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[ CAS No. 13682-77-4 ] {[proInfo.proName]}

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Chemical Structure| 13682-77-4
Chemical Structure| 13682-77-4
Structure of 13682-77-4 * Storage: {[proInfo.prStorage]}
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Product Details of [ 13682-77-4 ]

CAS No. :13682-77-4 MDL No. :MFCD02093335
Formula : C2H3BF3K Boiling Point : -
Linear Structure Formula :- InChI Key :ZCUMGICZWDOJEM-UHFFFAOYSA-N
M.W : 133.95 Pubchem ID :23679353
Synonyms :

Calculated chemistry of [ 13682-77-4 ]

Physicochemical Properties

Num. heavy atoms : 7
Num. arom. heavy atoms : 0
Fraction Csp3 : 0.0
Num. rotatable bonds : 1
Num. H-bond acceptors : 3.0
Num. H-bond donors : 0.0
Molar Refractivity : 19.28
TPSA : 0.0 Ų

Pharmacokinetics

GI absorption : Low
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.28 cm/s

Lipophilicity

Log Po/w (iLOGP) : 0.0
Log Po/w (XLOGP3) : 2.59
Log Po/w (WLOGP) : 2.82
Log Po/w (MLOGP) : 1.45
Log Po/w (SILICOS-IT) : 0.45
Consensus Log Po/w : 1.46

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 3.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -2.24
Solubility : 0.778 mg/ml ; 0.00581 mol/l
Class : Soluble
Log S (Ali) : -2.24
Solubility : 0.773 mg/ml ; 0.00577 mol/l
Class : Soluble
Log S (SILICOS-IT) : -1.12
Solubility : 10.2 mg/ml ; 0.0759 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.36

Safety of [ 13682-77-4 ]

Signal Word:Danger Class:8
Precautionary Statements:P280-P305+P351+P338-P310 UN#:3261
Hazard Statements:H314 Packing Group:
GHS Pictogram:

Application In Synthesis of [ 13682-77-4 ]

* 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.

  • Downstream synthetic route of [ 13682-77-4 ]

[ 13682-77-4 ] Synthesis Path-Downstream   1~63

  • 1
  • [ 623-00-7 ]
  • potassium vinyltrifluoroborate [ No CAS ]
  • [ 3435-51-6 ]
YieldReaction ConditionsOperation in experiment
83% With caesium carbonate; triphenylphosphine In tetrahydrofuran; water at 85℃; for 22h;
76% With triethylamine In water; isopropyl alcohol for 6h; Heating;
69% With caesium carbonate In tetrahydrofuran; water for 6h; Heating;
63% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; triethylamine In water; isopropyl alcohol at 100℃; for 16h; Inert atmosphere; I.1.1 1.1.1 Synthesis of 4-vinylbenzonitrile To a solution of 4-bromobenzonitrile (58.0 g, 318 mmol) in a mixture of propan-2-ol/water (600 mL/300 ml.) was added potassium vinyltrifluoroborate (42.7 g, 318 mmol), triethylamine (96.7 g, 956 mmol) and [1 ,T-Bis(diphenylphosphino)ferrocene]dichloropalladium(ll) (5.22 g, 6.37 mmol) at 25°C. Then the reaction was stirred at 100°C under nitrogen atmosphere for 16 hours. The reaction mixture was concentrated and extracted with methyl tert- butyl ether. The organic layers were combined and concentrated. The crude product was purified by flash chromatography to afford the title compound (26.0 g, 63%) as a yellow oil. 1H NMR (CDCIs, 400 MHz): d [ppm] = 5.41 (d, 1 H), 5.84 (d, 1 H), 6.69 (dd, 1 H), 7.44 (d, 2 H), 7.52 - 7.62 (m, 2 H).
46 % Chromat. With sodium acetate In 1-methyl-pyrrolidin-2-one at 100℃; for 24h;
With caesium carbonate; triphenylphosphine; palladium dichloride In tetrahydrofuran; water at 85℃; for 24h; Inert atmosphere;

  • 2
  • [ 6630-33-7 ]
  • [ 13682-77-4 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
95% With palladium diacetate; Cs2CO3; triphenylphosphine In tetrahydrofuran; lithium hydroxide monohydrate at 85℃; for 2.5h;
87% With palladium diacetate; Cs2CO3; triphenylphosphine In tetrahydrofuran; lithium hydroxide monohydrate at 70℃; for 14h; Inert atmosphere;
84% With palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; triethylamine In isopropanol at 80℃; for 18h; Inert atmosphere;
77% With palladium diacetate; Cs2CO3; triphenylphosphine In tetrahydrofuran; lithium hydroxide monohydrate at 70℃; for 4h; Inert atmosphere; Sealed tube;
76% Stage #1: ortho-bromobenzaldehyde With tetrakis-(triphenylphosphine)-palladium In ethylene glycol dimethyl ether at 20℃; for 0.333333h; Stage #2: trifluoro(vinyl)-λ4-borane potassium salt With potassium carbonate In ethylene glycol dimethyl ether; lithium hydroxide monohydrate for 16h; Reflux;
71% With palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; triethylamine In isopropanol at 85℃; for 18h; Inert atmosphere;
65% With triethylamine In propyl alcohol for 3h; Heating;
60% With Cs2CO3; triphenylphosphine; palladium (II) chloride In tetrahydrofuran; lithium hydroxide monohydrate at 85℃; for 24h;
With palladium diacetate; Cs2CO3; triphenylphosphine In tetrahydrofuran; lithium hydroxide monohydrate at 20 - 90℃;
With palladium diacetate; Cs2CO3; triphenylphosphine In tetrahydrofuran; lithium hydroxide monohydrate at 70℃; Inert atmosphere;
With palladium diacetate; Cs2CO3; triphenylphosphine In tetrahydrofuran; lithium hydroxide monohydrate at 70℃; for 4h;
With palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; triethylamine In isopropanol Reflux;

Reference: [1]Wu, Wenxi; Mu, Yu; Tan, Junfeng; Wang, Zixuan; Zhang, Chen; Li, Guiding; Jin, Ying; Huang, Xueshi; Han, Li [Organic and Biomolecular Chemistry, 2022, vol. 20, # 34, p. 6831 - 6843]
[2]Häfliger, Joel; Sokolova, Olga O.; Lenz, Madina; Daniliuc, Constantin G.; Gilmour, Ryan [Angewandte Chemie - International Edition, 2022, vol. 61, # 30][Angew. Chem., 2022, vol. 134, # 30]
[3]Calder, Ewen D. D.; McGonagle, Fiona I.; Harkiss, Alexander H.; McGonagle, Grant A.; Sutherland, Andrew [Journal of Organic Chemistry, 2014, vol. 79, # 16, p. 7633 - 7648]
[4]Jarrige, Lucie; Carboni, Aude; Dagousset, Guillaume; Levitre, Guillaume; Magnier, Emmanuel; Masson, Géraldine [Organic Letters, 2016, vol. 18, # 12, p. 2906 - 2909]
[5]Hemric, Brett N.; Chen, Andy W.; Wang, Qiu [Journal of Organic Chemistry, 2019, vol. 84, # 3, p. 1468 - 1488]
[6]Kerim, Mansour Dolé; Cattoen, Martin; Fincias, Nicolas; Dos Santos, Aurélie; Arseniyadis, Stellios; El Kaïm, Laurent [Advanced Synthesis and Catalysis, 2018, vol. 360, # 3, p. 449 - 454]
[7]Molander, Gary A.; Rivero, Marta Rodriguez [Organic Letters, 2002, vol. 4, # 1, p. 107 - 109]
[8]Li, Lamei; Wang, Songping; Wei, Wentao; Yan, Ming; Zhou, Jingwei [Green Chemistry, 2020, vol. 22, # 11, p. 3421 - 3426]
[9]Fustero, Santos; Rodriguez, Elsa; Lazaro, Ruben; Herrera, Lidia; Catalan, Silvia; Barrio, Pablo [Advanced Synthesis and Catalysis, 2013, vol. 355, # 6, p. 1058 - 1064]
[10]Zheng, Purui; Han, Xiaoyu; Hu, Jiao; Zhao, Xiaoming; Xu, Tao [Organic Letters, 2019, vol. 21, # 15, p. 6040 - 6044]
[11]Shen, Wen-Bo; Tang, Xiang-Ting; Zhang, Ting-Ting; Lv, Dong-Can; Zhao, Dan; Su, Tong-Fu; Meng, Lei [Organic Letters, 2021, vol. 23, # 4, p. 1285 - 1290]
[12]Roth, Hudson G.; Nicewicz, David A. [Synlett, 2021, vol. 33, # 1, p. 48 - 51]
  • 3
  • [ 4595-59-9 ]
  • [ 13682-77-4 ]
  • [ 53967-68-3 ]
YieldReaction ConditionsOperation in experiment
79% With caesium carbonate; triphenylphosphine In tetrahydrofuran; water at 85℃; for 22h;
78% With caesium carbonate; triphenylphosphine; palladium dichloride In tetrahydrofuran; water at 85℃; for 22h; Inert atmosphere; Glovebox; Schlenk technique; Sealed tube;
53% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; triethylamine In propan-1-ol at 100℃; Inert atmosphere; 3.A A.
Preparation of 5-vinylpyrimidine A. Preparation of 5-vinylpyrimidine 5-Bromopyrimidine (7.0 g, 44 mmol, 1.0 eq), [1,1'-Bis(diphenylphosphino)-ferrocene]dichloropalladium (1.44 g, 1.76 mmol, 0.040 eq), and potassium vinyltrifluoroborate (7.08 g, 52.9 mmol, 1.2 eq) were added to a pressure vessel. The vessel was purged with argon and degassed n-propanol (220 mL) and triethylamine (7.4 mL, 53 mmol, 1.2 eq) were added. The reaction was heated at 100° C. overnight at which point it was cooled to room temperature and diethyl ether (300 mL) was added. The combined organics were washed with H2O (3*), dried (MgSO4), and concentrated taking care to keep the flask cold as the product is somewhat volatile. Purification by flash chromatography on silica gel using ether/hexanes afforded 2.5 g (53%) of the title compound as a red oil. 1H NMR (400 MHz, DMSO-d6) δ 9.06 (s, 1H), 8.93 (s, 2H), 6.74 (dd, J=17.9, 11.2 Hz, 1H), 6.13 (d, J=17.9 Hz, 1H), 5.51 (d, J=11.2 Hz, 1H); ES-MS [M+1]+: 107.2.
53% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; triethylamine In isopropyl alcohol at 100℃; Sealed tube;
With caesium carbonate In tetrahydrofuran; water at 85℃; for 24h; Inert atmosphere; 30A A solution of potassium vinyltrifluoroborate (843 mg, 6.29 mmol; Aldrich), palladium(II) chloride (22 mg, 0.124 mmol; Aldrich), triphenylphosphine (99 mg, 0.377 mmol; Aldrich), cesium carbonate (6.15 g, 18.87 mmol; Aldrich), and 5-bromopyrimidine (843 mg, 6.29 mmol; Aldrich) in tetrahydrofuran/H2O (9:1; 10 mL) was heated at 85 0C under a nitrogen atmosphere for 24 hours. The reaction mixture was cooled to room temperature, diluted with water (15 mL), and extracted with dichloromethane (2x25 mL). The combined organic extracts were dried over MgSO4, filtered, concentrated, and the crude material was purified by flash chromatography (silica gel, 5-60% ethyl acetate in hexanes) to afford the title compound: 1H NMR (300 MHz, CDCl3) δ ppm 5.52 (d, J=I 1.1 Hz, 1 H), 5.93 (d, J= 17.9 Hz, 1 H), 6.66 (dd, J=17.5, 11.1 Hz, 1 H), 8.76 (s, 2 H), 9.10 (s, I H).

  • 4
  • [ 10075-50-0 ]
  • potassium vinyltrifluoroborate [ No CAS ]
  • [ 77132-99-1 ]
YieldReaction ConditionsOperation in experiment
83% With caesium carbonate In tetrahydrofuran; water for 16h; Reflux; Inert atmosphere; 32.1 Example 32Preparation of tert-butyl-5-vinyl-1H-indole-1-carboxylate (BI17) Step 1. 5-Vinyl-1H-indole (BI18); A mixture of 5-bromo-1H-indole (2.5 g, 12.82 mmol), potassium vinyltrifluoroborate (2.57 g, 19.2 mmol), Cs2CO3 (12.53 g, 38.46 mmol) and triphenylphosphine (201 mg, 0.769 mmol) in THF/water (9:1, 75 ml) was degassed with argon for 20 min, then charged with PdCl2 (45.3 mg, 0.256 mmol). The reaction mixture was heated to reflux for 16 h, then cooled to RT, filtered through celite bed and washed with ethyl acetate. The filtrate was again extracted with ethyl acetate, and the combined organic layer washed with water and brine, dried over Na2SO4 and concentrated under reduced pressure to afford the crude compound. The crude compound was purified by column chromatography (SiO2, 100-200 mesh; 2% ethyl acetate/petroleum ether) to afford the title compound as a light brown gummy material (1.5 g, 83%): 1H NMR (400 MHz, CDCl3) δ 8.20 (br, 1H), 7.68 (s, 1H), 7.45 (s, 2H), 7.21 (m, 1H), 6.90 (dd, J=16.0, 10.8 Hz, 1H), 6.55 (m, 1H), 5.75 (d, J=10.5 Hz, 1H), 5.21 (d, J=10.5 Hz, 1H); ESIMS m/z 142.05 ([M-H]-).
83% With caesium carbonate; triphenylphosphine; palladium dichloride In tetrahydrofuran; water for 16h; Inert atmosphere; Reflux; 32.1 Step 1. 5-Vinyl-lH-indole (BI18): Step 1. 5-Vinyl-lH-indole (BI18): A mixture of 5-bromo-lH-indole (2.5 g, 12.82 mmol), potassium vinyltrifluoroborate (2.57 g ,19.2 mmol), Cs2CC>3 (12.53 g, 38.46 mmol) and triphenylphosphine (201 mg, 0.769 mmol) in THF/water (9: 1, 75 ml) was degassed with argon for 20 min, then charged with PdCl2 (45.3 mg,0.256 mmol). The reaction mixture was heated to reflux for 16 h, then cooled to RT, filtered through celite bed and washed with ethyl acetate. The filtrate was again extracted with ethyl acetate, and the combined organic layer washed with water and brine, dried over Na2S04 and concentrated under reduced pressure to afford the crude compound. The crude compound was purified by column chromatography (Si02, 100-200 mesh; 2% ethyl acetate/ petroleum ether) to afford the title compound as a light brown gummy material (1.5 g, 83%): ]H NMR (400 MHz, CDC13) δ 8.20 (br, 1H), 7.68 (s, 1H), 7.45 (s, 2H), 7.21 (m, 1H), 6.90 (dd, 7 =16.0, 10.8 Hz, 1H), 6.55 (m, 1H), 5.75 (d, / = 10.5 Hz, 1H), 5.21 (d, / = 10.5 Hz, 1H); ESIMS m/z 142.05 ([M-H]").
83% With caesium carbonate; triphenylphosphine; palladium dichloride In tetrahydrofuran; water for 16h; Inert atmosphere; Reflux; 32.1 Step 1. 5-Vinyl-1H-indole (BI18) A mixture of 5-bromo-1H-indole (2.5 g, 12.82 mmol), potassium vinyltrifluoroborate (2.57 g, 19.2 mmol), Cs2CO3 (12.53 g, 38.46 mmol) and triphenylphosphine (201 mg, 0.769 mmol) in THF/ water (9:1, 75 ml) was degassed with argon for 20 min, then charged with PdCl2 (45.3 mg, 0.256 mmol). The reaction mixture was heated to reflux for 16 h, then cooled to ambient temperature, filtered through celite bed and washed with ethyl acetate. The filtrate was again extracted with ethyl acetate, and the combined organic layer washed with water and brine, dried over Na2SO4 and concentrated under reduced pressure to afford the crude compound. The crude compound was purified by column chromatography (SiO2, 100-200 mesh; 2% ethyl acetate/petroleum ether) to afford the title compound as a light brown gummy material (1.5 g, 83%): 1H NMR (400 MHz, CDCl3) δ 8.20 (br, 1H), 7.68 (s, 1H), 7.45 (s, 2H), 7.21 (m, 1H), 6.90 (dd, J=16.0, 10.8 Hz, 1H), 6.55 (m, 1H), 5.75 (d, J=10.5 Hz, 1H), 5.21 (d, J=10.5 Hz, 1H); ESIMS m/z 142.05 ([M-H]-).
83% With caesium carbonate; triphenylphosphine; palladium dichloride In tetrahydrofuran; water for 16h; Inert atmosphere; Reflux; 32.1 Step 1. 5-Vinyl-1H-indole (BI18) A mixture of 5-bromo-1H-indole (2.5 g, 12.82 mmol), potassium vinyltrifluoroborate (2.57 g, 19.2 mmol), Cs2CO3 (12.53 g, 38.46 mmol) and triphenylphosphine (201 mg, 0.769 mmol) in THF/water (9:1, 75 ml) was degassed with argon for 20 min, then charged with PdCl2 (45.3 mg, 0.256 mmol). The reaction mixture was heated to reflux for 16 h, then cooled to RT, filtered through celite bed and washed with ethyl acetate. The filtrate was again extracted with ethyl acetate, and the combined organic layer washed with water and brine, dried over Na2SO4 and concentrated under reduced pressure to afford the crude compound. The crude compound was purified by column chromatography (SiO2, 100-200 mesh; 2% ethyl acetate/petroleum ether) to afford the title compound as a light brown gummy material (1.5 g, 83%): 1H NMR (400 MHz, CDCl3) δ 8.20 (br, 1H), 7.68 (s, 1H), 7.45 (s, 2H), 7.21 (m, 1H), 6.90 (dd, J=16.0, 10.8 Hz, 1H), 6.55 (m, 1H), 5.75 (d, J=10.5 Hz, 1H), 5.21 (d, J=10.5 Hz, 1H); ESIMS m/z 142.05 ([M-H]-).
83% Stage #1: 5-bromo-1H-indole; potassium vinyltrifluoroborate With caesium carbonate; triphenylphosphine In tetrahydrofuran; water for 0.333333h; Inert atmosphere; Stage #2: With palladium dichloride In tetrahydrofuran; water for 16h; Inert atmosphere; Reflux; 32.1 5-Vinyl-1 -indole (BI18) A mixture of 5-bromo-1H-indole (2.5 g, 12.82 mmol), potassium vinyltrifluoroborate (2.57 g ,19.2 mmol), Cs2CO3 (12.53 g, 38.46 mmol) and triphenylphosphine (201 mg, 0.769 mmol) in THF/water (9: 1, 75 ml) was degassed with argon for 20 min, then charged with PdCl2 (45.3 mg,0.256 mmol). The reaction mixture was heated to reflux for 16 h, then cooled to RT, filtered through celite bed and washed with ethyl acetate. The filtrate was again extracted with ethyl acetate, and the combined organic layer washed with water and brine, dried over Na2S04 and concentrated under reduced pressure to afford the crude compound. The crude compound was purified by column chromatography (SiO2, 100-200 mesh; 2% ethyl acetate/ petroleum ether) to afford the title compound as a light brown gummy material (1.5 g, 83%): 1H NMR (400 MHz, CDC13) δ 8.20 (br, 1H), 7.68 (s, 1H), 7.45 (s, 2H), 7.21 (m, 1H), 6.90 (dd, 7 =16.0, 10.8 Hz, 1H), 6.55 (m, 1H), 5.75 (d, / = 10.5 Hz, 1H), 5.21 (d, / = 10.5 Hz, 1H); ESIMS m/z 142.05 ([M-H]").
83% Stage #1: 5-bromo-1H-indole; potassium vinyltrifluoroborate With caesium carbonate; triphenylphosphine In tetrahydrofuran; water for 0.333333h; Inert atmosphere; Stage #2: With palladium dichloride In tetrahydrofuran; water for 16h; Inert atmosphere; Reflux; 32.1 Step 1. 5-Vinyl-1H-indole (BI18) Example 32 Preparation of tert-Butyl-5-vinyl-1H-indole-1-carboxylate (BI17) Step 1. 5-Vinyl-1H-indole (BI18) A mixture of 5-bromo-1H-indole (2.5 g, 12.82 mmol), potassium vinyltrifluoroborate (2.57 g, 19.2 mmol), Cs2CO3 (12.53 g, 38.46 mmol) and triphenylphosphine (201 mg, 0.769 mmol) in THF/water (9:1, 75 ml) was degassed with argon for 20 min, then charged with PdCl2 (45.3 mg, 0.256 mmol). The reaction mixture was heated to reflux for 16 h, then cooled to ambient temperature, filtered through celite bed and washed with ethyl acetate. The filtrate was again extracted with ethyl acetate, and the combined organic layer washed with water and brine, dried over Na2SO4 and concentrated under reduced pressure to afford the crude compound. The crude compound was purified by column chromatography (SiO2, 100-200 mesh; 2% ethyl acetate/petroleum ether) to afford the title compound as a light brown gummy material (1.5 g, 83%): 1H NMR (400 MHz, CDCl3) δ 8.20 (br, 1H), 7.68 (s, 1H), 7.45 (s, 2H), 7.21 (m, 1H), 6.90 (dd, J=16.0, 10.8 Hz, 1H), 6.55 (m, 1H), 5.75 (d, J=10.5 Hz, 1H), 5.21 (d, J=10.5 Hz, 1H); ESIMS m/z 142.05 ([M-H]-).
38% With caesium carbonate; triphenylphosphine In tetrahydrofuran; water at 85℃; for 22h;
With triphenylphosphine In tetrahydrofuran; water; ethyl acetate 32.1 Step 1. Step 1. 5-Vinyl-1H-indole (BI18) A mixture of 5-bromo-1H-indole (2.5 g, 12.82 mmol), potassium vinyltrifluoroborate (2.57 g, 19.2 mmol), Cs2CO3 (12.53 g, 38.46 mmol) and triphenylphosphine (201 mg, 0.769 mmol) in THF/water (9:1, 75 ml) was degassed with argon for 20 min, then charged with PdCl2 (45.3 mg, 0.256 mmol). The reaction mixture was heated to reflux for 16 h, then cooled to ambient temperature, filtered through Celite bed and washed with EtOAc. The filtrate was again extracted with EtOAc, and the combined organic layer washed with water and brine, dried over Na2SO4 and concentrated under reduced pressure to afford the crude compound. The crude compound was purified by column chromatography (SiO2, 100-200 mesh; 2% EtOAc/petroleum ether) to afford the title compound as a light brown gummy material (1.5 g, 83%): 1H NMR (400 MHz, CDCl3) δ 8.20 (br, 1H), 7.68 (s, 1H), 7.45 (s, 2H), 7.21 (m, 1H), 6.90 (dd, J=16.0, 10.8 Hz, 1H), 6.55 (m, 1H), 5.75 (d, J=10.5 Hz, 1H), 5.21 (d, J=10.5 Hz, 1H); ESIMS m/z 142.05 ([M-H]-).

  • 5
  • [ 372198-69-1 ]
  • potassium vinyltrifluoroborate [ No CAS ]
  • [ 1004550-09-7 ]
YieldReaction ConditionsOperation in experiment
92% With triethylamine;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In propan-1-ol; at 100℃; for 18h; Ethyl 6-bromoimidazo[l,2-alpha]pyridine-3-carboxylate (1.50 g, 5.58 mmol), potassium vinyltrifiuoroborate (1.49 g, 11.2 mmol), PdCl2(dppf)-CH2Cl2 (228 mg, 0.28 mmol), triethylamine (1.60 mL, 11.2 mmol) and n-PrOH (50 mL) were combined in a sealed tube, purged with N2 and heated to 100 0C. After 18 h, the reaction mixture was cooled to rt and concentrated under reduced pressure. The residue was diluted with EtOAc, washed with water and brine and the aqueous layers were back-extracted with EtOAc. The combine extracts were dried overNa2SO4 and decolorizing carbon, filtered through a pad of Celite and concentrated under reduced pressure. The residue was purified by silica gel chromatography (EtOAc) to give 1.11 g (92%) of the title compound as a red solid. MS(ES)+ m/e 217.0 [M+H]+.
  • 6
  • [ 1004550-10-0 ]
  • [ 13682-77-4 ]
  • [ 1004550-11-1 ]
YieldReaction ConditionsOperation in experiment
89% With triethylamine In propan-1-ol at 100℃; for 4h; 2.b 6-Bromo-Λ/-ethylimidazo[l,2-α]pyridine-3-carboxamide (402 mg, 1.50 mmol), potassium vinyltrifluoroborate (402 mg, 3.0 mmol), PdCl2(dppf)-CH2Cl2 (61 mg, 0.08 mmol), triethylamine (0.42 mL (3.0 mmol) and n-PrOH (15 mL) were combined in a sealed tube, purged with N2 and heated to 100 0C. After 4 h, the reaction mixture was cooled to rt and concentrated under reduced pressure. The residue was purified by silica gel chromatography (96.5:3.0:0.5 CH2Cl2/MeOH/conc. NH4OH) to give 287 mg (89%) of the title compound as a tan foam. MS(ES)+ m/e 216.0 [M+H]+.
  • 7
  • [ 1004550-13-3 ]
  • [ 13682-77-4 ]
  • [ 1004550-14-4 ]
YieldReaction ConditionsOperation in experiment
85% With triethylamine In propan-1-ol at 100℃; for 18h; 3.d 6-Bromo-3-(4-pyridinyl)imidazo[l,2-α]pyridine (1.50 g, 5.47 mmol), potassium vinyltrifluoroborate (1.46 g, 10.9 mmol), PdCl2(dppf)-CH2Cl2 (223 mg, 0.274 mmol), triethylamine (1.5 mL, 10.9 mmol) and n-PrOH (50 mL) were combined in a sealed tube, purged with N2 and heated to 100 0C. After 18 h, the reaction mixture was cooled to rt and concentrated under reduced pressure. The residue was diluted with EtOAc, washed with water and brine and the aqueous layers were back-extracted with EtOAc. The combine extracts were dried over Na2SO4 and decolorizing carbon, filtered through a pad of Celite and concentrated under reduced pressure. The residue was purified by silica gel chromatography (96.5:3.0:0.5 CH2Cl2/MeOH/conc. NH4OH) to give 1.04 g (85%) of the title compound as a grey solid. MS(ES)+ m/e 221.9 [M+H]+.
  • 8
  • [ 393-36-2 ]
  • potassium vinyltrifluoroborate [ No CAS ]
  • [ 863676-04-4 ]
YieldReaction ConditionsOperation in experiment
79% With tert-butylamine;PdCl2(dppf)2.2(dichloromethane) complex; In water; isopropyl alcohol; at 80℃; for 20h; Example 185 1-[4-(2-Dimethylamino-ethyl)-3-(trifluoromethyl)-phenyl]-3-[4-(6-(methylamino)purin-9-yl)phenyl]urea (Table 2, Compound No. 68) Step A Preparation of 3-trifluoromethyl-4-vinylaniline [Show Image] [Show Image] In 20 mL of isopropanol, 10 mL of water and 5 mL of t-butylamine, 4.0g (16.7 mmol) of <strong>[393-36-2]4-bromo-3-(trifluoromethyl)aniline</strong> was dissolved, and 4.0 g (29.9 mmol) of potassium (trifluoro)vinylborate and 300 mg (0.37 mmol) of PdCl2(dppf)2·2(dichloromethane) complex were added thereto, and the mixture solution was stirred in an argon atmosphere at 80C for 20 hours. The reaction solution was concentrated and the residue was partitioned between water and ethyl acetate, and the organic layer was washed with a saturated sodium chloride solution and concentrated under reduced pressure. The product was purified by a silica gel column (n-hexane:ethyl acetate=6:1) to obtain 2.475 g (79%) of a target product as a pale yellow oil. 1H-NMR (270 MHz, CDCl3) delta (ppm): 3.84(2H,s), 5.20(1H,dd,J=1.8, 10.9 Hz), 5.56(1H,d,J=17.1 Hz), 6.78(1H,dd,J=10.9, 17.1Hz), 6.88-7.04(2H,m), 7.48(1H, d,J=8.4 Hz) ESI (LC-MS positive mode) m/z 188 (M+H)
79% With tert-butylamine;PdCl2(1,1?-bis(diphenylphosphino)ferrocene)*2(dichloromethane); In water; isopropyl alcohol; at 80℃; for 20h; Preparation of 3-trifluoromethyl-4-vinylaniline <strong>[393-36-2]4-Bromo-3-(trifluoromethyl)aniline</strong> (4.0 g, 16.7 mmol) was dissolved in isopropanol (20 mL), water (10 mL), and t-butylamine (5 mL). To the solution, potassium(trifluoro)vinylborate (4.0 g, 29.9 mmol), PdCl2(dppf)2·2-dichloromethane complex (300 mg, 0.37 mmol) were added. The resulting mixture was stirred under argon atmosphere at 80C for 20 hours and then concentrated. The residue was partitioned between water and ethyl acetate, and the organic layer was washed with saturated brine and concentrated under reduced pressure. The resulting product was purified by silica-gel column chromatography (n-hexane: ethyl acetate = 6:1) to give 3-trifluoromethyl-4-vinylaniline (2.475 g, 79%) as a light-yellow oil. 1H-NMR (270MHz, CDCl3) delta (ppm): 3.84 (2H, s), 5.20 (1H, dd, J=1.8, 10.9Hz), 5.56 (1H, d, J=17.1Hz), 6.78 (1H, dd, J=10.9, 17.1Hz), 6.88-7.04 (2H, m), 7.48 (1H, d, J=8.4Hz).
  • 9
  • [ 863675-93-8 ]
  • [ 13682-77-4 ]
  • [ 863675-94-9 ]
YieldReaction ConditionsOperation in experiment
75% With diisopropylamine In propan-1-ol at 80℃; for 7h; 166.B Preparation of methyl-(9-{4-[3-(3-trifluoromethyl-4-vinylphenyl)ureido]phenyl}-9H-purin-6-yl)-carbamic acid tert-butyl ester Step B Preparation of methyl-(9-{4-[3-(3-trifluoromethyl-4-vinylphenyl)ureido]phenyl}-9H-purin-6-yl)-carbamic acid tert-butyl ester [Show Image] In 10 mL of 1-propanol and 680 µL of diisopropylamine, 900 mg (1.48 mmol) of (9-{4-[3-(4-bromo-3-(trifluoromethyl)phenyl)ureido]phenyl}-9H-purin-6-yl)-methyl-carbamic acid tert-butyl ester was dissolved, and 330 mg (2.46 mmol) of potassium (trifluoro)vinylborate and 70 mg(0.09 mmol) of dichlorobistriphenylphosphine palladium were added thereto and the mixture solution was stirred at 80°C for seven hours in an argon atmosphere. The reaction solution was concentrated, and the residue was partitioned between water and ethyl acetate, and the organic layer was washed with a saturated sodium chloride solution and concentrated under reduced pressure. The product was purified by a silica gel column (ethyl acetate) to obtain 618 mg (75%) of a target product as a white crystal. 1H-NMR (270 MHz, DMSO-d6) δ (ppm): 1.46(9H,s), 3.40(3H,s), 5.40(1H,d,J=11.9 Hz), 5.86(1H,d,J=17.1 Hz), 6.91(1H,dd,J=11.9, 17.1 Hz), 7.60-7.80(6H,m), 8.02(1H,d,J=2.6 Hz), 8.79(1H,s), 8.91(1H,s), 9.12(1H,s) 9.20(1H,s) ESI (LC-MS positive mode) m/z 554 (M+H)
  • 10
  • [ 870997-72-1 ]
  • [ 13682-77-4 ]
  • [ 870997-73-2 ]
YieldReaction ConditionsOperation in experiment
82% With triethylamine In butan-1-ol at 100℃; for 24h; 4.3 (3) 5-Bromo-2-[(1-cyclobutylpiperidin-4-yl)oxy]pyridine (3.80 g, 12.2 mmol), potassium vinyltrifluoroborate (2.45 g, 18.3 mmol), (1,1'-bis(diphenylphosphino)ferrocene)dichloropalladium (498 mg, 0.605 mmol), and triethylamine (1.69 mL, 12.2 mmol) were stirred in n-butanol (30 mL) at 100°C for 24 hours. After cooled, the solvent and others were evaporated off under reduced pressure, and the residue was purified through silica gel column chromatography (hexane/ethyl acetate = 9/1 to 1/1 to 0/1) to obtain the intended compound (2.59 g, 82 %) as a brown solid.
  • 11
  • [ 103966-66-1 ]
  • potassium vinyltrifluoroborate [ No CAS ]
  • [ 883901-80-2 ]
YieldReaction ConditionsOperation in experiment
77% With triethylamine;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In propan-1-ol; at 100℃; for 3h;Inert atmosphere; 4.32 g (31.31 mmol) of potassium trifluorovinylborate and 3.12 mL (22.37 mmol) of triethylamine are added to a mixture of 5.19 g (22.37 mmol) of the product prepared in step 4.1 in 56 mL of n-propanol, under argon, and argon is bubbled through for 10 minutes. 0.36 g (0.45 mmol) of PdCl2dppf.CH2Cl2 is added and the mixture is heated under argon at 100 C. for 3 hours. After cooling to room temperature, the reaction mixture is concentrated to dryness and then taken up in a dichloromethane/water mixture. After separation of the phases by settling, the organic phase is washed twice with water and once with saturated aqueous NaCl. The organic phase is dried over Na2SO4, filtered and concentrated under vacuum. The residue obtained is purified by chromatography on a column of silica, eluting with a cyclohexane/ethyl acetate gradient (95/5 to 70/30). 3.1 g of the expected product are obtained in the form of a brown oil, which is used as obtained in the following step. Yield=77%.
58% With triethylamine;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In propan-1-ol; at 100℃; for 3h; To 5-bromo-2-nitrophenyl methyl ether (8.0 g, 34.47 mmol) in 80 mL of n-propanol was added, PdCl2(dppf)*DCM (0.5 g, 0.69 mmol), potassium ethenyl(trifluoro)borate (6.47 g, 48.3 mmol), and TEA (3.48 g, 34.47 mmol). The mixture was heated to 100 C. for 3 h. The mixture was poured into 250 mL of H2O and extracted with DCM, dried (Na2SO4), filtered, and rotovaped down, and purified by flash chromatography to give the title compound of step B (3.58 g, 19.98 mmol, 58%). 1H NMR (400 MHz, CDCl3) delta ppm 7.82-7.87 (m, 1H), 7.02-7.07 (m, 2H), 6.70 (dd, J=17.58, 10.80 Hz, 1H), 5.87 (d, J=17.58 Hz, 1H), 5.46 (d, J=10.99 Hz, 1H), 3.97 (s, 3H).
  • 12
  • [ 330794-02-0 ]
  • [ 13682-77-4 ]
  • [ 2092669-80-0 ]
YieldReaction ConditionsOperation in experiment
86% With triethylamine In propan-1-ol at 100℃; for 3h; 127.B To 5-bromo-4-fluoro-2-nitrophenyl methyl ether (4.0 g, 16 mmol) in 40 mL of n-propanol was added, PdCl2(dppf)*DCM (0.234 g, 0.31 mmol), potassium ethenyl(trifluoro)borate (2.57 g, 19.2 mmol), and TEA (1.62 g, 16 mmol). The mixture was heated to 100° C. for 3 h. The mixture was poured into 250 mL of H2O and extracted with DCM, dried (Na2SO4), filtered, and rotovaped down to give the title compound of step B (2.73 g, 13.84 mmol, 86%). 1H NMR (400 MHz, CDCl3) δ ppm 7.64 (d, J=9.52 Hz, 1H), 7.11 (d, J=6.04 Hz, 1H), 6.84 (dd, J=17.76, 11.17 Hz, 1H), 5.95 (d, J=17.76 Hz, 1H), 5.59 (d, J=11.17 Hz, 1H), 3.97 (s, 3H).
  • 13
  • [ 623-00-7 ]
  • [ 13682-77-4 ]
  • [ 3435-51-6 ]
  • [ 6292-62-2 ]
YieldReaction ConditionsOperation in experiment
1: 82% 2: 3% With 2C8H8NO2(1-)*2Cl(1-)*2Pd(2+); tetrabutylammomium bromide; potassium carbonate In water at 120℃; for 14h; Sealed vessel;
  • 14
  • [ 845827-13-6 ]
  • potassium vinyltrifluoroborate [ No CAS ]
  • [ 1186518-59-1 ]
YieldReaction ConditionsOperation in experiment
75% With caesium carbonate;triphenylphosphine; palladium dichloride; In tetrahydrofuran; water; at 80℃; for 16h; To a stirred suspension of potassium vinyltrifluoroborate (3.32 g, 24.8 mmol), PdCl2 (0.1 g, 0.56 mmol) and PPh3 (0.45 g, 1.71 mmol) in 60 mL of THF-H2O (9:1) were added Cs2CO3 (20.2 g, 62 mmol) and <strong>[845827-13-6]5-bromo-2-(difluoromethyl)pyridine</strong> (4.3 g, 20.7 mmol). The resulting reaction mixture was heated to 80 0C and stirred for 16 h. After completion of the reaction, the reaction mixture was cooled to room temperature, treated with water and extracted with CH2Cl2. The organic layer was dried over anhydrous Na2SO4 and the solvents were evaporated in vacuo. The residue was purified by column chromatography (SiO2, 5% Et2O/pentane) to afford the title compound (2.46 g, 75% yield). MS: 156 [M+l]+; 1H-NMR (300 MHz, CDCl3): delta 8.64 (s, IH), 7.86 (d, IH, J= 8.3 Hz), 7.60 (d, IH, J= 8.3 Hz), 6.74 (dd, IH, J= 18, 11.2 Hz), 6.63 (t, IH, J= 55.6 Hz), 5.91 (d, IH, J= 18 Hz), 5.48 (d, IH, J= 11.2 Hz).
  • 15
  • [ 1195768-23-0 ]
  • potassium vinyltrifluoroborate [ No CAS ]
  • [ 1195769-46-0 ]
YieldReaction ConditionsOperation in experiment
84% With triethylamine;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In propan-1-ol; at 100℃; Example 251; N-[3-(2-(1,1-dimethylethyl)-5-{2-[2-(methylsulfonyl)ethyl]-4-pyrimidinyl}-1,3-thiazol-4-yl)-2-fluorophenyl]-2,6-difluorobenzenesulfonamide; Step A: N-{3-[2-(1,1-dimethylethyl)-5-(2-ethenyl-4-pyrimidinyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide; <strong>[1195768-23-0]N-{3-[5-(2-chloro-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide</strong> (0.421 g, 0.781 mmol), potassium vinyl trifluoroborate (0.262 g, 1.953 mmol), PdCl2(dppf)2 (0.057 g, 0.078 mmol), and triethylamine (1.089 ml, 7.81 mmol) in n-propanol (7.81 ml) were heated at 100 C. in a screw-top vial overnight. The reaction mixture was filtered through celite and the celite rinsed with EtOAc. The combined organic portions were washed with water, dried over MgSO4, filtered and concentrated to dryness. The crude mixture was placed on silica gel and chromatography (0 to 80% DCM/EtOAc, gradient) to obtain the title compound (350 mg, 84%). 1H NMR (400 MHz, DMSO-d6) d ppm 10.88 (s, 1H), 8.56 (d, J=5.31 Hz, 1H), 7.67 (ddd, J=14.28, 8.15, 6.13 Hz, 1H), 7.43 (t, J=7.60 Hz, 2H), 7.31 (t, J=7.69 Hz, 1H), 7.22 (t, J=9.25 Hz, 2H), 6.74 (m, 2H), 6.44 (dd, J=17.58, 1.65 Hz, 1H), 5.75 (dd, J=10.62, 2.01 Hz, 1H), 1.43 (m, 9H); MS (ESI): 531 [M+H]+.
  • 16
  • [ 1208864-44-1 ]
  • [ 13682-77-4 ]
  • [ 1208864-25-8 ]
YieldReaction ConditionsOperation in experiment
90% With triethylamine In tetrahydrofuran; isopropyl alcohol at 60℃; 11.I; 14.C To tert-butyl (l-(2-(7-iodo-[l,2,4]triazolo[4,3-a]pyridin-3-yl)quinolin-8-yl)piperidin-4-yl)methylcarbamate (91 mg, 0.16 mmol) in THF/IPA (2/ImL) was added C2H3BF3K (31 mg, 0.23 mmol), PdCl2(dppf) dichloromethane adduct (13 mg, 0.016 mmol) and triethylamine (24 mg, 0.23 mmol). The reaction was stirred for 2 hours, and then heated at 60 0C overnight. The reaction was cooled to ambient temperature and concentrated. The crude material was purified by silica gel chromatography (20:1 Hexane/EtOAc) to provide the final product.; Step C : Preparation of tert-butvUl-(2-(7-vinyl-ri.2.41triazolor4.3-alpyridin-3- yl)quinolin-8-yl)piperidin-4-yl)methylcarbamate: To tert-butyl (l-(2-(7-iodo-[l,2,4]triazolo[4,3-a]pyridin-3-yl)quinolin-8-yl)piperidin-4-yl)methylcarbamate (91 mg, 0.16 mmol) in THF/IPA (2/ImL) was added C2H3BF3K (31 mg, 0.23 mmol), PdCl2(dppf) dichloromethane adduct (13 mg, 0.016 mmol) and triethylamine (24 mg, 0.23 mmol). The reaction was stirred for 2 hours, followed by heating at 60 0C overnight. The reaction was then cooled to ambient temperature and concentrated, and the residue was purified by flash column chromatography (20:1 Hexane/EtOAc) providing the desired product (90% yield; 0.068 g).
  • 17
  • [ 1236971-07-5 ]
  • [ 13682-77-4 ]
  • [ 1236971-08-6 ]
YieldReaction ConditionsOperation in experiment
92% With caesium carbonate; triphenylphosphine In tetrahydrofuran-water; ethyl acetate; Petroleum ether 1 1.4 2,5,7-Trimethyl-1-oxo-6-vinyl-indan-2-carboxylic acid ethyl ester (6) 1.4 2,5,7-Trimethyl-1-oxo-6-vinyl-indan-2-carboxylic acid ethyl ester (6) A solution of potassium vinyltrifluoroborate (0.186 g, 1.38 mmol), PdCl2, (0.033 g, 0.18 mmol), PPh3 (0.073 g, 0.27 mmol), Cs2CO3 (1.2 g, 3.69 mmol) and compound 5 (0.3 g, 0.92 mmol) in THF/H2O (9:1) (3 mL) was heated at 85° C. under an Argon atmosphere in a sealed tube. The reaction mixture was stirred at 85° C. for 48 h, then cooled to room temperature and diluted with H2O (6 mL) followed by extraction with ethyl acetate (30 mL), dried (Na2SO4) and concentrated in vacuo. Purification by column chromatography (SiO2, 2 to 4% EtOAc in petroleum ether eluant) gave pure compound 6 (0.23 g, 92%).
92% With caesium carbonate; triphenylphosphine; palladium dichloride In tetrahydrofuran; water at 85℃; for 48h; Inert atmosphere; Sealed tube; 1.4 1.4 2,5,7-Trimethyl-1-oxo-6-vinyl-indan-2-carboxylic acid ethyl ester (6) A solution of potassium vinyltrifluoroborate (0.186 g, 1.38 mmol), PdCl2, (0.033 g, 0.18 mmol), PPh3 (0.073 g, 0.27 mmol), Cs2CO3 (1.2 g, 3.69 mmol) and compound 5 (0.3 g, 0.92 mmol) in THF/H2O (9:1) (3 mL) was heated at 85 °C under an Argon atmosphere in a sealed tube. The reaction mixture was stirred at 85 °C for 48 h, then cooled to room temperature and diluted with H2O (6 mL) followed by extraction with ethyl acetate (30 mL), dried (Na2SO4) and concentrated in vacuo. Purification by column chromatography (SiO2, 2 to 4% EtOAc in petroleum ether eluant) gave pure compound 6 (0.23 g, 92 %).
90% With caesium carbonate; triphenylphosphine; palladium dichloride In tetrahydrofuran; water at 85℃; for 48h; Inert atmosphere; Sealed tube; 4.2.4 2,5,7-Trimethyl-1-oxo-6-vinyl-indan-2-yl-carboxylic acid ethyl ester 2 A solution of potassium vinyltrifluoroborate, 9 (186 mg, 1.38 mmol), PdCl2 (33 mg, 0.18 mmol), PPh3 (73 mg, 0.27 mmol), Cs2CO3 (1.2 g, 3.7 mmol), and compound 3 (0.30 g, 0.92 mmol) in THF/ H2O (9:1) (3 mL) was heated at 85 °C with stirring under an argon atmosphere in a sealed tube for 48 h. After cooled to room temperature, the reaction mixture was diluted with H2O (6 mL) and extracted with ethyl acetate (3×10 mL). The combined extract was dried (anhydrous Na2SO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (4% EtOAc in petroleum ether as eluent) to give an inseparable mixture of compounds 2 and 10 (0.23 g, 90% in total yield). Compound 2: 1H NMR: δ 1.21 (t, J=7.2 Hz, 3H), 1.46 (s, 3H), 2.33 (s, 3H), 2.59 (s, 3H), 2.83 (d, J=16.8 Hz, 1H), 3.58 (d, J=16.8 Hz, 1H), 4.15 (m, 2H), 5.22 (dd, J=18.0, 2.0 Hz, 1H), 5.61 (dd, J=11.2, 2.0 Hz, 1H), 6.61 (dd, J=11.2, 18.0 Hz, 1H), 7.11 (s, 1H); 13C NMR: δ 13.94, 14.05, 21.21, 21.80, 38.84, 56.26, 61.21, 120.71, 124.92, 130.13, 133.80, 137.46, 138.49, 143.90, 151.93, 172.30, 203.8; HRMS: calcd for C17H20O3: 272.1412, found: 272.1416; IR (KBr) 3083, 1736, 1705, 1439.
  • 18
  • [ 1237838-71-9 ]
  • [ 13682-77-4 ]
  • [ 1237840-18-4 ]
YieldReaction ConditionsOperation in experiment
92% Stage #1: 3-[1-(6-bromo-3-chloro-8-trifluoromethyl-imidazo[1,2-a]pyridine-2-carbonyl)-piperidin-4-yl]-oxazolidin-2-one; potassium vinyltrifluoroborate With triethylamine In propan-1-ol at 90℃; for 0.5h; Stage #2: With sodium periodate; osmium(VIII) oxide In tetrahydrofuran; water at 20℃; for 3h; 56.A Example 563-(l- { [3-chlor o-6-(difluor omethyl)-8-(trifluoromethyl)imidazo [ 1 ,2-a] pyridin-2- yl]carbonyl}-4-piperidinyl)-l,3-oxazolidin-2-one (Compound 157) Step A : 3-chloro-2-[4-(2-oxo-l,3-oxazolidin-3-yl)-l-piperidinyl]carbonyl}-8- (trifluoromethyl)imidazo [ 1 ,2-α] pyridine-6-carbaldehydeA solution of 3-(l-[6-bromo-3-chloro-8-(trifluoromethyl)imidazo[l,2-a]pyridin-2-yl]carbonyl}- 4-piperidinyl)-l,3-oxazolidin-2-one (500 mg, 1.009 mmol), potassium vinyl trifluoroborate (270 mg, 2.017 mmol), Et3N (0.703 mL, 5.04 mmol) and PdCl2(dppf)-CH2Cl2 adduct (82 mg, 0.101 mmol) in propanol (5 mL) was stirred at 90 0C for 30 minutes. The reaction mixture was diluted with EtOAc and washed with water. The solvent was removed and the crude material was diluted with THF (5.00 mL) and water (5.00 mL). Osmium tetroxide (4.0% in water) (0.791 mL, 0.101 mmol) and sodium periodate (647 mg, 3.03 mmol) was added and the mixture was stirred at RT for 3 hours. The reaction mixture was diluted with EtOAc and washed with water. The solvent was removed and the crude material was purified via silica gel chromatography to give 3-chloro- 2- [4-(2-oxo- 1 ,3-oxazolidin-3-yl)- 1 -piperidinyljcarbonyl} -8-(trifluoromethyl)imidazo[ 1 ,2- a]pyridine-6-carbaldehyde (412 mg, 0.926 mmol, 92 % yield). ES-LCMS : 445.5 (M+l)
  • 19
  • [ CAS Unavailable ]
  • [ 13682-77-4 ]
  • [ 1255209-07-4 ]
YieldReaction ConditionsOperation in experiment
90% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine In ethanol at 85℃; for 12h; Inert atmosphere; Sealed tube; Intermediate 42C: 4cye1opropyI-5vinyIisobenzofuran I (3H)one To a stirred solution of intermediate 42B (C. 84 ,3. 32 mmol) and potassium vinyltrifluoroborate (0.53 g, 3.98 mmol) in EtOH (25 rnL) was added TEA (1.39 mL, 9.96 mmol) and resulting mixture was degassed with nitrogen for 10 minutes. ThenPdCl2(dppfThCH2Cl2 (0(33 g, 0.03 rnmol) was added and the resulting mixture was sealed and heated to 85 °C for 12 h. The reaction mixture was cooled to ambient temperature, filtered through celite and washed with ethyl acetate (100 mL) and the filtrate was evaporated under reduced pressure. The residue was purified by column chromatography (Redisep-24 g, 0-10% EtOAc/n-[lexane) to obtain intermediate 42C (0.60 g, 90.00%) as an off white solid. ‘H NMR(400 MHz, DMSO-do) ö ppm 0.63 0.64 (m, 2 H), 0.97 1.01 (m, 2 H), 5.50 (s, 2 H), 5.52 5.56(dd,J 1.2 Hz,J 11.2 Hz, 2 H), 5.92 5.96 (dd.J 0.8 Hz,J 17.6Hz, 1 H), 735-742(dd,] 11.2Hz,] 17.6 Hz, I H), 7.67-7.69 (d, J= 8Hz, 1 H), 7.77-7.79 (d, J 7.6 Hz, IFl). LCMS (Method-I): retention time 1.25 miii, [M+Fl] 201.4.
With triethylamine In ethanol for 8h; Reflux; Inert atmosphere; D A mixture of 5-bromo-4-cyclopropyl-2-benzofuran-l(3H)-one (760 mg, 3.004 mmol), potassium vinyltrifluoroborate (805 mg, 6.008 mmol) and Pd(dppf)Cl2 (100 mg) in 20 mL of TEA and 20 mL of EtOH was heated to reflux under N2 for 8 hours. When TLC showed complete reaction most of the solvent was removed, and the residue was dissolved in EtOAc (100 mL). The solution was washed with 0.1 N HCl, sodium bicarbonate, and brine, dried over sodium sulfate, filtered and concentrated. The resulting oil was purified by column chromatography to give 4- cyclopropyl- 5 - vinyl-2-benzofuran- 1 (3H)-one . 1H-NMR (400 MHz5 CDCl3) δ ppra 7.74 (d, J=8.6 Hz5 IH), 7.67 (d, J=7.8 Hz, IH)5 7.34-7.41 (m, IH), 5.81 (d, /=17.2 Hz, IH), 5.50 (d5 J=I l .0 Hz5 IH)5 5.38 (s, 2H), 1.84-1.90 (m, IH), 1.04- 1.09 (m, 2H), 0.61-0.65 (m, 2H).
With Pd(dppf)Cl2 In ethanol; triethylamine for 8h; Reflux; Inert atmosphere; 34.D Step D: 4-cyclopropyl-5-vinyl-2-benzofuran-1(3H)-one Step D: 4-cyclopropyl-5-vinyl-2-benzofuran-1(3H)-one: A mixture of 5-bromo-4-cyclopropyl-2- benzofuran-1(3H)-one (760 mg, 3.004 mmol), potassium vinyltrifluoroborate (805 mg, 6.008mmol) and Pd( dppf)Cl2 (1 00 mg) in 20 mL of TEA and 20 mL of EtOH was heated to refluxunder N2 for 8 hours. When TLC showed complete reaction most of the solvent was removed,and the residue was dissolved in EtOAc (100 mL). The solution was washed with 0.1 N HCl,sodium bicarbonate, and brine, dried over sodium sulfate, filtered and concentrated. The resulting oil was purified by column chromatography to give 4-cyclopropyl-5-vinyl-2-benzofuran-1 (3H)-one.
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; triethylamine In ethanol for 8h; Reflux; Inert atmosphere; 50.D Step D: 4-cyclopropyl-5-vinyl-2-benzofuran-l(3H -one: A mixture of 5-bromo-4-cyclopropyl-2- benzofuran-l(3H)-one (760 mg, 3.004 mmol), potassium vinyltrifluoroborate (805 mg, 6.01 mmol) and Pd(dppf)Cl2 (100 mg) in 20 mL of TEA and 20 mL of EtOH was heated to reflux under N2 for 8 hours. After TLC showed complete reaction, then most of the solvent was removed and the residue was dissolved in EtOAc (100 mL). The solution was washed with 0.1 N HCl, sodium bicarbonate, and brine, dried over sodium sulfate, filtered and concentrated. The resulting oil was purified by column chromatography to give the title compound.
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; triethylamine In ethanol for 8h; Reflux; Inert atmosphere; 8.D Step D: 4-cyclopropyl-5-yinyl-2-benzofuran-1(3H)-one: A mixture of 5-bromo-4-cyclopropyl-2- benzofuran-1(3H)-one („760 mg, 3.004 mmol), potassium yinyltrifluoroborate (805 mg, 6.008mmol) and Pd(dppf)C12 (100 mg) in 20 m of TEA and 20 m of EtOH was heated to reflux under N2 for 8 hours. When TLC showed complete reaction most of the solyent was remoyed, and the residue was dissolyed in EtOAc (100 mL). The solution was washed with 0.1 N HC1, sodium bicarbonate, and brine, dried oyer sodium sulfate, filtered and concentrated. The resulting oil was purified by column chromatography to giye 4-cyclopropyl-5-yinyl-2-benzofuran- 1 (3H)-one.
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; triethylamine In ethanol for 8h; Inert atmosphere; Reflux; D Step D: 4-cyclopropyl-5 -vinyl-2-benzofuran- 1 (3Th-one: Step D: 4-cyclopropyl-5 -vinyl-2-benzofuran- 1 (3Th-one: A mixture of 5 -bromo-4-cyclopropyl-2-benzofuran-1(3H)-one (760 mg, 3.004 mmol), potassium vinyltrifluoroborate (805 mg, 6.008mmol) and Pd(dppf)C12 (100 mg) in 20 mL of TEA and 20 mL of EtOH was heated to reflux under N2 for 8 hours. When TLC showed complete reaction most of the solvent was removed, and the residue was dissolved in EtOAc (100 mL). The solution was washed with 0.1 N HC1, sodium bicarbonate, and brine, dried over sodium sulfate, filtered and concentrated. Theresulting oil was purified by column chromatography to give 4-cyclopropyl-5-vinyl-2- benzofuran- 1 (3H)-one.
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; triethylamine In ethanol for 8h; Reflux; Inert atmosphere; D Step D: 4-cyclopropyl-5-vinyl-2-benzofuran-1(3H)-one General procedure: A mixture of 5-bromo-4-cyclopropyl-2-benzofuran-1(3H)-one(760 mg, 3.004 mmol), potassium vinyltrifluoroborate (805 mg, 6.008 mmol) and Pd(dppf)Cl2 (100 mg) in 20 mL ofTEA and 20 mL of EtOH was heated to reflux under N2 for 8 hours. When TLC showed complete reaction most ofthe solvent was removed, and the residue was dissolved in EtOAc (100 mL). The solution was washed with 0.1 NHCl, sodium bicarbonate, and brine, dried over sodium sulfate, filtered and concentrated. The resulting oil waspurified by column chromatography to give 4-cyclopropyl-5-vinyl-2-benzofuran-1(3H)-one.

  • 20
  • [ 1257705-04-6 ]
  • [ 13682-77-4 ]
  • [ 1257706-92-5 ]
YieldReaction ConditionsOperation in experiment
87% With triethylamine In propan-1-ol at 90℃; for 6h; Inert atmosphere; 196.196a To a suspension of 8-bromo-2-chloro-[l,2,4]triazolo[l,5-a]pyridine (0.50 g, 2.2 mmol), potassium vinyltrifluoroborate (0.34 g, 2.6 mmol) and [1,1'- bis(diphenylphosphino)ferrocene]dichloropalladium(II),complex with dichloromethane (1 :1) (35 mg, 0.043 mmol) in 1-propanol (10 mL) was added triethylamine (0.30 mL, 2.2 mmol). The mixture was heated at 900C for 6 hours under an atmosphere of nitrogen. The mixture was cooled to room temperature and the volatiles were evaporated under reduced pressure. The residue was diluted with dichloromethane (50 mL) and filtered through a plug of diatomaceous earth. The filtrate was washed with 2N Hydrochloric acid (2 x 10 mL) and saturated aqueous sodium chloride, dried over magnesium sulfate, filtered and evaporated. The residue was purified via chromatography (silica gel column 24 g and0%→2% methanol: dichloromethane). 2-Chloro-8-vinyl-[l,2,4]triazolo[l,5-a]pyridine was isolated as a white solid (0.336 g, 87%). 1H NMR (400 MHz, CDCl3, δ, ppm): 8.40 (d, J=6.8 Hz, IH), 7.53 (d, J=7.3 Hz, IH), 7.08-6.94 (m, 2H), 6.59 (d, J=17.6 Hz, IH), 5.70 (d, J=I 1.2 Hz, IH). MS = 180, 182 (MH)+.
  • 21
  • [ 65000-13-7 ]
  • [ 13682-77-4 ]
  • [ 51119-86-9 ]
YieldReaction ConditionsOperation in experiment
70% With bis-triphenylphosphine-palladium(II) chloride; water; caesium carbonate In tetrahydrofuran at 85℃; for 22h; Inert atmosphere;
  • 22
  • [ 174265-12-4 ]
  • [ 13682-77-4 ]
  • [ 1313762-44-5 ]
YieldReaction ConditionsOperation in experiment
88% With palladium diacetate; Cs2CO3; triphenylphosphine In tetrahydrofuran; lithium hydroxide monohydrate at 70℃;
86% With palladium diacetate; Cs2CO3; triphenylphosphine In tetrahydrofuran; lithium hydroxide monohydrate at 70℃; for 16h; Inert atmosphere;
81% With Cs2CO3; triphenylphosphine; palladium (II) chloride In tetrahydrofuran; lithium hydroxide monohydrate at 85℃; for 22h; sealed tube; Inert atmosphere;
80% With Cs2CO3; triphenylphosphine; palladium (II) chloride In tetrahydrofuran; lithium hydroxide monohydrate at 85℃; for 6h; Sealed tube; 5-Chloro-2-vinylbenzaldehyde (MDW-1-75) According to a literature procedure, a resealable tube was charged with 2-bromo-5-chlorobenzaldehyde (1.800 g, 27.34 mmol), potassium vinyltrifluoroborate (1.428 g, 10.66 mmol), PdC12 (0.117 g, 0.660 mmol),triphenylphosphine (0.517 g, 1.97 mmol), and cesium carbonate (8.022 g, 24.62 mmol).’ A solution of degassed THF/water (20.5 mL, 9:1) was added to the tube, whereupon it was sealed and stirred at 85 °C for 6 h. The reaction mixture was allowed to cool to room temperature, diluted with water (30 mL), and extracted using Et20 (3 x 30 mL). The organic layer was washed with brine (1 x 30 mL), dried (Na2SO4), and concentrated under reduced pressure toprovide an orange oil. The crude residue was purified via flash chromatography (Si02), eluting with 1 hexanes/EtOAc (99:1) affording 1.091 g (80%) of MDW-1-75 as a pale yellow solid. ‘H NMR consistent with those reported in literature
80% With Cs2CO3; triphenylphosphine; palladium (II) chloride In tetrahydrofuran; lithium hydroxide monohydrate
With palladium diacetate; Cs2CO3; triphenylphosphine In tetrahydrofuran; lithium hydroxide monohydrate at 20 - 90℃;
With palladium diacetate; Cs2CO3; triphenylphosphine In tetrahydrofuran; lithium hydroxide monohydrate at 70℃; for 4h;
With palladium diacetate; Cs2CO3; triphenylphosphine In tetrahydrofuran; lithium hydroxide monohydrate at 70℃; for 4h; Inert atmosphere;

  • 23
  • [ 149104-99-4 ]
  • [ 13682-77-4 ]
  • [ 1253924-10-5 ]
YieldReaction ConditionsOperation in experiment
90% With caesium carbonate In tetrahydrofuran; water at 85℃; for 21h; Inert atmosphere; sealed tube; 10-2 A mixture of 4-bromo-3,N,N-trimethyl-benzamide (798 mg, 3.30 mmol), potassium vinyltrifluoroborate (579 mg, 4.32 mmol), PdCl2 (59.0 mg, 0.333 mmol), PPh3 (265 mg, 1.01 mmol) and Cs2CO3 (3.22 g, 9.90 mmol) in THF (6.5 ml)-H2O (0.65 ml) was heated with stirring at 85°C for 21 hours in a sealed test tube in an N2 atmosphere. The reaction mixture was cooled to room temperature and then extracted with ether. The organic layer was washed with water, and then dried over MgSO4 and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate = 2/1) to give 3,N,N-trimethyl-4-vinyl-benzamide (565 mg, 90%). 1H-NMR (400 MHz) (CDCl3) δ 2.36 (3H, s), 3.00 (3H, br s), 3.10 (3H, br s), 5.35 (1H, dd, J = 11.0 and 1.0 Hz), 5.68 (1H, dd, J = 17.5 and 1.0 Hz), 6.93 (1H, dd, J = 17.5 and 11.0 Hz), 7.21 (1H, d, J = 8.0 Hz), 7.22 (1H, s), 7.48 (1H, d, J = 8.0 Hz). MS (ESI) m/z = 190 (M+H)+.
  • 24
  • [ 1246350-28-6 ]
  • [ 13682-77-4 ]
  • [ 1367874-82-5 ]
YieldReaction ConditionsOperation in experiment
78% With triethylamine In tetrahydrofuran; isopropyl alcohol at 90℃; Intermediate 454-( Cyclohexyloxy)-3-ethenyl-1-trityl- 1 H-pyrazolo[4, 3-c]pyridine A round bottomed flask was charged with Intermediate 11 (1 g, 1.71 mmol), potassium vinyltrifluoroborate (690 mg, 5.12 mmol), [1 ,1 - bis(diphenylphosphino)ferrocene]dichloropalladium(ll) (140 mg, 0.17 mmol) and triethylamine (710 μΙ, 5.12 mmol), IPA (40 ml) and THF (10 ml). The solution was degassed for 15 minutes, prior to heating the reaction mixture to 90 °C overnight. The mixture was allowed to cool to rt, concentrated, and the residue was diluted with DCM and H20. The organic layer was separated, dried and concentrated. Purification by column chromatography using an Isolera 4 (petroleum ether/EtOAc gradient) gave the product as a white solid (646 mg, 78% yield). 1H NMR (400 MHz, CDCI3) δ ppm 1.24 - 1.88 (m, 10 H), 5.23 - 5.38 (m, 2 H), 5.66 - 5.74 (m, 1 H), 6.13 - 6.22 (m, 1 H), 7.10 - 7.38 (m, 16 H), 7.38 - 7.59 (m, 1 H); m/z (ES+APCI)+: 486 [M+H]+.
  • 25
  • [ 1256577-57-7 ]
  • [ 13682-77-4 ]
  • [ 1256577-86-2 ]
YieldReaction ConditionsOperation in experiment
80% With triethylamine In propan-1-ol at 60℃; for 4h; Inert atmosphere; 118 Under nitrogen atmosphere, trifluoro-methanesulfonic acid 3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl ester (Compound B1, 1.00 g, 2.302 mmol) was added with n-propanol (20 mL), potassium vinyltrifluoroborate (854 mg, 3.0 eq.), dichloro-((bis-diphenylphosphino)ferrocenyl)palladium (217 mg, 0.1 eq.) and triethylamine (1.11 ml, 3.0 eq.) in order and the resultant was stirred at 60° C. for 4 hr. Upon the completion of the reaction, water was added to the reaction solution. The resulting precipitates were filtered and washed with distilled water, and the residues were dried to obtain the title compound (666 mg, 80%).1H-NMR (400 MHz, CDCl3) δ: 8. 90 (1H, s), 8. 55 (1H, d, J=7.9 Hz), 8. 40 (1H, d, J=8.5 Hz), 7. 79 (1H, s), 7.58-7. 61 (3H, m), 6. 85 (1H, dd, J=17.7, 11. 0 Hz), 5. 95 (1H, d, J=17. 1 Hz), 5. 46 (1H, d, J=11. 0 Hz), 1. 84 (6H, s)LCMS: m/z 313 [M+H]+ HPLC retention time: 3.75 min (analysis condition W)
  • 26
  • [ 1350918-95-4 ]
  • [ 13682-77-4 ]
  • [ 1365993-16-3 ]
YieldReaction ConditionsOperation in experiment
93% With triethylamine In propan-1-ol at 100℃; for 0.5h; Inert atmosphere; Sealed tube; 2.111.1 Example 111 : {6-[2-(2-Chloro-6-fluorophenyl)-7-fluoro-2H^yrazolo[43-c]pyl}-methanol hydrochloride saltStep 1 :(2-Methyl-6-vinyl-aminopyrimidin-4-yl)-Z>is-carbamic acid terf-butyl esterTo a solution of (2-methyl-6-chloro-aminopyrimidin-4-yl)-6/5-carbamic acid ferf-butyl ester (1.50 g, 4.4 mmol), potassium vinyltrifluoroborate (884 mg, 6.6 mmol) and triethylamine (3.3 mL, 22 mmol) in «PrOH (40 mL) was added Pd(dppf)Cl2.CHCi3 (180 mg, 0.22 mmol). The reaction mixture was degassed with nitrogen and then heated at 100 °C for 30 minutes in a sealed vial. The resulting mixture was allowed to cool and was then partitioned between ethyl acetate and saturated sodium bicarbonate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The resultant residue was purified by column chromatography on silica gel eluting with 10% ethyl acetate in cyclohexane to afford the title compound as an oil (1.99 g, 93% yield). NMR (400 MHz, CDC13): δ 7.45 (s, 1H), 6.70(dd, J = 17.3, 1.3 Hz, 1H), 6.42 (dd, J= 17.3, 10.7 Hz, 1H), 5.64 (dd, J= 10.7, 1.3 Hz, 1H), 2.61 (s, 3H), 1.54 (s, 18H).
  • 27
  • [ 78686-79-0 ]
  • potassium vinyltrifluoroborate [ No CAS ]
  • [ 1384262-75-2 ]
YieldReaction ConditionsOperation in experiment
76% With triethylamine;palladium bis[bis(diphenylphosphino)ferrocene] dichloride; In ethanol; at 80℃; for 1h; Methyl 5-bromo-2-chloronicotinate (500 mg, 2.0 mmol) was dissolved in EtOH (20 mL) with potassium vinyltrifluoroborate (269 mg, 2.0 mmol), TEA (0.28 mL, 2.0 mmol), and [1,1'-Bis (diphenylphosphino)ferrocene]dichloropalladium(II) (PdCl2(dppf)) (29 mg, 0.04 mmol). The reaction was heated at 80 C. for 1 h, filtered through a Celite pad. The filtrate was concentrated, partitioned between EtOAc (50 mL) and H2O (50 mL). The organic layer was separated, dried over MgSO4 and concentrated. Purification over silica gel using automated flash chromatography (EtOAc/hexanes 0-20%) affords the compound, methyl-5-bromo-2-vinylnicotinate, as a white solid (484 mg, 76%). LC-MS (M+H)=242.1.
51.1% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; triethylamine; In ethanol; at 80℃; for 2.5h;Inert atmosphere; Preparation 363: methyl 5-bromo-2-formylnicotinate (2171) Triethylamine (6.12 ml, 43.9 mmol) was added to a stirred suspension of methyl 5-bromo-2- chloronicotinate (10.0 g, 39.9 mmol) and potassium vinyltrifluoroborate (5.88 g, 43.9 mmol) in ethanol (200 ml, 39.9 mmol). The system was evacuated and back-filled with nitrogen (x 3). PdCl2(dppf)2 (0.584 g, 0.798 mmol) was added and the system was evacuated and back-filled with nitrogen (x 3). The mixture was heated to 80 C and stirred under nitrogen for 2.5 h. After cooling to room temperatrue, the mixture was filtered through Celite. The filtrate was concentrated and partitioned between EtOAc (200 mL) and water (200 mL). The organic phase was dried (MgSC ), filtered and concentrated in vacuo. The crude product was purified by chromatography (220 g column, 0 - 20% EtOAc in isohexane) to afford the title compound (4.993 g, 20.42 mmol, 51.1 % yield) as a pale green solid. LCMS: [M+H]+ = 242.
With triethylamine;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In ethanol; Compounds are represented in generic form, with sub stituents as noted in compound descriptions elsewhere herein. A more specific example is set forth below. In one aspect, ethers of type 6.7 can be prepared beginning with the commercially available 5-bromo-2-chloronicotinic acid, which is converted to the corresponding ester by reaction with methanol in the presence of an acid such as hydrochloric acid to yield compound 6.2. Alkylation to provide compound 6.3 is accomplished by use of a Suzuki cross coupling reaction using potassium allyltrifluoroborate in the presence of [1,1'-Bis(diphenylphosphino)ferrocene]dichloropalladium(II). Reaction with 4-methoxybenzylamine affords compound 6.4. A cross-coupling reaction between compound 6.4 and benzyl alcohol in the presence of CuI, Cs2CO3, and a diamine ligand yields the aryl ether, compound 6.5. The p-methoxybenzyl protecting group is removed using cerium(IV) ammonium nitrate (CAN), followed by reduction of the carbonyl using lithium aluminum hydride. The amide, compound 6.7, is formed by reaction of the 3-(benzyloxy)-5,6,7,8-tetrahydro-1,6-naphthyridine, formed in the previous step, with benzoyl chloride.
  • 28
  • [ 1384262-74-1 ]
  • [ 13682-77-4 ]
  • [ 1384262-77-4 ]
YieldReaction ConditionsOperation in experiment
76% With caesium carbonate In ethanol at 150℃; for 1h; Microwave synthesizer; 11.a.1 2-chloro-6-(4-methoxybenzyl)-7,8-dihydro-1,6-naphthyridin-5(6H)-one, (1.5 g, 4.97 mmol) was dissolved in EtOH with potassium vinyltrifluoroborate (865 mg, 6.46 mmol), Cs2CO3 (2.42 g, 7.46 mmol) and Pd(PPh3)4 (115 mg, 0.01 mmol). The reaction was heated in a microwave synthesizer at 150° C. for 1 h. It was then concentrated and purified over silica gel (EtOAc/hexanes) to give after solvent removal and drying in vacuo the compound as an off-white solid (1.1 g, 76%). LC-MS (M+H)=295.2.
56% With tetrakis(triphenylphosphine) palladium(0); caesium carbonate In ethanol at 150℃; for 1h; Inert atmosphere; Microwave irradiation;
  • 29
  • [ 1395084-26-0 ]
  • [ 13682-77-4 ]
  • [ 1395084-27-1 ]
YieldReaction ConditionsOperation in experiment
85% With triethylamine In tetrahydrofuran; water at 120℃; for 2h; Microwave irradiation; 1.A A solution of the starting material (1.0 g, 2.85 mmol) in 9: 1 THF:H20 (8.0 mL) was treated with PdCl2 (0.010 g, 0.057 mmol, 0.02 eq), PPh3 (0.045 g, 0.171 mmol, 0.06 eq), vinyl-BF3K (0.381 g, 2.85 mmol, 1 eq) and Et3N (1.18 mL, 8.55 mmol, 3 eq). The solution was heated to 120 °C in a microwave vial for 2 h. The solution was then filtered, concentrated, and purified by flash chromatography (0-10% EtOAc-hexanes) to afford the final product (0.604 g, 85%) as clear oil. 1H NMR (600 MHz, CDC13) δ 7.13 (1H, s), 6.69 (1H, dd, J = 6.2, 10.9 Hz), 6.42 (1H, br s), 5.53 (1H, d, J = 17.4 Hz), 5.27 (1H, d, J = 10.8 Hz), 2.18 (3H, s), 1.52 (9H, s). LCMS m/z 272.1821 ([M + Na+, Ci2Hi6IN03 requires 272.1257).
  • 30
  • [ 1094347-65-5 ]
  • [ 13682-77-4 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
88% With triethylamine In propan-1-ol at 100℃; 233.C A solution of 2-({3-[(3-bromo-5-chlorophenyl)oxy]-4-chloro-2-fluorophenyl}methyl)-5- (3,5-dimethyl-4-isoxazolyl)-1 ,3,4-oxadiazole (1 10 mg, 0.21 mmol), potassium vinyltrifluoroborate (56 mg, 0.42 mmmol), PdCI2(dppf)-DCM (7 mg, 0.0084 mmol) and triethylamine (59 μl_, 0.42 mmol) in n-PrOH (2 mL) was heated at 100 °C overnight, cooled to rt and purified by Reverse-Phase HPLC (water/acetonitrile with 0.1% TFA) to afford the title compound as the trifluoroacetate salt. The salt was diluted with EtOAc (20 mL) and washed with saturated sodium bicarbonate solution (20 mL) dried over Na2SO4, filtered and concentrated to afford the title compound (85 mg, 88%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ ppm 7.53-7.45 (m, 2H), 7.34-7.33 (m, 1 H), 7.02-6.99 (m, 1 H), 6.83-6.82 (m, 1 H), 6.69-6.61 (m, 1 H), 5.90 (d, 1 H), 5.32 (d, 1 H), 4.44 (s, 2H), 2.60 (s, 3H), 2.36 (s, 3H). MS: m/z 459.98 (M+1 ).
  • 31
  • [ 261732-38-1 ]
  • potassium vinyltrifluoroborate [ No CAS ]
  • [ 1158744-48-9 ]
YieldReaction ConditionsOperation in experiment
73% With potassium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In dimethyl sulfoxide; at 100℃; for 3h;Inert atmosphere; Step 3. tert-Butyl-5-vinylindoline-1-carboxylate (BI10); A stirred solution of tert-butyl-5-bromoindoline-1-carboxylate (2.0 g, 6.73 mmol), potassium vinyl trifluoroborate (2.6 g, 20.20 mmol) and K2CO3 (2.78 g, 20.2 mmol) in DMSO (50.0 mL) was degassed with argon for 20 min at RT. PdCl2(dppf) (0.49 g, 0.67 mmol) was added at RT, then the reaction mixture was heated to 100 C. for 3 h. The reaction mixture was cooled to RT and filtered through a celite bed under vacuum and washed with diethyl ether. The reaction mixture was extracted with diethyl ether. The combined diethyl ether layer was dried over Na2SO4 and concentrated under reduced pressure to afford crude product. The crude compound was purified by column chromatography (SiO2, 100-200 mesh; eluting with 2% ethyl acetate/petroleum ether) to afford the title compound as a off-white solid (1.2 g, 73%): Mp 85.5-88.6 C.; 1H NMR (400 MHz, CDCl3) delta 7.23 (m, 3H), 6.69 (dd, J=17.4, 10.8 Hz, 1H), 5.64 (d, J=10.5 Hz, 1H), 5.13 (d, J=10.5 Hz, 1H), 4.00 (t, J=9.0 Hz, 2H), 3.10 (t, J=9.0 Hz, 2H), 1.55 (bs, 9H).
1.2 g Step 3. fert-Butyl-5-vinylindoline-l-carboxylate (BI10): A stirred solution of tert- butyl-5-bromoindoline-l-carboxylate (2.0 g, 6.73 mmol), potassium vinyl trifluoroborate (2.6 g, 20.20 mmol) and K2C03 (2.78 g, 20.2 mmol) in DMSO (50.0 mL) was degassed with argon for 20 min at RT. PdCl2(dppf) (0.49 g, 0.67mmol) was added at RT, then the reaction mixture was heated to 100 C for 3 h. The reaction mixture was cooled to RT and filtered through a celite bed under vacuum and washed with diethyl ether. The reaction mixture was extracted with diethyl ether. The combined diethyl ether layer was dried over Na2S04 and concentrated under reduced pressure to afford crude product. The crude compound was purified by column chromatography (Si02, 100-200 mesh; eluting with 2% ethyl acetate/ petroleum ether) to afford the title compound as an off-white solid (1.2 g, 73%): Mp 85.5 - 88.6 C; ]H NMR (400 MHz, CDC13) delta 7.23 (m, 3H), 6.69 (dd, / = 17.4, 10.8 Hz, 1H), 5.64 (d, / = 10.5 Hz, 1H), 5.13 (d, / = 10.5 Hz, 1H), 4.00 (t, J = 9.0 Hz, 2H), 3.10 (t, J = 9.0 Hz, 2H), 1.55 (bs, 9H).
1.2 g With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In dimethyl sulfoxide; at 100℃; for 3h;Inert atmosphere; A stirred solution of ten-butyl-5-bromoindoline-1-carboxylate (2.0 g, 6.73 mmol), potassium vinyl trifluoroborate (2.6 g, 20.20 mmol) and K2CO3 (2.78 g, 20.2 mmol) in DMSO (50.0 mL) was degassed with argon for 20 min at ambient temperature. PdCl2(dppf) (0.49 g, 0.67 mmol) was added at ambient temperature, then the reaction mixture was heated to 100 C. for 3 h. The reaction mixture was cooled to ambient temperature and filtered through a celite bed under vacuum and washed with diethyl ether. The reaction mixture was extracted with diethyl ether. The combined diethyl ether layer was dried over Na2SO4 and concentrated under reduced pressure to afford crude product. The crude compound was purified by column chromatography (SiO2, 100-200 mesh; eluting with 2% ethyl acetate/petroleum ether) to afford the title compound as an off-white solid (1.2 g, 73%): Mp 85.5-88.6 C.; 1H NMR (400 MHz, CDCl3) delta 7.23 (m, 3H), 6.69 (dd, J=17.4, 10.8 Hz, 1H), 5.64 (d, J=10.5 Hz, 1H), 5.13 (d, J=10.5 Hz, 1H), 4.00 (t, J=9.0 Hz, 2H), 3.10 (t, J=9.0 Hz, 2H), 1.55 (bs, 9H).
1.2 g With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In dimethyl sulfoxide; at 100℃; for 3h;Inert atmosphere; A stirred solution of tert-butyl-5-bromoindoline-1-carboxylate (2.0 g, 6.73 mmol), potassium vinyl trifluoroborate (2.6 g, 20.20 mmol) and K2CO3 (2.78 g, 20.2 mmol) in DMSO (50.0 mL) was degassed with argon for 20 min at RT. PdCl2(dppf) (0.49 g, 0.67 mmol) was added at RT, then the reaction mixture was heated to 100 C. for 3 h. The reaction mixture was cooled to RT and filtered through a celite bed under vacuum and washed with diethyl ether. The reaction mixture was extracted with diethyl ether. The combined diethyl ether layer was dried over Na2SO4 and concentrated under reduced pressure to afford crude product. The crude compound was purified by column chromatography (SiO2, 100-200 mesh; eluting with 2% ethyl acetate/petroleum ether) to afford the title compound as an off-white solid (1.2 g, 73%): Mp 85.5-88.6 C.; 1H NMR (400 MHz, CDCl3) delta 7.23 (m, 3H), 6.69 (dd, J=17.4, 10.8 Hz, 1H), 5.64 (d, J=10.5 Hz, 1H), 5.13 (d, J=10.5 Hz, 1H), 4.00 (t, J=9.0 Hz, 2H), 3.10 (t, J=9.0 Hz, 2H), 1.55 (bs, 9H).
A stirred solution of tert-butyl-5-bromoindoline-1-carboxylate (2.0 g, 6.73 mmol), potassium vinyl trifluoroborate (2.6 g, 20.20 mmol) and K2C03 (2.78 g, 20.2 mmol) in DMSO (50.0 mL) was degassed with argon for 20 min at RT. PdCl2(dppf) (0.49 g, 0.67mmol) was added at RT, then the reaction mixture was heated to 100 C for 3 h. The reaction mixture was cooled to RT and filtered through a celite bed under vacuum and washed with diethyl ether. The reaction mixture was extracted with diethyl ether. The combined diethyl ether layer was dried over Na2S04 and concentrated under reduced pressure to afford crude product. The crude compound was purified by column chromatography (Si02, 100-200 mesh; eluting with 2% ethyl acetate/ petroleum ether) to afford the title compound as an off-white solid (1.2 g, 73%): Mp 85.5 - 88.6 C; 1H NMR (400 MHz, CDC13) delta 7.23 (m, 3H), 6.69 (dd, / = 17.4, 10.8 Hz, 1H), 5.64 (d, J = 10.5 Hz, 1H), 5.13 (d, J = 10.5 Hz, 1H), 4.00 (t, J = 9.0 Hz, 2H), 3.10 (t, J = 9.0 Hz, 2H), 1.55 (bs, 9H).
1.2 g Step 3. tert-Butyl-5-vinylindoline-1-carboxylate (BI10) A stirred solution of ten-butyl-5-bromoindoline-1-carboxylate (2.0 g, 6.73 mmol), potassium vinyl trifluoroborate (2.6 g, 20.20 mmol) and K2CO3 (2.78 g, 20.2 mmol) in DMSO (50.0 mL) was degassed with argon for 20 min at ambient temperature. PdCl2(dppf) (0.49 g, 0.67 mmol) was added at ambient temperature, then the reaction mixture was heated to 100 C. for 3 h. The reaction mixture was cooled to ambient temperature and filtered through a celite bed under vacuum and washed with diethyl ether. The reaction mixture was extracted with diethyl ether. The combined diethyl ether layer was dried over Na2SO4 and concentrated under reduced pressure to afford crude product. The crude compound was purified by column chromatography (SiO2, 100-200 mesh; eluting with 2% ethyl acetate/petroleum ether) to afford the title compound as a off-white solid (1.2 g, 73%): Mp 85.5-88.6 C.; 1H NMR (400 MHz, CDCl3) delta 7.23 (m, 3H), 6.69 (dd, J=17.4, 10.8 Hz, 1H), 5.64 (d, J=10.5 Hz, 1H), 5.13 (d, J=10.5 Hz, 1H), 4.00 (t, J=9.0 Hz, 2H), 3.10 (t, J=9.0 Hz, 2H), 1.55 (bs, 9H).

  • 32
  • [ 75884-70-7 ]
  • potassium vinyltrifluoroborate [ No CAS ]
  • [ 1416980-15-8 ]
YieldReaction ConditionsOperation in experiment
63% With potassium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In dimethyl sulfoxide; at 80℃; for 2h;Inert atmosphere; Step 3. 6-vinylphthalazine-1(2H)-one (BI27); A solution of <strong>[75884-70-7]6-bromophthalazine-1(2H)-one</strong> (0.25 g, 1.11 mmol), potassium vinyl trifluoroborate (0.446 g, 3.33 mmol) and K2CO3 (0.46 g, 3.33 mmol) in DMSO (2 mL) was degassed with argon for 20 min at RT. PdCl2(dppf) (0.04 g, 0.055 mmol) was added at RT, and the reaction mixture was heated to 80 C. for 2 h. The reaction mixture was cooled to RT and filtered through celite bed under vacuum and washed with ethyl acetate. The reaction mixture was extracted with ethyl acetate and the combined ethyl acetate layer dried over Na2SO4 and concentrated under reduced pressure to afford the crude product. The crude compound was purified by column chromatography (SiO2, 100-200 mesh; 50% ethyl acetate/petroleum ether) to afford the title compound as a brown solid (0.12 g, 63%): 1H NMR (400 MHz, DMSO-d6) delta 13.61 (br, 1H), 8.33 (m, 1H), 8.19 (m, 1H), 8.01 (m, 2H), 6.97 (m, 1H), 6.15 (m, 1H), 5.56 (d, J=10.8 Hz, 1H); ESIMS m/z 172.93 ([M+H]+); IR (thin film) 1748, 1655, 3241 cm-1.
63% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In dimethyl sulfoxide; at 80℃; for 2h;Inert atmosphere; A solution of <strong>[75884-70-7]6-bromophthalazine-1(2H)-one</strong> (0.25 g, 1.11 mmol), potassium vinyl trifluoroborate (0.446 g, 3.33 mmol) and [0441] K2CO3 (0.46 g, 3.33 mmol) in DMSO (2 mL) was degassed with argon for 20 min at ambient temperature. PdCl2(dppf) (0.04 g, 0.055 mmol) was added at ambient temperature, and the reaction mixture was heated to 80 C. for 2 h. The reaction mixture was cooled to ambient temperature and filtered through celite bed under vacuum and washed with ethyl acetate. The reaction mixture was extracted with ethyl acetate and the combined ethyl acetate layer dried over Na2SO4 and concentrated under reduced pressure to afford the crude product. The crude compound was purified by column chromatography (SiO2, 100-200 mesh; 50% ethyl acetate/petroleum ether) to afford the title compound as a brown solid (0.12 g, 63%): 1H NMR (400 MHz, DMSO-d6) delta 13.61 (br, 1H), 8.33 (m, 1H), 8.19 (m, 1H), 8.01 (m, 2H), 6.97 (m, 1H), 6.15 (m, 1H), 5.56 (d, J=10.8 Hz, 1H); ESIMS m/z 172.93 ([M+H]+); IR (thin film) 1748, 1655, 3241 cm-1.
63% A solution of <strong>[75884-70-7]6-bromophthalazine-1(2H)-one</strong> (0.25 g, 1.11 mmol), potassium vinyl trifluoroborate (0.446 g, 3.33 mmol) and K2CO3 (0.46 g, 3.33 mmol) in DMSO (2 mL) was degassed with argon for 20 min at RT. PdCl2(dppf) (0.04 g, 0.055 mmol) was added at RT, and the reaction mixture was heated to 80 C for 2 h. The reaction mixture was cooled to RT and filtered through celite bed under vacuum and washed with ethyl acetate. The reaction mixture was extracted with ethyl acetate and the combined ethyl acetate layer dried over Na2S04 and concentrated under reduced pressure to afford the crude product. The crude compound was purified by column chromatography (Si02, 100-200 mesh; 50% ethyl acetate/ petroleum ether) to afford the title compound as a brown solid (0.12 g, 63%): ]H NMR (400 MHz, DMSO-d6) delta 13.61 (br, 1H), 8.33 (m, 1H), 8.19 (m, 1H), 8.01 (m, 2H), 6.97 (m, 1H), 6.15 (m, 1H), 5.56 (d, / = 10.8 Hz, 1H); ESIMS m/z 172.93 ([M+H] +); IR (thin film) 1748, 1655, 3241 cm"1
0.12 g With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In dimethyl sulfoxide; at 80℃; for 2h;Inert atmosphere; Step 3. 6-Vinylphthalazine-l(2H)-one (BI27): A solution of 6-bromophthalazine- l(2H)-one (0.25 g, 1.11 mmol), potassium vinyl trifluoroborate (0.446 g, 3.33 mmol) and K2CO3 (0.46 g, 3.33 mmol) in DMSO (2 mL) was degassed with argon for 20 min at RT. PdCl2(dppf) (0.04 g, 0.055 mmol) was added at RT, and the reaction mixture was heated to 80 C for 2 h. The reaction mixture was cooled to RT and filtered through celite bed under vacuum and washed with ethyl acetate. The reaction mixture was extracted with ethyl acetate and the combined ethyl acetate layer dried over Na2S04 and concentrated under reduced pressure to afford the crude product. The crude compound was purified by column chromatography (Si02, 100-200 mesh; 50% ethyl acetate/ petroleum ether) to afford the title compound as a brown solid (0.12 g, 63%): ]H NMR (400 MHz, DMSO-d6) delta 13.61 (br, 1H), 8.33 (m, 1H), 8.19 (m, 1H), 8.01 (m, 2H), 6.97 (m, 1H), 6.15 (m, 1H), 5.56 (d, / = 10.8 Hz, 1H); ESIMS m/z 172.93 ([M+H] +); IR (thin film) 1748, 1655, 3241 cm"1.
0.12 g With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In dimethyl sulfoxide; at 20 - 80℃; for 2h;Inert atmosphere; A solution of <strong>[75884-70-7]6-bromophthalazine-1(2H)-one</strong> (0.25 g, 1.11 mmol), potassium vinyl trifluoroborate (0.446 g, 3.33 mmol) and K2CO3 (0.46 g, 3.33 mmol) in DMSO (2 mL) was degassed with argon for 20 min at RT. PdCl2(dppf) (0.04 g, 0.055 mmol) was added at RT, and the reaction mixture was heated to 80 C. for 2 h. The reaction mixture was cooled to RT and filtered through celite bed under vacuum and washed with ethyl acetate. The reaction mixture was extracted with ethyl acetate and the combined ethyl acetate layer dried over Na2SO4 and concentrated under reduced pressure to afford the crude product. The crude compound was purified by column chromatography (SiO2, 100-200 mesh; 50% ethyl acetate/petroleum ether) to afford the title compound as a brown solid (0.12 g, 63%): 1H NMR (400 MHz, DMSO-d6) delta 13.61 (br, 1H), 8.33 (m, 1H), 8.19 (m, 1H), 8.01 (m, 2H), 6.97 (m, 1H), 6.15 (m, 1H), 5.56 (d, J=10.8 Hz, 1H); ESIMS m/z 172.93 ([M+H]+); IR (thin film) 1748, 1655, 3241 cm-1.
0.12 g Step 3. 6-Vinylphthalazine-1(2H)-one (BI27) A solution of <strong>[75884-70-7]6-bromophthalazine-1(2H)-one</strong> (0.25 g, 1.11 mmol), potassium vinyl trifluoroborate (0.446 g, 3.33 mmol) and K2CO3 (0.46 g, 3.33 mmol) in DMSO (2 mL) was degassed with argon for 20 min at ambient temperature. PdCl2(dppf) (0.04 g, 0.055 mmol) was added at ambient temperature, and the reaction mixture was heated to 80 C. for 2 h. The reaction mixture was cooled to ambient temperature and filtered through celite bed under vacuum and washed with ethyl acetate. The reaction mixture was extracted with ethyl acetate and the combined ethyl acetate layer dried over Na2SO4 and concentrated under reduced pressure to afford the crude product. The crude compound was purified by column chromatography (SiO2, 100-200 mesh; 50% ethyl acetate/petroleum ether) to afford the title compound as a brown solid (0.12 g, 63%): 1H NMR (400 MHz, DMSO-d6) delta 13.61 (br, 1H), 8.33 (m, 1H), 8.19 (m, 1H), 8.01 (m, 2H), 6.97 (m, 1H), 6.15 (m, 1H), 5.56 (d, J=10.8 Hz, 1H); ESIMS m/z 172.93 ([M+H]+); IR (thin film) 1748, 1655, 3241 cm-1.

  • 33
  • [ 1261645-83-3 ]
  • [ 13682-77-4 ]
  • [ 1416979-61-7 ]
YieldReaction ConditionsOperation in experiment
56% With caesium carbonate In tetrahydrofuran; water for 16h; Reflux; Inert atmosphere; 8 Example 8Preparation of ethyl 2-bromo-4-vinylbenzoate (AI51); To a stirred solution of ethyl 2-bromo-4-iodobenzoate (5 g, 14.3 mmol) in THF/water (100 mL, 9:1) was added potassium vinyltrifluoroborate (1.89 g, 14.3 mmol), Cs2CO3 (18.27 g, 56.07 mmol) and triphenylphosphine (0.22 g, 0.85 mmol) and the reaction mixture was degassed with argon for 20 min, then charged with PdCl2 (0.05 g, 0.28 mmol). The reaction mixture was heated to reflux for 16 h. The reaction mixture was cooled to RT and filtered through a celite bed and washed with ethyl acetate. The filtrate was again extracted with ethyl acetate and the combined organic layers washed with water and brine, dried over Na2SO4 and concentrated under reduced pressure to afford crude compound. The crude compound was purified by column chromatography (SiO2, 100-200 mesh; eluting with 2% ethyl acetate/petroleum ether) to afford the title compound as a light brown gummy material (2 g, 56%): 1H NMR (400 MHz, CDCl3) δ 7.78 (d, J=8.4 Hz, 1H), 7.71 (d, J=1.2 Hz, 1H), 7.51 (d, J=8.4 Hz, 1H), 6.69 (dd, J=17.6, 10.8 Hz, 1H), 5.86 (d, J=17.6 Hz, 1H), 5.42 (d, J=11.2 Hz, 1H), 4.42 (q, J=7.2 Hz, 2H), 1.43 (t, J=3.6 Hz, 3H); ESIMS m/z 255.18 ([M+H]+); IR (thin film) 1729 cm-1.
56% With caesium carbonate; triphenylphosphine; palladium dichloride In tetrahydrofuran; water for 16h; Inert atmosphere; Reflux; 8 Example 8: Preparation of Ethyl -bromo-4-vinylbenzoate (AI51) Example 8: Preparation of Ethyl -bromo-4-vinylbenzoate (AI51) To a stirred solution of ethyl 2-bromo-4-iodobenzoate (5 g, 14.3 mmol) in THF/water (100 mL, 9: 1) was added potassium vinyltrifluoroborate (1.89 g, 14.3 mmol), CS2CO3 (18.27 g, 56.07 mmol) and triphenylphosphine (0.22 g, 0.85 mmol) and the reaction mixture was degassed with argon for 20 min, then charged with PdCl2 (0.05 g,0.28 mmol). The reaction mixture was heated to reflux for 16 h. The reaction mixture was cooled to RT and filtered through a celite bed and washed with ethyl acetate. The filtrate was again extracted with ethyl acetate and the combined organic layers washed with water and brine, dried over Na2S04 and concentrated under reduced pressure to afford crude compound. The crude compound was purified by column chromatography (Si02, 100-200 mesh; eluting with 2% ethyl acetate/ petroleum ether) to afford the title compound as a light brown gummy material (2 g, 56%): 'H NMR (400 MHZ, CDCI3) δ 7.78 (d, 7 = 8.4 Hz, 1H), 7.71 (d, / = 1.2 Hz, 1H), 7.51 (d, / = 8.4 Hz, 1H), 6.69 (dd, J = 17.6, 10.8 Hz, 1H), 5.86 (d, / = 17.6 Hz, 1H), 5.42 (d, / = 11.2 Hz, 1H), 4.42 (q, 7 = 7.2Hz, 2H), 1.43 (t, 7 = 3.6 Hz, 3H); ESIMS m/z 255.18 ([M+H]+); IR (thin film) 1729 cm"1.
56% With caesium carbonate; triphenylphosphine; palladium dichloride In tetrahydrofuran; water for 16h; Inert atmosphere; Reflux; 8 Example 8 Preparation of Ethyl 2-bromo-4-vinylbenzoate (AI51) To a stirred solution of ethyl 2-bromo-4-iodobenzoate (5 g, 14.3 mmol) in THF/ water (100 mL, 9:1) was added potassium vinyltrifluoroborate (1.89 g, 14.3 mmol), Cs2CO3 (18.27 g, 56.07 mmol) and triphenylphosphine (0.22 g, 0.85 mmol) and the reaction mixture was degassed with argon for 20 min, then charged with PdCl2 (0.05 g, 0.28 mmol). The reaction mixture was heated to reflux for 16 h. The reaction mixture was cooled to ambient temperature and filtered through a celite bed and washed with ethyl acetate. The filtrate was again extracted with ethyl acetate and the combined organic layers washed with water and brine, dried over Na2SO4 and concentrated under reduced pressure to afford crude compound. The crude compound was purified by column chromatography (SiO2, 100-200 mesh; eluting with 2% ethyl acetate/petroleum ether) to afford the title compound as a light brown gummy material (2 g, 56%): 1H NMR (400 MHz, CDCl3) δ 7.78 (d, J=8.4 Hz, 1H), 7.71 (d, J=1.2 Hz, 1H), 7.51 (d, J=8.4 Hz, 1H), 6.69 (dd, J=17.6, 10.8 Hz, 1H), 5.86 (d, J=17.6 Hz, 1H), 5.42 (d, J=11.2 Hz, 1H), 4.42 (q, J=7.2 Hz, 2H), 1.43 (t, J=3.6 Hz, 3H); ESIMS m/z 255.18 ([M+H]+); IR (thin film) 1729 cm-1.
56% Stage #1: ethyl 2-bromo-4-iodobenzoate; potassium vinyltrifluoroborate With triphenylphosphine In tetrahydrofuran; water for 0.333333h; Inert atmosphere; Stage #2: With palladium dichloride In tetrahydrofuran; water for 16h; Reflux; Inert atmosphere; 8 Preparation of ethyl 2-bromo-4-vinylbenzoate (AI51) To a stirred solution of ethyl 2-bromo-4-iodobenzoate (5 g, 14.3 mmol) in THF/water (100 mL, 9: 1) was added potassium vinyltrifluoroborate (1.89 g, 14.3 mmol), CS2CO3 (18.27 g, 56.07 mmol) and triphenylphosphine (0.22 g, 0.85 mmol) and the reaction mixture was degassed with argon for 20 min, then charged with PdCl2 (0.05 g,0.28 mmol). The reaction mixture was heated to reflux for 16 h. The reaction mixture was cooled to RT and filtered through a celite bed and washed with ethyl acetate. The filtrate was again extracted with ethyl acetate and the combined organic layers washed with water and brine, dried over Na2S04 and concentrated under reduced pressure to afford crude compound. The crude compound was purified by column chromatography (SiO2, 100-200 mesh; eluting with 2% ethyl acetate/ petroleum ether) to afford the title compound as a light brown gummy material (2 g, 56%): 'H NMR (400 MHZ, CDCI3) δ 7.78 (d, 7 = 8.4 Hz, 1H), 7.71 (d, / = 1.2 Hz, 1H), 7.51 (d, / = 8.4 Hz, 1H), 6.69 (dd, J = 17.6, 10.8 Hz, 1H), 5.86 (d, / = 17.6 Hz, 1H), 5.42 (d, / = 11.2 Hz, 1H), 4.42 (q, / = 7.2Hz, 2H), 1.43 (t, / = 3.6 Hz, 3H); ESIMS m/z 255.18 ([M+H]+); IR (thin film) 1729 cm"1.
56% Stage #1: ethyl 2-bromo-4-iodobenzoate; potassium vinyltrifluoroborate With caesium carbonate; triphenylphosphine In tetrahydrofuran; water for 0.333333h; Inert atmosphere; Stage #2: With palladium dichloride In tetrahydrofuran; water for 16h; Inert atmosphere; Reflux; 8 Example 8 Preparation of Ethyl 2-bromo-4-vinylbenzoate (AI51) Example 8 Preparation of Ethyl 2-bromo-4-vinylbenzoate (AI51) To a stirred solution of ethyl 2-bromo-4-iodobenzoate (5 g, 14.3 mmol) in THF/water (100 mL, 9:1) was added potassium vinyltrifluoroborate (1.89 g, 14.3 mmol), Cs2CO3 (18.27 g, 56.07 mmol) and triphenylphosphine (0.22 g, 0.85 mmol) and the reaction mixture was degassed with argon for 20 min, then charged with PdCl2 (0.05 g, 0.28 mmol). The reaction mixture was heated to reflux for 16 h. The reaction mixture was cooled to ambient temperature and filtered through a celite bed and washed with ethyl acetate. The filtrate was again extracted with ethyl acetate and the combined organic layers washed with water and brine, dried over Na2SO4 and concentrated under reduced pressure to afford crude compound. The crude compound was purified by column chromatography (SiO2, 100-200 mesh; eluting with 2% ethyl acetate/petroleum ether) to afford the title compound as a light brown gummy material (2 g, 56%): 1H NMR (400 MHz, CDCl3) δ 7.78 (d, J=8.4 Hz, 1H), 7.71 (d, J=1.2 Hz, 1H), 7.51 (d, J=8.4 Hz, 1H), 6.69 (dd, J=17.6, 10.8 Hz, 1H), 5.86 (d, J=17.6 Hz, 1H), 5.42 (d, J=11.2 Hz, 1H), 4.42 (q, J=7.2 Hz, 2H), 1.43 (t, J=3.6 Hz, 3H); ESIMS m/z 255.18 ([M+H]+); IR (thin film) 1729 cm-1.
56% With caesium carbonate; triphenylphosphine; palladium dichloride In tetrahydrofuran; water for 16h; Inert atmosphere; Reflux; 8 Preparation of ethyl 2-bromo-4-vinylbenzoate (C65) Example 8 Preparation of ethyl 2-bromo-4-vinylbenzoate (C65) To a stirred solution of ethyl 2-bromo-4-iodobenzoate (C60) (5.00 g, 14.3 mmol) in tetrahydrofuran/water (100 mL, 9:1) was added potassium vinyltrifluoroborate (1.89 g, 14.3 mmol), cesium carbonate (18.3 g, 56.1 mmol), and triphenylphosphine (0.220 g, 0.850 mmol). The reaction mixture was degassed with argon for 20 minutes, then charged with dichloropalladium(II) (0.0500 g, 0.280 mmol). The reaction mixture was heated to reflux for 16 hours. The reaction mixture was cooled to ambient temperature and filtered through a Celite bed and washed with ethyl acetate. The filtrate was again extracted with ethyl acetate and the combined organic layers washed with water and brine, dried over sodium sulfate, and concentrated under reduced pressure to afford crude compound. The crude compound was purified by flash column chromatography using 2% ethyl acetate/petroleum ether as eluent to afford the title compound as a light brown gummy material (2.00 g, 56%): 1H NMR (400 MHz, CDCl3) δ 7.78 (d, J=8.4 Hz, 1H), 7.71 (d, J=1.2 Hz, 1H), 7.51 (d, J=8.4 Hz, 1H), 6.69 (dd, J=17.6, 10.8 Hz, 1H), 5.86 (d, J=17.6 Hz, 1H), 5.42 (d, J=11.2 Hz, 1H), 4.42 (q, J=7.2 Hz, 2H), 1.43 (t, J=3.6 Hz, 3H); ESIMS m/z 255 ([M+H]+); IR (thin film) 1729 cm-1.
With triphenylphosphine In tetrahydrofuran; water 8 Preparation of Ethyl 2-bromo-4-vinylbenzoate (AI51) Example 8 Preparation of Ethyl 2-bromo-4-vinylbenzoate (AI51) To a stirred solution of ethyl 2-bromo-4-iodobenzoate (5 g, 14.3 mmol) in THF/water (100 mL, 9:1) was added potassium vinyltrifluoroborate (1.89 g, 14.3 mmol), Cs2CO3 (18.27 g, 56.07 mmol) and triphenylphosphine (0.22 g, 0.85 mmol) and the reaction mixture was degassed with argon for 20 min, then charged with PdCl2 (0.05 g, 0.28 mmol). The reaction mixture was heated to reflux for 16 h. The reaction mixture was cooled to ambient temperature and filtered through a Celite bed and washed with EtOAc. The filtrate was again extracted with EtOAc and the combined organic layers washed with water and brine, dried over Na2SO4 and concentrated under reduced pressure to afford crude compound. The crude compound was purified by column chromatography (SiO2, 100-200 mesh; eluting with 2% EtOAc/petroleum ether) to afford the title compound as a light brown gummy material (2 g, 56%): 1H NMR (400 MHz, CDCl3) δ 7.78 (d, J=8.4 Hz, 1H), 7.71 (d, J=1.2 Hz, 1H), 7.51 (d, J=8.4 Hz, 1H), 6.69 (dd, J=17.6, 10.8 Hz, 1H), 5.86 (d, J=17.6 Hz, 1H), 5.42 (d, J=11.2 Hz, 1H), 4.42 (q, J=7.2 Hz, 2H), 1.43 (t, J=3.6 Hz, 3H); ESIMS m/z 255.18 ([M+H]+); IR (thin film) 1729 cm-1.

  • 34
  • [ 76008-74-7 ]
  • [ 13682-77-4 ]
  • [ 1269027-12-4 ]
YieldReaction ConditionsOperation in experiment
69% With potassium carbonate In dimethyl sulfoxide at 80℃; for 1h; Inert atmosphere; 9 Example 9Preparation of ethyl 2-chloro-4-vinylbenzoate (AI54); To a stirred solution of ethyl 2-chloro-4-bromobenzoate (2 g, 7.63 mmol) in dimethylsulfoxide (20 mL) was added potassium vinyltrifluoroborate (3.06 g, 22.9 mmol) and potassium carbonate (3.16 g, 22.9 mmol). The reaction mixture was degassed with argon for 30 min Bistriphenylphosphine(diphenylphosphinoferrocene)palladium dichloride (0.27 g, 0.38 mmol) was added and the reaction mixture was heated to 80° C. for 1 h. The reaction mixture was diluted with water (100 mL), extracted with ethyl acetate (2×50 mL), washed with brine, dried over Na2SO4 and concentrated under reduced pressure to obtain the compound as brown gummy material (1.1 g, 69%): 1H NMR (400 MHz, CDCl3) δ 7.81 (d, J=8.4 Hz, 1H), 7.46 (s, 1H), 7.33 (d, J=8.4 Hz, 1H), 6.70 (dd, J=17.6, 11.2 Hz, 1H), 5.87 (d, J=17.6 Hz, 1H), 5.42 (d, J=10.8 Hz, 1H), 4.41 (q, J=7.2 Hz, 2H), 1.43 (t, J=7.2 Hz, 3H); ESIMS m/z 211.22 ([M+H]+); IR (thin film) 1729, 886 cm-1.
69% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate In dimethyl sulfoxide at 80℃; for 1h; Inert atmosphere; 9 Example 9: Preparation of Ethyl -chloro-4-vinylbenzoate (AI54) Example 9: Preparation of Ethyl -chloro-4-vinylbenzoate (AI54) To a stirred solution of ethyl 2-chloro-4-bromobenzoate (2 g, 7.63 mmol) in dimethylsulfoxide (20 mL) was added potassium vinyltrifluoroborate (3.06 g, 22.9 mmol) and potassium carbonate (3.16 g, 22.9 mmol). The reaction mixture was degassed with argon for 30 min. Bistriphenylphosphine(diphenylphosphinoferrocene)palladium dichloride (0.27 g, 0.38 mmol) was added and the reaction mixture was heated to 80 °C for 1 h. The reaction mixture was diluted with water (100 mL), extracted with ethyl acetate (2 x 50 mL), washed with brine, dried over Na2SC>4 and concentrated under reduced pressure to obtain the compound as brown gummy material (1.1 g, 69%): ]H NMR (400 MHz, CDC13) δ 7.81 (d, 7 = 8.4 Hz, 1H), 7.46 (s, 1H), 7.33 (d, 7 = 8.4 Hz, 1H), 6.70 (dd, 7 = 17.6, 11.2 Hz, 1H), 5.87 (d, J = 17.6 Hz, 1H), 5.42 (d, J = 10.8 Hz, 1H), 4.41 (q, J = 7.2 Hz,2H), 1.43 (t, J = 7.2 Hz, 3H); ESIMS m/z 211.22 ([M+H]+); IR (thin film) 1729, 886 cm"1.
69% With potassium carbonate In dimethyl sulfoxide at 80℃; for 1h; Inert atmosphere; 9 Example 9 Preparation of Ethyl 2-chloro-4-vinylbenzoate (AI54) To a stirred solution of ethyl 2-chloro-4-bromobenzoate (2 g, 7.63 mmol) in dimethylsulfoxide (20 mL) was added potassium vinyltrifluoroborate (3.06 g, 22.9 mmol) and potassium carbonate (3.16 g, 22.9 mmol). The reaction mixture was degassed with argon for 30 min Bistriphenylphosphine(diphenylphosphinoferrocene)palladium dichloride (0.27 g, 0.38 mmol) was added and the reaction mixture was heated to 80° C. for 1 h. The reaction mixture was diluted with water (100 mL), extracted with ethyl acetate (2×50 mL), washed with brine, dried over Na2SO4 and concentrated under reduced pressure to obtain the compound as brown gummy material (1.1 g, 69%): 1H NMR (400 MHz, CDCl3) δ 7.81 (d, J=8.4 Hz, 1H), 7.46 (s, 1H), 7.33 (d, J=8.4 Hz, 1H), 6.70 (dd, J=17.6, 11.2 Hz, 1H), 5.87 (d, J=17.6 Hz, 1H), 5.42 (d, J=10.8 Hz, 1H), 4.41 (q, J=7.2 Hz, 2H), 1.43 (t, J=7.2 Hz, 3H); ESIMS m/z 211.22 ([M+H]+); IR (thin film) 1729, 886 cm-1.
69% With bistriphenylphosphine(diphenylphosphinoferrocene)palladium dichloride; potassium carbonate In dimethyl sulfoxide at 80℃; for 1h; Inert atmosphere; 9 Preparation of Ethyl 2-chloro-4-vinylbenzoate (AI54) To a stirred solution of ethyl 2-chloro-4-bromobenzoate (2 g, 7.63 mmol) in dimethylsulfoxide (20 mL) was added potassium vinyltrifluoroborate (3.06 g, 22.9 mmol) and potassium carbonate (3.16 g, 22.9 mmol). The reaction mixture was degassed with argon for 30 min Bistriphenylphosphine(diphenylphosphinoferrocene)palladium dichloride (0.27 g, 0.38 mmol) was added and the reaction mixture was heated to 80° C. for 1 h. The reaction mixture was diluted with water (100 mL), extracted with ethyl acetate (2*50 mL), washed with brine, dried over Na2SO4 and concentrated under reduced pressure to obtain the compound as brown gummy material (1.1 g, 69%): 1H NMR (400 MHz, CDCl3) δ 7.81 (d, J=8.4 Hz, 1H), 7.46 (s, 1H), 7.33 (d, J=8.4 Hz, 1H), 6.70 (dd, J=17.6, 11.2 Hz, 1H), 5.87 (d, J=17.6 Hz, 1H), 5.42 (d, J=10.8 Hz, 1H), 4.41 (q, J=7.2 Hz, 2H), 1.43 (t, J=7.2 Hz, 3H); ESIMS m/z 211.22 ([M+H]+); IR (thin film) 1729, 886 cm-1.
69% Stage #1: Ethyl 4-bromo-2-chlorobenzoate; potassium vinyltrifluoroborate With potassium carbonate In dimethyl sulfoxide for 0.5h; Inert atmosphere; Stage #2: With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride In dimethyl sulfoxide at 80℃; for 1h; Inert atmosphere; 9 Preparation of ethyl 2-chloro-4-vinylbenzoate (AI54) To a stirred solution of ethyl 2-chloro-4-bromobenzoate (2 g, 7.63 mmol) in dimethylsulfoxide (20 mL) was added potassium vinyltrifluoroborate (3.06 g, 22.9 mmol) and potassium carbonate (3.16 g, 22.9 mmol). The reaction mixture was degassed with argon for 30 min. Bistriphenylphosphine(diphenylphosphinoferrocene)palladium dichloride (0.27 g, 0.38 mmol) was added and the reaction mixture was heated to 80 °C for 1 h. The reaction mixture was diluted with water (100 mL), extracted with ethyl acetate (2 x 50 mL), washed with brine, dried over Na2S04 and concentrated under reduced pressure to obtain the compound as brown gummy material (1.1 g, 69%): 1H NMR (400 MHz, CDC13) δ 7.81 (d, J = 8.4 Hz, 1H), 7.46 (s, 1H), 7.33 (d, 7 = 8.4 Hz, 1H), 6.70 (dd, / = 17.6, 11.2 Hz, 1H), 5.87 (d, / = 17.6 Hz, 1H), 5.42 (d, / = 10.8 Hz, 1H), 4.41 (q, / = 7.2 Hz,2H), 1.43 (t, 7 = 7.2 Hz, 3H); ESIMS m/z 211.22 ([M+H]+); IR (thin film) 1729, 886 cm-1.
69% Stage #1: Ethyl 4-bromo-2-chlorobenzoate; potassium vinyltrifluoroborate With potassium carbonate In dimethyl sulfoxide for 0.5h; Inert atmosphere; Stage #2: With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride In dimethyl sulfoxide at 80℃; for 1h; Inert atmosphere; 9 Example 9 Preparation of Ethyl 2-chloro-4-vinylbenzoate (AI54) Example 9 Preparation of Ethyl 2-chloro-4-vinylbenzoate (AI54) To a stirred solution of ethyl 2-chloro-4-bromobenzoate (2 g, 7.63 mmol) in dimethylsulfoxide (20 mL) was added potassium vinyltrifluoroborate (3.06 g, 22.9 mmol) and potassium carbonate (3.16 g, 22.9 mmol). The reaction mixture was degassed with argon for 30 min. Bistriphenylphosphine(diphenylphosphinoferrocene)palladium dichloride (0.27 g, 0.38 mmol) was added and the reaction mixture was heated to 80° C. for 1 h. The reaction mixture was diluted with water (100 mL), extracted with ethyl acetate (2×50 mL), washed with brine, dried over Na2SO4 and concentrated under reduced pressure to obtain the compound as brown gummy material (1.1 g, 69%): 1H NMR (400 MHz, CDCl3) δ 7.81 (d, J=8.4 Hz, 1H), 7.46 (s, 1H), 7.33 (d, J=8.4 Hz, 1H), 6.70 (dd, J=17.6, 11.2 Hz, 1H), 5.87 (d, J=17.6 Hz, 1H), 5.42 (d, J=10.8 Hz, 1H), 4.41 (q, J=7.2 Hz, 2H), 1.43 (t, J=7.2 Hz, 3H); ESIMS m/z 211.22 ([M+H]+); IR (thin film) 1729, 886 cm-1.
69% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate In dimethyl sulfoxide at 80℃; for 1h; Inert atmosphere; 9 Preparation of ethyl 2-chloro-4-vinylbenzoate (C68) Example 9 Preparation of ethyl 2-chloro-4-vinylbenzoate (C68) To a stirred solution of ethyl 2-chloro-4-bromobenzoate (C61) (2.00 g, 7.63 mmol) in dimethylsulfoxide (20 mL) was added potassium vinyltrifluoroborate (3.06 g, 22.9 mmol), and potassium carbonate (3.16 g, 22.9 mmol). The reaction mixture was degassed with argon for 30 minutes. Bistriphenylphosphine(diphenylphosphino ferrocene)palladium(II) dichloride (0.270 g, 0.380 mmol) was added and the reaction mixture was heated to 80° C. for 1 hour. The reaction mixture was diluted with water (100 mL), extracted with ethyl acetate (2*50 mL), washed with brine, dried over sodium sulfate, and concentrated under reduced pressure to obtain the compound as brown gummy material (1.10 g, 69%)
With potassium carbonate In dimethyl sulfoxide 9 Preparation of Ethyl 2-chloro-4-vinylbenzoate (AI54) Example 9 Preparation of Ethyl 2-chloro-4-vinylbenzoate (AI54) To a stirred solution of ethyl 2-chloro-4-bromobenzoate (2 g, 7.63 mmol) in DMSO (20 mL) was added potassium vinyltrifluoroborate (3.06 g, 22.9 mmol) and K2CO3 (3.16 g, 22.9 mmol). The reaction mixture was degassed with argon for 30 min Bistriphenylphosphine(diphenylphosphinoferrocene)palladium dichloride (0.27 g, 0.38 mmol) was added and the reaction mixture was heated to 80° C. for 1 h. The reaction mixture was diluted with water (100 mL), extracted with EtOAc (2*50 mL), washed with brine, dried over Na2SO4 and concentrated under reduced pressure to obtain the compound as brown gummy material (1.1 g, 69%): 1H NMR (400 MHz, CDCl3) δ 7.81 (d, J=8.4 Hz, 1H), 7.46 (s, 1H), 7.33 (d, J=8.4 Hz, 1H), 6.70 (dd, J=17.6, 11.2 Hz, 1H), 5.87 (d, J=17.6 Hz, 1H), 5.42 (d, J=10.8 Hz, 1H), 4.41 (q, J=7.2 Hz, 2H), 1.43 (t, J=7.2 Hz, 3H); ESIMS m/z 211.22 ([M+H]+); IR (thin film) 1729, 886 cm-1.

  • 35
  • [ 509142-48-7 ]
  • potassium vinyltrifluoroborate [ No CAS ]
  • [ 1416979-95-7 ]
YieldReaction ConditionsOperation in experiment
47% With potassium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In dimethyl sulfoxide; at 80℃; for 1h;Inert atmosphere; Example 118Preparation of (E)-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-2-(trifluoromethoxy)benzamide (AC116) Step 1. 2-(Trifluoromethoxy)-4-vinylbenzoic acid (A179); To a stirred solution of <strong>[509142-48-7]4-bromo-2-(trifluoromethoxy)benzoic acid</strong> (1 g, 3.67 mmol) in DMSO (20 mL) was added potassium vinyltrifluoroborate (1.47 g, 11.02 mmol) and potassium carbonate (1.52 g, 11.02 mmol). The reaction mixture was degassed with argon for 30 min. Bistriphenylphosphine(diphenylphosphinoferrocene)palladium dichloride (0.13 g, 0.18 mmol) was added and the reaction mixture was heated to 80 C. for 1 h. The reaction mixture was diluted with water (100 mL), extracted with ethyl acetate (2×50 mL), washed with brine, and dried over Na2SO4. Concentration under reduced pressure furnished the crude compound which was purified by flash column chromatography to afford the product as pale yellow gummy material (0.4 g, 47%): 1H NMR (400 MHz, CDCl3) delta 8.05 (d, J=8.1 Hz, 1H), 7.44 (d, J=1.8 Hz, 1H), 7.35 (s, 1H), 6.78 (dd, J=17.4.1, 11.1 Hz, 1H), 5.92 (d, J=17.4 Hz, 1H), 5.51 (d, J=10.8 Hz, 1H); ESIMS m/z 232.97 ([M+H]+).
47% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In dimethyl sulfoxide; at 80℃; for 1h;Inert atmosphere; Step 1. 2-(Trifluoromethoxy)-4-vinylbenzoic acid (AI79): To a stirred solution of <strong>[509142-48-7]4-bromo-2-(trifluoromethoxy)benzoic acid</strong> (1 g, 3.67 mmol) in DMSO (20 mL) was added potassium vinyltrifluoroborate (1.47 g, 11.02 mmol) and potassium carbonate (1.52 g, 11.02 mmol). The reaction mixture was degassed with argon for 30 min. Bistriphenylphosphine(diphenylphosphinoferrocene)palladium dichloride (0.13 g, 0.18 mmol) was added and the reaction mixture was heated to 80 C for 1 h. The reaction mixture was diluted with water (lOOmL), extracted with ethyl acetate (2 x 50 mL), washed with brine, and dried over Na2S04. Concentration under reduced pressure furnished the crude compound which was purified by flash column chromatography to afford the product as pale yellow gummy material (0.4 g, 47%): ]H NMR (400 MHz, CDC13) delta 8.05 (d, 7 = 8.1 Hz, 1H), 7.44 (d, / = 1.8 Hz, 1H), 7.35 (s, 1H), 6.78 (dd, 7 =17.4.1, 11.1 Hz, 1H), 5.92 (d, / = 17.4 Hz, 1H), 5.51 (d, / = 10.8 Hz, 1H); ESIMS m/z 232.97 ([M+H]+).
47% With potassium carbonate; In dimethyl sulfoxide; at 80℃; for 1h;Inert atmosphere; To a stirred solution of <strong>[509142-48-7]4-bromo-2-(trifluoromethoxy)benzoic acid</strong> (1 g, 3.67 mmol) in DMSO (20 mL) was added potassium vinyltrifluoroborate (1.47 g, 11.02 mmol) and potassium carbonate (1.52 g, 11.02 mmol). The reaction mixture was degassed with argon for 30 min Bistriphenylphosphine(diphenylphosphinoferrocene)palladium dichloride (0.13 g, 0.18 mmol) was added and the reaction mixture was heated to 80 C. for 1 h. The reaction mixture was diluted with water (100 mL), extracted with ethyl acetate (2×50 mL), washed with brine, and dried over Na2SO4. Concentration under reduced pressure furnished the crude compound which was purified by flash column chromatography to afford the product as pale yellow gummy material (0.4 g, 47%): 1H NMR (400 MHz, CDCl3) delta 8.05 (d, J=8.1 Hz, 1H), 7.44 (d, J=1.8 Hz, 1H), 7.35 (s, 1H), 6.78 (dd, J=17.4.1, 11.1 Hz, 1H), 5.92 (d, J=17.4 Hz, 1H), 5.51 (d, J=10.8 Hz, 1H); ESIMS m/z 232.97 ([M+H]+).
47% With bistriphenylphosphine(diphenylphosphinoferrocene)palladium dichloride; potassium carbonate; In dimethyl sulfoxide; at 80℃; for 1h;Inert atmosphere; To a stirred solution of <strong>[509142-48-7]4-bromo-2-(trifluoromethoxy)benzoic acid</strong> (1 g, 3.67 mmol) in DMSO (20 mL) was added potassium vinyltrifluoroborate (1.47 g, 11.02 mmol) and potassium carbonate (1.52 g, 11.02 mmol). The reaction mixture was degassed with argon for 30 min Bistriphenylphosphine(diphenylphosphinoferrocene)palladium dichloride (0.13 g, 0.18 mmol) was added and the reaction mixture was heated to 80 C. for 1 h. The reaction mixture was diluted with water (100 mL), extracted with ethyl acetate (2*50 mL), washed with brine, and dried over Na2SO4. Concentration under reduced pressure furnished the crude compound which was purified by flash column chromatography to afford the product as pale yellow gummy material (0.4 g, 47%): 1H NMR (400 MHz, CDCl3) delta 8.05 (d, J=8.1 Hz, 1H), 7.44 (d, J=1.8 Hz, 1H), 7.35 (s, 1H), 6.78 (dd, J=17.4.1, 11.1 Hz, 1H), 5.92 (d, J=17.4 Hz, 1H), 5.51 (d, J=10.8 Hz, 1H); ESIMS m/z 232.97 ([M+H]+).
47% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In dimethyl sulfoxide; at 80℃; for 1h;Inert atmosphere; To a stirred solution of <strong>[509142-48-7]4-bromo-2-(trifluoromethoxy)benzoic acid</strong> (1 g, 3.67 mmol) in DMSO (20 mL) was added potassium vinyltrifluoroborate (1.47 g, 11.02 mmol) and potassium carbonate (1.52 g, 11.02 mmol). The reaction mixture was degassed with argon for 30 min. Bistriphenylphosphine(diphenylphosphinoferrocene)palladium dichloride (0.13 g, 0.18 mmol) was added and the reaction mixture was heated to 80 C for 1 h. The reaction mixture was diluted with water (lOOmL), extracted with ethyl acetate (2 x 50 mL), washed with brine, and dried over Na2S04. Concentration under reduced pressure furnished the crude compound which was purified by flash column chromatography to afford the product as pale yellow gummy material (0.4 g, 47%): ]H NMR (400 MHz, CDC13) delta 8.05 (d, 7 = 8.1 Hz, 1H), 7.44 (d, / = 1.8 Hz, 1H), 7.35 (s, 1H), 6.78 (dd, 7 =17.4.1, 11.1 Hz, 1H), 5.92 (d, / = 17.4 Hz, 1H), 5.51 (d, / = 10.8 Hz, 1H); ESIMS m/z 232.97 ([M+H]+).
47% Example 118 Preparation of (E)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-2-(trifluoromethoxy)benzamide (AC116) Step 1. 2-(Trifluoromethoxy)-4-vinylbenzoic acid (AI79) To a stirred solution of <strong>[509142-48-7]4-bromo-2-(trifluoromethoxy)benzoic acid</strong> (1 g, 3.67 mmol) in DMSO (20 mL) was added potassium vinyltrifluoroborate (1.47 g, 11.02 mmol) and potassium carbonate (1.52 g, 11.02 mmol). The reaction mixture was degassed with argon for 30 min Bistriphenylphosphine(diphenylphosphinoferrocene)palladium dichloride (0.13 g, 0.18 mmol) was added and the reaction mixture was heated to 80 C. for 1 h. The reaction mixture was diluted with water (100 mL), extracted with ethyl acetate (2×50 mL), washed with brine, and dried over Na2SO4. Concentration under reduced pressure furnished the crude compound which was purified by flash column chromatography to afford the product as pale yellow gummy material (0.4 g, 47%): 1H NMR (400 MHz, CDCl3) delta 8.05 (d, J=8.1 Hz, 1H), 7.44 (d, J=1.8 Hz, 1H), 7.35 (s, 1H), 6.78 (dd, J=17.4.1, 11.1 Hz, 1H), 5.92 (d, J=17.4 Hz, 1H), 5.51 (d, J=10.8 Hz, 1H); ESIMS m/z 232.97 ([M+H]+).
47% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In dimethyl sulfoxide; at 80℃; for 1h;Inert atmosphere; Step 1. 2-(Trifluoromethoxy)-4-vinylbenzoic acid (C100) To a stirred solution of <strong>[509142-48-7]4-bromo-2-(trifluoromethoxy)benzoic acid</strong> (1.00 g, 3.67 mmol) in dimethylsulfoxide (20 mL) was added potassium vinyltrifluoroborate (1.47 g, 11.0 mmol), and potassium carbonate (1.52 g, 11.0 mmol). The reaction mixture was degassed with argon for 30 minutes. Bistriphenylphosphine(diphenylphosphino ferrocene)palladium(II) dichloride (0.130 g, 0.180 mmol) was added and the reaction mixture was heated to 80 C. for 1 hour. The reaction mixture was diluted with water (100 mL), extracted with ethyl acetate (2*50 mL), washed with brine, and dried over sodium sulfate. Concentration under reduced pressure furnished the crude compound which was purified by flash column chromatography to afford the product as pale yellow gummy material (0.400 g, 47%): 1H NMR (400 MHz, CDCl3) delta 8.05 (d, J=8.1 Hz, 1H), 7.44 (d, J=1.8 Hz, 1H), 7.35 (s, 1H), 6.78 (dd, J=17.4.1, 11.1 Hz, 1H), 5.92 (d, J=17.4 Hz, 1H), 5.51 (d, J=10.8 Hz, 1H); ESIMS m/z 233 ([M+H]+).
With potassium carbonate; In dimethyl sulfoxide; Step 1. 2-(Trifluoromethoxy)-4-vinylbenzoic acid (AI79) To a stirred solution of <strong>[509142-48-7]4-bromo-2-(trifluoromethoxy)benzoic acid</strong> (1 g, 3.67 mmol) in DMSO (20 mL) was added potassium vinyltrifluoroborate (1.47 g, 11.02 mmol) and K2CO3 (1.52 g, 11.02 mmol). The reaction mixture was degassed with argon for 30 min Bistriphenylphosphine(diphenylphosphinoferrocene)palladium dichloride (0.13 g, 0.18 mmol) was added and the reaction mixture was heated to 80 C. for 1 h. The reaction mixture was diluted with water (100 mL), extracted with EtOAc (2*50 mL), washed with brine, and dried over Na2SO4. Concentration under reduced pressure furnished the crude compound which was purified by flash column chromatography to afford the product as pale yellow gummy material (0.4 g, 47%): 1H NMR (400 MHz, CDCl3) delta 8.05 (d, J=8.1 Hz, 1H), 7.44 (d, J=1.8 Hz, 1H), 7.35 (s, 1H), 6.78 (dd, J=17.4.1, 11.1 Hz, 1H), 5.92 (d, J=17.4 Hz, 1H), 5.51 (d, J=10.8 Hz, 1H); ESIMS m/z 232.97 ([M+H]+).

  • 36
  • [ 1093262-17-9 ]
  • [ 13682-77-4 ]
  • [ 1093262-19-1 ]
YieldReaction ConditionsOperation in experiment
87% With triethylamine In propan-1-ol at 120℃; for 0.5h; Microwave irradiation; 143.E 3-[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-bromobenzonitrile (0.70 g, 1.969 mmol) was combined with potassium vinyl trifluoroborate (0.396 g, 2.95 mmol), [1 ,1 '- bis(diphenylphosphino)ferrocene]dichloropalladium(ll), dichloromethane complex (1 :1 ) (0.058 g, 0.079 mmol) and TEA (0.412 ml_, 2.95 mmol) in n-propanol (10 ml.) and heated in a microwave reactor at 120 0C for 30 min. The reaction mixture was filtered through Celite and concentrated to dryness. The residue was dissolved in DCM, washed with saturated aqueous NaHCOβ, dried over MgSOφ filtered and concentrated to dryness. The crude material was purified on silica gel (eluted with 0 to 10% CH3OH/DCM) to give 3-[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5- ethenylbenzonitrile (0.52 g, 1.718 mmol, 87 % yield) as an orange solid. 1 H NMR (400 MHz, DMSOd6) δ ppm 7.79 (s, 1 H), 7.45 - 7.55 (m, 2 H), 7.40 (s, 1 H), 7.25 (s, 1 H), 6.75 (dd, 1 H), 6.04 (d, 1 H), 5.43 (d, 1 H), 3.77 (s, 2 H), 2.05 (br. s., 2 H). LC- MS (ES+) m/z 303.32, 305.30 [M+H].
  • 37
  • [ 1093256-24-6 ]
  • [ 13682-77-4 ]
  • [ 1093256-27-9 ]
YieldReaction ConditionsOperation in experiment
82% With triethylamine In propan-1-ol at 100℃; for 6h; 162 A solution of λ/-({3-[(3-bromo-5-chlorophenyl)oxy]-4-chloro-2-fluorophenyl}methyl)-4- chloro-2-ethyl-1/-/-imidazole-5-carboxamide (240 mg, 0.46 mmol), potassium vinyltrifluoroborate (122 mg, 0.92 mmmol), PdCI2(dppf)-DCM (15 mg, 0.0184 mmol) and triethylamine (0.13 ml_, 0.92 mmol) in n-PrOH (5 ml_). The reaction was heated at 100 0C for 6 h, cooled to rt and water was added (20 ml_). The aqueous mixture was extracted with EtOAc (3 x 20 ml.) and the organic extracts were combined, dried over Na2SO4, filtered and concentrated. The crude material was purified by column chromatography (5% to 100% EtOAc/hexanes gradient) to afford the title compound (177 mg, 82%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ ppm 8.14 (br s, 1 H), 7.47 (d, 1 H), 7.35-7.30 (m, 2H), 7.01 (s, 1 H), 6.81 (d, 1 H), 6.72-6.64 (m, 2H), 5.92 (d, 1 H), 5.35 (d, 1 H), 4.51 (d, 2H), 2.58 (q, 2H), 1.16 (t, 3H).
  • 38
  • [ 64169-34-2 ]
  • potassium vinyltrifluoroborate [ No CAS ]
  • [ 876156-35-3 ]
YieldReaction ConditionsOperation in experiment
83% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine; In ethanol; at 85℃; for 16h;Inert atmosphere; 5-bromoisobenzofuran-l(3H)-one (5.00 g, 23.5 mmol) was combined with potassium vinyltrifluoroborate (4.72 g, 35.2 mmol), PdCl2(dppf)CH2Cl2 (1.91 g, 2.35 mmol) and TEA (6.54 mL, 46.9 mmol) in ethanol (50 mL). The reaction mixture was purged with nitrogen gas and stirred at 85 C for 16 h. The reaction mixture was cooled to room temperature, diluted with water and extracted with EtOAc (3 x 50 mL). The combined extracts were washed with brine (30 mL), dried over sodium sulfate and concentrated under reduced pressure. The crude was purified by column chromatography using CombiFlash (Redisep-40 g, 15 % EtOAc in -hexane) to give Intermediate 1-3 A (3.60 g, 83.0 %) as an off white solid. 1H NMR (300 MHz, DMSO^e) delta ppm 5.41 (s, 2 H), 5.49 (d, J= 10.9 Hz, 1 H), 6.07 (d, J = 17.4 Hz, 1 H), 6.90 (dd, J= 17.8, 10.9 Hz, 1 H), 7.65-7.72 (m, 1 H), 7.76 (s, 1 H), 7.78-7.86 (m, 1 H). LCMS (Method R), retention time: 0.64 min, (M+H) 161.1
65.3% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine; In N,N-dimethyl-formamide; at 100℃; 10 g (0.04 mol) of <strong>[64169-34-2]5-bromophthalide</strong> and 8.18 g (0.06 mol) of potassium vinyl trifluoroborate were added to a 250 ml three-necked flask.3 g (0.003 mol) of catalyst PdCl2(dppf)-CH2Cl2, 10 ml of triethylamine, 50 ml of DMF as solvent,Nitrogen protection, set the temperature of 100 C reaction 5-10h;The mixture was poured into water, extracted with ethyl acetate, washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate and evaporated.The petroleum ether: dichloromethane (3:1) system was passed through a column, and dried in an oven to obtain 4.9 g of a pale yellow solid, yield 65.3%.
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine; In ethanol; for 8h;Inert atmosphere; Reflux; 5-Bromophthalide (50g, 235 mmol), potassium vinyl trifluoroborate (62.9 g, 469 mmol), and PdCl2(dppf)-CH2Cl2 Adduct (9.58 g, 11.7 mmol) were added to ethanol (500 mL) then TEA (65.4 mL, 469 mmol) was added. The reaction mixture was degassed then heated at reflux for 8 h. The reaction was worked up by diluting with ethyl acetate and washing with brine twice. The organic layer was dried and evaporated to dryness. The crude product was purified by MPLC (silica, 600g column) with 25% EtOAc/hexane (3 L) then with 30% EtOAc/Hexane (2 L) to yield the title compound.
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine; In ethanol; for 8h;Reflux; Step A: 5-ethenyl-2-benzofuran-1(3H)-one: 5-Bromophthalide (50g, 235 mmol), potassium vinyltrifluoroborate (62.9 g, 469 mmol), and PdCl2(dppf)-CH2Cl2 Adduct (9.58 g, 11.7 mmol) wereadded to ethanol (500 mL) then TEA (65.4 mL, 469 mmol) was added. The reaction mixture wasdegassed then heated at reflux for 8 h. The reaction was worked up by diluting with ethyl acetate and washing with brine twice. The organic layer was dried and evaporated to dryness. The crudeproduct was purified by MPLC (silica, 600g column) with 25% EtOAc/hexane (3 L) then with30% EtOAc/Hexane (2 L) to yield the title compound.
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine; In ethanol; for 8h;Reflux; Step A: 5-ethenyl-2-benzofuran-1(3H)-one: 5-Bromophthalide (50g, 235 mmol), potassium vinyl trifluoroborate (62.9 g, 469 mmol), and PdC12(dppf)-CH2C12 Adduct (9.58 g, 11.7 mmol) were added to ethanol (500 mL) then TEA (65.4 mL, 469 mmol) was added. The reaction mixture wasdegassed then heated at reflux for 8 h. The reaction was worked up by diluting with ethyl acetate and washing with brine twice. The organic layer was dried and evaporated to dryness. The crude product was purified by MPLC (silica, 600g column) with 25% EtOAc/hexane (3 L) then with 30% EtOAc/Hexane (2 L) to yield the title compound
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine; In ethanol; for 8h;Reflux; 5-Bromophthalide (50g, 235 mmol), potassium yinyl trifluoroborate (62.9 g, 469 mmol), and PdC12(dppf)-CH2C12 Adduct (9.58 g, 11.7 mmol) were added to ethanol (500 mL) then TEA (65.4 mL, 469 mmol) was added. The reaction mixture was degassed then heated at reflux for 8 h. The reaction was worked up by diluting with ethyl acetateand washing with brine twice. The organie layer was dried and eyaporated to dryness. The crudeproduct was purified by MPLC (silica, 600g column) with 25% EtOAclhexane (3 L) then with30% EtOAc/Hexane (2 L) to yield the title compound.
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine; In ethanol; for 8h;Reflux; 5-Bromophthalide (50g, 235 mmol), potassium vinyl trifluoroborate (62.9g, 469 mmol), and PdCl2(dppf)-CH2Cl2 Adduct (9.58 g, 11.7 mmol) were added to ethanol (500 mL) then TEA (65.4mL, 469 mmol) was added. The reaction mixture was degassed then heated at reflux for 8 h. The reaction wasworked up by diluting with ethyl acetate and washing with brine twice. The organic layer was dried and evaporatedto dryness. The crude product was purified by MPLC (silica, 600g column) with 25% EtOAc/hexane (3 L) then with30% EtOAc/Hexane (2 L) to yield the title compound

  • 39
  • [ 1426566-04-2 ]
  • [ 13682-77-4 ]
  • [ 1426566-05-3 ]
YieldReaction ConditionsOperation in experiment
89% With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; palladium diacetate; potassium carbonate In 1,4-dioxane; water at 85 - 90℃; for 5h; Inert atmosphere; 19.6 Step 6; 2-((tert-butvldimethvlsilvloxv)methvl)-l-methyl-6-vinvl-lH-indole-5- carbaldehyde Step 6; 2-((tert-butvldimethvlsilvloxv)methvl)-l-methyl-6-vinvl-lH-indole-5- carbaldehyde 2-((tert-butyldimethylsilyloxy)methyl)-6-chloro-l -methyl- lH-indole-5-carbaldehyde (3.80 g, 11.24 mmol), potassium vinyltrifluoroborate (2.30 g, 17.17 mmol), Pd(OAc)2 (76 mg, 0.34 mmol, 3 mol%), S-Phos ligand (280 mg, 0.68 mmol, 6 mol%) and K2C03 (4.70 g, 34.0 mmol) were mixed together in a 100 mL round bottom flask. The flask was placed under vacuum and back filled with Argon, then dioxane (45 mL) and H20 (7.5 mL) were added. The mixture was heated at 85-90 °C for 5 h and monitored by LC/MS. After complete consumption of the starting material, the reaction mixture was cooled to room temperature. Water (30 mL) was added to the mixture and the product was extracted with DCM (3x80 mL). The combined organics were washed with NaCl (aqueous saturated, 80 mL) and dried over Na2S04. After concentration of the solvent, the residue was purified by column chromatography (EtOAc/hexanes, 0-10% gradient), affording the product as a white solid (3.32 g, 89 %). XH NMR (500 MHz, CHCh-d) δ ppm 0.09 (s, 6 H) 0.91 (s, 9 H) 3.84 (s, 3 H) 4.85 (s, 3 H) 5.42 (dd, J=10.7, 1.7 Hz, 1 H) 5.69 (dd, J=17.2, 1.7 Hz, 2 H) 6.51 (s, 1 H) 7.43 (s, 2 H) 7.75 (dd, J=17.3, 10.7 Hz, 1 H) 8.07 (s, 1 H) 10.24 (s, 1 H). LC-MS 330.3 [M+H]+, RT 1.74 min.
89% With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; palladium diacetate; potassium carbonate In 1,4-dioxane; water at 85 - 90℃; for 5h; Inert atmosphere; Intermediate 22-((tert-Butyldimethylsilyloxy)methyl)-l-methyl-6-vinyl-lH-indole-5-carbaldehyde Intermediate 22-((tert-Butyldimethylsilyloxy)methyl)-l-methyl-6-vinyl-lH-indole-5-carbaldehyde 2-((tert-Butyldimethylsilyloxy)methyl)-6-chloro-l-methyl-lH-indole-5-carbaldehyde (Intermediate 1, 3.80 g, 11.24 mmol), potassium vinyltrifluoroborate (2.30 g, 17.17 mmol), Pd(OAc)2(76 mg, 0.34 mmol, 3 mol%), S-Phos ligand (280 mg, 0.68 mmol, 6 mol%) and K2C03(4.70 g, 34.0 mmol) were mixed together in a 100 mL round bottom flask. The flask was vacuumed and backfilled with argon before dioxane (45 mL) and H20 (7.5 mL) were added. The mixture was heated at 85-90 °C for 5 hrs and the reaction was monitored by LC/MS until the starting material was completely consumed. The reaction was cooled to room temperature and water (30 mL) was added. The product was extracted with CH2C12(3x80 mL). The combined organics were washed with NaCl (aq. satd., 80 mL), dried over Na2S04and concentrated. The residue was purified by column chromatography(EtOAc/hexanes, 0-10% gradient) affording the product as a white solid (3.32 g, 89 %). LC-MS: 330.3 [M+H]+, RT 1.74 min. 1H NMR (500 MHz, CDC13) δ ppm 0.09 (s, 6H), 0.91 (s, 9H), 3.84 (s, 3H), 4.85 (s, 2H), 5.42 (dd, J=10.7, 1.7 Hz, 1H), 5.69 (dd, J=17.2, 1.7 Hz, 1H), 6.51 (s, 1H), 7.43 (s, 1H), 7.75 (dd, J=17.3, 10.7 Hz, 1H), 8.07 (s, 1H), 10.24 (s, 1H)
89% With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; palladium diacetate; potassium carbonate In 1,4-dioxane; water at 85 - 90℃; for 5h; Inert atmosphere;
  • 40
  • [ 1426566-95-1 ]
  • [ 13682-77-4 ]
  • [ 1426566-96-2 ]
YieldReaction ConditionsOperation in experiment
95% With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; palladium diacetate; potassium carbonate In 1,4-dioxane; water at 75℃; for 1h; Inert atmosphere; 5 2-(((tert-Butyldimethylsilyl)oxy)methyl)-1-methyl-4-vinyl-1H-indole-5-carbaldehyde A mixture of 2-(((tert-butyldimethylsilyl)oxy)methyl)-4-chloro- 1-methyl-1 H-indole-5-carbaldehyde (14.02 g, 41.5 mmol), potassium trifluoroborate (11.12 g, 83 mmol), palladium acetate (0.279 g, 1.245 mmol), 5-Phos ligand (1.022 g, 2.49 mmol) and K2C03 (17.18 g, 124.5 mmol) in a 1 L flask was degassed and back-filled with nitrogen. i,4-Dioxane (334 mL) and water (66 mL) were added and the mixture was heated at 75°C for 1 hr. The reaction was then cooled to room temperature, extracted with ether and washed with water. The organics were dried and concentrated to give crude product which was purified by a filtration column (160 g silica) with 0-5% EtOAc/hexanes to afford the title compoundg, 95%) as an off-white solid.LC-MS 330.3 [M+Hf’, RT 1.72 mm. ‘H NMR (500 MHz, acetone-d6) ppm 0.12 (s, 6H),0.92 (s, 9H), 3.89 (s, 3H), 4.97 (d, J=0.6 Hz, 2H), 5.70 (dd, J=17.5, 1.6 Hz, 1H), 5.76 (dd,J=11.2, 1.6 Hz, 1H), 6.77 (s, 1H), 7.49 (d, J=8.8 Hz, 1H), 7.60 (dd, J=17.5, 11.2 Hz, 1H),7.74 (d, J=8.8 Hz, 1H), 10.34 (s, 1H).
65% With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; palladium diacetate; potassium carbonate In 1,4-dioxane; water at 85℃; for 2h; Inert atmosphere; 60.7 Step_7_2-((tert-butyldimethylsilyloxy)methyl)-l-methyl-4-vinyl-lH-indole-5- carbaldehyde Step_7_2-((tert-butyldimethylsilyloxy)methyl)-l-methyl-4-vinyl-lH-indole-5- carbaldehyde 2-((tert-butyldimethylsilyloxy)methyl)-4-chloro- 1 -methyl- 1 H-indole-5-carbaldehyde (0.2744 g, 0.81 mmol), potassium vinyltrifluoroborate (0.22 g, 1.64 mmol), Pd(OAc)2 (5.5 mg, 0.02 mmol, 3 mol%), S-Phos ligand (20 mg, 0.05 mmol, 6 mol%) and K2C03 (0.34 g, 2.46 mmol) were mixed together in a vial. The vial was placed under vacuum and back filled with Argon, then dioxane (3.2 mL) and 0 (0.5 mL) were added. The mixture was heated at 85 °C for 2 h and then cooled to room temperature. Water (5 mL) was added to the reaction mixture and the product was extracted with DCM (2x15 mL). The combined organics were washed with NaCl (aqueous saturated, 10 mL) and dried over Na2S04. After concentration of the solvent, the residue was purified by column chromatography (EtOAc/hexanes, 0-10% gradient), affording the product as a white solid (0.170 g, 65 %). XH NMR (500 MHz, CHCl3-i/) δ ppm 0.09 (s, 6 H) 0.91 (s, 9 H) 3.83 (s, 3 H) 5.69 (dd, J=17.7, 1.6 Hz, 1 H) 5.79 (dd, J=11.2, 1.6 Hz, 1 H) 7.31 (d, J=8.5 Hz, 1 H) 7.47 (dd, J=17.7, 11.2 Hz, 1 H) 7.81 (d, J=8.5 Hz, 1 H) 10.36 (s, 1 H). LC-MS 330.3 [M+H]+, RT 1.72 min.
65% With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; palladium diacetate; potassium carbonate In 1,4-dioxane; water at 85℃; for 2h; Inert atmosphere;
  • 41
  • [ 1426073-33-7 ]
  • [ 13682-77-4 ]
  • [ 1426073-34-8 ]
YieldReaction ConditionsOperation in experiment
With Pd(dppf)Cl2 In ethanol; triethylamine at 20℃; for 4h; Inert atmosphere; 33.G Step G: 2-fluoro-3-methoxyA-vinylbenzonitrile Step G: 2-fluoro-3-methoxyA-vinylbenzonitrile: A mixture of 4-bromo-2-fluoro-3-methoxybenzonitrile (6.0 g, 26 mmol), potassium vinyltrifluoroborate ( 4.20 g, 31.3 mmol) andPd(dppf)Cl2 (0.8 g) in 60 mL of EtOH and 60 mL of TEA was refluxed under Ar for 4 hours. The resulting mixture was concentrated and the residue was purified by column chromatography(PE: EtOAc = 20 :1) to afford 2-fluoro-3-methoxy-4-vinylbenzonitrile.
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; triethylamine In ethanol for 4h; Reflux; Inert atmosphere; 21.G Step G: 2-fluoro-3-methoxy-4-yinylbenzonitrile: A mixture of 4-bromo-2-fluoro-3- methoxybenzonitrile (6.0 g, 26 mmol), potassium yinyltrifluoroborate (4.20 g, 31.3 mmol) and Pd(dppf)c12 (0.8 g) in 60 m of EtOH and 60 m of TEA was refluxed under Ar for 4 hours. The resulting mixture was concentrated and the residue was purified by column chromatography (PE: EtOAc = 20 :1) to afford 2-fluoro-3-methoxy-4-yinylbenzonitrile.
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; triethylamine In ethanol for 4h; Reflux; Inert atmosphere; G Step G: 2-fluoro-3-methoxy-4-vinylbenzonitrile: General procedure: A mixture of 4-bromo-2-fluoro-3-methoxybenzonitrile (6.0 g, 26mmol), potassium vinyltrifluoroborate (4.20 g, 31.3 mmol) and Pd(dppf)Cl2 (0.8 g) in 60 mL of EtOH and 60 mL ofTEA was refluxed under Ar for 4 hours. The resulting mixture was concentrated and the residue was purified bycolumn chromatography (PE : EtOAc = 20 :1) to afford 2-fluoro-3-methoxy-4-vinylbenzonitrile
  • 42
  • [ 1617498-15-3 ]
  • [ 13682-77-4 ]
  • [ 1617498-16-4 ]
YieldReaction ConditionsOperation in experiment
98% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine In isopropyl alcohol at 85℃; for 1h; Inert atmosphere; 3.1 Step 1: Synthesis of Compound 3A [0188] The mixture of compound 1C (10.8 g, 33.1 mmol), potassium vinyl trifluoroborate (5.3 g, 39.8 mmol), triethylamine (6.7 g, 9.3 mL, 66.2 mmol) and PdCl2(dppf) (1.35 g, 1.65 mmol) in i-PrOH (200 mL) was degassed for three times and flushed with nitrogen. The mixture was stirred at 85° C. for 1 hour. After concentrated to dryness, the residue was purified by column chromatography (ethyl acetate/hexanes, v/v, 1/1001/40) to give the titled compound 3A (6.6 g, 98% yield) as a slightly yellow oil.
98% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; triethylamine In isopropyl alcohol at 85℃; for 1h; Inert atmosphere;
75% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; triethylamine In isopropyl alcohol for 15h; Inert atmosphere; Reflux; 22.3 Synthesis of compound 22D The mixture of compound 22C (6.55 g, 20 mmol), potassium vinyltrifluoroborate (3.22 g, 24 mmol), triethylamine (5.6 mL, 40 mmol) and PdCl2(dppf) (820 mg, 1 mmol) in 2-propanol (150 mL) was degassed and filled with nitrogen (3 times) and refluxed for 15 hours. The reaction mixture was cooled down and concentrated to dryness. The residue was purified by column chromatography (ethyl acetate/hexanes, v/v, 1/6 to 1/3) to give the titled compound 22D (4.1 g, 75%) as a slightly yellow solid. 1H-NMR(400 MHZ, CDC13) δ 7.86 (d, 1H), 7.72 (d, 1H), 7.18 (t, 1H), 6.86 (dd, 1H), 5.82 (d, 1H), 5.39 (d, 1H), 1.77 (s, 6H).
  • 43
  • [ 26218-78-0 ]
  • [ 13682-77-4 ]
  • [ 103440-76-2 ]
YieldReaction ConditionsOperation in experiment
95% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine In isopropyl alcohol at 100℃; for 2h; Inert atmosphere; a (a) methyl 6-vinylnicotinate To a solution of methyl 6-bromonicotinate (10 g, 46.5 mmol) in z'-PrOH (100 mL) was added potassium vinyltrifluoroborate (12.4 g, 93 mmol), Et3N (14.1 g, 140 mmol), and Pd(dppf)Cl2-DCM (1.1 g). The mixture was stirred at 100 °C for 2 h under nitrogen. The reaction was complete detected by TLC. The mixture was concentrated and the residue was purified by column chromatography on silica gel eluted with PE/EA = 15/1 to give methyl 6-vinylnicotinate (7.2 g, 95%).1H-NMR(CDC13, 400 MHz) δ 3.94 (s, 3 H), 5.55 (d, / = 12.0 Hz, 1 H), 6.36 (d, / = 20.0 Hz, 1 H), 6.85 (dd, /= 17.41, 10.76 Hz, 1 H), 7.39 (d, /= 8.22 Hz, 1 H), 8.23 (dd, /= 8.22, 2.35 Hz, 1 H), 9.15 (d, /= 1.56 Hz, 1 H).
95% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine In isopropyl alcohol at 100℃; for 2h; Inert atmosphere; a (a) methyl 6-vinylnicotinate (a) methyl 6-vinylnicotinate To a solution of methyl 6-bromonicotinate (10 g, 46.5 mmol) in i-PrOH (100 mL) was added potassium vinyltrifluoroborate (12.4 g, 93 mmol), Et3N (14.1 g, 140 mmol), and Pd(dppf)Cl2.DCM (1.1 g). The mixture was stirred at 100° C. for 2 h under nitrogen. The reaction was complete detected by TLC. The mixture was concentrated and the residue was purified by column chromatography on silica gel eluted with PE/EA=15/1 to give methyl 6-vinylnicotinate (7.2 g, 95%). 1H-NMR (CDCl3, 400 MHz) δ 3.94 (s, 3H), 5.55 (d, J=12.0 Hz, 1H), 6.36 (d, J=20.0 Hz, 1H), 6.85 (dd, J=17.41, 10.76 Hz, 1H), 7.39 (d, J=8.22 Hz, 1H), 8.23 (dd, J=8.22, 2.35 Hz, 1H), 9.15 (d, J=1.56 Hz, 1H).
95% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine In dichloromethane; isopropyl alcohol at 100℃; for 2h; Inert atmosphere; 214.1 Step 1: Methyl 6-vinylnicotinate (1) To a solution of methyl 6-bromonicotinate (10 g, 46.5 mmol) in i-PrOH (100 mL) were added potassium vinyltrifluoroborate (12.4 g, 93 mmol), Et3N (14.1 g, 140 mmol), and Pd(dppf)Cl2- DCM (1.1 g). The mixture was stirred at 100 °C for 2 h under nitrogen. The reaction was complete monitored by TLC. The mixture was concentrated and the residue was purified by column chromatography on silica gel eluted with PE/EA = 15/1 to give methyl 6-vinylnicotinate 1 (7.2 g, 95%).1H MR (400 MHz, CDC1): δ 9.15 (d, J = 1.56 Hz, 1H), 8.23 (dd, J = 8.22, 2.35 Hz, 1H), 7.39 (d, J= 8.22 Hz, 1H), 6.85 (dd, J= 17.41, 10.76 Hz, 1H), 6.36 (d, J= 20.0 Hz, 1H), 5.55 (d, J = 12.0 Hz, 1H), 3.94 (s, 3 H).
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine In isopropyl alcohol at 100℃; for 2h; Inert atmosphere; a (a) methyl 6-vinylnicotinate To a solution of methyl 6-bromonicotinate (10 g, 465 mmoi) in i-PrOH (100 mL) was added potassium vinyltrifluorohorate (12.4 g, 93 mmol), Et3N (14.1 g, 140 mmol), and Pd(dppf)C12DCM (1.1 g). The mixture was stirred at 100 °C for 2 h under nitrogen. The reaction was complete detected by T]LC The mixture was concentrated and the residue was purified by column chromatography on silica gel eluted with PE/EA = 15/1 to give methyl 6-vinylnicotinate.‘H-NMR(CDCI3, 400 MHz) ö 3.94 (s, 3 H), 5.55 (d, .1 = 12.0 Flz, I H), 6.36 (d, j:zr. 20.0 Hz, I H), 6.85 (ddJ= 17.41, 10.76 Hz, I H), T39 (d,J= 8.22 Hz, I H), 8.23 (dd,J= 8.22, 235 Hz, I H), 9,15 (d, J= 1.56 Hz, I H) ppm.

  • 44
  • [ 1476759-52-0 ]
  • [ 13682-77-4 ]
  • [ 1476759-56-4 ]
YieldReaction ConditionsOperation in experiment
91% With palladium diacetate; potassium carbonate; catacxium A In water; toluene at 90℃; for 18h; Inert atmosphere; 115 [Example 115] Compound b28 2-Amino-5-trifluoromethyl-4-vinyl-benzoic acid ethyl ester [Example 115] Compound b28 2-Amino-5-trifluoromethyl-4-vinyl-benzoic acid ethyl ester [0392] water (112 ml) was added to a suspension of 2-amino-4-chloro-5-trifluoromethyl-benzoic acid ethyl ester (Compound b27, 9.00 g, 34 mmol), potassium vinyltrifluoroborate (6.31 g, 47 mmol), BuPAd2 (1.21 g, 3.4 mmol), palladium acetate (378 mg, 1.7 mmol), and potassium carbonate (13.9 g, 100 mmol) in toluene (336 ml), and the mixture was stirred at 90°C under an argon atmosphere for 18 hours. The reaction solution was cooled to room temperature, and ethyl acetate was then added thereto, and this was washed with water. The organic layer was dried over anhydrous sodium sulfate. The drying agent was removed by filtration. After concentration under reduced pressure, the resulting residue was purified by silica gel column chromatography (ethyl acetate/hexane) to yield the title compound (7.93 g, 91%) as a yellow solid. LCMS: m/z 260 [M+H]+ HPLC retention time: 0.94 min (analysis condition A)
91% With palladium diacetate; potassium carbonate; catacxium A In water; toluene at 90℃; for 18h; Inert atmosphere; 21 2-Amino-5-trifluoromethyl-4-vinyl-benzoic acid ethyl ester Distilled water (112 ml) was added to a suspension of 2-amino-4-chloro-5-trifluoromethyl-benzoic acid ethyl ester (Compound 20, 9.00 g, 34 mmol), potassium vinyltrifluoroborate (6.31 g, 47 mmol), BuPAd2 (1.21 g, 3.4 mmol), palladium acetate (378 mg, 1.7 mmol), and potassium carbonate (13.9 g, 100 mmol) in toluene (336 ml), and the mixture was stirred at 90°C under argon atmosphere for 18 hours. The reaction solution was cooled to room temperature, and ethyl acetate was then added thereto, and this was washed with water. The organic layer was dried over anhydrous sodium sulfate. The drying agent was removed by filtration, and the residue obtained by concentration under reduced pressure was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (7.93 g, 91%) as a yellow solid. LCMS: m/z 260 [M+H]+ HPLC retention time: 0.94 min (analysis condition D)
91% With palladium diacetate; potassium carbonate; catacxium A In water; toluene at 90℃; for 18h; Inert atmosphere; 108 ethyl 2-amino-4-vinyl-5-(trifluoromethyl)benzoate 107,9.00g, 34mmol), potassium vinyltrifluoroborate (6.31g, 47mmol),BuPAd2 (1.21g, 3.4mmol), palladium acetate (378mg, 1.7mmol) and potassium carbonate(13.9g, lOOmmol) suspension of toluene (336ml) in force □ distilled water(112ml), under argon atmosphere at 90 ° C for 18 hours. The reaction was cooled to roomAfter the temperature ethyl acetate was added, washed with water, and the organic layer was dried over anhydrous sodium sulfatedry. After the desiccant was filtered off and concentrated under reduced pressure and the obtained residue was purified by silica gel column chromatography(Ethyl acetate / hexane) to give the title compound (7.93g, 91%) of a yellow solidbody.
  • 45
  • [ 2007081-81-2 ]
  • [ 13682-77-4 ]
  • [ 2007081-82-3 ]
YieldReaction ConditionsOperation in experiment
93% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 In 1,4-dioxane; water at 100℃; for 15h; 13.3 The third step 3-nitro-1-((2-(trimethylsilyl)ethoxy)methyl)-5-vinyl-1H-pyrazole 13d Compound 13c (6.5g, 17.60mmol) was dissolved in 1,4-dioxane (80mL) and water (10mL). Potassium ethylenetrifluoroborate (4.72g, 35.24mmol) was added sequentially at room temperature,Potassium phosphate (7.47g, 35.20mmol) and Pd(dppf)Cl2 dichloromethane complex (645mg, 0.88mmol) were heated to 100°C and stirred for 15 hours. TLC showed that the reaction was complete. The reaction solution was cooled to room temperature, water was added, extracted with ethyl acetate, and the organic phases were combined.Washed with water, washed with saturated brine, dried with anhydrous sodium sulfate, concentrated, and purified by silica gel column chromatography to obtain the title compound 13d as an oil (4.4g, yield 93%).
85% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate In tetrahydrofuran; water at 70℃; for 17h; Reflux;
73.1% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate In tetrahydrofuran; water at 100℃; for 24h; Inert atmosphere; 185 Synthesis of compound 185.3 To a solution of 185.2 (0.15g, 0.406mmol, l .Oeq) and potassium vinyl trifluoroborate (0.098g, 0.731mmol, 1.8eq) in mixture of tetrahydrofuran (lmL) and water (0.2mL) was added potassium carbonate (0.168g, 1.22mmol, 3.0eq). The reaction mixture was degassed for 10 min. under argon atmosphere. The [Ι, -Bis(diphenylphosphino)ferrocene]palladium(II) dichloride dichloromethane complex (0.017g, 0.020mmol, 0.05eq) was added, again reaction mixture was degassed for 10 min. under argon atmosphere. The reaction was stirred at 100°C for 24h. After completion of reaction, reaction mixture was transferred in water and extracted with ethyl acetate. Combined organic layer was washed with brine, dried over sodium sulphate and concentrated under reduced pressure to obtain crude material. This was further purified by column chromatography using 5% ethyl acetate in hexane to obtain pure 185.3 (0.080g, 73.10%). MS(ES): m/z 270.38 [M+H]+
  • 46
  • [ 22536-61-4 ]
  • potassium vinyltrifluoroborate [ No CAS ]
  • 5-methyl-2-vinylpyrimidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
70% With caesium carbonate; triphenylphosphine; palladium dichloride; In tetrahydrofuran; water; at 62℃;Inert atmosphere; [0397j 5-methyl-2-vinylpyrimidine, Example 11.01. A 3 L 3-necked round bottomed flask was fitted with a reflux condenser, a temperature controller and a septum and was charged with <strong>[22536-61-4]2-chloro-5-methylpyrimidine</strong> (81 mL, 778 mmol), potassium vinyltrifluoroborate (156 g, 1167 mmol), triphenylphosphine (18.02 mL, 78 mmol), cesium carbonate (156 mL, 1945 mmol) and a large stir bar. Water (1565 mL) was added and the mixture was stirred for several minutes and then THF (244 mL) was added. Argon was bubbled through the mixture for 5 mm and then added palladium (II) chloride (1.72 g, 38.9 mmol) was added. The reaction was further sparged with argon for 5 mins. The temperature was raised to 62 C and stirring continued to completion. The reaction was then cooled to RT and filtered through two Whatman GF/F filter cups, rinsing with ether. The mixture was transferred to a separatory funnel, and the the layers were separated. The aqueous layer was further extracted with diethyl ether (4 x 200 mL). The organic layers were combined and dried over anydrous MgSO4 and then filtered. The mixture was partially concentrated on the roto evaporator at 20 C and 115 torr for an extended period of time to give an orange liquid. The material was further purified by Kugelrohr distillation to isolate the title compound (65.4 g, 70%) as a light yellow oil. ?HNMR(400MHz, CDC13)E2.31 (s, 3H), 5.68 (d,J10.56Hz, 1H), 6.55 (d,J17.22Hz, 1H), 6.86 (dd, J=17.41, 10.56 Hz, 1H), 8.54 (s, 2H). LCMS-ESI (pos.) mlz: 121.1 (M+H).
70% With caesium carbonate; triphenylphosphine; palladium dichloride; In tetrahydrofuran; water; at 62℃;Inert atmosphere; 5-Methyl-2-vinylpyrimidine, Example 28.1 A 3 L 3-necked round bottomed flask was fitted with a reflux condenser, a temperature controller and a septum and was charged with <strong>[22536-61-4]2-chloro-5-methylpyrimidine</strong> (81 mL, 778 mmol), potassium vinyltrifluoroborate (156 g, 1167 mmol), triphenylphosphine (18.02 mL, 78 mmol), cesium carbonate (156 mL, 1945 mmol) and a large stir bar. Water (1565 mL) was added, and the mixture was stirred for several min and then THF (244 mL) was added. Argon was bubbled through the mixture for 5 min and then palladium (II) chloride (1.72 g, 38.9 mmol) was added. The reaction was further sparged with argon for 5 mins. The temperature was raised to 62 C. and stirring continued to completion. The reaction was then cooled to RT and filtered through two Whatman GF/F filter cups, rinsing with ether. The mixture was transferred to a separatory funnel, and the layers were separated. The aqueous layer was further extracted with diethyl ether (4*200 mL). The organic layers were combined and dried over anhydrous MgSO4 and then filtered. The mixture was partially concentrated on a rotary evaporator at 20 C. and 115 torr for an extended period of time to give an orange liquid. The material was further purified by Kugel Rohr distillation to isolate the title compound (65.4 g, 70%) as a light yellow oil. 1H NMR (400 MHz, CDCl3) delta 2.31 (s, 3H), 5.68 (d, J=10.56 Hz, 1H), 6.55 (d, J=17.22 Hz, 1H), 6.86 (dd, J=17.41, 10.56 Hz, 1H), 8.54 (s, 2H). LCMS-ESI (pos) m/z:121.1 (M+H)+.
70% A 3-necked 3 L RBF was fitted with a reflux condenser, a temperature controller and a septum and was charged with <strong>[22536-61-4]2-chloro-5-methylpyrimidine</strong> (81 mL, 778 mmol), potassium vinyltrifluoroborate (156 g, 1167 mmol), triphenylphosphine (18.02 mL, 78 mmol), and cesium carbonate (156 mL, 1945 mmol). Water (1565 mL) was added, and the mixture was stirred for 2 min and then THF (244 mL) was added. Argon was sparged through the mixture for 5 min and then palladium (II) chloride (1.72 g, 38.9 mmol) was added. The reaction was further sparged with argon for 5 min. The temperature was raised to 62 C and stirring was continued until completion. The reaction was cooled to RTand filtered through two Whatman GF/F filter cups, rinsing with diethyl ether. The mixture was transfered to a separatory funnel and the layers were separated. The aqueous layer was further extracted with diethyl ether (4X). The combined organic layers were dried over anhydrous magnesium sulfate and partially concentrated in vacuo at 20 C and 115 torr for an extended period of time to give an orange liquid. The initial product was purified by Kugelrohr distillation to provide 405.01 (65.4 g, 70% yield) as a light yellow oil. LCMS- ESI (pos.) m/z: 121.1 (M+H)+.
70% A 3 L 3-necked round bottom flask was fitted with a reflux condenser, a temperature controller and a septum and was charged with <strong>[22536-61-4]2-chloro-5-methylpyrimidine</strong> (81 mL, 778 mmol), potassium vinyltrifluoroborate (156g, 1167 mmol), triphenylphosphine (18.02 mL, 78 mmol), cesium carbonate (156 mL, 1945 mmol) and a large stir bar. Water (1565 mL) was addedand the mixture was stirred for several mm and then THF (244 mL) was added. Argon was bubbled through the mixture for 5 mm and then palladium (II) chloride (1.72 g, 38.9 mmol) was added. The reaction was further sparged with argon for 5 mins. The temperature was raised to 62 C and stirring was continued to completion. The reaction was then cooled to RT and filtered through two Whatman GF/F filter cups, rinsing with ether. The mixture was transferred to a separatory funnel, and the layers were separated. The aqueous layer was further extracted with diethyl ether (4 x 200 mL). The organic layers were combined and dried over anhydrous MgSO4 and then filtered. The mixture was partially concentrated on the rotory evaporator at 20 C and 115 torr for an extended period of time to give an orange liquid. The material was further purified by Kugelrohr distillation to isolate the title compound (65.4g, 70%) as a light yellow oil. 1H NMR (400 MHz, CDC13) oe 2.31 (s, 3H), 5.68 (d,J10.56 Hz, 1H), 6.55 (d,J17.22 Hz, 1H), 6.86 (dd,J17.41, 10.56 Hz, 1H), 8.54 (s, 2H). LCMS-ESI (pos.)m/z:121.1 (M+H)t
70% With caesium carbonate; triphenylphosphine; palladium dichloride; In tetrahydrofuran; water; at 62℃;Inert atmosphere; A 3 L 3 -neck round bottomed flask was fitted with a reflux condenser, a temperature controller and a septum and charged with <strong>[22536-61-4]2-chloro-5-methylpyrimidine</strong> (81 mL, 778 mmol), potassium vinyltrifluoroborate (156 g, 1167 mmol), triphenylphosphine (18.02 mL, 78 mmol), cesium carbonate (156 mL, 1945 mmol) and a large stir bar. Water (1565 mL) was added, and the mixture was stirred for several min before THF (244 mL) was added. Argon was bubbled through the mixture for 5 min and then palladium (II) chloride (1.72 g, 38.9 mmol) was added. The reaction was further sparged with argon for 5 mins. The temperature was raised to 62 C and stirring was continued to completion. The reaction was then cooled to RT and filtered through two Whatman GF/F filter cups, rinsing with ether. The mixture was transferred to a separatory funnel, and the layers were separated. The aqueous layer was further extracted with diethyl ether (4 x 200 mL). The organic layers were combined and dried over anhydrous MgS04 and then filtered. The mixture was partially concentrated on the rotary evaporator at 20 C and 115 torr for an extended period of time to give an orange liquid. The material was further purified by Kugelrohr distillation to isolate the title compound (65.4g, 70%) as a light yellow oil. NMR (400 MHz, CDC13) delta 2.31 (s, 3H), 5.68 (d, J=10.56 Hz, 1H), 6.55 (d, J=17.22 Hz, 1H), 6.86 (dd, J=17.41, 10.56 Hz, 1H), 8.54 (s, 2H). LCMS-ESI (pos.) m/z: 121.1 (M+H)+.
70% A 3-necked 3 L RBF was fitted with a reflux condenser, a temperature controller and a septum and was charged with <strong>[22536-61-4]2-chloro-5-methylpyrimidine</strong> (100 g, 778 mmol), potassium vinyltrifluoroborate (156 g, 1167 mmol), triphenyiphosphine (20.5 g, 78 mmol), cesium carbonate (633.7 g, 1945 mmol), and a large stir bar. Water (1565 mL) was added, and the mixture was stirred for several mm and then THF (244 mL) was added. Argon was bubbled through the mixture for 5 mm and then palladium (II) chloride (1.72 g, 38.9 mmol) was added. The reaction was then further sparged with argon for 5 mm. The temperature was raised to 62 C, and the mixture was stirred until completion. The reaction was ten cooled to RT and filtered through two Whatman GF/F filter cups rinsing with ether. The mixture was transferred to a separatory funnel and the layers were separated. The aqueous layer was further extracted with Et20 (4X). The combined organic layers were dried over anhydrous MgSO4 and partially concentrated in vacuo at 20 C and 115 ton for an extended period of time to give an orange liquid. The initial product was purified by Kugelrohr distillation to provide Example 356.01 (65.4 g, 70% yield) as a light yellow oil. LCMS-ESI (pos.) m/z: 121.1 (M+H)t
70% With caesium carbonate; triphenylphosphine; palladium dichloride; In tetrahydrofuran; at 62℃;Inert atmosphere; A 3 L 3-necked round bottom flask was fitted with a reflux condenser, a temperature controller and a septum and then charged with 2-chloro-5-methylpyrimidme (81 mL, 778 mmol), potassium vinyltrifluoroborate (156 g, 1167 mmol), triphenylphosphine (18.02 mL, 78 mmol), cesium carbonate (156 mL, 1945 mmol) and a large stir bar. Water (1.6 L) was added and the mixture was stirred for several mm and then THF (244 mL) was added. Argon was bubbled through the mixture for 5 mm and then palladium (II) chloride (1.72 g, 38.9 mmol) was added. The reaction was further sparged with argon for 5 mm. The temperature was raised to 62 C and stirring was continued to completion. The reaction was then cooled to RT and filtered through two Whatman GF/F filter cups, rinsing with ether. The mixture was transferred to a separatory funnel and the layers were separated. The aqueous layer was further extracted with diethyl ether (4 x 200 mL). The organic layers were combined and dried over anhydrous MgSO4 and then filtered. The mixture was partially concentrated on the rotory evaporator at 20 C and 115 torr for an extended period of time to give an orange liquid. The material was further purified by Kugelrohr distillation to provide the title compound (65.4 g, 70%) as a light yellow oil. 1H NMR (400 MHz, CDC13) oe 2.31 (s, 3H), 5.68 (d,J10.56 Hz, 1H), 6.55 (d,J17.22 Hz, 1H), 6.86 (dd,J=17.41, 10.56 Hz, 1H), 8.54 (s, 2H). LCMS-ESI (pos.)m/z:121.1 (M+H)t

  • 47
  • [ CAS Unavailable ]
  • [ 13682-77-4 ]
  • [ 98217-79-9 ]
YieldReaction ConditionsOperation in experiment
90% With palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; triethylamine In propan-1-ol at 100℃; for 4h; Inert atmosphere; 2.1.2. Synthesis of 6,6'-divinyl-2,2'-bipyridine 2 g 6,6'-dibromo-2,2'-bipyridine, 2.6 g potassium vinyltrifluoroborate,and 0.27 g [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) PdCl2(dppf) was dissolved in 5.5 ml triethylamineand 20 ml n-propanol under Ar atmosphere. The mixturewas stirred and refluxed under 100 °C for 4 h. The reaction wasquenched by the addition of 20 ml water, and the aqueous partphase was extracted with ethyl acetate for four times. The organicphase was dried over Na2SO4, filtered, and evaporated underreduced pressure. After purifying by column chromatography onsilica gel, 6,6'-divinyl-2,2'-bipyridine was obtained in 90% yield.1H NMR in Fig. S2 (400 MHz, CDCl3, TMS) δ 5.52 (2H), 6.34 (2H),6.90 (2H), 7.35 (2H), 7.78 (2H), 8.42 (2H) ppm; 13C NMR inFig. S2 (CDCl3, 100 MHz) δ 118.20, 119.82, 121.37, 137.00,139.34, 154.86, 155.67 ppm.
88% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II) dichloromethane adduct; triethylamine In propan-1-ol at 100℃; for 3h; Inert atmosphere;
84% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II) dichloromethane adduct; triethylamine In isopropanol for 16h; Reflux;
  • 48
  • [ 16650-55-8 ]
  • potassium vinyltrifluoroborate [ No CAS ]
  • 4-vinyl-1-naphthoic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
62% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In dimethyl sulfoxide; at 80℃; for 18h; To a stirred solution of <strong>[16650-55-8]4-bromo-1-naphthoic acid</strong> (2.50 g, 9.98 mmol) in dimethyl sulfoxide (32.3 mL) was added potassium vinyltrifluoroborate (1.33 g, 9.96 mmol), potassium carbonate (3.85 g, 27.9 mmol) and [1,1?-bis(diphenylphosphino)ferrocene]-dichloropalladium(II) (0.364 g, 0.498 mmol). The reaction mixture was heated in an 80 C. bath for 18 hours. The reaction mixture was cooled to ambient temperature and diluted with 1 N aqueous hydrochloric acid solution (150 mL) and water (150 mL). The mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated under reduced pressure to afford the crude compound. The crude compound was purified by column chromatography (SiO2, eluting with 0-100% ethyl acetate in hexanes) to afford the title compound as a bright yellow solid (1.36 g, 62%): mp 147-155 C.; 1H NMR (300 MHz, acetone-d6) delta 11.42 (s, 1H), 9.16-9.03 (m, 1H), 8.31-8.25 (m, 2H), 7.77 (dd, J=7.7, 0.7 Hz, 1H), 7.70-7.57 (m, 3H), 5.95 (dd, J=17.2, 1.5 Hz, 1H), 5.62 (dd, J=11.1, 1.5 Hz, 1H); ESIMS m/z 197.1 ([M-H]-)
62% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In dimethyl sulfoxide; at 80℃; for 18h; Example 32 Preparation of 4-vinyl-1-naphthoic acid (C75) To a stirred solution of <strong>[16650-55-8]4-bromo-1-naphthoic acid</strong> (2.50 g, 9.98 mmol) in dimethyl sulfoxide (32.3 mL) was added potassium vinyltrifluoroborate (1.33 g, 9.96 mmol), potassium carbonate (3.85 g, 27.9 mmol) and [1,1'-bis(diphenylphosphino)ferrocene]-dichloropalladium(II) (0.364 g, 0.498 mmol). The reaction mixture was heated in an 80 C. bath for 18 hours. The reaction mixture was cooled to ambient temperature and diluted with 1 N aqueous hydrochloric acid solution (150 mL) and water (150 mL). The mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated under reduced pressure to afford the crude compound. The crude compound was purified by column chromatography (SiO2, eluting with 0-100% ethyl acetate in hexanes) to afford the title compound as a bright yellow solid (1.36 g, 62%): mp 147-155 C.; 1H NMR (300 MHz, acetone-d6) delta 11.42 (s, 1H), 9.16-9.03 (m, 1H), 8.31-8.25 (m, 2H), 7.77 (dd, J=7.7, 0.7 Hz, 1H), 7.70-7.57 (m, 3H), 5.95 (dd, J=17.2, 1.5 Hz, 1H), 5.62 (dd, J=11.1, 1.5 Hz, 1H); ESIMS m/z 197.1 ([M-H]-).
62% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In dimethyl sulfoxide; at 80℃; for 18h; Example 23: Preparation of 4-vinyl-1-naphthoic acid (C145) (0727) (0728) To a stirred solution of 631 <strong>[16650-55-8]4-bromo-1-naphthoic acid</strong> (2.50 g, 9.98 mmol) in 632 dimethyl sulfoxide (32.3 mL) was added 633 potassium vinyltrifluoroborate (1.33 g, 9.96 mmol), 634 potassium carbonate (3.85 g, 27.9 mmol) and 635 [1,1?-bis(diphenylphosphino)ferrocene]-dichloropalladium(II) (0.364 g, 0.498 mmol). The reaction mixture was heated in an 80 C. bath for 18 hours. The reaction mixture was cooled to ambient temperature and diluted with 1 N aqueous hydrochloric acid solution (150 mL) and water (150 mL). The mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated under reduced pressure to afford the crude compound. The crude compound was purified by column chromatography (SiO2, eluting with 0-100% ethyl acetate in hexanes) to afford the 636 title compound as a bright yellow solid (1.36 g, 62%): mp 147-155 C.; 1H NMR (300 MHz, acetone-d6) delta 11.42 (s, 1H), 9.16-9.03 (m, 1H), 8.31-8.25 (m, 2H), 7.77 (dd, J=7.7, 0.7 Hz, 1H), 7.70-7.57 (m, 3H), 5.95 (dd, J=17.2, 1.5 Hz, 1H), 5.62 (dd, J=11.1, 1.5 Hz, 1H); ESIMS m/z 197 ([M-H]-).
62% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In dimethyl sulfoxide; at 80℃; for 18h; To a stirred solution of <strong>[16650-55-8]4-bromo-1-naphthoic acid</strong> (2.50 g, 9.98 mmol) in dimethyl sulfoxide (32.3 mL) was added potassium vinyltrifluoroborate (1.33 g, 9.96 mmol), potassium carbonate (3.85 g, 27.9 mmol) and [1,1'-bis(diphenylphosphino)ferrocene]-dichloropalladium(II) (0.364 g, 0.498 mmol). The reaction mixture was heated in an 80 C. bath for 18 hours. The reaction mixture was cooled to ambient temperature and diluted with 1 N aqueous hydrochloric acid solution (150 mL) and water (150 mL). The mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated under reduced pressure to afford crude compound. The crude compound was purified by column chromatography (SiO2, eluting with 0-100% ethyl acetate in hexanes) to afford the title compound as a bright yellow solid (1.36 g, 62%): mp 147-155 C.; 1H NMR (300 MHz, acetone-d6) delta 11.42 (s, 1H), 9.16-9.03 (m, 1H), 8.31-8.25 (m, 2H), 7.77 (dd, J=7.7, 0.7 Hz, 1H), 7.70-7.57 (m, 3H), 5.95 (dd, J=17.2, 1.5 Hz, 1H), 5.62 (dd, J=11.1, 1.5 Hz, 1H); ESIMS m/z 197.1 ([M-H]-).
62% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In dimethyl sulfoxide; at 80℃; for 18h; Example 49 Preparation of 4-vinyl-1-naphthoic Acid (C101) To a stirred solution of <strong>[16650-55-8]4-bromo-1-naphthoic acid</strong> (2.50 g, 9.98 mmol) in dimethyl sulfoxide (32.3 mL) was added potassium vinyltrifluoroborate (1.33 g, 9.96 mmol), potassium carbonate (3.85 g, 27.9 mmol) and [1,1'-bis(diphenylphosphino)ferrocene]-dichloropalladium(II) (0.364 g, 0.498 mmol). The reaction mixture was heated in an 80 C. bath for 18 hours. The reaction mixture was cooled to ambient temperature and diluted with 1 N aqueous hydrochloric acid solution (150 mL) and water (150 mL). The mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated under reduced pressure to afford crude compound. The crude compound was purified by column chromatography (SiO2, eluting with 0-100% ethyl acetate gradient in hexanes) to afford the title compound as a bright yellow solid (1.36 g, 62%): mp 147-155 C.; 1H NMR (300 MHz, acetone-d6) delta 11.42 (s, 1H), 9.16-9.03 (m, 1H), 8.31-8.25 (m, 2H), 7.77 (dd, J=7.7, 0.7 Hz, 1H), 7.70-7.57 (m, 3H), 5.95 (dd, J=17.2, 1.5 Hz, 1H), 5.62 (dd, J=11.1, 1.5 Hz, 1H); ESIMS m/z 197 ([M-H]-).

  • 49
  • [ 84459-33-6 ]
  • potassium vinyltrifluoroborate [ No CAS ]
  • [ 1370529-71-7 ]
YieldReaction ConditionsOperation in experiment
70% With caesium carbonate; triphenylphosphine; palladium dichloride; In tetrahydrofuran; water; at 85℃; for 6h;Sealed tube; In a modification of a literatureprocedure, a resealable tube was charged with <strong>[84459-33-6]2-bromo-4-chlorobenzaldehyde</strong> (6.0 g, 27.34mmol), potassium vinyltrifluoroborate (4.76 g, 35.54 mmol), PdC12 (0.388 g, 2.19 mmol),triphenylphosphine (1.72 g, 6.56 mmol), and cesium carbonate (26.72 g, 82.02 mmol).? Asolution of THF/water (150 mL, 9:1) was added to the tube, whereupon it was sealed and stirredat 85 C for 6 h. The reaction mixture was allowed to cool to room temperature, diluted with water (30 mL), and extracted using Et20 (3 x 30 mL). The organic layer was washed with brine (1 x 30 mL), dried (Na2SO4), and concentrated under reduced pressure to provide an orange oil. The cmde residue was purified via flash chromatography (Si02), eluting with 1 hexanes/EtOAc(99:1) affording 3.18 g (70%) of MDW-1-106 as a pale yellow solid. ?H NMR (400 MHz, CDC13) oe 10.07 (s, 1 H), 7.59 (d, J 8.3 Hz, 1 H), 7.39-7.30 (m, 2 H), 7.21 (dd, J= 8.3, 2.1 Hz, 1 H), 5.58 (dd,J= 17.4, 1.0Hz, 1H), 5.41 (dd,J= 11.0, 1.0Hz, 1 H)
  • 50
  • [ 49562-28-9 ]
  • potassium vinyltrifluoroborate [ No CAS ]
  • isopropyl 2-methyl-2-(4-(4-vinylbenzoyl)phenoxy)propanoate [ No CAS ]
  • 51
  • [ 2304950-88-5 ]
  • [ 13682-77-4 ]
  • [ 2304950-97-6 ]
YieldReaction ConditionsOperation in experiment
74% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate In 1,4-dioxane; water at 100℃; for 8h; Inert atmosphere; 2; 17.2 Example 2 Synthesis of 4-(4-methoxy-4-methylpiperidin-1-yl)-2-oxo-6-vinyl-1,2-dihydro-1, 7-diazanaph thalene-3-carbonitrile (compound 70) Intermediate 6-chloro-4-(4-methoxy-4-methylpiperidin- 1-yl)-2-oxo-1,2-dihydro-1,7-diazanaphth alene-3-carbonitrile (20.1 g, 60.40 mmol, 1.0 eq) was dissolved in 1,4-dioxane (600 mL) and H2O (150 mL). Trifluoro(vinyl)potassium borate (12.14 g, 90.6 mmol, 1.5 eq), cesium carbonate (58 g, 181.2 mmol, 3.0 eq) and [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (4.4 g, 6.04 mmol, 1.0 eq) were added, and reacted at 100°C for 8 hours under nitrogen protection. LC-MS detection showed that the reaction was completed. Water (20 mL) was added. Dichloromethane (30 mL * 3) was used for extraction. The organic phase was washed with water (10 mL * 3), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified over silica gel column chromatography (DCM : MeOH = 50 : 1) to obtain a product (14.63 g, yield: 74%). 1H NMR (400 MHz, DMSO-d6) δ (ppm): 12.03 (s, 1H), 8.64 (s, 1H), 7.56 (s, 1H), 6.89-6.96 (m, 1H), 6.15-6.19 (m, 1H), 5.39-5.42 (m, 1H), 3.61-3.64 (m, 4H), 3.19 (s, 3H), 1.77-1.93 (m, 4H), 1.21 (s, 3H). Molecular formula: C18H20N4O2 Molecular weight: 324.38 LC-MS (Pos, m/z) = 325.16 [M+H]+.
74% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate In 1,4-dioxane; water at 100℃; for 8h; Inert atmosphere; 2; 17.2 Example 2 Synthesis of 4-(4-methoxy-4-methylpiperidin-1-yl)-2-oxo-6-vinyl-1,2-dihydro-1, 7-diazanaph thalene-3-carbonitrile (compound 70) Intermediate 6-chloro-4-(4-methoxy-4-methylpiperidin- 1-yl)-2-oxo-1,2-dihydro-1,7-diazanaphth alene-3-carbonitrile (20.1 g, 60.40 mmol, 1.0 eq) was dissolved in 1,4-dioxane (600 mL) and H2O (150 mL). Trifluoro(vinyl)potassium borate (12.14 g, 90.6 mmol, 1.5 eq), cesium carbonate (58 g, 181.2 mmol, 3.0 eq) and [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (4.4 g, 6.04 mmol, 1.0 eq) were added, and reacted at 100°C for 8 hours under nitrogen protection. LC-MS detection showed that the reaction was completed. Water (20 mL) was added. Dichloromethane (30 mL * 3) was used for extraction. The organic phase was washed with water (10 mL * 3), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified over silica gel column chromatography (DCM : MeOH = 50 : 1) to obtain a product (14.63 g, yield: 74%). 1H NMR (400 MHz, DMSO-d6) δ (ppm): 12.03 (s, 1H), 8.64 (s, 1H), 7.56 (s, 1H), 6.89-6.96 (m, 1H), 6.15-6.19 (m, 1H), 5.39-5.42 (m, 1H), 3.61-3.64 (m, 4H), 3.19 (s, 3H), 1.77-1.93 (m, 4H), 1.21 (s, 3H). Molecular formula: C18H20N4O2 Molecular weight: 324.38 LC-MS (Pos, m/z) = 325.16 [M+H]+.
43% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate In 1,4-dioxane; water at 100℃; for 8h; 71.2; 79 Step 2: synthesis of 4-(4-methoxy-4-methyl-piperidin-1-yl)-2-oxo-6-vinyl-1,2-dihydro-1,7-naphthyridin-3-carbonitrile The intermediate, 6-chloro-4-(4-methoxy-4-methyl-piperidin-1-yl)-2-oxo-1,2-dihydro-1,7-naphthyridine-3-carbonitrile (2.7g crude, 8.11mmol, 1.0eq) was dissolved in 1,4-dioxane (20mL) and H2O (5mL), potassium vinyltrifluoroborate (1.63g, 12.17mmol, 1.5eq), cesium carbonate (3.965g, 12.17mmol, 1.5eq) and [1,1'-bis (diphenylphosphino)ferrocene]palladium dichloride (297mg, 0.41mmol, 0.05eq), was added under nitrogen, the reaction stirred for 100 °C, 8 hours. LC-MS the reaction was complete, water (20 mL), dichloromethane (30mL × 3). The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure, the crude product was purified by silica gel column chromatography (DCM: MeOH = 70 : 1) to afford the product as a yellow solid (1.15g, yield: 43%).
1.15 g With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate In 1,4-dioxane; water at 100℃; for 8h; Inert atmosphere; 8.2 Step 2: 4-(4-Methoxy-4-methylpiperidin-1-yl)-2-oxo-6-vinyl-1,2-dihydro-1,7-naphthalene- 3-carbonitrileSynthesis The intermediate 6-chloro-4-(4-methoxy-4-methylpiperidin-1-yl)-2-oxo-1,2-dihydro-1,7-naphthalene-3-carbonitrile(2.7g crude product, 8.11mmol, 1.0eq)Dissolved in 1,4-dioxane (20mL) and H2O (5mL),Add potassium vinyl trifluoroborate (1.63g, 12.17mmol, 1.5eq),Cesium carbonate (3.965g, 12.17mmol, 1.5eq)And [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (297mg, 0.41mmol, 0.05eq),React at 100°C for 8 hours under nitrogen protection.LC-MS detects that the reaction is complete,Add water (20mL),Dichloromethane (30mL×3) extraction,The organic phase is dried with anhydrous sodium sulfate,Filtered, concentrated under reduced pressure,The crude product was purified by silica gel column chromatography (DCM:MeOH=70:1) to obtain a yellow solid product (1.15g, yield: 43%).
1.15 g With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate In 1,4-dioxane; water at 100℃; for 8h; Inert atmosphere; 1.2 Step 2: 4-(4-Methoxy-4-methylpiperidin-1-yl)-2-oxo-6-vinyl-1,2-dihydro-1,7-naphthalene- Synthesis of 3-carbonitrile The intermediate 6-chloro-4-(4-methoxy-4-methylpiperidin-1-yl)-2-oxo-1,2-dihydro-1,7-naphthalene-3 -Formonitrile (2.7g crude product, 8.11mmol, 1.0eq) dissolved in 1,4-dioxane (20mL) and H2O (5mL),Add potassium vinyl trifluoroborate (1.63g, 12.17mmol, 1.5eq),Cesium carbonate (3.965g, 12.17mmol, 1.5eq) and [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (297mg, 0.41mmol, 0.05eq),React at 100°C for 8 hours under nitrogen protection.LC-MS detects that the reaction is complete,Add water (20mL),Dichloromethane (30mL×3) extraction,The organic phase is dried with anhydrous sodium sulfate,filter,Concentrate under reduced pressure,The crude product was purified by silica gel column chromatography (DCM:MeOH=70:1) to obtain a yellow solid product (1.15g, yield: 43%).

  • 52
  • [ 2635-13-4 ]
  • potassium vinyltrifluoroborate [ No CAS ]
  • [ 7315-32-4 ]
YieldReaction ConditionsOperation in experiment
77% With bis-triphenylphosphine-palladium(II) chloride; caesium carbonate; In water; acetonitrile; at 100℃; for 24h;Inert atmosphere; General procedure: In an inert gas atmosphere 3a (1.01 g, 5.00 mmol, 1.00 equiv), potassium vinyltrifluoroborate (871 mg, 6.50 mmol, 1.30 equiv), Cs2CO3 (4.50 g, 13,81 mmol, 2.76 equiv) and PdCl2(PPh3)2 (175 mg, 0.25 mmol, 0.01 equiv) were mixed and suspended in a degassed mixture of acetonitrile and water (10:1, 45 mL). The reaction mixture was stirred at 120 C for 1.5 h, then cooled to room temperature and filtered through a pad of Celite. The filtrate was taken up in EtOAc (30 mL) and aq. sat. NH4Cl-solution (25 mL) and the phases separated. The watery phase was extracted with EtOAc (3 × 10 mL) and the combined organic phases washed with aq. sat. NaClsolution (20 mL) and dried over MgSO4. After evaporation of the solvent under reduced pressure, the residue was purified by silica gel column chromatography (EtOAc/MeOH 95:5). The product was obtained as yellow solid (570 mg, 3.85 mmol, 78%)
  • 53
  • [ 2300099-98-1 ]
  • [ 13682-77-4 ]
  • [ 2357116-01-7 ]
YieldReaction ConditionsOperation in experiment
59% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate In 1,4-dioxane at 120℃; for 16h; Inert atmosphere; 1 Step 1 - 3-(3-Methyl-2-oxo-5-vinyl-benzimidazol-1-yl)piperidine-2,6-dione A mixture of 3-(5-bromo-3-methyl-2-oxo-benzimidazol-1-yl)piperidine-2,6-dione (2.00 g, 5.91 mmol, Intermediate E), trifluoro-potassio-vinyl-boron (2,38 g, 17.74 mmol, CASNo. 13682-77-4), Pd(dppf)Cl2*CH2Cl2 (483 mg, 591 umol), Cs2CO3 (5.78 g, 17.7 mmol) in dioxane (30 mL) was degassed and purged with N2 three times. Then the mixture was stirred at 120 °C for 16 hours under N2 atmosphere. On completion, the mixture was quenched with the solution of sodium thiosulfate (20 mL) and extracted with dichloromethane (25 mL 3). The combined organic phase was dried over anhydrous sodium sulfate, filtered and concentrated to give a residue. The residue was purified by column chromatography (SiO2, petroleum ether/ethyl acetate=1:0 to 0: 1) to give the title compound (1.00 g, 59% yield) as a yellow solid. LC-MS (ESI+) m/z 286.2 (M+H)+.
59% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate In 1,4-dioxane at 120℃; for 16h; Inert atmosphere; 1 Step 1 - 3-(3-Methyl-2-oxo-5-vinyl-benzimidazol-1-yl)piperidine-2,6-dione A mixture of 3-(5-bromo-3-methyl-2-oxo-benzimidazol-1-yl)piperidine-2,6-dione (2.00 g, 5.91 mmol, Intermediate E), trifluoro-potassio-vinyl-boron (2,38 g, 17.74 mmol, CASNo. 13682-77-4), Pd(dppf)Cl2*CH2Cl2 (483 mg, 591 umol), Cs2CO3 (5.78 g, 17.7 mmol) in dioxane (30 mL) was degassed and purged with N2 three times. Then the mixture was stirred at 120 °C for 16 hours under N2 atmosphere. On completion, the mixture was quenched with the solution of sodium thiosulfate (20 mL) and extracted with dichloromethane (25 mL 3). The combined organic phase was dried over anhydrous sodium sulfate, filtered and concentrated to give a residue. The residue was purified by column chromatography (SiO2, petroleum ether/ethyl acetate=1:0 to 0: 1) to give the title compound (1.00 g, 59% yield) as a yellow solid. LC-MS (ESI+) m/z 286.2 (M+H)+.
58% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium hydride; caesium carbonate In 1,4-dioxane at 80℃; for 3h; Inert atmosphere; 1 Step 1-3-(3-Methyl-2-oxo-5-vinyl-benzimidazol-1-yl)piperidine-2,6-dione A mixture of 3-(5-bromo-3-methyl-2-oxo-benzimidazol-1-yl)piperidine-2,6-dione (3.00 g, 8.87 mmol, Intermediate HN), potassium hydride, trifluoro (vinyl)boron (3.57 g, 26.6 mmol), Cs2CO3 (2 M solution, 8.87 mL), Pd(dppf)Cl2-CH2Cl2 (724 mg, 887 umol) and in dioxane (30 mL) was degassed and purged with N2 for 3 times, and then the mixture was stirred at 80° C. for 3 hours under N2 atmosphere. On completion, the reaction mixture was concentrated in vacuo to give a residue. The residue was purified by reverse phase (TFA condition) to give the title compound (1.60 g, 58% yield) as a yellow solid. LC-MS (ESI+) m/z 286.0 (M+H)+.
58% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate In 1,4-dioxane at 80℃; for 3h; Inert atmosphere; 1 Step 1 - 3-(3-Methyl-2-oxo-5-vinyl-benzimidazol-1-yl)piperidine-2,6-dione A mixture of 3-(5-bromo-3-methyl-2-oxo-benzimidazol-1-yl)piperidine-2,6-dione (3.00 g, 8.87 mmol, Intermediate HN), potassium hydride, trifluoro (vinyl)boron (3.57 g, 26.6 mmol), Cs2CO3 (2 M solution, 8.87 mL), Pd(dppf)Cl2CH2Cl2 (724 mg, 887 umol) and in dioxane (30 mL) was degassed and purged with N2for 3 times, and then the mixture was stirred at 80 °C for 3 hours under N2 atmosphere. On completion, the reaction mixture was concentrated in vacuo to give a residue. The residue was purified by reverse phase (TFA condition) to give the title compound (1.60 g, 58% yield) as a yellow solid. LC-MS (ESI+) m/z 286.0 (M+H)+.
58% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate In 1,4-dioxane at 80℃; for 3h; Inert atmosphere; 1 Step 1 - 3-(3-Methyl-2-oxo-5-vinyl-benzimidazol-1-yl)piperidine-2,6-dione A mixture of 3-(5-bromo-3-methyl-2-oxo-benzimidazol-1-yl)piperidine-2,6-dione (3.00 g, 8.87 mmol, Intermediate HN), potassium hydride, trifluoro (vinyl)boron (3.57 g, 26.6 mmol), Cs2CO3 (2 M solution, 8.87 mL), Pd(dppf)Cl2.CH2Cl2 (724 mg, 887 umol) and in dioxane (30 mL) was degassed and purged with N2 for 3 times, and then the mixture was stirred at 80 °C for 3 hours under N2 atmosphere. On completion, the reaction mixture was concentrated in vacuo to give a residue. The residue was purified by reverse phase (TFA condition) to give the title compound (1.60 g, 58% yield) as a yellow solid. LC-MS (ESI+) m/z 286.0 (M+H)+.

  • 54
  • [ 1914946-33-0 ]
  • [ 13682-77-4 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate In 1,4-dioxane; water at 90℃; for 2h; Inert atmosphere; 27.1 Step 1: Step 1: Preparation of ethyl 5-vinylisoxazole-3-carboxylate To a mixture of ethyl 5-bromoisoxazole-3-carboxylate (0.400 g, 1.83 mmol) and potassium vinyltrifluoroborate (0.295 g, 2.20 mmol) in 1,4-dioxane (8 mL) and water (2 mL) was added [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.067 g, 0.092 mmol) and cesium carbonate (1.19 g, 3.66 mmol). The reaction was heated at 90° C. for 2 h under nitrogen. The reaction mixture was cooled then diluted with water (50 mL), filtered through Celite, and washed with ethyl acetate (20 mL). The filtrate was extracted with ethyl acetate (20 mL*3). The combined organic layers were washed with brine (30 mL), dried over sodium sulfate, filtered and concentrated in vacuo to give ethyl 5-vinylisoxazole-3-carboxylate (0.380 g, crude) as a brown oil that was used in the next step without further purification. LCMS (ESI) m/z: 168.1 [M+H]+.
  • 55
  • [ 2304754-51-4 ]
  • [ 13682-77-4 ]
  • [ 2434842-16-5 ]
YieldReaction ConditionsOperation in experiment
71% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate In 1,4-dioxane at 80℃; for 12h; Inert atmosphere; 1.1 Step 1: 3-(3-methyl-2-oxo-4-vinyl-benzimidazol-1-yl)piperidine-2,6-dione A mixture of 3-(4-bromo-3-methyl-2-oxo-benzimidazol-1-yl)piperidine-2,6-dione (0.2 g, 591 umol), potassium hydride;trifluoro(vinyl)boron (237 mg, 1.77 mmol), Cs2CO3 (2 M, 591.44 uL), Pd(dppf)Cl2.CH2Cl2(48 mg, 59.1 umol) and in dioxane (6 mL) was degassed and purged with N2 for 3 times, and then the mixture was stirred at 80 °C for 12 hr under N2 atmosphere. The reaction mixture was concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO2, Petroleum ether/Ethyl acetate=1/1 to 0:1) to give the title compound (0.14 g, 71% yield) as a yellow solid. LC-MS (ESI+) m/z 286.0 (M+H)+.
67% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate In 1,4-dioxane at 90℃; for 2h; Inert atmosphere; 3-(3-Methyl-2-oxo-4-vinyl-benzimidazol-1-yl)piperidine-2,6-dione (Intermediate AAV) A mixture of 3-(4-bromo-3-methyl-2-oxo-benzimidazol-1-yl)piperidine-2,6-dione (10.0 g, 29.5 mmol, Intermediate HP), potassium;trifluoro(vinyl)boranuide (11.8 g, 88.7 mmol, CAS 13682-77-4), Cs2CO3(2 M in water, 29.5 mL) and Pd(dppf)Cl2.CH2Cl2(1.69 g, 2.07 mmol) in dioxane (300 mL) was stirred at 90 °C for 2 hrs under nitrogen. On completion, the reaction mixture was filtered and the filtrated was concentrated in vacuo. The residue was purified by silica gel chromatography (petroleum ether: ethyl acetate = 1: 2) to give the title compound (5.70 g, 67% yield) as yellow solid.1H NMR (400 MHz, DMSO-d6) d 11.10 (s, 1H), 7.40 (dd, J = 10.8, 17.2 Hz, 1H), 7.18 (d, J = 7.2 Hz, 1H), 7.10 - 6.98 (m, 2H), 5.72 (d, J = 17.2 Hz, 1H), 5.47 - 5.31 (m, 2H), 3.54 (s, 3H), 2.96 - 2.82 (m, 1H), 2.79 - 2.57 (m, 2H), 2.06 - 1.94 (m, 1H).
67% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate In 1,4-dioxane; water at 90℃; for 2h; Inert atmosphere; 3-(3-Methyl-2-oxo-4-vinyl-benzimidazol-1-yl)piperidine-2,6-dione (Intermediate AAV) A mixture of 3-(4-bromo-3-methyl-2-oxo-benzimidazol-1-yl)piperidine-2,6-dione (10.0 g, 29.5 mmol, Intermediate HP), potassium;trifluoro(vinyl)boranuide (11.8 g, 88.7 mmol, CAS 13682-77-4), Cs2CO3 (2 M in water, 29.5 mL) and Pd(dppf)Cl2.CH2Cl2 (1.69 g, 2.07 mmol) in dioxane (300 mL) was stirred at 90 °C for 2 hrs under nitrogen. On completion, the reaction mixture was filtered and the filtrated was concentrated in vacuo. The residue was purified by silica gel chromatography (petroleum ether: ethyl acetate = 1: 2) to give the title compound (5.70 g, 67% yield) as yellow solid.1H NMR (400 MHz, DMSO-d6) d 11.10 (s, 1H), 7.40 (dd, J = 10.8, 17.2 Hz, 1H), 7.18 (d, J = 7.2 Hz, 1H), 7.10 - 6.98 (m, 2H), 5.72 (d, J = 17.2 Hz, 1H), 5.47 - 5.31 (m, 2H), 3.54 (s, 3H), 2.96 - 2.82 (m, 1H), 2.79 - 2.57 (m, 2H), 2.06 - 1.94 (m, 1H).
67% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate In 1,4-dioxane at 90℃; for 2h; Inert atmosphere; 3-(3-Methyl-2-oxo-4-vinyl-benzimidazol-1-yl)piperidine-2,6-dione (Intermediate AAV) A mixture of 3-(4-bromo-3-methyl-2-oxo-benzimidazol-1-yl)piperidine-2,6-dione (10.0 g, 29.5 mmol, Intermediate HP), potassium;trifluoro(vinyl)boranuide (11.8 g, 88.7 mmol, CAS 13682-77-4), Cs2CO3 (2 M in water, 29.5 mL) and Pd(dppf)Cl2.CH2Cl2 (1.69 g, 2.07 mmol) in dioxane (300 mL) was stirred at 90 °C for 2 hrs under nitrogen. On completion, the reaction mixture was filtered and the filtrated was concentrated in vacuo. The residue was purified by silica gel chromatography (petroleum ether: ethyl acetate = 1: 2) to give the title compound (5.70 g, 67% yield) as yellow solid.1H NMR (400 MHz, DMSO-d6) d 11.10 (s, 1H), 7.40 (dd, J = 10.8, 17.2 Hz, 1H), 7.18 (d, J = 7.2 Hz, 1H), 7.10 - 6.98 (m, 2H), 5.72 (d, J = 17.2 Hz, 1H), 5.47 - 5.31 (m, 2H), 3.54 (s, 3H), 2.96 - 2.82 (m, 1H), 2.79 - 2.57 (m, 2H), 2.06 - 1.94 (m, 1H).
67% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate In 1,4-dioxane; water at 90℃; for 2h; Inert atmosphere; [0083] 3-(3-Meth l-2-oxo-4-vin l-benzimidazol-1- l) i eridine-26-dione (Intermediate AAV) [0084] A mixture of 3-(4-bromo-3-methyl-2-oxo-benzimidazol-1-yl)piperidine-2,6-dione (10.0 g, 29.5 mmol, Intermediate HP), potassium;trifluoro(vinyl)boranuide (11.8 g, 88.7 mmol, CASNo. 13682-77-4), Cs2CO3 (2 M in water, 29.5 mL) and Pd(dppf)Cl2.CH2Cl2 (1.69 g, 2.07 mmol) in dioxane (300 mL) was stirred at 90 °C for 2 hrs under nitrogen. On completion, the reaction mixture was filtered and the filtrated was concentrated in vacuo. The residue was purified by silica gel chromatography (petroleum ether: ethyl acetate = 1: 2) to give the title compound (5.70 g, 67% yield) as yellow solid.1H NMR (400 MHz, DMSO-d6) δ 11.10 (s, 1H), 7.40 (dd, J = 10.8, 17.2 Hz, 1H), 7.18 (d, J = 7.2 Hz, 1H), 7.10 - 6.98 (m, 2H), 5.72 (d, J = 17.2 Hz, 1H), 5.47 - 5.31 (m, 2H), 3.54 (s, 3H), 2.96 - 2.82 (m, 1H), 2.79 - 2.57 (m, 2H), 2.06 - 1.94 (m, 1H).
67% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate In 1,4-dioxane; water at 90℃; for 2h; Inert atmosphere; 3-(3-Methyl-2-oxo-4-vinyl-benzimidazol-1-yl)piperidine-2,6-dione (Intermediate BZ) A mixture of 3-(4-bromo-3-methyl-2-oxo-benzimidazol-1-yl)piperidine-2,6-dione (10.0 g, 29.5 mmol, Intermediate B), potassium;trifluoro(vinyl)boranuide (11.8 g, 88.7 mmol, CASNo. 13682-77-4), Cs2CO3 (2 M in water, 29.5 mL) and Pd(dppf)Cl2.CH2Cl2 (1.69 g, 2.07 mmol) in dioxane (300 mL) was stirred at 90 °C for 2 hrs under nitrogen. On completion, the reaction mixture was filtered and the filtrated was concentrated in vacuo. The residue was purified by silica gel chromatography (petroleum ether: ethyl acetate = 1 : 2) to give the title compound (5.70 g, 67% yield) as yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 11.10 (s, 1H), 7.40 (dd, J= 10.8, 17.2 Hz, 1H), 7.18 (d, J= 7.2 Hz, 1H), 7.10 - 6.98 (m, 2H), 5.72 (d, J= 17.2 Hz, 1H), 5.47 - 5.31 (m, 2H), 3.54 (s, 3H), 2.96 - 2.82 (m, 1H), 2.79 - 2.57 (m, 2H), 2.06 - 1.94 (m, 1H).
67% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate In 1,4-dioxane; water at 90℃; for 2h; Inert atmosphere; 3-(3-Methyl-2-oxo-4-vinyl-benzimidazol-1-yl)piperidine-2,6-dione (Intermediate BZ) A mixture of 3-(4-bromo-3-methyl-2-oxo-benzimidazol-1-yl)piperidine-2,6-dione (10.0 g, 29.5 mmol, Intermediate B), potassium;trifluoro(vinyl)boranuide (11.8 g, 88.7 mmol, CASNo. 13682-77-4), Cs2CO3 (2 M in water, 29.5 mL) and Pd(dppf)Cl2.CH2Cl2 (1.69 g, 2.07 mmol) in dioxane (300 mL) was stirred at 90 °C for 2 hrs under nitrogen. On completion, the reaction mixture was filtered and the filtrated was concentrated in vacuo. The residue was purified by silica gel chromatography (petroleum ether: ethyl acetate = 1 : 2) to give the title compound (5.70 g, 67% yield) as yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 11.10 (s, 1H), 7.40 (dd, J= 10.8, 17.2 Hz, 1H), 7.18 (d, J= 7.2 Hz, 1H), 7.10 - 6.98 (m, 2H), 5.72 (d, J= 17.2 Hz, 1H), 5.47 - 5.31 (m, 2H), 3.54 (s, 3H), 2.96 - 2.82 (m, 1H), 2.79 - 2.57 (m, 2H), 2.06 - 1.94 (m, 1H).

  • 56
  • [ 1356113-40-0 ]
  • [ 13682-77-4 ]
  • [ 2581798-87-8 ]
YieldReaction ConditionsOperation in experiment
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II) dichloromethane adduct; triethylamine In ethanol at 120℃; for 0.333333h; Inert atmosphere; Microwave irradiation; 42.a a) 2-fluoro-5-vinylbenzonitrile General procedure: 5-bromo-2-fluorobenzonitrile (500 mg, 2.5 mmol), potassium trifluoro(vinyl)borate (402 mg, 3 mmol), l,r-bis(diphenylphosphino)fenOcene-palladium(II)di chloride dichloromethane complex (102 mg, 125 pmol) and triethylamine (253 mg, 2.5 mmol) were dispersed in 12 ml ethanol, degassed with argon and reacted in the microwave (120 °C, 20 min). The mixture was then concentraed in vacuo, diluted with EtOAc, washed with water, dried over Na2SC>4, filtered and concentrated in vacuo before it was purified by silica column chromatography (50 g, EtOAc in Hept 0% to 50%). The product was obtained as a white solid (312 mg). Product confirmed by 1H-NMR
With palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; potassium carbonate In 1,4-dioxane; water monomer at 100℃; for 12h; 5-fluoro-4-(trifluoromethyl)picolinaldehyde Step 1: 5-fluoro-4-(trifluoromethyl)-2-vinylpyridine. To a mixture of 2-chloro-5-fluoro-4-(trifluoromethyl)pyridine (1.0 g, 5.0 mmol), potassium trifluoro(vinyl)borate (1.0 g, 7.5 mmol) and K2CO3 (1.4 g, 10 mmol) in dioxane (15 mL) and water (1.5 mL) was add Pd(dppf)Cl2 (0.37 g, 0.50 mmol). The mixture was stirred at 100°C. for 12 h. Then water was added, and the mixture was extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo to give the title compound.
With palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; potassium carbonate In 1,4-dioxane; water monomer at 100℃; for 12h; 5-fluoro-4-(trifluoromethyl)picolinaldehyde Step 1: 5-fluoro-4-(trifluoromethyl)-2-vinylpyridine. To a mixture of 2-chloro-5-fluoro-4-(trifluoromethyl)pyridine (1.0 g, 5.0 mmol), potassium trifluoro(vinyl)borate (1.0 g, 7.5 mmol) and K2CO3 (1.4 g, 10 mmol) in dioxane (15 mL) and water (1.5 mL) was add Pd(dppf)Cl2 (0.37 g, 0.50 mmol). The mixture was stirred at 100°C. for 12 h. Then water was added, and the mixture was extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo to give the title compound.
  • 57
  • [ 1258833-77-0 ]
  • [ 13682-77-4 ]
  • [ 2642339-53-3 ]
YieldReaction ConditionsOperation in experiment
89% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; triethylamine In ethanol at 80℃; for 16h; D Step D, Preparation of 8-fluoro-6-vinylisoquinoHne. To a solution of 6-bromo-8- fuoroisoquinolme (1.17 g, 5.17 mmol, 1 equiv) in EtOH (35 mL) was added potassium tnfluoro(vinyl)borate (970.0 mg, 7.24 mmol, 1.5 equiv), PdCh(dppf) (171.0 mg, 0.21 mmol, 0.04 equiv), and EtsN (1.8 mL, 12.9 mmol, 2.5 equiv). The mixture was stirred at 80 °C for 16 h then concentrated. The residue was dissolved m EtOAc and washed with brine/ ater, dried (NazSiH), filtered, and concentrated. The residue was purified by flash chromatography (Combi-flash Rf, Hex/EtOAc :::: 0-40% gradient) to afford the title compound (800 mg, 4.6 mmol, 89% yield). NMR (400 MHz, Chloroform-*/) d 9.47 (s, IH), 8.58 (d, J = 5.6 Hz, 1H), 7.62 (d, J = 6.0 Hz, 111). 7.51 (s, IH), 7.39 (dd, J = 1.2, 11.6 Hz, 111). 6.86 (dd, J= 10.8, 17.6 Hz, 1H), 5.93 (d, J = 17.6 Hz, IH), 5.50 (d, J= 10.8 Hz, 1H).
  • 58
  • [ 112121-86-5 ]
  • [ 13682-77-4 ]
  • [ 2694870-56-7 ]
YieldReaction ConditionsOperation in experiment
46.5% With methanesulfonic acid; chloro(2-dicyclohexylphosphino-2′,6′-diisopropoxy-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II); sodium carbonate In monoethylene glycol diethyl ether; water at 90℃; for 6h; Inert atmosphere; 1.3 The third step: Synthesis of 2-isopropyl-6-vinylaniline Add 2-chloro-6-isopropylaniline (6.0g, 35.5mmol)And potassium trifluoro(vinyl) borate(7.1g, 53.2mmol) dissolved in ethylene glycol dimethyl ether(30mL) and water (20mL) mixed solvent, add methanesulfonic acid to it(2-Dicyclohexylphosphino-2',6'-dimethoxy-1,1'-biphenyl)(2'-amino-1,1'-biphenyl-2-yl)palladium(II )(3.0g, 3.5mmol), sodium carbonate(11.0 g, 88.8 mmol). Under nitrogen protection, the mixture was stirred at 90°C for 6 hours, the reaction was stopped, and the organic layer was separated.The aqueous phase was extracted with ethyl acetate (30mL*2), the organic layers were combined,Wash with brine, dry with anhydrous sodium sulfate, filter,Concentrate under reduced pressure to remove the solvent,The residue is separated by a fast silica gel column2-isopropyl-6-vinylaniline (1.6 g, yield: 46.5%).
  • 59
  • [ 1161497-23-9 ]
  • [ 13682-77-4 ]
  • [ 196519-60-5 ]
YieldReaction ConditionsOperation in experiment
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate In 1,4-dioxane at 100℃; for 14h; Inert atmosphere; 2.1 1-fluoro-4-methoxy-2-vinylbenzene (Compound I-2B) Add 2-bromo-1-fluoro-4-methoxybenzene (compound I-2A) (1.02g, 5.0mmol) to 1,4-dioxane (20mL) at room temperature, Add potassium vinyl fluoroborate (740mg, 5.52mmol), [1,1-bis(diphenylphosphino)ferrocene]palladium dichloride (430mg, 0.50mmol), potassium carbonate (1.52g, 11.0mmol) , Heat to 100°C under the protection of nitrogen, and stir for 14h. Cooled to room temperature, diluted with water (200mL), extracted with DCM (80mL×3), separated, combined the organic phases, dried over anhydrous sodium sulfate, filtered, concentrated, and the residue was separated and purified by silica gel column (pure petroleum) Ether) to obtain a colorless liquid crude product 1-fluoro-4-methoxy-2-vinylbenzene (compound I-2B) (680 mg, yield 89.9%).
  • 60
  • [ 1261588-35-5 ]
  • [ 13682-77-4 ]
  • [ 2744207-17-6 ]
YieldReaction ConditionsOperation in experiment
67% With bis-triphenylphosphine-palladium(II) chloride; caesium carbonate In tetrahydrofuran; water at 85℃; for 22h; Sealed tube; Inert atmosphere; General procedure: Under nitrogen, to a stirred solution of methyl 4-bromo-2-methoxybenzoate (0.73 g,3.0 mmol, 1.0 eq) in THF/H2O (9:1 v/v, 6.0 mL) was added potassiumvinyltrifluoroborate (0.40 g, 3.0 mmol, 1.0 eq), Cs2CO3 (2.9 g, 9.0 mmol, 3.0 eq) andPdCl2(PPh3)2 (42 mg, 0.06 mmol, 0.02 eq) in a sealed tube, the resulting solution wasstirred at 85°C for 22 h. After being cooled to room temperature, the solution wasdiluted with EtOAc (20 mL), the aqueous layer was extracted with EtOAc (3 × 20mL). The combined EtOAc layers were washed with brine (3 × 10 mL), dried overNa2SO4, and concentrated in vacuo. Purification by flash column chromatography(PE : EtOAc = 30:1, v/v) afforded the desired product 6f.
  • 61
  • [ 1227511-58-1 ]
  • [ 13682-77-4 ]
  • [ 2756247-21-7 ]
YieldReaction ConditionsOperation in experiment
7.A.a.n.d.7.1 (S)-N-((R)-(5-fluoro-6-(trifluoromethyl)pyridin-2-yl)(4-(trifluoromethoxy)phenyl)methyl)-2-oxoimidazolidine-4-carboxamide and (S)-N-((S)-(5-fluoro-6-(trifluoromethyl)pyridin-2-yl)(4-(trifluoromethoxy)phenyl)methyl)-2-oxoimidazolidine-4-carboxamide Step 1: 3-fluoro-2-(trifluoromethyl)-6-vinylpyridine. To a mixture of 6-chloro-3-fluoro-2-(trifluoromethyl)pyridine (0.20 g, 1.0 mmol), potassium trifluoro (vinyl)borate (0.13 g, 1.0 mmol) and potassium carbonate (0.42 g, 3.0 mmol) in THF (3 mL) and water (0.3 mL) was added PdCl2(PPh3)2 (35 mg, 0.050 mmol). The mixture was stirred at 70° C. for 12 h. Then water was added, and the mixture was extracted with DCM. The combined organic layers were dried over Na2SO4, and filtered. The filtrate was concentrated in vacuo to give the title compound.
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); potassium carbonate In tetrahydrofuran; water monomer at 70℃; for 12h; 7A.1 Examples 7A and 7B (S)-N-((R)-(5-fluoro-6-(trifluoromethyl)pyridin-2-yl)(4-(trifluoromethoxy)phenyl)methyl)-2-oxoimidazolidine-4-carboxamide and (S)-N-((S)-(5-fluoro-6-(trifluoromethyl)pyridin-2-yl)(4-(trifluoromethoxy)phenyl)methyl)-2-oxoimidazolidine-4-carboxamide [1243] Step 1: 3-fluoro-2-(trifluoromethyl)-6-vinylpyridine. To a mixture of No.153 6-chloro-3-fluoro-2-(trifluoromethyl)pyridine (0.20 g, 1.0 mmol), No.133 potassium trifluoro (vinyl)borate (0.13 g, 1.0 mmol) and No.18 potassium carbonate (0.42 g, 3.0 mmol) in No.58 THF (3 mL) and No.40 water (0.3 mL) was added No.135 PdCl2(PPh3)2 (35 mg, 0.050 mmol). The mixture was stirred at 70°C. for 12 h. Then water was added, and the mixture was extracted with DCM. The combined organic layers were dried over Na2SO4, and filtered. The filtrate was concentrated in vacuo to give the No.154 title compound.
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); potassium carbonate In tetrahydrofuran; water monomer at 70℃; for 12h; 7A.1 Examples 7A and 7B (S)-N-((R)-(5-fluoro-6-(trifluoromethyl)pyridin-2-yl)(4-(trifluoromethoxy)phenyl)methyl)-2-oxoimidazolidine-4-carboxamide and (S)-N-((S)-(5-fluoro-6-(trifluoromethyl)pyridin-2-yl)(4-(trifluoromethoxy)phenyl)methyl)-2-oxoimidazolidine-4-carboxamide [1243] Step 1: 3-fluoro-2-(trifluoromethyl)-6-vinylpyridine. To a mixture of No.153 6-chloro-3-fluoro-2-(trifluoromethyl)pyridine (0.20 g, 1.0 mmol), No.133 potassium trifluoro (vinyl)borate (0.13 g, 1.0 mmol) and No.18 potassium carbonate (0.42 g, 3.0 mmol) in No.58 THF (3 mL) and No.40 water (0.3 mL) was added No.135 PdCl2(PPh3)2 (35 mg, 0.050 mmol). The mixture was stirred at 70°C. for 12 h. Then water was added, and the mixture was extracted with DCM. The combined organic layers were dried over Na2SO4, and filtered. The filtrate was concentrated in vacuo to give the No.154 title compound.
  • 62
  • [ 1311197-88-2 ]
  • [ 13682-77-4 ]
  • [ 2844383-77-1 ]
YieldReaction ConditionsOperation in experiment
With palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; potassium carbonate In 1,4-dioxane; lithium hydroxide monohydrate at 100℃; for 6h; 109.1 Step 2: Synthesis of Compound L-043-3 General procedure: Into the reaction flask were sequentially added L-043-2 (500mg, 1.26mmol), 1-methylpyrazole-4-boronic acid pinacol ester (392mg, 1.89mmol), Pd(dppf)Cl2 (103mg, 0.13mmol) , K 2CO 3 (435 mg, 3.15 mmol), dioxane (5 mL), H 2O (1 mL), and reacted at 100° C. for 6 h. The reaction solution was cooled to room temperature, 25 mL of water was added, extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and spin-dried. The crude product was subjected to column chromatography (dichloromethane/methanol=15:1) to obtain the target product L-043-2 (400 mg).
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