluoroanisol</strong>e</strong>, 2-methylphenyl boronic acid, tetrakis(triphenylphosphine) palladium (5percent mol) and sodium carbonate (0.23 g, 2.1 ramol) in 20 ml of water/EtOH/toluene (1 :2:4) was heated to reflux for 5 h. TLC (EtOAc:hexane /2:98) showed that the reaction was over. The solvents was removed. Water (10 ml) was added. The organic was extracted with methylene chloride (3x 50 ml). The combined methylene chloride layers were washed with brine, and dried over sodium sulfate. The title compound was obtained after purification with preparative TLC using 2percent EtOAc in hexane as the eluant.
With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,2-dimethoxyethane; water; at 80℃; for 16h;
EXAMPLE 5OB ethyl 3-ortho-tolyl-lH-indole-2-carboxylateA mixture of EXAMPLE 31B (1.08 g), ortho-tolylboronic acid (1.1 g), (1,1'- bis(diphenylphosphino)ferrocene)dichloropalladium(II) (140 mg) in dimethoxyethane:2N aqueous Na2CO3 (25 mL:5 mL) was stirred under nitrogen at 8O C for 16 hours, diluted with ethyl acetate and was washed with water and brine. The organic phase was dried (MgSO4), filtered, and concentrated. The concentrate was purified by flash chromatography on silica gel with 0-10% ethyl acetate/hexanes.
tris-(dibenzylideneacetone)dipalladium(0); In water; ethyl acetate; toluene;
Step 1. A mixture of 8.1 g (51.5 mmol) of 2-bromopyridine, 7 g (51.5 mmol) o-tolylboronic acid, 0.47 g (0.51 mmol) of Pd2(dba)3, 0.84 g (2.06 mmol) of 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl and 32 g (154.5 mmol) of potassium phosphate tribasic, 100 mL of toluene and 30 mL of water was purged with nitrogen. The solution was heated to reflux for 12 hours. Upon cooling, the organic layer was separated, and dried with MgSO4. The product was separated by column chromatography using hexanes/ethyl acetate (5% ethyl acetate) as the eluent. The solvent was removed by rotary evaporation, and the product was dried under vacuum resulting in 6 g (35.5 mmol) of 2-(o-tolyl)pyridine.
With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; toluene; for 4h;
60 g (160 mmol) of diethyl dibromoterephthalate, 43 g (320 mmol) of o-tolylboronic acid, 365 mg (0.32 mmol) of Pd(PPh3)4 and 92 g (660 mmol) of K2CO3 are heated at the boil for 4 h in 300 ml of toluene and 300 ml of water. The mixture is subsequently partitioned between toluene and water, and the organic phase is washed three times with water and dried over Na2SO4. The residue remaining is recrystallised twice from heptane to give colourless crystals. The yield is 51 g (127 mmol, 81%).
With potassium carbonate; In water; at 20℃; for 5h;
General procedure: To a stirred solution of phenylboronic acid (1.0 mmol), aniline (1.0 mmol), and K2CO3 (2.0 mmol) in deionized H2O (10 mL) at room temperature was added an aqueous suspension of FePd nanowires (3.0 mol % in 3 mL of H2O). The mixture was stirred at room temperature for 5h. After completion of the reaction (as monitored by TLC), 2 M HCl was added and the catalyst was separated by applying an external magnet. The catalyst was washed with EtOAc. The mixture was extracted with EtOAc (2 * 20 mL), dried, and concentrated. The residue was subjected to gel permeation chromatography to afford pure product.
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).
General procedure: Pyridine substrates 7 and 8 were prepared according to literatureprocedures. Substrates 1-6 and 9 were synthesized via Suzuki coupling of 2-bromo-3-methylpyridine with the correspondingarylboronic acids. Pyridine substrates 11e13 were alsoprepared Suzuki couplings of 2-bromopyridine derivatives with otolylphenylboronicacid. Substrate 10 was prepared by Suzuki coupling of 2-methoxyphenylboronic acid with 2-chloropyridine.Potassium 2,6-dimethylphenyltrifluoroborate and potassium 3-acetylphenyltrifluoroborate were synthesized from the correspondingboronic acids and KHF2.
With oxygen; sodium hydroxide; copper dichloride; In methanol; for 13h;Reflux;
General procedure: A mixture of 1.6 mmol of C-nitro-NH-azole (1a-e), 2.6 mmol of arylboronic acid (2a-n), 1.6 mmol of sodium hydroxide, 0.2 mmol of CuCl2 and methanol (15 mL) was refluxed while air was bubbled through the reaction mixture. After completion of the reaction, determined on the basis of TLC analysis, the solvent was removed under reduced pressure using a rotary evaporator. The obtained crude product was purified by silica gel column chromatography with 5:95 v/v MeOH/CHCl3 as an eluent to give corresponding N-aryl-C-nitroazole. The product was crystallized from methanol/water.
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 1,2-dimethoxyethane; water; for 2.0h;Reflux; Inert atmosphere;
A suspension of <strong>[959236-97-6]4-bromo-2-(methylthio)pyrimidine</strong> (9 A, 1.18g, 7.35 mmol) , potassium carbonate (37ml, 0.4 M in water), o-tolylboronic acid (1 g, 7.35 mmol) andtetrakis(triphenylphosphine)palladium(0) (425 mg, 0.37 mmol) in DME (40 ml) was degassed for 20 minutes. It was then heated at reflux for 2 hours. The reaction mixture was cooled and filtered through celite. The filtrate was extracted with EtOAc (2 x 30 ml). The organic layer was dried with Na2S04, filtered and concentrated. The crude product was purified by flash column (Rf: 0.3 10%EtOAc/Hexanes). The yield was 98%. MS (m/z) 217 [M+H]+
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,2-dimethoxyethane; water; for 2h;Reflux; Inert atmosphere;
To a suspension of <strong>[55758-02-6]3-bromopicolinonitrile</strong> (l .Og, 5.46 mmol), potassium carbonate (27ml, 0.4M in water), o-tolylboronic acid (1A, 0.74g, 5.46 mmol) and tetrakis(triphenylphosphine) palladium (310 mg, 0.27 mmol) in DME (40 ml) , was degassed for 20 minutes. The mixture was then heated at reflux. After 2 hours the reaction was filtered through celite and the filtrate was extracted with EtOAc (30 ml) twice. The organic layer was dried over Na2S04, filtered and concentrated. The crude product was purified by flash column (Rf: 0.3 EtOAc/Hexanes = 20%). The yield was 94%. MS (m/z) 195 [M+H]+
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In toluene; at 90℃; for 1h;Inert atmosphere;
A flask was charged with <strong>[460081-18-9]ethyl 2-chlorooxazole-4-carboxylate</strong> (500 mg, 2.85 mmol), 2-methylbenzeneboronic acid (387 mg, 2.85 mmol), Pd(PPh3)4 (132 mg, 0.114 mmol), K2CO3 (787 mg, 5.7 mmol), and toluene (29 mL).The reaction mixture was degassed under a stream of N2, and was then heated to 90 C. for 1 h. The reaction was thendiluted with EtOAc and washed with 1M aqueous NaOH. The organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified on via flash chromatography on silica gel (hexanes:EtOAc) to give a 2:1 mixture of product to <strong>[460081-18-9]ethyl 2-chlorooxazole-4-carboxylate</strong> (360 mg) that was carried on without further purification.
With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); In water; toluene; for 16h;Inert atmosphere; Reflux;
2-methylphenyl boronic acid (5.1 g, 37.59 mmol), <strong>[27012-25-5]2-phenyl-5-bromopyridine</strong> (8.0 g, 34.17 mmol), 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl (561 mg, 1.366 mmol), and potassium phosphate tribasic (23.50 g, 102.51 mmol), 250 mL of toluene and 25 mL of water were placed in a 1 L round-bottom flask. Nitrogen was bubbled directly into the mixture for 30 min after which tris(dibenzylideneacetone)dipalladium(0) (312 mg, 0.341 mmol) was added. Nitrogen was then bubbled for another 15 minutes and the reaction mixture was heated to reflux for 16 h under nitrogen. The mixture was cooled and the organic layer was separated from the aqueous layer. The organic layer was washed with saturated brine solution, dried over magnesium sulfate, filtered, and the solvent removed under vacuum to give an off-white solid as the crude. The crude was purified by column chromatography using silica gel as the stationary phase and 2% ethyl acetate in hexanes as the mobile phase. 6.5 g of desired product was obtained after purification (78% yield).
4 g
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; toluene; at 120℃; for 2h;Inert atmosphere;
Compound 2-1 4 g (17 mmol), o-tolylboronic acid 2.8 g (20 mmol), and Pd(PPh3)4 1 g (0.9 mmol) were dissolved in toluene 80 mL, ethanol 40 mL, and 2M Na2CO3 40 mL in the presence of nitrogen, and then stirred under reflux at 120. Upon completion of the reaction after 2 hours, the resultant material was washed with distilled water, and extracted with ethyl acetate. The organic layer was dried over MgSO4 and the solvent was removed by a rotary evaporator, followed by purification using column chromatography, thereby obtaining Compound 2-2 (4 g, 15 mmol).
With bis(tri-tert-butylphosphine)palladium(0); sodium hydroxide; In 1,4-dioxane; at 85℃; for 15h;Inert atmosphere;
Intermediate 1 (1 .0 g, 4.3 mmol) is suspended in 10 mL of dioxane and 2.5 ml. of 5N NaOH solution. The mixture is purged with argon. Then 2-methylphenylboronic acid (1.09 g, 7.86 mmol) and Pd[P(fBu)3]2 (75 mg, 0,14 mmol) are added under argon atmosphere. The reaction mixture is heated to 85C and stirred for 15 h. After cooling to room temperature the reaction mixture is filtered over celite and washed with dichloromethane. The combined organic layers are washed with water, dried over anhydrous sodium sulphate and concentrated under vacuum. The residue is purified via column chromatography (silica, eluent: n-hexane/ THF) and the de- sired product is obtained in 93% yield (1 .2 g). 1H-NMR (400 MHz, CD2CI2): delta = 2.24 (s, 3H), 6.76 (d, 1 H), 7.13 (s, 1 H), 7.15 (d, 1 H), 7.18 - 7.26 (m, 4H), 7.31 (d, 2H), 7.40 (t, 2H), 8.22 (d, 1 H), 9.54 (s, 1 H).
4-bromo-1-(2-methylphenyl)-2-nitrobenzene[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
88.9%
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; toluene; at 40 - 50℃; for 2h;Inert atmosphere;
Under nitrogen atmosphere, 500mL three-necked round flask was added 32.8g (0.1mol) 4- bromo-1-iodo-2-nitrobenzene, 16.3g (0.12mol) 2- methyl-phenylboronic acid, 2.31g (2mol%) Pd (PPh 3) 4, and a mixture of100mL of toluene and 100mL of ethanol was added 35mL concentration 2molL sodium carbonatesolution, an oil-bath at 40-50 C the reaction was stirred for 2h, cooled, separated and the organic phase, afterthe organic phase washed with water 2-3 times and dried over anhydrous MgSO 4, the organic solvent wasremoved by rotary evaporation to give the crude product. Recrystallization from absolute ethanol to give theintermediate 4-bromo-1-(2-methylphenyl)-2-nitrobenzene25.9g. Yield 88.9%.
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In tetrahydrofuran; water; at 130℃; for 0.5h;Microwave irradiation;
Step 1 (0582) Compound iii-54 (800mg, 3.11mmol), PdCl2 (dppf)CH2Cl2 (254mg, 0.331mmol) and 2 mol/L sodium carbonate aqueous solution (6.22mL, 12.5mmol) were added into THF (16mL) solution of o-tolylboronic acid (465mg, 3.42mmol), and the mixture was stirred for 30 minutes with heating to 130C by microwave device. After brine was added into the reaction mixture, the mixture was extracted with chloroform. After the organic layer was dried with magnesium sulfate anhydrous, the solvent was removed in vacuo. The obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to give Compound iii-55 (674mg, 81%). Measurement condition A, HPLC: RT=2.92min
To a three-necked flask equipped with a Dean-Stark trap was added 30 mL of toluene,Then 2-methylbenzeneboronic acid (0.21 g, 1.55 mmol) was added,Pinacol-H2O (0.22 g, 1.86 mmol),The resulting mixture was heated to reflux for two hours.After the reaction,The mixture was washed with water (30 mL x 3)Unreacted pinacol and phenylboronic acid were removed,The separated organic phase was then evaporated under reduced pressure to remove the toluene solvent.The resulting crude product was dissolved with dichloromethane (50 mL)After washing again (30 mL)To the resulting organic phase, anhydrous sodium sulfate was added for drying,The dried solution was evaporated under reduced pressure to give 0.32 g of crude product.The resulting crude product (0.32 g, 1.47 mmol)NBS (N-bromosuccinimide, 0.39 g, 2.2 mmol),AIBN (azobisisobutyronitrile, 0.003 g, 0.018 mmol) dissolved in acetonitrile (10 mL).The resulting reaction solution was refluxed at 90 C for two hours.After cooling at room temperature,The solvent was distilled off under reduced pressure,Crude product.The resulting crude product was purified by silica gel column chromatography,With petroleum ether (60 ~ 90 ) / ethyl acetate (v / v) = 1: 1 as eluent,The product was obtained as a white solid (0.53 g, 80% yield).
With palladium diacetate; potassium carbonate; triphenylphosphine; In methanol; acetonitrile; at 60℃; for 24h;Inert atmosphere;
To a flask charged with <strong>[39919-65-8]3,6-dibromo-2-methylpyridine</strong> (2.50 g, 9.96 mmol), 2-methyl phenyl boronic acid (1.59 g, 11.7 mmol), palladium acetate (112 mg, 0.498 mmol), triphenylphosphine (261 mg, 0.996 mmol), and potassium carbonate (2.75 g, 19.9 mmol) under a N2 atmosphere was added acetonitrile (75 5 mL) and methanol (38 mL) at room temperature. The flask was attached to a refluxcondenser and heated to 60 °C. After 24 h, the crude reaction mixture was cooled to rt, and the volatiles were removed under reduced pressure. The resulting residue was dissolved in dichloromethane, and the organic layer was washed with water and brine. The washed organic layer was dried over Na2S04, filtered and concentrated. The resulting residue was10 purified via silica gel chromatography, eluted with hexane: CH2CI2 = 5:1, to afford the product as a white solid in 52percent yield.
With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; tris-(dibenzylideneacetone)dipalladium(0); potassium carbonate; In ethanol; water; toluene; at 90℃; for 10h;Inert atmosphere;
Under nitrogen atmosphere, <strong>[131001-86-0]methyl 2-bromo-3-methylbenzoate</strong> acid (6.87 g, 30.0 mmol, 1.0 equiv), o-tolylboronic acid (6.12 g, 45.0 mmol, 1.5 equiv), Pd2(dba)3 (0.229 g, 0.25 mmol, 0.83 mol%), S-Phos (0.410 g, 1.0 mmol, 3.3 mol%), K2CO3 (12.44 g, 90.0 mmol, 3.0 equiv) in a mixture of toluene (45.0 mL), EtOH (15.0 mL) and H2O (15.0 mL), was heated at 90C for 10 h. After being cooled to room temperature, the solution was diluted with water (50 mL) and extracted with EtOAc (30 mL × 3). The combined organic layer was washed with brine (20 mL × 3) and dried over anhydrous Na2SO4. After filtration the solvent was removed by evaporation to give crude product S1, which was used without further purification.
2-chloro-2'-methyl-[1,1'-biphenyl]-4-carbonitrile[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
95%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In water; at 100℃; for 2h;Inert atmosphere; Microwave irradiation;
<strong>[57418-97-0]3-chloro-4-bromobenzonitrile</strong> (300 mg, 1.39 mmol, 1.0 equiv), o-tolylboronic acid(189 mg, 1.39 mmol, 1.0 equiv), Pd(PPh3)4 (80 mg, 0.07 mmol, 0.05 equiv) and K2CO3 (383 mg, 2.77 mmol, 2.0 equiv) were weighed into a microwave tube and solvated with DME (3.0 mL) and H2O (1.0 mL). The reaction mixture was degassed by bubbling nitrogen through the solution for 5 minutes and then heated to 100 C under microwave irradiation for 2 hours. The reaction was allowed to cool to room temperature, filtered through celite washing with Et2O and the solvent removed under reduced pressure. The residue was dissolved in CH2Cl2/H2O and extracted three times with CH2Cl2. The combined organic extracts were washed with a saturated aqueous solution of NaCl, dried over MgSO4, filtered and concentrated in vacuo. The crude product was purified by flash column chromatography (silica gel, 1:9 EtOAc:pet ether) to provide the title compound as a clear oil (300 mg, 1.32 mmol, 95%):
With tert.-butylhydroperoxide; potassium iodide; In methanol; at 20℃;
Weighing 0.5 mmol 2 - methyl phenyl boronic acid, 0.6 mmol potassium iodide reagent to put into 3 ml methanol solution mixing, slowly adding 2 mmol tert-butyl hydroperoxide (TBHP), stirring at the room temperature reaction 10 - 14 hr, to the reaction solution.The resulting reaction solution by adding ethyl acetate dissolved, the use of sodium thiosulfate washing, to collect organic phase dried, concentrated, then ethyl acetate/petroleum ether=1/30 to (v/v) as developing agent, to the concentrate to column chromatography separation, shall be 77.9 mg the target product.This embodiment of the target product yield is 71%.
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In water; toluene; at 100℃;Inert atmosphere;
Compound 64a. To a solution of ethyl 3-bromoisonicotinate (0.3 g, 1.38 mmol, 1.0 equiv) in Toluene (15 mL) and water (2 mL) was added o-tolylboronic acid (0.288 g, 1.66 mmol, 1.2 equiv), K2CO3 (0.571 g, 4.14 mmol, 3.0 equiv) and resulting reaction mixture purged with N2 gas for 10 minute, followed by the addition of Pd(PPh3)4 (0.08 g, 0.007 mmol. 0.05 equiv). The resulting reaction mixture was heated at 90 C. for overnight. Product formation was confirmed by LCMS. After the completion of reaction, the mixture was filtered through celite bed, washed with ethyl acetate (100 mL). Filtrate was concentrated under reduced pressure. The crude product obtained was purified by flash chromatography (0-20% ethyl acetate in hexane as an eluent) to obtain methyl 3-(o-tolyl)isonicotinate (0.300 g, 95%) as yellow liquid. (0813) LCMS 228.3 [M+H]+ (0814) 1H NMR (400 MHz, DMSO-d6) delta 8.76 (d, J=5.3 Hz, 1H), 8.55 (s, 1H), 7.77 (d, J=4.8 Hz, 1H), 7.39-7.14 (m, 3H), 7.08 (d, J=7.5 Hz, 1H), 3.33 (s, 3H), 2.02 (s, 3H)