* 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] Chemical Communications, 2010, vol. 46, # 6, p. 907 - 909
[2] Dalton Transactions, 2013, vol. 42, # 3, p. 746 - 752
[3] Dalton Transactions, 2013, vol. 42, # 3, p. 746 - 752
5
[ 25015-63-8 ]
[ 110-83-8 ]
[ 25240-59-9 ]
[ 110-82-7 ]
[ 10221-56-4 ]
[ 87100-15-0 ]
[ 141091-37-4 ]
Reference：
[1] Letters in Organic Chemistry, 2012, vol. 9, # 4, p. 257 - 262
6
[ 28075-50-5 ]
[ 73183-34-3 ]
[ 141091-37-4 ]
Reference：
[1] Journal of the American Chemical Society, 2002, vol. 124, # 27, p. 8001 - 8006
[2] Journal of Medicinal Chemistry, 2000, vol. 43, # 22, p. 4288 - 4312
[3] Chemistry Letters, 2000, # 2, p. 126 - 127
[4] Journal of the American Chemical Society, 2002, vol. 124, # 27, p. 8001 - 8006
[5] Chemistry Letters, 2000, # 2, p. 126 - 127
7
[ 2044-08-8 ]
[ 73183-34-3 ]
[ 141091-37-4 ]
Reference：
[1] Journal of the American Chemical Society, 2002, vol. 124, # 27, p. 8001 - 8006
[2] Chemistry Letters, 2000, # 2, p. 126 - 127
[3] Journal of the American Chemical Society, 2002, vol. 124, # 27, p. 8001 - 8006
[4] Chemistry Letters, 2000, # 2, p. 126 - 127
8
[ 17497-53-9 ]
[ 73183-34-3 ]
[ 141091-37-4 ]
Reference：
[1] Journal of the American Chemical Society, 2017, vol. 139, # 2, p. 607 - 610
[2] Patent: CN106632440, 2017, A, . Location in patent: Paragraph 0083-0087
[3] Journal of the American Chemical Society, 2002, vol. 124, # 27, p. 8001 - 8006
[4] Journal of the American Chemical Society, 2002, vol. 124, # 27, p. 8001 - 8006
9
[ 212127-65-6 ]
[ 141091-37-4 ]
Reference：
[1] Journal of the American Chemical Society, 1998, vol. 120, # 31, p. 7995 - 7996
With bis-triphenylphosphine-palladium(II) chloride; potassium phenolate; triphenylphosphine; In toluene; at 50℃; for 5h;Inert atmosphere;
Under nitrogen protection, 20 g (0.12 mol) of <strong>[2044-08-8]1-bromo-1-cyclohexene</strong> and 34.7 g (0.14 mol) of pinacol borate were added to the three-necked flask.2.0 g (6 mol%) of triphenylphosphine,2.6 g (3 mol%) of trans-bis(triphenylphosphine)palladium(II) dichloride,Potassium phenolate 24.6 g (0.19 mol) and anhydrous toluene 250 mL.After nitrogen substitution, the reaction was stirred at 50 C for 5 hours.The system was then cooled to room temperature and quenched with water.The reaction mixture was extracted with a benzene solvent and brine.The organic phase was dried over anhydrous magnesium sulfate.The dried mixture was filtered and concentrated under reduced pressure.Purified by silica gel column or distillation21.9 g (yield: 85%) cyclohexene-1-boronic acid pinacol ester.
85%
With trans-bis(triphenylphosphine)palladium dichloride; potassium phenolate; triphenylphosphine; In toluene; at 50℃; for 5h;Inert atmosphere;
Add 20 g (0.12 mol) of <strong>[2044-08-8]1-bromo-1-cyclohexene</strong> to a three-necked flask under nitrogen atmosphere.34.7 g (0.14 mol) of bis(pinacolato)diboron and 2.0 g (6 mol%) of triphenylphosphine,2.6 g (3 mol%) of trans-bis(triphenylphosphine)palladium(II) dichloride, 24.6 g of potassium phenolate (0.19 mol) and 250 mL of anhydrous toluene.After nitrogen substitution, the reaction was stirred at 50 C for 5 hours, then the system was cooled to room temperature and quenched with water.The reaction mixture was extracted with a benzene solvent and brine.The organic phase was dried over anhydrous magnesium sulfate.The dried mixture is filtered and concentrated under reduced pressure, and purified by silica gel chromatography or by distillation.21.9 g (yield: 85% cyclohexene-1-boronic acid pinacol ester).
85%
With bis-triphenylphosphine-palladium(II) chloride; potassium phenolate; triphenylphosphine; In toluene; at 50℃; for 5h;Inert atmosphere;
Add 20 g (0.12 mol) of <strong>[2044-08-8]1-bromo-1-cyclohexene</strong> to a three-necked flask under nitrogen atmosphere.34.7 g (0.14 mol), 2.0 g (6 mol%) of triphenylphosphine,Trans-bis(triphenylphosphine)palladium dichloride (II)2.6 g (3 mol%), potassium phenate 24.6 g (0.19 mol) andAnhydrous toluene 250 mL.After nitrogen substitution, the reaction was stirred at 50 C for 5 hours.The system was then cooled to room temperature and quenched with water.The reaction mixture was extracted with a benzene solvent and brine.The organic phase was dried over anhydrous magnesium sulfate.The dried mixture was filtered and concentrated under reduced pressure.Purified by silica gel column or distillation21.9 g (yield: 85%) cyclohexene-1-boronic acid pinacol ester
85%
With bis-triphenylphosphine-palladium(II) chloride; potassium phenolate; triphenylphosphine; In toluene; at 50℃; for 5h;Inert atmosphere;
Under nitrogen protection, 20 g (0.12 mol) of <strong>[2044-08-8]1-bromo-1-cyclohexene</strong> and 34.7 g (0.14 mol) of pinacol borate were added to the three-necked flask.2.0 g (6 mol%) of triphenylphosphine,2.6 g (3 mol%) of trans-bis(triphenylphosphine)palladium(II) dichloride,Potassium phenolate 24.6 g (0.19 mol) and anhydrous toluene 250 mL.After nitrogen substitution, the reaction was stirred at 50 C for 5 hours.The system was then cooled to room temperature and quenched with water.The reaction mixture was extracted with a benzene solvent and brine.The organic phase was dried over anhydrous magnesium sulfate.The dried mixture was filtered and concentrated under reduced pressure.It can be purified by silica gel column or distillation to obtain 21.9 g (yield: 85%)Cyclohexene-1-boronic acid pinacol ester.
85%
With trans-bis(triphenylphosphine)palladium dichloride; potassium phenolate; triphenylphosphine; In toluene; at 50℃; for 5h;Inert atmosphere;
Add 20 g (0.12 mol) of <strong>[2044-08-8]1-bromo-1-cyclohexene</strong> to a three-necked flask under nitrogen atmosphere.34.7 g (0.14 mol) of pinacol borate and 2.0 g (6 mol%) of triphenylphosphine,2.6 g (3 mol%) of trans-bis(triphenylphosphine)palladium(II) dichloride,Potassium phenolate 24.6 g (0.19 mol) and anhydrous toluene 250 mL.After nitrogen substitution, the reaction was stirred at 50 C for 5 hours.The system was then cooled to room temperature and quenched with water.The reaction mixture was extracted with a benzene solvent and brine.The organic phase was dried over anhydrous magnesium sulfate. The dried mixture was filtered and concentrated under reduced pressure.Purification by silica gel column or distillation gave 21.9 g (yield: 85%) of cyclohexene-1-boronic acid pinacol.
85%
With bis-triphenylphosphine-palladium(II) chloride; potassium phenolate; triphenylphosphine; In toluene; at 50℃; for 5h;Inert atmosphere;
Under nitrogen protection, 20 g (0.12 mol) of <strong>[2044-08-8]1-bromo-1-cyclohexene</strong>, 34.7 g (0.14 mol) ofpinacol borate and2.0 g (6 mol%) of triphenylphosphine wereadded to the three-necked flask. 2.6 g(3 mol%) of p-di(triphenylphosphine)palladium(II) chloride, 24.6 g (0.19 mol) of potassium phenate and 250 mL of anhydrous toluene.After nitrogen substitution, the reaction was stirred at 50 C for 5hours, then the system was cooled to room temperature and quenched with water.The reaction mixture was extracted with a benzene solvent and brine.Theorganic phase was dried over anhydrous magnesium sulfate.The dried mixture was filtered and concentrated under reduced pressure, and purified by silica gel chromatography or distillationto give 21.9 g (yield: 85%) of cyclohexene-1-boronic acid pinacol ester.
85%
With bis-triphenylphosphine-palladium(II) chloride; potassium phenolate; triphenylphosphine; In toluene; at 50℃; for 5h;Inert atmosphere;
<strong>[2044-08-8]1-bromo-1-cyclohexene</strong> (20 g, 124.2 mol), boronic acid pinacol ester (34.7 g, 136.6 mol) was added to a three-necked flask under nitrogen atmosphere.Triphenylphosphine (6 mol%), trans-bis(triphenylphosphine)palladium(II) chloride (3 mol%), potassium phenate (24.6 g, 186.3 mol)And anhydrous toluene (250 mL).After nitrogen substitution, the reaction was stirred at 50 C for 5 hours.The system was then cooled to room temperature and quenched with water.The reaction mixture was extracted with a benzene solvent and brine.The organic phase was dried over anhydrous magnesium sulfate.The dried mixture was filtered and concentrated under reduced pressure.Can be carried out by silica gel column or distillationPurification afforded cyclohexene-1-boronic acid pinacol ester (21.9 g, yield: 85%)
85%
With trans-bis(triphenylphosphine)palladium dichloride; potassium phenolate; triphenylphosphine; In toluene; at 50℃; for 5h;Inert atmosphere;
<strong>[2044-08-8]1-bromo-1-cyclohexene</strong> (20 g, 124.2 mol), pinacol borate (34.7 g, 136.6 mol), triphenylphosphine (6 mol%), was added to a three-necked flask under nitrogen atmosphere.Trans - bis (triphenylphosphine) palladium (II) dichloride (3mol%), potassium phenolate (24.6g, 186.3mol) and anhydrous toluene (250mL). After nitrogen substitution, the reaction was stirred at 50 C for 5 hours.The system was then cooled to room temperature and quenched with water. The reaction mixture was extracted with a benzene solvent and brine.The organic phase was dried over anhydrous magnesium sulfate. The dried mixture was filtered and concentrated under reduced pressure.Purification by silica gel column or distillation gave cyclohexene-1-boronic acid pinacol ester (21.9 g, yield: 85%).
85%
With trans-bis(triphenylphosphine)palladium dichloride; potassium phenolate; triphenylphosphine; In toluene; at 50℃; for 5h;Inert atmosphere;
<strong>[2044-08-8]1-bromo-1-cyclohexene</strong> (20 g, 124.2 mol) was added to a three-necked flask under nitrogen atmosphere.Bornazolium diborate (34.7 g, 136.6 mol),Triphenylphosphine (6 mol%), trans-bis(triphenylphosphine)palladium(II) chloride (3 mol%), potassium phenate (24.6 g, 186.3 mol) and anhydrous toluene (250 mL).After nitrogen substitution, the reaction was stirred at 50 C for 5 hours, then the system was cooled to room temperature and quenched with water. The reaction mixture was extracted with a benzene solvent and brine. The organic phase was dried over anhydrous magnesium sulfate. The dried mixture was filtered and concentrated under reduced pressure.Purification by silica gel column or distillation to obtain cyclohexene-1-boronic acid pinacol ester (21.9 g,Yield: 85%)
With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate;tris-(dibenzylideneacetone)dipalladium(0); In toluene; at 100℃; for 3h;
To a slurry of 1-(4-amino-3-bromo-phenyl)-ethanone (20.5 g, 0.960 mol, as prepared in the previous step), 2-dicyclohexylphosphino-2',6'-dimethoxy-1,1'-biphenyl (3.94 g, 9.60 mmol), and K3PO4 (61.0 g, 0.280 mol) in 250 mL of toluene was added 2-(4,4-dimethyl-cyclohex-1-enyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (24.9 g, 0.100 mol) followed by Pd2(dba)3 (4.39 g, 4.80 mmol). The resultant mixture was heated to 100 C. with vigorous stirring. After 3 h, the reaction was filtered and concentrated in vacuo. Purification of the residue by column chromatography (20% EtOAc-hexane) afforded the title compound (15.0 g, 64%). Mass spectrum (ESI, m/z): Calcd. for C16H21NO, 244.1 (M+H), found 244.2.
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; toluene; at 90℃; for 2.5h;
A stirred mixture of <strong>[90902-84-4]2,5-dibromopyridin-3-amine</strong> (0.2135 g, 0.848 mmol), 1-cyclohexen-1-yl-boronic acid pinacol ester (0.30 mL, 1.40 mmol), tetrakis(triphenylphosphine)palladium (0.098 g, 0.084 mmol), and 2.0M sodium carbonate (2.0 mL, 4.00 mmol) in toluene (1.5 mL) and ethanol (0.5 mL) was heated to 90 C. After 2.5 h, the reaction was cooled to rt then diluted with water. After extraction with EtOAc, the organic extraction was dried over anhydrous sodium sulfate. After filtration and concentration, the residue was purified on silica gel (0-35% EtOAc in hexanes) to afford a white solid as 5-bromo-2-cyclohexenylpyridin-3-amine. 1H NMR (400 MHz, CDCl3) delta ppm 8.01 (1H, d, J=2.0 Hz), 7.10 (1H, d, J=2.3 Hz), 6.00 (1H, tt, J=3.7, 2.0 Hz), 3.96 (2H, br. s.), 2.45 (2H, m), 2.26 (2H, m), 1.87 (4H, m). 2,5-Dicyclohexenylpyridin-3-amine was also isolated. 1H NMR (400 MHz, CDCl3) delta ppm 8.07 (1H, d, J=2.0 Hz), 6.95 (1H, d, J=2.0 Hz), 6.16 (1H, m), 6.05 (1H, m), 3.81 (2H, br. s.), 2.48 (4H, m), 2.27 (4H, m), 1.87 (8H, m).
25.1
To a solution of 6-bromo-3,4-dihydroquinolin-2(1H)-one (3.39 g) in methanol (85 ml), sodium methoxide (2.43 g), 2-(1-cyclohexen-1-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborane (3.39 g) and dichloro(bistriphenylphosphine)palladium (526 mg) were added and the mixture was heated under reflux for an hour. To the reaction system, water and ethyl acetate were added and after filtering the insolubles through Celite, the organic layer was recovered from the filtrate. After drying the resulting organic layer over anhydrous sodium sulfate, the desiccant was filtered off and the solvent was removed in vacuo. The residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate = 4:1 to 2:1) to give the titled compound (2.90 g) as a colorless powder. MS(ESI/APCI Dual): 228(M+H) 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.60 - 1.71 (m, 2 H), 1.72 - 1.82 (m, 2 H), 2.15 - 2.24 (m, 2 H), 2.33 - 2.41 (m, 2 H), 2.59 - 2.67 (m, 2 H), 2.92 - 3.00 (m, 2 H), 6.03 - 6.09 (m, 1 H), 6.65 - 6.71 (m, 1 H), 7.16 - 7.22 (m, 2 H), 7.77 (br. s., 1 H)
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; water; at 90℃; for 3h;Inert atmosphere;
To a solution of <strong>[685892-23-3]methyl 2-bromo-6-chlorobenzoate</strong> (520 mg, 2.00 mmol) and 1-cyclohexenylboronic acid pinacol ester (500 mg, 2.40 mmol) in 10 mL of dioxane and 2 mL of water under nitrogen was added sodium carbonate (500 mg, 4.60 mmol) and Pd(dppf)Cl2 (10 mg), and the resulting mixture was stirred at 90 C for 3 hrs. The mixture was concentrated and the residue was purified on silica gel by column chromatography(petroleum as eluent) to give the title compound (520 mg, 100%) as colorless oil. LCMS (ESI) calc?d for C14H15ClO2 [M+H]+: 251, found: 251.
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 100℃; for 16h;
a. Preparation of Compound A mixture of <strong>[1241752-31-7]5-bromo-2-ethoxy-3-methoxypyridine</strong> (279 mg, 1.0 mmol), 1-cyclohexenyl boronic acid pinacole ester (250 mg, 1.2 mmol), Pd(PPh3)4 (139 mg, 0.12 mmol) and K2C03 (277 mg, 2.0 mmol) in 1,4- dioxane (3.0 ml) and H20 (1.0 ml) was degassed for 30 min. This mixture was heated to 100 C and stirred for 16 h. The reaction mixture was cooled to room temperature and partitioned between NaHC03 and EtOAc (3x), and washed with NaCl (lx). The organic phase was dried over Na2S04 and was concentrated. The resulting residue was purified by ISCO flash chromatography using 10% EtOAc in hexane to give 551 mg (97%) of the desired product. NMR (300 MHz, CDC13) delta: 7.7 (s, IH), 7.04 (s, IH), 6.0 (m, IH), 4.4 (qt, 2H), 3.84 (s, 3H), 2.36 (m, 2H), 2.18 (m, 2H), 1.78 (m, 2H), 1.7 (m, 2H), 1.4 (t, 3H)
With potassium phosphate; tetrakis(triphenylphosphine) palladium(0) In 1,4-dioxane at 90℃; for 2h;
9.1.1 Step 1 : 4-(cyclohex-l-en-l-yl)-5-methyl-l,3-thiazol-2-amine.
To a solution of 4-bromo-5-methyl-l,3-thiazol-2-amine (from Example 4.1, Step 5) (130 mg, 0.67 mmol) in 1,4-dioxane (2 mL) was added 2-(cyclohex-l-en-l-yl)-4,4,5,5-tetramethyl-l,3,2- dioxaborolane (140 mg, 0.67 mmol), potassium phosphate (171 mg, 0.81 mmol) and tetrakis(triphenylphosphine)palladium (78 mg, 0.070 mmol). The reaction mixture was stirred for 2 h at 90 °C and concentrated in vacuo. The residue was purified by silica gel chromatography with 3.3% methanol in dichloromethane to afford 4-(cyclohex-l-en-l-yl)-5-methyl-l,3-thiazol-2-amine as a yellow solid (140 mg). The crude product was used in next step without further purification. LCMS (ESI): M+H+ = 194.8.
5-chloro-3-(cyclohex-1-en-1-yl)pyridazin-4-amine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 In 1,4-dioxane; water at 100℃; for 4h; Inert atmosphere;
1 Intermediate 6s: 5-chJoro-3-(Cyclohex-1-en-1-yI)pyridazin-4-amine
Intermediate 6s: 5-chJoro-3-(Cyclohex-1-en-1-yI)pyridazin-4-amine To a stirred mixture of 3,5-dichloropyridazine-4-amine (200 mg, 1.22 mmol) and cyciohex-i-en-i-y1boronic acid pinacole ester (250 mg, 1.22 mmol) in dioxane:water (8 mL, 5:1) under an atmosphere of nitrogen was added K3P04 (0.65 g, 3.06 mmol). The reaction mixture was degassed with nitrogen for 10 mm. [i,i’bis(diphenylphosphino)ferrocenejdicffloropalladium(II), complex with dichioromethane (CM 95464-05-4; 0.044 g, 0.061 mmol) was added and the reaction mixture was heated at 100 “C for 4 h. After completion, reaction niixture was poured into water and extracted with EtOAc. Combined organic layer was washed with brine, dried over sodium sulphate and concentrated in vacuo. The crude compound was purified by column chromatography (silica, 0-30% EtOAc / petroleum ether) to afford the title compound.‘11 NMR (400 MHz, DMSO-d6) 8 ppm 1.68-1.76 (m, 411) 2.17-2.20 (m, 211) 2.28-2.30 (m, 2H) 5.96-5.98 (m, iH) 6.32 (br. s, 2H) 8.6o (s, iH)MS ES: 210
3-bromo-5-(cyclohex-1-en-1-yl)-1-methyl-1H-pyrazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
345 mg
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,2-dimethoxyethane at 80℃; for 20h; Inert atmosphere;
100 Reference Example 100 3-bromo-5-(cyclohex-1-en-1-yl)-1-methyl-1H-pyrazole
Reference Example 100 3-bromo-5-(cyclohex-1-en-1-yl)-1-methyl-1H-pyrazole (1128) (1129) A mixture of 3,5-dibromo-1-methyl-1H-pyrazole (500 mg) obtained in Reference Example 3, 2-(cyclohex-1-en-1-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (520 mg), tetrakis(triphenylphosphine)palladium(0) (241 mg), aqueous sodium carbonate solution (2 M, 2.08 mL) and 1,2-dimethoxyethane (10 mL) was heated under an argon atmosphere at 80°C for 20 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (345 mg). MS (ESI+): [M+H]+ 240.8.
With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; palladium diacetate; In tetrahydrofuran; water; for 11h;Inert atmosphere; Reflux;
To a 100 mL reactor thoroughly dried and replaced with argon, Organometallics 2006, 25, 1217. 3.60 g (16.0 mmol) of <strong>[174702-59-1]4-bromo-2-methyl-1-indanone</strong> synthesized by the method described, 5.00 g (24.0 mmol) of 2- (1-cyclohexenyl) -4,4,5,5-tetramethyl-1,3,2-dioxaborolane, 6.79 g (32.0 mmol) of tripotassium phosphate, 0.37 g (0.16 mmol) of palladium acetate, 0.13 g (0.32 mmol) of 2-dicyclohexylphosphino-2 ', 6'- dimethoxybiphenyl (S-Phos), 30 mL of tetrahydrofuran and 7.5 mL of distilled water were charged, And heated under reflux in an oil bath for 11 hours. After the reaction solution was cooled to room temperature, insoluble components were filtered through celite and thoroughly washed with dichloromethane. The fraction was washed with saturated saline and dried over anhydrous magnesium sulfate. After filtration of the magnesium sulfate, the filtrate was distilled off and the residue obtained was purified by silica gel column chromatography to quantitatively obtain the target compound (hereinafter referred to as compound (5a)) represented by the following formula (5a) It was done.
6-bromo-N-(1H-pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-amine[ No CAS ]
[ 141091-37-4 ]
[ 89490-05-1 ]
6-(cyclohex-1-en-1-yl)-N-(1H-pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-amine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
46%
A flask was charged with 6-bromo-N-(1H-pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-amine (4.40 g, 15.7 mmol), 2-(cyclohex-1-en-1-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane(5.23 g, 25.1 mmol), PdCl2(dppf) (1.149 g, 1.571 mmol) and potassium phosphate (8.34 g, 39.3mmol). 1,4-dioxane (60 mL) and water (15 mL) were added. The mixture was sparged withnitrogen for 5 min and heated at 90C for 16 h. The reaction mixture was cooled and chargedwith cyclohex-1-en-1-ylboronic acid (0.989 g, 7.85 mmol) and PdCl2(dppf) (0.575 g, 0.785mmol). The flask was degassed and then stirred at 90C overnight. The mixture was diluted withwater (200 mL) and filtered. The precipitate was stirred in MeOH and filtered again. The precipitatewas kept aside. The filtrate was concentrated and the residue was suspended in MeOH andfiltered to give an additional batch of precipitate. The two batches were combined and trituratedwith MeOH:AcOH:THF (4:1:1) to give the title compound (2.02 g, 46percent); 1H NMR (400 MHz,DMSO-d6) delta 10.13 (s, 1H), 8.49 (s, 1H), 8.15 (s, 1H), 8.01 (s, 2H), 6.85 (td, J = 3.9, 1.9 Hz, 1H),2.41 (td, J = 6.1, 2.3 Hz, 2H), 2.26 (qd, J = 5.8, 3.7, 3.3 Hz, 2H), 1.78±1.57 (m, 4H).
6-chloro-3-(cyclohex-1-en-1-yl)imidazo[1,2-a]pyridine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
83%
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate; In 1,4-dioxane; water; at 50.0℃; for 5.0h;Inert atmosphere;
General procedure: To an oven dried 5 mL microwave vessel was addedPd(dppf)Cl2·CH2Cl2 (4 mol%), halide/pseudohalide (1 equiv),boron coupling partner (1 equiv), and Cs2CO3 (3 equiv). Thevessel was then capped and purged with N2 before addition ofCyrene (1 mL, 0.25 M) and H2O (1.8 mL). The reaction mixturewas heated to 50 C and maintained at this temperature withstirring for 5 h before the vessel was vented and decapped. Thesolution was then diluted with Et2O (10 mL) and washed withwater (2 × 20 mL) and brine (2 × 20 mL). The organics were thenpassed through a hydrophobic frit and concentrated underreduced pressure to give a residue, which was purified by flashchromatography (silica gel) to afford the title compound.
62%
With potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; isosorbide dimethyl ether; In water; at 60.0℃; for 1.0h;Microwave irradiation; Inert atmosphere;
General procedure: To an oven-dried 5 mL microwave vessel was addedPd(dppf)Cl2·CH2Cl2 (4 mol%), aryl halide/pseudohalide (1equiv.), organoboron (1 equiv.), and K3PO4 (3 equiv.). The vesselwas then capped and purged with N2 before addition of DMI (1mL, 0.25 M) and H2O (5 equiv.). The reaction mixture washeated to 60 C and maintained at this temperature with stirringfor 1 h before the vessel was vented and decapped. Thesolution was then diluted with EtOAc (10 mL) and washed withwater (2 × 20 mL) and brine (2 × 20 mL). The organics were thenpassed through a hydrophobic frit and concentrated underreduced pressure to give a residue, which was purified by flashchromatography (silica gel) to afford the product.
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 110℃; for 3h;Microwave irradiation;
To A solution of intermediate l-04a (1 .6 g, 4.52 mmol) in 1 ,4-dioxane/H20 (10:1 , 1 1 mL) was added K2C03(1 .25 g, 9.04 mmol), Pd(PPh3)4(0.53 g, 0.452 mmol) and methylboronic acid (R-02a, 0.30 g, 4.98 mmol) and the solution was heated to 1 10 C for 3 hours under Microwave. Then the mixture was concentrated and extracted with EtOAc. The combined organic layers were washed with brine, dried over anhydrous Na2S04.filtered and concentrated to give the crude product which was purified by column chromatography (Si02, DCM/MeOH = 1 :0 to 4:1 ) to give pure intermediate l-05a (0.18 g, 12%) as a yellow solid. ESI-MS (M+1 ): 335 calc. for Ci8H23CIN202: 334.1 .
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran at 80℃; for 12h; Inert atmosphere;
4 4. Synthesis of 2-(cyclohex-1-en-1-yl)quinoline
Under the protection of nitrogen,To the three-necked bottle, 6 g of 2-chloroquinoline (36.7 mmol) was added.Cyclohexene-1-boronic acid pinacol ester 8.4 g (40.3 mmol),2M-potassium carbonate 60mL was dissolved in 60mL of tetrahydrofuran. Nitrogen replacement for 30 minutes,The catalyst tetrakistriphenylphosphine palladium (1 mol%) was added. The reaction system was heated to 80 ° C,Stirring was carried out for 12 hours. Cool to room temperature and quench the reaction with water.The reaction solution was extracted with ethyl acetate and brine. Wash two or three times with saturated saline solution.Take the organic phase. The organic phase was dried over anhydrous magnesium sulfate and concentrated. Purification by silica gel chromatography gave 6.4 g (yield: 80%) of 2-(cyclohex-1-en-1-yl)quinoline.
methyl 3-(cyclohex-1-en-1-yl)isonicotinate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
42.4%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In toluene; at 100℃;Inert atmosphere;
Compound 43a. To a solution of ethyl 3-bromoisonicotinate (0.4 g, 1.85 mmol, 1.0 equiv) in toluene (20 mL) was added 2-(cyclohex-1-en-1-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.58 g, 2.77 mmol, 1.5 equiv), K2CO3 (0.51 g, 3.78 mmol, 2.0 equiv) and resulting reaction mixture purged with N2 gas for 10 min. followed by the addition of Pd(PPh3)4 (0.065 g, 0.093 mmol. 0.05 equiv). The resulting reaction mixture was heated at 100 C. for overnight. Product formation was confirmed by LCMS. After the completion of reaction, the reaction 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 (0-10% ethyl acetate in hexane as an eluent) to obtain methyl 3-(cyclohex-1-en-1-yl)isonicotinate (0.170 g, 42.4%) as colorless oil. (0763) LCMS 218.2 [M+H]+ (0764) 1H NMR (400 MHz, DMSO-d6) delta 8.60 (d, J=5.3 Hz, 1H), 8.52 (s, 1H), 7.56 (d, J=5.3 Hz, 1H), 5.62 (br. s., 1H), 2.24-2.06 (m, 4H), 1.77-1.54 (m, 4H).
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran at 80℃; for 12.5h; Inert atmosphere;
7 7. Synthesis of Ligand L-4
To a three-necked flask was added 2-chloro-5-methylpyridine (10 g, 78.4 mmol), cyclohexene-1-boronic acid pinacol ester (17.9 g, 86.2 mmol), 2M-potassium carbonate (under nitrogen). 100 mL) was dissolved in tetrahydrofuran (100 mL). Nitrogen was replaced for 30 minutes, and a catalyst tetrakistriphenylphosphine palladium (3 mol%) was added. The reaction system was warmed to 80 ° C and stirred under reflux for 12 hours. After cooling to room temperature, the reaction mixture was quenched with water and ethyl acetate and brine. Wash two to three times with saturated brine and take the organic phase. The organic phase was dried over anhydrous magnesium sulfate and concentrated. The ligand L-4 (11.0 g, yield: 81%) was obtained by separation and purification on silica gel chromatography.
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