Name: 89490-05-1|Cyclohex-1-en-1-ylboronic acid|97%
Brand: Ambeed
SKU: A275978
Rating: 95 (40 reviews)

1
[ 53848-17-2 ]
[ 89490-05-1 ]
[ 418760-99-3 ]

Reference： [1]Tetrahedron Letters,2005,vol. 46,p. 1779 - 1782

2
[ 954124-99-3 ]
[ 89490-05-1 ]
[ 954125-01-0 ]

Yield	Reaction Conditions	Operation in experiment
70%	With potassium phosphate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In N,N-dimethyl-formamide; at 60℃; for 9h;	To a mixture of 2-(3-bromo-4-nitro-phenyl)-malonic acid dimethyl ester (as prepared in the previous step, 300 mg, 0.903 mmol), cyclohex-1-enyl boronic acid (125 mg, 0.994 mmol) and dichloro[1,1'-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (Pd(dppf)Cl2) (66.0 mg, 0.0903 mmol) in 5 mL of DMF was added K3PO4 (765 mg, 3.61 mmol). The resulting mixture was stirred at 60° C. for 9 h under Ar. After cooling to RT, the mixture was treated with 50 mL of EtOAc, washed with H2O (3.x.10 mL) and brine (10 mL). The organic layer was dried (Na2SO4) and concentrated in vacuo. The residue was purified by flash chromatography on silica gel with 10percent EtOAc-hexane to afford 210 mg (70percent) of the title compound as a yellow oil: Mass spectrum (ESI, m/z): Calcd. for C17H19NO6, 334.1 (M+H), found 334.0.
70%	With potassium phosphate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In N,N-dimethyl-formamide; at 60℃; for 9h;	b) 2-(3-Cyclohex-1-enyl-4-nitro-phenyl)-malonic acid dimethyl ester To a mixture of 2-(3-bromo-4-nitro-phenyl)-malonic acid dimethyl ester (as prepared in the previous step, 300 mg, 0.903 mmol), cyclohexane-1-enyl boronic acid (125 mg, 0.994 mmol) and dichloro[1,1'-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (Pd(dppf)Cl2-CH2Cl2) (66.0 mg, 0.0903 mmol) in 5 mL of DMF was added K3PO4 (765 mg, 3.61 mmol). The resulting mixture was stirred at 60° C. for 9 h under Ar. After cooling to RT, the mixture was treated with 50 mL of EtOAc, washed with H2O (3*10 mL) and brine (10 mL). The organic layer was dried (Na2SO4) and concentrated in vacuo. The residue was purified by flash chromatography on silica gel with 10percent EtOAc-hexane to afford 210 mg (70percent) of the title compound as a yellow oil: Mass spectrum (ESI, m/z): Calcd. for C17H19NO6, 334.1 (M+H), found 334.0.

Reference： [1]Patent: US2007/249649,2007,A1 .Location in patent: Page/Page column 42
[2]Patent: US2007/249593,2007,A1 .Location in patent: Page/Page column 41

3
[ 954424-43-2 ]
[ 89490-05-1 ]
[ 954424-44-3 ]

Yield	Reaction Conditions	Operation in experiment
99%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 80℃; for 2.5h;	A solution of 133 mg (0.381 mmol) of 2-bromo-4-[2-(morpholine-4-sulfonyl)-ethyl]-phenylamine (as prepared in the previous step) in toluene (6 mL) and EtOH (3 mL) was treated with 1.52 mL (3.05 mmol) of 2.0 M aqueous Na2CO3 and 60.0 mg (0.476 mmol) of <strong>[89490-05-1]cyclohex-1-enylboronic acid</strong>. The mixture was degassed via sonication, placed under Ar, treated with 30.8 mg (0.027 mmol) of Pd(PPh3)4, and heated to 80° C. for 2.5 h. The mixture was cooled to RT, diluted with EtOAc (20 mL), and washed with saturated aqueous NaHCO3 (1.x.15 mL) and brine (1.x.15 mL). The organic layer was dried (MgSO4) and concentrated in vacuo to afford 132 mg (99percent) of the title compound as a tan solid: Mass spectrum (ESI, m/z): Calcd. for C18H26N2O3S, 351.2 (M+H), found 351.1.

Reference： [1]Patent: US2007/249649,2007,A1 .Location in patent: Page/Page column 52
[2]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 6363 - 6369

4
[ 954424-50-1 ]
[ 89490-05-1 ]
2-(4-amino-3-cyclohex-1-enyl-phenyl)-ethanesulfonic acid dimethylamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 80℃; for 17.5h;	A solution of 477 mg (1.55 mmol) of 2-(4-amino-3-bromo-phenyl)-ethanesulfonic acid dimethylamide (as prepared in the previous step) in toluene (13 mL) and EtOH (6.5 mL) was treated with 215 mg (1.71 mg) of <strong>[89490-05-1]cyclohex-1-enylboronic acid</strong> and 6.21 mL (12.4 mmol) of 2.0 M aqueous Na2CO3. The mixture was degassed via sonication, placed under Ar, treated with 179 mg (0.155 mmol) of Pd(PPh3)4, and heated to 80° C. for 17.5 h. The mixture was cooled to RT, diluted with EtOAc (50 mL), and washed with water (2.x.25 mL). The aqueous layer was extracted with EtOAc (30 mL). The combined organic layers were dried (MgSO4) and concentrated in vacuo. Silica gel chromatography of the residue on a 50-g Varian MegaBond Elut SPE column with 50percent EtOAc-hexane afforded 365 mg (76percent) of the title compound as a white solid: 1H-NMR (CD3CN; 400 MHz): delta 6.90 (dd, 1H, J=8.4, 2.4 Hz), 6.84 (d, 1H, J=2.4 Hz), 6.62 (d, 1H, J=8.4 Hz), 5.70-5.66 (m, 1H), 4.03 (br s, 2H), 3.20-3.13 (m, 2H), 2.93-2.87 (m, 2H), 2.83 (s, 6H), 2.24-2.17 (m, 4H), 1.82-1.74 (m, 2H), 1.74-1.66 (m, 2H). Mass spectrum (ESI, m/z): Calcd. for C16H24N2O2S, 309.2 (M+H), found 309.1.

Reference： [1]Patent: US2007/249649,2007,A1 .Location in patent: Page/Page column 54

5
[ 954424-55-6 ]
[ 89490-05-1 ]
2-(4-amino-3-cyclohex-1-enyl-phenyl)-ethanesulfonic acid methylamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 80℃; for 19h;	A solution of 177 mg (0.604 mmol) of 2-(4-amino-3-bromo-phenyl)-ethanesulfonic acid methylamide (as prepared in the previous step) in toluene (5 mL) and EtOH (2.5 mL) was treated with 83.7 mg (0.664 mmol) of <strong>[89490-05-1]cyclohex-1-enylboronic acid</strong> and 2.40 mL (4.83 mmol) of 2.0 M aqueous Na2CO3. The mixture was degassed via sonication, placed under Ar, treated with 67.3 mg (0.0604 mmol) of Pd(PPh3)4, and heated to 80° C. for 19 h. The mixture was diluted with EtOAc (15 mL) and washed with water (1.x.10 mL). The aqueous layer was extracted with EtOAc (1.x.10 mL), and the combined organic layers were dried (MgSO4) and concentrated in vacuo. Silica gel chromatography of the residue on a 25-g Varian MegaBond Elut SPE column with 50percent EtOAc-hexane afforded 123 mg (69percent) of the title compound as a white solid: 1H-NMR (CD3CN; 400 MHz): delta 6.90 (dd, 1H, J=8.0, 2.0 Hz), 6.83 (d, 1H, J=2.0 Hz), 6.32 (d, 1H, J=8.0 Hz), 5.70-5.66 (m, 1H), 4.97-4.90 (m, 2H), 4.08-3.99 (br s, 2H), 3.24-3.17 (m, 2H), 2.91-2.84 (m, 2H), 2.66 (d, 3H, J=5.2 Hz), 2.24-2.15 (m, 4H), 1.82-1.74 (m, 2H), 1.74-1.66 (m, 2H).

Reference： [1]Patent: US2007/249649,2007,A1 .Location in patent: Page/Page column 57

6
[ 954124-25-5 ]
[ 89490-05-1 ]
[ 954124-27-7 ]

Yield	Reaction Conditions	Operation in experiment
100%		k) 4-(4-Amino-3-cyclohex-1-enyl-phenyl)-piperidine-2,6-dione A solution of 69.0 mg (0.244 mmol) of 4-(4-amino-3-bromo-phenyl)-piperidine-2,6-dione (as prepared in the previous step) in toluene (10 mL) and dioxane (10 mL) was treated with 30.7 mg (0.244 mmol) of <strong>[89490-05-1]cyclohex-1-enylboronic acid</strong>, 104 mg (0.487 mmol) of K3PO4, and 34.2 mg (0.0975 mmol) of 2-(dicyclohexylphosphino)biphenyl. The mixture was degassed via sonication, placed under Ar, treated with 5.50 mg (0.0244 mmol) of Pd(OAc)2, and heated to 90° C. for 5 h. The mixture was diluted with EtOAc (30 mL) and washed with water (2*20 mL). The organic layer was dried (MgSO4) and concentrated in vacuo to afford 73.5 mg (106percent, some solvent trapped) of the title compound as a tan solid: Mass spectrum (ESI, m/z): Calcd. for C17H20N2O2, 285.2 (M+H), found 285.2.

Reference： [1]Patent: US2007/249593,2007,A1 .Location in patent: Page/Page column 25

7
[ 954124-93-7 ]
[ 89490-05-1 ]
[ 954124-95-9 ]

Yield	Reaction Conditions	Operation in experiment
100%		d) 4-(4-Amino-3-cyclohex-1-enyl-phenyl)-1-methyl-piperidine-2,6-dione A suspension of 265 mg (0.892 mmol) of 4-(4-amino-3-bromo-phenyl)-1-methyl-piperidine-2,6-dione (as prepared in the previous step) in toluene (15 mL) and dioxane (15 mL) was treated with 379 mg (1.78 mmol) of K3PO4, 146 mg (1.16 mmol) of <strong>[89490-05-1]cyclohex-1-enylboronic acid</strong>, and 125 mg (0.357 mmol) of 2-(dicyclohexylphosphino)-biphenyl. The mixture was degassed via sonication, placed under Ar, treated with 20.0 mg (0.00892 mmol) of Pd(OAc)2, and heated to 80° C. for 2.5 h. The mixture was diluted with EtOAc (70 mL) and washed with water (2*50 mL). The combined organic layers were dried (MgSO4) and concentrated in vacuo. Silica gel chromatography of the residue on a 50-g Varian MegaBond Elut SPE column with 25-50percent EtOAc-hexane afforded 266 mg (100percent) of the title compound as a tan solid: Mass spectrum (ESI, m/z): Calcd. for C18H22N2O2, 299.2 (M+H), found 299.1.

Reference： [1]Patent: US2007/249593,2007,A1 .Location in patent: Page/Page column 40

8
[ 915005-98-0 ]
[ 89490-05-1 ]
[ 915005-99-1 ]

Yield	Reaction Conditions	Operation in experiment
100%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 80℃; for 8h;	c) 2-Cyclohex- 1 -enyl-4-( 1 -oxy-pyridin-4-yl)-phenylamine; To a mixture of 2-bromo-4-(l-oxy-pyridin-4-yl)-phenylamine (as prepared in the previous step, 240 mg, 0.905mmol), cyclohexen-1-yl boronic acid (126 mg, 0.996 mmol) and Pd(PPh3)4 (105 mg, 0.091mmol) in 9 mL of 1,4-dioxane was added 2.0 M aq Na2CO3 solution (3.62 mL, 7.24 mmol). The resulting mixture was stirred at 80 C for 8 h under Ar, and then cooled to RT. Treated with 20 mL of brine, the mixture was extracted with DCM (4 x 20 mL). The combined organic layers were concentrated in vacuo and purified by flash chromatography on silica gel (2-5 percent MeOH/DCM) to give 241 mg (100 percent) of the title compound as a light <n="53"/>yellow solid. 1H-NMR (CDCl3; 400 MHz): delta 8.18 (d, 2H, J = 7.3 Hz), 7.44 (d, 2H, J = 7.3 Hz), 7.30 (dd, IH, J = 8.4, 2.2 Hz), 6.76 (d, IH, J = 8.4 Hz), 5.80 (m, IH), 3.0-4.2 (br s, 2H), 2.17- 2.28 (m, 4H), 1.68-1.82 (m, 4H). Mass spectrum (ESI, m/z): Calcd. for C17H18N2O, 267.1 I(M+H), found 267.1.

Reference： [1]Patent: WO2007/123516,2007,A1 .Location in patent: Page/Page column 50-51
[2]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 3925 - 3929

9
[ 51605-97-1 ]
[ 89490-05-1 ]
[ 915006-03-0 ]

Yield	Reaction Conditions	Operation in experiment
95%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 80℃; for 8h;	Example 22; 4-Cyano-lH-imidazole-2-carboxylic acid (2-cyclohex-l-enyl-4-isopropyl-phenyl)-amide; a) 2-Cyclohex- 1 -enyl-4-isopropyl-phenylamine; <n="60"/>To a mixture of 2-bromo-4-isopropyl-phenylamine (214 mg, 1.00 mmol), cyclohexane-1- enyl boronic acid (139 mg, 1.10 mmol) and Pd(PPh3)4 (116 mg, 0.100 mmol) in 5 mL of 1,4- dioxane was added 2.0 M aqueous Na2CO3 solution (4.0 mL, 8.0 mmol). The resulting mixture was stirred at 80 C for 8 h under Ar, and then cooled to RT. The reaction was treated with EtOAc (20 mL) and washed with H2O (2 x 10 mL) and brine (10 mL). The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (DCM) to give 205 mg (95 percent) of the title compound as a light brown oil. Mass spectrum (ESI, m/z): Calcd. for C15H21N, 216.2 (M+H), found 216.1.

Reference： [1]Patent: WO2007/123516,2007,A1 .Location in patent: Page/Page column 57-58

10
[ 915006-30-3 ]
[ 89490-05-1 ]
[ 915006-31-4 ]

Yield	Reaction Conditions	Operation in experiment
40%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 80℃; for 3.5h;	b) 2-Cyclohex-l-enyl-4-(morpholine-4-sulfonyl)-phenylamine; <n="94"/>A solution of 50.0 mg (0.156 mmol) of 2-bromo-4-(morpholine-4-sulfonyl)- phenylamine (as prepared in the previous step) in toluene (4 niL) and EtOH (2 mL) was treated with 623 muL (1.25 mmol) of 2.0 M aqueous Na2CO3 and 20.6 mg (0.163 mmol) of cyclohex-1- enylboronic acid. The mixture was degassed via sonication, placed under Ar, treated with 12.6 mg (0.0109 mmol) of Pd(PPh3)4, and heated to 80 0C for 3.5 h. The mixture was cooled to RT, stirred for 16 h, diluted with EtOAc (10 mL) and washed with saturated aqueous NaHCO3 (I x 10 mL) and brine (1 x 10 mL). The organic layer was dried (MgSO4) and concentrated in vacuo. Silica gel chromatography of the residue on a 25-g Varian MegaBond Elut SPE column with 25- 50 percent EtOAc-hexane afforded 20.0 mg (40 percent) of the title compound as an off-white solid: Mass spectrum (ESI, m/z): Calcd. for C16H22N2O3S, 323.1 (M+H), found 323.1.

Reference： [1]Patent: WO2007/123516,2007,A1 .Location in patent: Page/Page column 91-92
[2]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 6363 - 6369

11
[ 885693-07-2 ]
[ 89490-05-1 ]
2-cyclohex-1-enyl-4-(1,1-dioxo-hexahydro-1λ⁶-thiopyran-4-yl)-phenylamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 20℃; for 1h;	To a mixture of 2-bromo-4-(l,l-dioxo-hexahydro-llambda6-thiopyran-4-yl)-phenylamine (as prepared in the previous step, 150 mg, 0.493 mmol), cyclohexen-1-yl boronic acid (70 mg, 0.542 mmol) and Pd(PPh3J4 (57 mg, 0.0493 mmol) in 5 mL of 1,4-dioxane was added 2.0 M aq Na2CO3 solution (2.0 mL, 4.0 mmol). The resulting mixture was stirred at 80 °C for 8 h under Ar, and then cooled to RT. Treated with 50 mL of EtOAc, the mixture was washed with H2O (3 x 15 mL), brine (20 mL) and dried (Na2SO4). Removal of the solvent under reduced pressure followed by flash chromatography of the residue on silica gel (2-5 percent EtOAc/DCM) gave 130 mg (86 percent) of the title compound as a brown solid. 1H-NMR EPO <DP n="81"/>(CDCl3; 400 MHz): delta 6.89 (dd, IH, J = 8.4, 2.3 Hz), 6.84 (d, IH, J = 2.3 Hz), 6.65 (d, IH, J - 8.4 Hz), 5.74 (m, IH), 3.74 (br s, 2H), 3.08-3.17 (m, 4H), 2.66 (dddd, IH, J = 12.1, 12.1, 3.1, 3.1 Hz), 2.29-2.42 (m, 2H), 2.13-2.25 (m, 6H), 1.73-1.81 (m, 2H), 1.65-1.73 (m, 2H). Mass spectrum (ESI, m/z): Calcd. for Ci7H23NO2S, 306.1 (M+H), found 306.1.
86%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 80℃; for 8h;	To a mixture of 2-bromo-4-(1,1-dioxo-hexahydro-1lambda6-thiopyran-4-yl)-phenylamine (as prepared in the previous step, 150 mg, 0.493 mmol), cyclohexen-1-yl boronic acid (70 mg, 0.542 mmol) and Pd(PPh3)4 (57 mg, 0.0493 mmol) in 5 mL of 1,4-dioxane was added 2.0 M aq Na2CO3 solution (2.0 mL, 4.0 mmol). The resulting mixture was stirred at 80° C. for 8 h under Ar, and then cooled to RT. Treated with 50 mL of EtOAc, the mixture was washed with H2O (3.x.15 mL), brine (20 mL) and dried (Na2SO4). Removal of the solvent under reduced pressure followed by flash chromatography of the residue on silica gel (2-5percent EtOAc/DCM) gave 130 mg (86percent) of the title compound as a brown solid. 1H-NMR (CDCl3; 400 MHz): delta 6.89 (dd, 1H, J=8.4, 2.3 Hz), 6.84 (d, 1H, J=2.3 Hz), 6.65 (d, 1H, J=8.4 Hz), 5.74 (m, 1H), 3.74 (br s, 2H), 3.08-3.17 (m, 4H), 2.66 (dddd, 1H, J=12.1, 12.1, 3.1, 3.1 Hz), 2.29-2.42 (m, 2H), 2.13-2.25 (m, 6H), 1.73-1.81 (m, 2H), 1.65-1.73 (m, 2H). Mass spectrum (ESI, m/z): Calcd. for C17H23NO2S, 306.1 (M+H), found 306.1.
86%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 80℃; for 8h;	f) 2-Cyclohex-1-enyl-4-(1,1-dioxo-hexahydro-1lambda6-thiopyran-4-yl)-phenylamine To a mixture of 2-bromo-4-(1,1-dioxo-hexahydro-1lambda6-thiopyran-4-yl)-phenylamine (as prepared in the previous step, 150 mg, 0.493 mmol), cyclohexen-1-yl boronic acid (70 mg, 0.542 mmol) and Pd(PPh3)4 (57 mg, 0.0493 mmol) in 5 mL of 1,4-dioxane was added 2.0 M aq Na2CO3 solution (2.0 mL, 4.0 mmol). The resulting mixture was stirred at 80° C. for 8 h under Ar, and then cooled to RT. Treated with 50 mL of EtOAc, the mixture was washed with H2O (3*15 mL), brine (20 mL) and dried (Na2SO4). Removal of the solvent under reduced pressure followed by flash chromatography of the residue on silica gel (2-5percent EtOAc/DCM) gave 130 mg (86percent) of the title compound as a brown solid. 1H-NMR (CDCl3; 400 MHz): delta 6.89 (dd, 1H, J=8.4, 2.3 Hz), 6.84 (d, 1H, J=2.3 Hz), 6.65 (d, 1H, J=8.4 Hz), 5.74 (m, 1H), 3.74 (br s, 2H), 3.08-3.17 (m, 4H), 2.66 (dddd, 1H, J=12.1, 12.1, 3.1, 3.1 Hz), 2.29-2.42 (m, 2H), 2.13-2.25 (m, 6H), 1.73-1.81 (m, 2H), 1.65-1.73 (m, 2H). Mass spectrum (ESI, m/z): Calcd. for C17H23NO2S, 306.1 (M+H). found 306.1.

86%

With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 20 - 80℃; for 8h;

To a mixture of 2-bromo-4-(l,l-dioxo-hexahydro-llambda6-thiopyran-4-yl)-phenylamine (as prepared in the previous step, 150 mg, 0.493 mmol), cyclohexen-1-yl boronic acid (70 mg, 0.542 mmol) and Pd(PPh3)4 (57 mg, 0.0493 mmol) in 5 mL of 1 ,4-dioxane was added 2.0 M aq Na2CO3 solution (2.0 mL, 4.0 mmol). The resulting mixture was stirred at 80 °C for 8 h under Ar, and then cooled to RT. Treated with 50 mL of EtOAc, the mixture was washed with H2O (3 x 15 mL), brine (20 mL) and dried (Na2SO4). Removal of the solvent under reduced pressure followed by flash chromatography of the residue on silica gel (2-5 percent EtOAc/DCM) gave 130 mg (86 percent) of the title compound as a brown solid. 1H-NMR (CDCl3; 400 MHz): delta 6.89 (dd, IH, J = 8.4, 2.3 Hz), 6.84 (d, IH, J = 2.3 Hz), 6.65 (d, IH, J = 8.4 Hz)5 5.74 (m, IH), 3.74 (br s, 2H), 3.08-3.17 (m, 4H), 2.66 (dddd, IH, J = 12.1, 12.1, 3.1, 3.1 Hz), 2.29- 2.42 (m, 2H), 2.13-2.25 (m, 6H), 1.73-1.81 (m, 2H), 1.65-1.73 (m, 2H). Mass spectrum (ESI, m/z): Calcd. for C17H23NO2S, 306.1 (M+H), found 306.1.

Reference： [1]Patent: WO2006/47277,2006,A2 .Location in patent: Page/Page column 79-80
[2]Patent: US2006/281788,2006,A1 .Location in patent: Page/Page column 64-65
[3]Patent: US2008/51402,2008,A1 .Location in patent: Page/Page column 51
[4]Patent: WO2007/48088,2007,A2 .Location in patent: Page/Page column 97

12
[ 885693-49-2 ]
[ 89490-05-1 ]
5-amino-6-cyclohex-1-enyl-3',4',5',6'-tetrahydro-2'H-[2,4']bipyridinyl-1'-carboxylic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 80℃; for 16h;	To a mixture of 5-amino-6-bromo-3l,4l,5',6'-tetrahydro-2'H-[2,4']bipyridinyl-r- carboxylic acid tert-butyl ester (331 mg, 0.93 mmol) (as prepared in Example 54, step (c)) and cyclohexen-1-yl boronic acid (141 mg, 1.11 mmol) in 5 mL of EtOH , 10 mL of toluene and 5 mL of 2 M Na2CO3, was added Pd(PPh3)4 (107 mg, 0.0930 mmol) and the result was heated at 800C for 16 h. The reaction was diluted with 100 mL of ether and 100 mL of brine and the layers were separated. The organic layer was dried (Na2SO4) and concentrated in vacuo. Purification of the residue by column chromatography (silica gel, 30-60percent ether-hexanes) afforded 248 mg (74percent) the title compound as an light brown oil LC-MS (ESi, m/z): Calcd. for C2 , H32N3O2 (M+H), 358.2, found 358.1.
74%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 80℃; for 16h;	To a mixture of 5-amino-6-bromo-3',4',5',6'-tetrahydro-2'H-[2,4']bipyridinyl-1'-carboxylic acid tert-butyl ester (331 mg, 0.93 mmol) (as prepared in Example 54, step (c)) and cyclohexen-1-yl boronic acid (141 mg, 1.11 mmol) in 5 mL of EtOH, 10 mL of toluene and 5 mL of 2 M Na2CO3, was added Pd(PPh3)4 (107 mg, 0.0930 mmol) and the result was heated at 80° C. for 16 h. The reaction was diluted with 100 mL of ether and 100 mL of brine and the layers were separated. The organic layer was dried (Na2SO4) and concentrated in vacuo. Purification of the residue by column chromatography (silica gel, 30-60percent ether-hexanes) afforded 248 mg (74percent) the title compound as an light brown oil LC-MS (ESI, m/z): Calcd. for C21H32N3O2 (M+H), 358.2, found 358.1.
74%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 80℃; for 16h;	a) 5-Amino-6-cyclohex-1-enyl-3',4',5',6'-tetrahydro-2'H-[2,4']bipyridinyl-1'-carboxylic acid tert-butyl ester To a mixture of 5-amino-6-bromo-3',4',5',6'-tetrahydro-2'H-[2,4']bipyridinyl-1'-carboxylic acid tert-butyl ester (331 mg, 0.93 mmol) (as prepared in Example 54, step (c)) and cyclohexen-1-yl boronic acid (141 mg, 1.11 mmol) in 5 mL of EtOH, 10 mL of toluene and 5 mL of 2 M Na2CO3, was added Pd(PPh3)4 (107 mg, 0.0930 mmol) and the result was heated at 80° C. for 16 h. The reaction was diluted with 100 mL of ether and 100 mL of brine and the layers were separated. The organic layer was dried (Na2SO4) and concentrated in vacuo. Purification of the residue by column chromatography (silica gel, 30-60percent ether-hexanes) afforded 248 mg (74percent) the title compound as an light brown oil LC-MS (ESI, m/z): Calcd. for C21H32N3O2 (M+H), 358.2. found 358.1.

74%

With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 80℃; for 16h;

To a mixture of 5-amino-6-bromo-3',4',5',6'-tctraliydro-2'H-[2,4I]bipyridinyl-l '- carboxylic acid tert-butyl ester (331 mg, 0.93 mmol) (as prepared in Example 54, step (c)) and cyclohexen-1-yl boronic acid (141 mg, 1.11 mmol) in 5 mL of EtOH , 10 mL of toluene and 5 mL of 2 M Na2CO3, was added Pd(PPh3)4 (107 mg, 0.0930 mmol) and the result was heated at 80 0C for 16 h. The reaction was diluted with 100 mL of ether and 100 mL of brine and the layers were separated. The organic layer was dried (Na2SO4) and concentrated in vacuo. Purification of the residue by column chromatography (silica gel, 30-60percent ether-hexanes) afforded 248 mg (74percent) the title compound as an light brown oil LC-MS (ESI, m/z): Calcd. for C2IH32N3O2 (M+H), 358.2, found 358.1.

Reference： [1]Patent: WO2006/47277,2006,A2 .Location in patent: Page/Page column 127-128
[2]Patent: US2006/281788,2006,A1 .Location in patent: Page/Page column 87-88
[3]Patent: US2008/51402,2008,A1 .Location in patent: Page/Page column 73
[4]Patent: WO2007/48088,2007,A2 .Location in patent: Page/Page column 144

13
[ 166818-85-5 ]
[ 89490-05-1 ]
[ 885692-98-8 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 100℃; for 21h;	A mixture of 102 mg (0.340 mmol) l-(3-bromo-4-nitro-phenyl)-4-methyl- piperazine (as prepared in Example 9, step (a)), 59.7 mg (0.474 mmol) cyclohexen-1- ylboronic acid, 43.8 mg (0.0379 mmol) of tetrakis(triphenylphosphine)palladium (0) under Ar was treated with 206 muL (0.412 mmol) of 2.0 M degassed aq Na2CO3, 0.6 mL degassed anh toluene and 0.2 mL degassed anh EtOH and the mixture was heated at 100 °C for 21 h. After cooling to RT, the mixture was poured into EtOAc (10 mL), washed with brine (10 mL), dried (Na2SO4) and concentrated in vacuo. Chromatography on a 5-g silica SPE column with 1-3 percent EtOH in dichloromethane afforded 126 mg of the title compound (74 percent purity by RP-HPLC (C 18 column) as a mixture with triphenylphosphine) as a yellow oil EPO <DP n="56"/>that was used in the following reaction without further purification. Mass spectrum (ESI, m/z): Calcd. for CnH23N3O3, 302.2 (M+H), found 302.2.
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 100℃; for 21h;	A mixture of 102 mg (0.340 mmol) 1-(3-bromo-4-nitro-phenyl)-4-methyl-piperazine (as prepared in Example 9, step (a)), 59.7 mg (0.474 mmol) cyclohexen-1-ylboronic acid, 43.8 mg (0.0379 mmol) of tetrakis(triphenylphosphine)palladium (0) under Ar was treated with 206 muL (0.412 mmol) of 2.0 M degassed aq Na2CO3, 0.6 mL degassed anh toluene and 0.2 mL degassed anh EtOH and the mixture was heated at 100° C. for 21 h. After cooling to RT, the mixture was poured into EtOAc (10 mL), washed with brine (10 mL), dried (Na2SO4) and concentrated in vacuo. Chromatography on a 5-g silica SPE column with 1-3percent EtOH in dichloromethane afforded 126 mg of the title compound (74percent purity by RP-HPLC (C18 column) as a mixture with triphenylphosphine) as a yellow oil that was used in the following reaction without further purification. Mass spectrum (ESI, m/z): Calcd. for C17H23N3O3, 302.2 (M+H), found 302.2.
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 100℃; for 21h;	a) 1-(3-Cyclohex-1-enyl-4-nitro-phenyl)-4-methyl-piperazine A mixture of 102 mg (0.340 mmol) 1-(3-bromo-4-nitro-phenyl)-4-methyl-piperazine (as prepared in Example 9, step (a)), 59.7 mg (0.474 mmol) cyclohexen-1-ylboronic acid, 43.8 mg (0.0379 mmol) of tetrakis(triphenylphosphine)palladium (0) under Ar was treated with 206 muL (0.412 mmol) of 2.0 M degassed aq Na2CO3, 0.6 mL degassed anh toluene and 0.2 mL degassed anh EtOH and the mixture was heated at 100° C. for 21 h. After cooling to RT, the mixture was poured into EtOAc (10 mL), washed with brine (10 mL), dried (Na2SO4) and concentrated in vacuo. Chromatography on a 5-g silica SPE column with 1-3percent EtOH in dichloromethane afforded 126 mg of the title compound (74percent purity by RP-HPLC (C18 column) as a mixture with triphenylphosphine) as a yellow oil that was used in the following reaction without further purification. Mass spectrum (ESI, m/z): Calcd. for C17H23N3O3, 302.2 (M+H). found 302.2.

With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 100℃; for 21h;

A mixture of 102 mg (0.340 mmol) l-(3-bromo-4-nitro-phenyl)-4-methyl-piperazine (as prepared in Example 9, step (a)), 59.7 mg (0.474 mmol) cyclohexen-1-ylboronic acid, 43.8 mg (0.0379 mmol) of tetrakis(triphenylphospbine)palladium (0) under Ar was treated with 206 muL (0.412 mmol) of 2.0 M degassed aq Na2CO3, 0.6 mL degassed anh toluene and 0.2 mL degassed anh EtOH and the mixture was heated at 100 °C for 21 h. After cooling to RT, the mixture was poured into EtOAc (10 mL), <n="75"/>washed with brine (10 mL), dried (Na2SO4) and concentrated in vacuo. Chromatography on a 5-g silica SPE column with 1-3 percent EtOH in dichloromethane afforded 126 mg of the title compound (74 percent purity by RP-HPLC (Cl 8 column) as a mixture with triphenylphosphine) as a yellow oil that was used in the following reaction without further purification. Mass spectrum (ESI, m/z): Calcd. for C17H23N3O3, 302.2 (M+H), found 302.2.

Reference： [1]Patent: WO2006/47277,2006,A2 .Location in patent: Page/Page column 54-55
[2]Patent: US2006/281788,2006,A1 .Location in patent: Page/Page column 53
[3]Patent: US2008/51402,2008,A1 .Location in patent: Page/Page column 39-40
[4]Patent: WO2007/48088,2007,A2 .Location in patent: Page/Page column 72-73

14
[ 885693-00-5 ]
[ 89490-05-1 ]
[ 885693-01-6 ]

Yield	Reaction Conditions	Operation in experiment
85%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 80℃; for 3h;	A flask was charged with 4-(4-amino-3-bromo-phenyl)-piperidine-l -carboxylic acid tert-butyl ester (0.13 g, 0.36 mmol) (as prepared in the previous step), cyclohex-1-enyl EPO <DP n="61"/>boronic acid (0.060 g, 0.48 mmol), Pd(PPh3)4 (0.04 g, 10 mol percent), aqueous 2M Na2CO3 (1.5 mL), ethanol (1.5 mL), and toluene (3 mL), and heated at 800C for 3 h. The reaction was diluted EtOAc (10 mL), washed with NaHCO3 (2 x 10 mL) and brine (10 mL), and the organic layer was dried over Na2SO4 and then concentrated. The title compound was eluted from a 20-g SPE cartridge (silica) with 30 percent EtOAc/hexane to give 0.10 g (85 percent) of the title compound as a yellow oil. Mass spectrum (ESI, m/z): Calcd. for C22H32N2O2, 357.2 (M+H), found 357.1.
85%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 80℃; for 3h;	A flask was charged with 4-(4-amino-3-bromo-phenyl)-piperidine-1-carboxylic acid tert-butyl ester (0.13 g, 0.36 mmol) (as prepared in the previous step), cyclohex-1-enyl boronic acid (0.060 g, 0.48 mmol), Pd(PPh3)4 (0.04 g, 10 mol percent), aqueous 2M Na2CO3 (1.5 mL), ethanol (1.5 mL), and toluene (3 mL), and heated at 80° C. for 3 h. The reaction was diluted EtOAc (10 mL), washed with NaHCO3 (2.x.10 mL) and brine (10 mL), and the organic layer was dried over Na2SO4 and then concentrated. The title compound was eluted from a 20-g SPE cartridge (silica) with 30percent EtOAc/hexane to give 0.10 g (85percent) of the title compound as a yellow oil. Mass spectrum (ESI, m/z): Calcd. for C22H32N2O2, 357.2 (M+H), found 357.1.
85%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 80℃; for 3h;	d) 4-(4-Amino-3-cyclohex-1-enyl-phenyl)-piperidine-1-carboxylic acid tert-butyl ester A flask was charged with 4-(4-amino-3-bromo-phenyl)-piperidine-1-carboxylic acid tert-butyl ester (0.13 g, 0.36 mmol) (as prepared in the previous step), cyclohex-1-enyl boronic acid (0.060 g, 0.48 mmol), Pd(PPh3)4 (0.04 g, 10 mol percent), aqueous 2M Na2CO3 (1.5 mL), ethanol (1.5 mL), and toluene (3 mL), and heated at 80° C. for 3 h. The reaction was diluted EtOAc (10 mL), washed with NaHCO3 (2*10 mL) and brine (10 mL), and the organic layer was dried over Na2SO4 and then concentrated. The title compound was eluted from a 20-g SPE cartridge (silica) with 30percent EtOAc/hexane to give 0.10 g (85percent) of the title compound as a yellow oil. Mass spectrum (ESI, m/z): Calcd. for C22H32N2O2, 357.2 (M+H). found 357.1.

85%

With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 80℃; for 3h;

A flask was charged with 4-(4-amino-3-bromo-phenyl)-piperidine-l -carboxylic acid tert-butyl ester (0.13 g, 0.36 mmol) (as prepared in the previous step), cyclohex-1- enyl boronic acid (0.060 g, 0.48 mmol), Pd(PPh3)4 (0.04 g, 10 mol percent), aqueous 2MNa2CO3 (1.5 mL), ethanol (1.5 mL), and toluene (3 mL), and heated at 80 0C for 3 h.The reaction was diluted EtOAc (10 mL), washed with NaHCO3 (2 x 10 mL) and brine (10 mL), and the organic layer was dried over Na2SO4 and then concentrated.The title compound was eluted from a 20-g SPE cartridge (silica) with 30 percent EtOAc/hexane to give 0.10 g (85 percent) of the title compound as a yellow oil. Mass spectrum (ESI, m/z): Calcd. for C22H32N2O2, 357.2 (M+H), found 357.1.

Reference： [1]Patent: WO2006/47277,2006,A2 .Location in patent: Page/Page column 59-60
[2]Patent: US2006/281788,2006,A1 .Location in patent: Page/Page column 55-56
[3]Patent: US2008/51402,2008,A1 .Location in patent: Page/Page column 42
[4]Patent: WO2007/48088,2007,A2 .Location in patent: Page/Page column 77-78
[5]Journal of Medicinal Chemistry,2011,vol. 54,p. 7860 - 7883
[6]Patent: WO2020/6075,2020,A1 .Location in patent: Page/Page column 83

15
[ 914780-72-6 ]
[ 89490-05-1 ]
[ 914780-73-7 ]

Yield	Reaction Conditions	Operation in experiment
50%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; for 1.5h;Heating / reflux;	Nitrogen was bubbled through a solution of 5-bromo-3-[(cis-4-fluoro-cyclohexyl)- (trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester (20 mg, 0.043 mmol) and cyclohexen-1 -ylboronic acid (13 mg, 0.103 mmol) in 2M Na2CO3 (1.3 mL) and DME (2.6 mL) for 6 min. Pd(PPh3)4 (4.4 mg) was added and the mixture was refluxed for 1 h and 30 min. It was cooled, diluted with ethyl acetate, washed with water and brine, dried (MgSO4) and evaporated. The crude was purified by chromatography over silica gel (hexane: EtOAc-9:1 and 4: 1 as eluents) yielding pure 5-cyclohex-1 -enyl-3-[(cis-4-fluoro-cyclohexyl)-(trans-4-methyl- cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester (10 mg, 50percent).

Reference： [1]Patent: WO2006/119646,2006,A1 .Location in patent: Page/Page column 118; 119

16
[ 914781-01-4 ]
[ 89490-05-1 ]
[ 914778-81-7 ]

Yield	Reaction Conditions	Operation in experiment
82%		A solution of 5-bromo-3-[(trans-4-hydroxy-cyclohexyl)-(trans-4-methyl- cyclohexanecarbonyl)-amino]-thiophene-2-carboxylate (2.8 g, 6.3 mmol) and cyclohen-1 -ylboronic acid (1.18 g, 9.4 mmol) in a mixture of DME (40.0 mL) and 2M aqueous Na2CO3 (20.0 mL) was treated with Pd(PPh3)4 (145 mg, 0.126 mmol). The reaction was heated at reflux for 0.25h. The reaction mixture was diluted with ethyl acetate and water. The water layer was separated, washed with EtOAc and filtered on Celite. This solution was acidified to pH 4 with aq. 1 N HCl solution. The white solid was filtered. This residue was purified with silica gel column chromatography EPO <DP n="64"/>using CH2Cl2IMeOH as eluent to provide 5-cyclohex-1 -enyl-3-[(trans-4-hydroxy- cyclohexyl)-(4-trans-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid (2.3 g, 82percent) 1 H NMR (CD3OD, 400 MHz): delta [ppm] 6.8 (s, 1 H), 6.4-6.3 (bs, 1 H), 4.45-4.30 (m, 1 H), 3.35 (m, 1 H), 2.5-2.30 (m, 2H), 2.30-2.15 (m, 2H), 2.15-2.0 (m, 1H), 1.98-1.42 (m, 14H), 1.42-1.20 (m, 5H), 1.1 -0.9 (m, 1 H), 0.8 (d, J=6.5 Hz, 3H), 0.65-0.48 (m, 2H).

Reference： [1]Patent: WO2006/119646,2006,A1 .Location in patent: Page/Page column 60; 62; 63

17
[ 1735-53-1 ]
[ 89490-05-1 ]
[ 1034188-30-1 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium methylate;bis-triphenylphosphine-palladium(II) chloride; In methanol; at 80℃; for 0.166667h;Microwave irradiation;	Description 15; 4-(1 -cyclohexen-1-yl)-3-(trifluoromethyl)benzamide (D15); <strong>[1735-53-1]4-bromo-3-(trifluoromethyl)benzonitrile</strong> (1.2 g, 4.80 mmol), 1-cyclohexen-1-ylboronic acid (0.907 g, 7.20 mmol), sodium methoxide (0.778 g, 14.40 mmol) and bis(triphenylphosphine)palladium(ll) chloride (0.337 g, 0.480 mmol) were added to dry methanol (12 ml.) and the mixture heated in the microwave at 80 0C for 10 minutes. The reaction mixture was partitioned between ethyl acetate (40 ml.) and water (40 ml.) and then the organic phase washed with further water (40 ml_). The organic phase was dried (MgSO^, filtered and the solvent removed in vacuo. The crude product was purified by flash silica chromatography, eluting with 0-75 % ethyl acetate in hexane to give the title compound as a white solid (1.02 g). deltaH (CDCI3, 400 MHz): 8.08 (1 H, s), 7.90 (1 H, d), 7.32 (1 H, d), 6.3-5.8 (2H, m), 5.61 (1 H, s), 2.25- 2.13 (4H, m), 1.80-1.60 (4H, m) ppm. MS (ES+): Ci4H14F3NO requires 269; found 270 (M+H+).
	With methanol; sodium methylate;bis-triphenylphosphine-palladium(II) chloride; at 80℃; for 0.166667h;Microwave irradiation;	Description for D664-(1 -Cyclohexen-1 -yl)-3-(trifluoromethyl)benzamide (D66)<strong>[1735-53-1]4-bromo-3-(trifluoromethyl)benzonitrile</strong> (commercial) (1.2 g, 4.80 mmol), 1- cyclohexen-1-ylboronic acid (0.907 g, 7.20 mmol), sodium methoxide (0.778 g, 14.40 mmol) and bis(triphenylphosphine)palladium(ll) chloride (0.337 g, 0.480 mmol) were added to dry methanol (12 ml.) and the mixture heated in the microwave at 80 0C for 10 minutes. The reaction mixture was partitioned between ethyl acetate (40 ml.) and water (40 ml.) and then the organic phase washed with further water (40 ml_). The organic phase was dried (MgSC^), filtered and the solvent removed in vacuo. The crude product was purified by flash silica chromatography, eluting with 0-75 % ethyl acetate in hexane to give the title compound as a white solid (1.02 g). deltaH (CDCI3, 400 MHz): 8.09 (1 H, m), 7.90 (1 H, dd), 7.32 (1 H, d), 6.3-5.8 (2H, m) 5.61 (1 H, s), 2.25-2.13 (4H, m), 1.80-1.60 (4H, m). MS (ES): C14H14F3NO requires 269; found 270 (MH+).
	With sodium methylate;bis-triphenylphosphine-palladium(II) chloride; In methanol; at 80℃; for 0.166667h;In the microwave;	4-Bromo-3-(trifluoromethyl)benzonitrile (commercial) (1.2 g, 4.80 mmol), 1- cyclohexen-1-ylboronic acid (0.907 g, 7.20 mmol), sodium methoxide (0.778 g, 14.40 mmol) and bis(triphenylphosphine)palladium(ll) chloride (0.337 g, 0.480 mmol) were added to dry methanol (12 ml.) and the mixture heated in the microwave at 80 0C for 10 minutes. The reaction mixture was partitioned between ethyl acetate (40 ml.) and water (40 ml.) and then the organic phase washed with further water (40 ml_). The organic phase was dried (MgSC^), filtered and the solvent removed in vacuo. The crude product was purified by flash silica chromatography, eluting with 0-75 % ethyl acetate in hexane to give the title compound as a white solid (1.02 g). MS (ES): C14H14F3NO requires 269; found 270 (MH+).

Reference： [1]Patent: WO2008/74820,2008,A1 .Location in patent: Page/Page column 29
[2]Patent: WO2008/74821,2008,A1 .Location in patent: Page/Page column 72
[3]Patent: WO2008/128951,2008,A1 .Location in patent: Page/Page column 55

18
[ 1034688-97-5 ]
[ 89490-05-1 ]
[ 1034688-99-7 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium methylate;bis-triphenylphosphine-palladium(II) chloride; In methanol; at 80℃; for 0.166667h;Microwave irradiation;	Description for D174-(1 -Cyclohexen-1 -yl)-3-ethylbenzonitrile (D17) <n="44"/>A mixture of 3-ethyl-4-iodobenzonitrile (D16) (1.23 g, 4.80 mmol), 1-cyclohexen-1- ylboronic acid (907 mg, 7.20 mmol), sodium methoxide (778 mg, 14.4 mmol) and bis(triphenylphosphine)palladium (II) chloride (337 mg, 0.48 mmol) in anhydrous methanol (12 ml.) was heated at 80 0C for 10 minutes in the microwave. The reaction mixture was partitioned between ethyl acetate (40 ml.) and water (40 ml.) before the organic layer was further washed with water (40 ml_), dried (phase separator) and concentrated in vacuo. The crude material was purified by silica chromatography, eluting 0-5 percent EtOAc in hexane over 30 minutes to give the title compound as a yellow oil (824 mg, 3.91 mmol). deltaH (methanol-d4, 400 MHz) 7.56 (1 H, d), 7.46 (1 H, dd), 7.19 (1 H, d), 5.61-5.56 (1 H, m), 2.68 (2H, quart), 2.23-2.16 (4H, m), 1.85-1.68 (4H, m), 1.20 (3H, t). MS (ES): No mass ion observed.
	With sodium methylate;bis-triphenylphosphine-palladium(II) chloride; In methanol; at 80℃; for 0.166667h;In the microwave;	A mixture of 3-ethyl-4-iodobenzonitrile (D10) (1.23 g, 4.80 mmol), 1-cyclohexen-1- ylboronic acid (907 mg, 7.20 mmol), sodium methoxide (778 mg, 14.4 mmol) and bis(triphenylphosphine)palladium (II) chloride (337 mg, 0.48 mmol) in anhydrous methanol (12 ml.) was heated at 80 0C for 10 minutes in the microwave. The reaction mixture was partitioned between ethyl acetate (40 ml.) and water (40 ml.) before the organic layer was further washed with water (40 ml_), dried (phase separator) and concentrated in vacuo. The crude material was purified by silica chromatography, eluting 0-5 percent EtOAc in hexane over 30 minutes to give the title compound as a yellow oil (824 mg, 3.91 mmol). deltaH (methanol-d4, 400 MHz) 7.56 (1 H, d), 7.46 (1 H, dd), 7.19 (1 H, d), 5.61-5.56 (1 H, m), 2.68 (2H, quart), 2.23-2.16 (4H, m), 1.85-1.68 (4H, m), 1.20 (3H, t).

Reference： [1]Patent: WO2008/74821,2008,A1 .Location in patent: Page/Page column 41-42
[2]Patent: WO2008/128951,2008,A1 .Location in patent: Page/Page column 40

19
4-[2-amino-4-(3-bromo-4-fluorophenyl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]phenyl methanesulfonate [ No CAS ]
[ 89490-05-1 ]
[ 1035268-66-6 ]

Yield	Reaction Conditions	Operation in experiment
13%	With potassium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In tetrahydrofuran; at 140℃; for 4h;Irradiation in a microwave;	4-[2-Amino-4-(3-bromo-4-fluorophenyl)-l-methyl-5-oxo-4,5-dihydro-lH-imidazol-4- yl]phenyl methanesulfonate (320 mg, 0.7 mmol), 1-cyclohexenylboronic acid (95 mg, 0.75 mmol), [l,r-bis(diphenylphosphino)ferrocene]palladium(pi) chloride dichloromethane adduct (57 mg, 0.07 mmol) and potassium carbonate (0.58g , 4.2 mmol) in anhydrous tetrahydrofuran (5 mL) were mixed and irradiated under an argon atmosphere in a <n="229"/>microwave reactor at 140 °C for 4 h. Water and ethyl acetate was added, the organic phase was separated, dried over magnesium sulfate and concentrated. Column chromatography using 0-4percent 7 N ammonia (in methanol) and dichloromethane as eluent followed by preparative HPLC gave 45 mg (13percent yield) of the title compound: 1H NMR (400 MHz, DMSO-J6) delta ppm 7.49 - 7.54 (m, 2 H)5 7.39 - 7.44 (m, 1 H)5 7.34 - 7.39 (m, 1 H), 7.26 - 7.30 (m, 2 H)5 7.05 - 7.12 (m5 1 H), 5.81 - 5.84 (m, 1 H)5 3.35 (s, 3 H)5 2.98 (s, 3 H)5 2.22 - 2.28 (m, 2 H),.2.12 - 2.18 (m, 2 H)5 1.89 (s, 1.6 H5 acetate), 1.57 - 1.71 (m, 4 H).

Reference： [1]Patent: WO2008/76046,2008,A1 .Location in patent: Page/Page column 227-228

20
[ 13091-23-1 ]
[ 89490-05-1 ]
[ 1052705-83-5 ]

Yield	Reaction Conditions	Operation in experiment
82%	With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,2-dimethoxyethane; water; at 95℃; for 16h;	METHOD 6; Example 92; Synthesis of 4-cvclohexenyl-3-nitropyridine[0210] A solution of 4-chloro-3-nitro pyridine (1 eq.), cyclohexenyl boronic acid (1.7 eq.), and Pd(dppf)Cl2-CH2Cl2 (0.05 eq) in 3:1 DME/2M Na2CO3, at a concentration of 0.1 M was heated at 95°C for 16 hours. Upon cooling the reaction was partitioned between EtOAc and H2O, was washed with NaCl(sat.), dried over MgSO4, was filtered and the volatiles were removed in vacuo. The material was purified by SiO2 chromatography (20percent EtOAc/hexanes eluant) to yield 4-cyclohexenyl-3-nitropyridine (82percent). LCMS (m/z): 205.0 (MH+); LC R, = 3.84 min.

Reference： [1]Patent: WO2008/106692,2008,A1 .Location in patent: Page/Page column 79

21
[ 1161847-31-9 ]
[ 89490-05-1 ]
[ 1161846-52-1 ]

Yield	Reaction Conditions	Operation in experiment
66%	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 170℃; for 3h;Microwave irradiation;	Example 6.; A mixture of (6-chloro-imidazo[l,2-b]pyridazin-8-yl)-pyridin-2-yl-amine (0.063 g, 0.26 mmol), 2 mL of toluene, 0.5 mL of ethanol, cyclohexen-1-yl boronic acid (0.065 g, 0.51 mmol), Pd(PPh3)4 (0.032 g, 0.027 mmol), and 0.36 mL of a 2 M aq. potassium carbonate solution under N2 was stirred at 1700C in a microwave for 3 h. The mixture was partitioned between 10 mL of a 10percent NaOH solution and 10 mL of dichloromethane. The aqueous layer was further extracted with 10 mL of dichloromethane. The combined organic layers were dried over MgSO4, filtered and concentrated to 0.093 g of a pale yellow oil. Column chromatography (0 -> 33percent EtOAc/hexanes) afforded 0.050 g (66percent) of (6-cyclohex-l-enyl-imidazo[l,2-b]pyridazin-8-yl)-pyridin-2-yl-amine as a white solid.(6-phenyl-imidazo [ 1 ,2-delta]pyridazin-8-yl)-pyridin-2-yl-amine and [6-( 1 -methyl- lH-pyrrol- 2-yl)-imidazo[l,2-delta]pyridazin-8-yl]-pyridin-2-yl-amine were made in a similar fashion as (6-cyclohex-l-enyl-imidazo[l,2-delta]pyridazin-8-yl)-pyridin-2-yl-amine.

Reference： [1]Patent: WO2009/77334,2009,A1 .Location in patent: Page/Page column 83

22
[ 1161847-37-5 ]
[ 89490-05-1 ]
[ 1161846-83-8 ]

Yield	Reaction Conditions	Operation in experiment
82%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 170℃; for 0.5h;Microwave irradiation;	Example 30.; Procedures for connection of core to cyclohexene; 110.0 mg (0.472 mmol) 6-Bromo-imidazo[l,2-alpha]pyridin-8-ylamine, 73.6 ul (0.566 mmol; 1.2 eq.), cyclohexene 1-yl boronic acid, 54.54 mg (0.0472 mmo; 0.1 eq.) Pd(PPH3)4 and 150.0 mg (1.416 mmol; 3.0eq.) Na2CO3 in 2.5 ml DME and 1.2 ml H2O were stirred in the microwave at 170 C for 30 min.The black suspension was extracted with 2 x 30.0 ml AcOEt and 1 x 30.0 ml H2O. Organical layers were combined, dried over MgSO4, filtered and evaporated. The crude product was chromato graphed over a 12g RediSep column with Hexane:AcOEt 0-100percent in 15 min, to give: 82.4 mg of l-(6-Cyclohex-l-enyl-imidazo[l,2-a]pyridin-8-yl)-3- methyl-urea as a yellow oil. Yield =82percent

Reference： [1]Patent: WO2009/77334,2009,A1 .Location in patent: Page/Page column 92

23
[ 1055880-27-7 ]
[ 89490-05-1 ]
[ 1055880-67-5 ]

Yield	Reaction Conditions	Operation in experiment
85.4%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 95℃; for 12h;Inert atmosphere;	Example 37; 9-(cyclohexa-1-en-1-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepine hydrochloride; (1) tert-butyl 9-(cyclohexa-1-en-1-yl)-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate; A mixture of tert-butyl 9-bromo-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate (200 mg, 0.605 mmol), a solution of cyclohexen-1-ylboronic acid (115 mg, 0.912 mmol) in ethanol (0.7 ml), 2N aqueous sodium carbonate solution (2.5 ml), and tetrakis(triphenylphosphine)palladium(0) (84.0 mg, 0.0730 mmol) in toluene (5 ml) was stirred under a nitrogen atmosphere at 95°C for 12 hr. The reaction mixture was poured into water, and the mixture was extracted with ethyl acetate. The extract was washed with water, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1) to give the desired product (170 mg, 85.4percent) as an oil. 1H-NMR (CDCl3) delta; 1.42 (9H, s), 1.64-1.77 (4H, m), 2.16 (2H, br s), 2.33 (2H, br s), 3.77-3.80 (2H, m), 3.97-4.00 (2H, m), 4.39-4.45 (2H, m), 5.68 (1H, br s), 6.92-6.97 (2H, m), 7.05-7.08 (1H, m).

Reference： [1]Patent: EP2123644,2009,A1 .Location in patent: Page/Page column 63

24
[ 950674-36-9 ]
[ 89490-05-1 ]
[ 950674-50-7 ]

Yield	Reaction Conditions	Operation in experiment
60%	With potassium phosphate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 100℃;	Example 33A5-Cyclohex-1-en-1-yl-7-isopropyl-2,2-dimethyl-4-oxochroman-6-carbaldehyde A solution of 365 mg (930 mumol) of 6-formyl-7-isopropyl-2,2-dimethyl-4-oxo-3,4-dihydro-2H-chromen-5-yl trifluoromethanesulfonate (Example 19A), 152 mg (1.20 mmol) of cyclohex-1-en-1-ylboronic acid, 75 mg (60 mumol) of tetrakis(triphenylphosphine)palladium and 334 mg (1.57 mmol) of potassium phosphate in 5.5 ml of degassed dioxane is stirred at 100° C. overnight. After cooling to room temperature, ammonium chloride solution is added and the mixture is extracted twice with ethyl acetate. The combined organic phases are dried over sodium sulfate, the solvent is then removed under reduced pressure and the residue is purified by column chromatography on silica gel (mobile phase:cyclohexane/ethyl acetate 20:1).Yield: 203 mg (60percent of theory)LC/MS (method 8): Rt=3.21 minMS (ESIpos): m/z=327 (M+H)+ 1H-NMR (CDCl3, 300 MHz): delta=1.19 (d, 3H), 1.25 (d, 3H), 1.44 (s, 3H), 1.49 (s, 3H), 1.56-1.73 (m, 1H), 1.73-2.07 (m, 4H), 2.12-2.27 (m, 2H), 2.42-2.48 (m, 1H), 2.62 (d, 1H), 2.73 (d, 1H), 3.84-4.00 (m, 1H), 5.38-5.48 (m, 1H), 6.91 (s, 1H), 10.09 (s, 1H).

Reference： [1]Patent: US2009/306197,2009,A1 .Location in patent: Page/Page column 29; 30

25
[ 1254068-52-4 ]
[ 89490-05-1 ]
[ 1254068-08-0 ]

Yield	Reaction Conditions	Operation in experiment
75%	With potassium phosphate; tricyclohexylphosphine;palladium diacetate; In water; toluene; at 100℃; for 3h;Inert atmosphere;	N-(4-Bromo-3 -methoxyphenylethyl)-2-(3 ,4-dimethoxyphenyl)acetamide ( 100 mg), 1-cyclohexeneboronic acid (2 equivalents), palladium acetate (0.05 equivalents), potassium phosphate (3.5 equivalents), and tricyclohexylphospine (0.1 equivalents) were combined in a 2-neck round bottom flask and degassed for 1 hour under vacuum. 3 mL of a toluene/water solution (20:1) was then added to the flask, and the reaction mixed was refluxed at 1000C under nitrogen for 3 hours. The reaction mixture was then cooled to room temperature and the catalyst was filtered out. The organic layer was then washed with saturated NaHCO3 solution, dried over sodium sulfate, and concentrated under vacuum. Purification with chromatography on silica using 70percent ethyl acetate/hexane yielded product as a white solid in 75percent yield. 1H NMR (400 MHz) (CDCl3) delta 1.68 - 1.75 (m, 4H), 2.20 (m, 2H), 2.34 (m, 2H), 2.73 (t, 2H), 3.50 (m, 4H), 3.77 (s, 3H), 3.86 (s, 3H), 3.89 (s, 3H), 5.48 (bs, IH), 5.75 (m, IH), 6.59 (m, 2H), 6.81 (d, J = 8.0 Hz, IH), 7.00 (d, J = 8.0 Hz, IH).

Reference： [1]Patent: WO2010/127307,2010,A1 .Location in patent: Page/Page column 61

26
[ 1354188-81-0 ]
[ 89490-05-1 ]
[ 1354188-89-8 ]

Yield	Reaction Conditions	Operation in experiment
68%	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 85℃;Inert atmosphere;	Example 25: (S)-2-tert-butoxy-2-(5-cyclohexenyl-2-((dimethylamino)methyl)-7- methylquinolin-6-yl)acetic acid (25). (S)dimethylquinoline 1 -oxide me y qu no ne -ox e(S)-ethyl 2-ferf-butoxy-2-(5- 2. Me2NH(S)-ethyl 2-(2-(acetoxymethyl)-5- cyclohexenyl-2-(hydroxymethyl)- methanol cyclohexenyl-7-methylquinolin-6- 7-methylquinolin-6-yl)acetateyl)-2-terf-butoxyacetate(S)-ethyl 2-terf-butoxy-2-(5- 25cyclohexenyl-2- ((dimethylamino)methyl)-7- methylquinolin-6-yl)acetate (S)-2-ieri-butoxy-2-(5- cyclohexenyl-2- ((dimethylamino)methyl)-7- methylquinolin-6-yl)acetic acidPreparation of (S)-6-( 1 -tert-butoxy-2-ethoxy-2-oxoethyl)-5-cyclohexenyl-2,7- dimethylquinoline 1 -oxide: Pd(PPh3)4 (6 mg, 0.006 mmol) was added to a mixture (S)- 5-bromo-6-( 1 -tert-butoxy-2-ethoxy-2-oxoethyl)-2,7-dimethylquinoline 1 -oxide(compound of Example 20) (20 mg, 0.05 mmol), cyclohexenylboronic acid (12 mg, 0.1 mmol), K2C03 (0.09 mL 2 M in water, 0.17 mmol) in 1,2-dimethoxyethane (1 mL).The reaction mixture was flushed with nitrogen, heated at 85 °C for overnight, and then the volatile component was removed in vacuo. The residue was dissolved in ethyl acetate (30 mL), washed with NaHC03 solution, water and brine, dried over Na2S04, filtered and concentrated in vacuo. The obtained residue was purified by HPLC to provide the desired product (17 mg, 68percent). LCMS-ESI+ (m/z) 412.3 (M+H)+.

Reference： [1]Patent: WO2012/3498,2012,A1 .Location in patent: Page/Page column 193-195

27
[ 1402636-05-8 ]
[ 89490-05-1 ]
[ 1402636-10-5 ]

Yield	Reaction Conditions	Operation in experiment
83.6%	With cesium fluoride;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; at 60℃;	Example 1(2R)-4-r4-(cvclohex-1 -en-1 -yl)-1 H-pyrazol-1 -yl1-N-hvdroxy-2-methyl-2-(methylsulfonyl)butanamide Step A: ethyl (2R)-4-r4-(cvclohex-1 -en-1 -yl)-1 H-pyrazol-1 -yl1-2-methyl-2-(methylsulfonyl)butanoateTo a vial containing ethyl (2R)-4-(4-iodo-1 H-pyrazol-1 -yl)-2-methyl-2- (methylsulfonyl)butanoate (500 mg, 1 .25 mmol, 1 .0 eq), cyclohex-1 -en-1 -ylboronic acid (205 mg, 1 .62 mmol, 1 .3 eq), cesium fluoride (759 mg, 5.00 mmol, 4 eq) and Pd(PPh3) (100 mg 0.087 mmol, 0.07 eq) was added THF (5 ml_). The vial was sealed and the mixture was heated at 60 °C overnight. The mixture was filtered through celite, and eluted with EtOAc. The filtrate was absorbed onto silica gel and purified by flash chromatography, eluting with 0-20 percent EtOAc/Hpt then 5percentMeOH/EtOAc to give ethyl (2R)-4-[4-(cyclohex-1 -en-1 -yl)-1 H-pyrazol-1 -yl]-2-methyl- 2-(methylsulfonyl)butanoate (370 mg, 83.6 percent yield). LC-MS M+H+ 355.1 .

Reference： [1]Patent: WO2012/137099,2012,A1 .Location in patent: Page/Page column 38-39

28
[ 2157-52-0 ]
[ 89490-05-1 ]
[ 1402812-20-7 ]

Reference： [1]Organic Letters,2012,vol. 14,p. 5180 - 5183,4

29
[ 21190-87-4 ]
[ 89490-05-1 ]
[ 1415898-32-6 ]

Yield	Reaction Conditions	Operation in experiment
61.2%	With potassium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In water; at 100℃;Inert atmosphere;	Under an atmosphere of nitrogen, a solution of 6-bromo-pyridine-2-carboxylic acid (CAN 1190-87-4, 3 g, 6.4 mol), cyclohexenylboronic acid (CAN 21190-87-4, 0.89 g, 7.1 mmol), 1,1'-bis(diphenyl-phosphino)ferrocene-palladium(II)dichloride methylene chloride complex (CAN 95464-05-4, 8 mg, 0.13 mmol), potassium carbonate (1.78 g, 12.9 mmol) in H2O (30 mL) was heated to 100° C. overnight. The reaction mixture was extracted with ethyl acetate (50 mL). The pH of the aqueous layer was adjusted to 5 by addition of 1 N hydrochloric acid and the resulting mixture was extracted with ethyl acetate (3.x.50 mL). The combined organic extracts were washed with water and brine, dried over anhydrous sodium sulfate and evaporated. The residue was purified by prep-HPLC to yield the title compound (0.8 g, 3.94 mmol, 61.2percent) as yellow oil; MS (EI): m/e=204.2 [M+H]+.
61.2%		Under an atmosphere of nitrogen, a solution of 6-bromo-pyridine-2-carboxylic acid (CAN 1190-87-4, 3 g, 6.4 mol), cyclohexenylboronic acid (CAN 21190-87-4, 0.89 g, 7.1 mmol), 1 , 1 '-bis(diphenyl-phosphino)ferrocene-palladium(II)dichloride methylene chloride complex (CAN 95464-05-4, 8 mg, 0.13 mmol), potassium carbonate (1.78 g, 12.9 mmol) in H20 (30 mL) was heated to 100°C overnight. The reaction mixture was extracted with ethyl acetate (50 mL). The pH of the aqueous layer was adjusted to 5 by addition of 1 N hydrochloric acid and the resulting mixture was extracted with ethyl acetate (3><50 mL). The combined organic extracts were washed with water and brine, dried over anhydrous sodium sulfate and evaporated. The residue was purified by prep-HPLC to yield the title compound (0.8 g, 3.94 mmol, 61.2percent) as yellow oil; MS (EI): m/e = 204.2 [M+H]+.

Reference： [1]Patent: US2012/316147,2012,A1 .Location in patent: Page/Page column 29-30
[2]Patent: WO2012/168350,2012,A1 .Location in patent: Page/Page column 72; 73

30
[ 1253216-50-0 ]
[ 89490-05-1 ]
[ 1253216-51-1 ]

Yield	Reaction Conditions	Operation in experiment
100%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 90℃; for 0.666667h;Inert atmosphere;	Compound 13 (296 mg, 0.712 mmol) was dissolved in 1,4-dioxane (4 mL), and water (1 mL), potassium carbonate (295 mg, 2.14 mmol), and 1-cyclohexeneboronic acid (134 mg, 1.07 mmol) were added, and the mixture was purged with argon. Tetrakistriphenylphosphinepalladium(0) (25 mg, 0.021 mmol) was added, and the mixture was heated to 90°C. After stirring for 40 min, the mixture was allowed to cool to room temperature, filtered through celite, and thoroughly washed with ethyl acetate. To the filtrate was added saturated brine, and the mixture was extracted with ethyl acetate, and the extract was dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by silica gel column chromatography to give compound 14 (329 mg, 100percent).MS m/z 462 [M+H]+, APCI(+)

Reference： [1]Patent: EP2423194,2012,A1 .Location in patent: Paragraph 0256

31
[ 18242-39-2 ]
[ 89490-05-1 ]
[ 1445789-97-8 ]

Yield	Reaction Conditions	Operation in experiment
68%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate; In 1,4-dioxane; water; at 110℃; for 0.333333h;Inert atmosphere; Microwave irradiation;	Example 34 4-((3-cvclohexyl-5-(trifluoromethylsulfonamido)phenyl)amino)-7- (quanidinomethyl)quinoline-3-carboxamide 3',5'-dinitro-2,3A5-tetrahvdro-1 ,1 '-biphenyl. A mixture of 1 -bromo-3,5- dinitrobenzene (4.8 g, 19.43 mmol), cyclohexen-1-ylboronic acid (1.399 mL, 25.3 mmol), cesium carbonate (18.99 g, 58.3 mmol), and [1 , 1 - bis(diphenylphosphino)ferrocene]dichloropalladium(ll) dichloromethane adduct (1 .587 g, 1.943 mmol), 1 ,4-dioxane (36.1 mL) and water (18.04 mL) was purged with nitrogen, then irradiated in a microwave reactor for 20 minutes at 1 10 °C. The mixture was cooled and filtered. Sat. aq. sodium bicarbonate was added and the mixture extracted with ethyl acetate. The combined organic layers were washed with brine, dried (Na2S04), and concentrated. The residual black material was purifed (silica gel, 5-50percent ethyl acetate/hexane) to give the title compound (3.30 g, 68percent) as a tan solid. LCMS (ES+) m/e 249 [M+H]+.

Reference： [1]Patent: WO2013/96151,2013,A1 .Location in patent: Page/Page column 101

32
[ 161622-14-6 ]
[ 89490-05-1 ]
[ 1034188-31-2 ]

Yield	Reaction Conditions	Operation in experiment
89%	With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate; In butan-1-ol; at 100℃;	Step 5 (0262) [00248] 4-(cyclohex-1-en-1-yl)-3-(trifluoromethyl)benzoic acid: To a solution of 4- bromo-3-(trifluoromethyl)benzoic acid (7.12 g, 26.47 mmol, 1.00 equiv.) in n-BuOH (100 mL), (cyclohex-1-en-1-yl)boronic acid (3.67 g, 29.14 mmol, 1.10 equiv.), Pd(Pph3)2Cl2 (370 mg, 0.53 mmol, 0.02 equiv.), and potassium carbonate (5.48 g, 39.65 mmol, 1.50 equiv.) was added. The resulting solution was stirred overnight at 100 oC. The reaction mixture was cooled and quenched by water (200 ml). The resulting solution was extracted with ethyl acetate (3 x 100 mL) and the organic layers combined, then washed with brine (2 x 50 mL) and dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified by a silica gel column, eluted with ethyl acetate/petroleum ether (1:15). The collected fractions were combined and concentrated under vacuum to afford 6.4 g (89%) of 4-(cyclohex-1-en-1-yl)-3-(trifluoromethyl) benzoic acid as a light brown solid. LC-MS: m/z =269 [M-H]-.
	With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate; In methanol; at 95℃;Inert atmosphere;	In pressure reactor 20g <strong>[161622-14-6]4-bromo-3-(trifluoromethyl)benzoic acid</strong>, 9.37g cyclohexenylboronic acid, 0.52g bis(triphenylphosphine)palladium (II) chloride and 15.41 g potassium carbonate in 150ml methanol were carefully degassed and stirred under nitrogen at IT 95C until the reaction went to completion (3-4h). Ethylacetate (250ml) and 200ml 0.1 N HCI were added to the reaction mixture at IT = 20 - 25C. The phases were separated and the organic phase was washed with 2X 159 ml 10% NaCI in water. Then 5g charcoal were added to the organic phase, and the mixture is stirred for 30 min and filtrated. Evaporation to dryness gave 20.02g of an orange solid which contained ca 94% 4-cyclohex-1-enyl-3-trifluoromethyl-benzoic acid according to HPLC. This is used without further purification for the synthesis of 4-cyclohexyl-3- trifluoromethyl-benzoic acid 1H-NMR (400MHz, DMSO-d6): delta 1 .6-1 .8(4H,m), 2.1-2.3(41-1, m), 5.58(1 H,t), 7.48(1 H,d), 8.12- 8.17(2H,m) MS: 269.0799(M-H)"

Reference： [1]Patent: WO2017/120124,2017,A1 .Location in patent: Paragraph 00247-00248
[2]Patent: WO2013/113915,2013,A1 .Location in patent: Page/Page column 32-33

33
[ 89490-05-1 ]
[ 1230487-00-9 ]

Reference： [1]Patent: WO2013/113915,2013,A1
[2]Patent: WO2013/113915,2013,A1
[3]Patent: WO2017/120124,2017,A1

34
[ 1448538-28-0 ]
[ 89490-05-1 ]
[ 1448538-39-3 ]

Yield	Reaction Conditions	Operation in experiment
60%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; at 80℃;	General procedure: Tothe mixture of building block 1a or 1b (0.246 mmol, 1 eq), boronic acidderivative 7 (0.368 mmol, 1.5 eq), K2CO3(0.737 mmol, 3 eq) and Pd(PPh3)4(5 molpercent) in THF/H2O (4 mL/0.1 mL) was added. The reaction mixturewas heated at 80 oC for 24-48 h. Conversion of building block 1a or1b was monitored by TLC(PE/EtOAc=1/1). After the reaction was complete, water was added and theproduct 8 was extracted with EtOAc(3 x 10 mL). Organic layers were combined, washed with brine, dried over Na2SO4and evaporated. Crude product 8 waspurified by column chromatography on silica gel using PE:EtOAc (1:1) as an eluent.

Reference： [1]Tetrahedron Letters,2013,vol. 54,p. 4524 - 4525

35
[ 1462897-71-7 ]
[ 89490-05-1 ]
[ 1462897-39-7 ]

Yield	Reaction Conditions	Operation in experiment
49%	With potassium phosphate; palladium diacetate; tricyclohexylphosphine; In water; toluene; at 100℃; for 1h;Inert atmosphere;	Preparation example 2 : preparation of 5-chloro-N-[2-(cyclohex-1-en-1-yl)-5-fluorobenzyl]-N-cyclopropyl- 3-(difluoromethyl)-1 -methyl-1 H-pyrazole-4-carboxamide (compound 1.44) To a suspension of 300 mg (0.68 mmol) of N-(2-bromo-5-fluorobenzyl)-5-chloro-N-cyclopropyl-3- (difluoromethyl)-l -methyl-1 H-pyrazole-4-carboxamide in a 10/1 mixture of toluene / water degassed with argon, are successively added 190 mg (1.50 mmol) of cyclohex-1 -en-ylboronic acid, 38 mg (0.137 mmol) of tricyclohexylphosphine, 15 mg (0.069 mmol) of palladium (II) acetate and 437 mg (2.06 mmol) of tri- potassium phosphate. The mixture is heated at 1 00 °C for 1 hour. The reaction mixture is cooled to ambient temperature. 1 ml_ of water is added to the reaction mixture and the organic phase is filtered over a cake of diatomaceous earth. The cake is washed twice by dichloromethane and the combined organic phases are concentrated under vacuum to give 51 6 mg of crude material. A purification by column chromatography on silica gel (gradient heptane/ethyl acetate) yields 154 mg (49 percent yield) of 5-chloro-N-[2- (cyclohex-1 -en-1 -yl)-5-fluorobenzyl]-N-cyclopropyl-3-(difluoromethyl)-1 -methyl-1 H-pyrazole-4- carboxamide : (M+H) = 438.

Reference： [1]Patent: WO2013/144087,2013,A1 .Location in patent: Page/Page column 59-60

36
tert-butyl 2-(4-iodophenyl)-1-oxo-2,8-diazaspiro[4.5]decane-8-carboxylate [ No CAS ]
[ 89490-05-1 ]
tert-butyl1-oxo-2-(2',3',4',5'-tetrahydro-[1,1'-biphenyl]-4-yl)-2,8-diazaspiro[4.5]decane-8-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In 1,2-dimethoxyethane; water; at 120℃; for 0.5h;Microwave irradiation;	To a solution of 14 (77 mg, 0.169 mmol) in 1,2-Dimethoxyethane (5 mL) and water (5 mL) were added cyclohex-1-en-1-ylboronic acid (42.5 mg,0.337 mmol), PdCl2(dppf)-CH2Cl2 adduct (13.78mg, 0.017 mmol) and potassium carbonate (46.6 mg, 0.337 mmol). After the reaction mixture was stirred at 120 °C in a microwave reactor for 30 minutes. After cooling, water was added to the mixture. Then the mixture was extracted with DCM 3 times. The combined organic layers were dried over anhydrous Na2SO4. After filtration and concentration, the residue was purified by flash chromatography to give 48 mg 16 (69percent). LC/MS: tR = 4.25 min, m/z: 433.3 (M+Na)+.

Reference： [1]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 6349 - 6358

37
[ 50397-74-5 ]
[ 89490-05-1 ]
[ 915006-68-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 6363 - 6369

38
[ 290368-00-2 ]
[ 89490-05-1 ]
C₁₈H₂₂N₂O₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 1327 - 1333

39
C₁₁H₁₁IN₂O [ No CAS ]
[ 89490-05-1 ]
C₁₇H₂₀N₂O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 60℃; for 24h;Inert atmosphere; Sealed tube;	TP40. To 40 mg of TP14 (0.13 mmol) and 48 mg of 1-cyclohexenylboronic acid (0.38 mmol) in 0.9 mL of 1,4-dioxane was added 0.29 mL of a 2.0 M aqueous solution of a2C03 (0.57 mmol) and the mixture was sparged with nitrogen for 5 min. Tetrakis(triphenylphosphine)palladium(0) (14.7 mg, 0.013 mmol) was added, and the reaction was sparged for another minute before the vial was sealed under nitrogen and heated to 60 C for 24 h. After cooling, the reaction was diluted with water and rinsed several times with EtOAc, the combined EtOAc layers were dried, concentrated, and chromatographed with 0-30% EtOAc in hexane to give a tan solid which was dissolved in MeOH, treated with charcoal, filtered and concentrated to yield 31 mg of white solid (90%). NMR (500 MHz, CDC13) delta 9.14 (s, 1H), 7.73 (d, J= 8.5, 2H), 7.45 (d, J= 8.5, 2H), 6.24 (s, 1H), 3.47 - 3.29 (m, 1H), 2.73 (dd, J= 6.9, 16.9, 1H), 2.50 (d, J= 16.7, 1H), 2.44 (dd, J= 6.0, 7.8, 2H), 2.25 (dd, J= 2.4, 6.1, 2H), 1.86 - 1.76 (m, 2H), 1.76 - 1.63 (m, 2H), 1.27 (d, J= 7.4, 3H). 13C NMR (126 MHz, CDC13) delta 166.88, 153.90, 143.96, 135.72, 132.36, 126.01, 125.73, 125.02, 33.80, 27.88, 27.08, 25.89, 22.87, 21.97, 16.25. MS 269 (M + 1

Reference： [1]Patent: WO2014/164704,2014,A2 .Location in patent: Page/Page column 85-86
[2]ACS Medicinal Chemistry Letters,2019,vol. 10,p. 1537 - 1542

40
[ 887266-99-1 ]
[ 89490-05-1 ]
4-cyclohexen-1-yl-3-fluorobenzonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
980 mg	With bis-triphenylphosphine-palladium(II) chloride; sodium ethanolate; In ethanol; at 90℃; for 0.25h;Microwave irradiation;	(1) Synthesis of 4-cyclohexen-1-yl-3-fluorobenzonitrile To a mixture of <strong>[887266-99-1]3-fluoro-4-iodobenzonitrile</strong> (1.53 g), 1-cyclohexen-1-yl-boronic acid (938 mg), bis(triphenylphosphine)palladium(II) dichloride (435 mg) and ethanol (9.75 mL), sodium ethoxide (about 20%, solution in ethanol, 5.75 mL) was added and the mixture was stirred at 90C for 15 minutes under irradiation with microwaves. After being cooled to room temperature, the reaction mixture was poured into water and three extractions were conducted with chloroform. The combined organic layers were washed with saturated brine and passed through a phase separator to be concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate = 100:0-75:25) to give the titled compound as a pale yellow oil (980 mg). 1H NMR (300 MHz, CHLOROFORM-d) delta ppm 1.63 - 1.84 (m, 4 H) 2.18 - 2.29 (m, 2 H) 2.30 - 2.41 (m, 2 H) 6.01 - 6.10 (m, 1 H) 7.27 - 7.42 (m, 3 H). MS ESI/APCI Dual posi: 224[M+Na]+. MS ESI/APCI Dual nega: 236[M+Cl]-.

Reference： [1]Patent: EP2881384,2015,A1 .Location in patent: Paragraph 0539; 0540

41
[ 105752-11-2 ]
[ 89490-05-1 ]
[ 1052705-85-7 ]

Yield	Reaction Conditions	Operation in experiment
25%	With potassium phosphate; chloro(2-dicyclohexylphosphino-2?,4?,6?-triisopropyl-1,1'-biphenyl)[2-(2-aminoethyl)phenyl]palladium(II) methyl tert-butyl ether; In tetrahydrofuran; water; at 20℃; for 24h;	4-(Cyclohex-l-en-l-yl)pyridin-3-amine.The mixture of 4-iodopyridin-3 -amine (0.161 g, 0.734 mmol),cyclohex-l-en-l-ylboronic acid (0.0924 g, 0.734 mmol), XPhos precatalyst (0.023g, 0.029 mmol), Phosphoric acid, potassium salt (2M aq) (0.550 mL, 1.100 mmol)in THF (3.0 mL) was stirred at room temperature for 24 hours. The reaction wasdiluted with ethyl acetate and washed with water three times. The ethyl acetatelayer was separated, dried (Na2SC"4), filtered and concentrated. Flashcolumn eluted with ethyl acetate in hexane from 0 to 100% gave the desiredproduct (33 mg, 25% yield). MS(ES+) m/e 175 MS[M+H]+; 1H NMR (400MHz,CHLOROFORM-d) delta 8.06 (s, 1H), 7.95 (d, J=5.0 Hz, 1H), 6.89 - 6.85 (m, 1H), 5.86(dt, J=3.8, 1.9 Hz, 1H), 3.80 (br. s., 2H), 2.26 - 2.15 (m, 4H), 1.81 - 1.74(m, 2H), 1.73 - 1.64 (m, 2H).

Reference： [1]Patent: WO2015/69594,2015,A1 .Location in patent: Page/Page column 124

42
C₁₁H₁₆O₅ [ No CAS ]
[ 89490-05-1 ]
diisopropyl 2-(cyclohex-1-en-1-yl)-4-oxopentanedioate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	With L-Tartaric acid; In dichloromethane; at 60℃; for 18h;	General procedure: To a stirred solution of boronic acid 2 (2.5 equiv) and enedicarbonyl compound 1 (1.0 equiv) in anhydrous CH2Cl2 (1.0 mL/mmol) was added tartaric acid. After stirring overnight (18 h) at 60 °C, a saturated solution of Na2CO3 (10 mL) was added. The layers were separated and the aqueous layer was extracted with Et2O (3 × 10 mL). The combined organic layers were dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography over silica gel (hexane?EtOAc, 8:2).

Reference： [1]Synthesis,2015,vol. 47,p. 2233 - 2241

43
C₁₃H₁₃ClO₃ [ No CAS ]
[ 89490-05-1 ]
isopropyl 4-(4-chlorophenyl)-2-(cyclohex-1-en-1-yl)-4-oxobutanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	With L-Tartaric acid; In dichloromethane; at 60℃; for 18h;	General procedure: To a stirred solution of boronic acid 2 (2.5 equiv) and enedicarbonyl compound 1 (1.0 equiv) in anhydrous CH2Cl2 (1.0 mL/mmol) was added tartaric acid. After stirring overnight (18 h) at 60 °C, a saturated solution of Na2CO3 (10 mL) was added. The layers were separated and the aqueous layer was extracted with Et2O (3 × 10 mL). The combined organic layers were dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography over silica gel (hexane?EtOAc, 8:2).

Reference： [1]Synthesis,2015,vol. 47,p. 2233 - 2241

44
[ 1813-33-8 ]
[ 89490-05-1 ]
C₁₄H₁₂F₃N [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 1,1'-bis-(diphenylphosphino)ferrocene; tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; toluene; for 12h;Reflux;	General procedure: A mixture of 2-chloro-4-(trifluoromethyl)-benzonitrile (1.00 mmol), appropriate boronic acid (1.20 mmol)were dissolved in toluene/dioxane:2 N Na2CO3 (2:1:1) solution(6 ml). Tetrakis(triphenyl-phosphine)palladium(0) (0.10 mmol)and 1,10-Ferrocenediyl-bis(diphenylphosphine) (0.20 mmol) wasadded to the mixture and it was refluxed for 12 h. After cooleddown to ambient temperature, the reaction was filtered over celiteand extracted with EtOAc twice. The combined organic extractswere dried over MgSO4, filtered, and concentrated in vacuo. Theresidue was purified by flash column chromatography on silicagel using EtOAc/hexanes (1:10) eluant condition. (R-B(OH)2 =1-pentenyl boronic acid for 53, 1-cyclohexenylboronicacid for 54).

Reference： [1]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 6844 - 6854

45
[ 5292-43-3 ]
[ 89490-05-1 ]
tert-butyl 2-(cyclohex-1-en-1-ylsulfonyl)acetate [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2016,vol. 55,p. 747 - 750
Angew. Chem.,2016,vol. 128,p. 757 - 760,4
[2]Chemical Communications,2017,vol. 53,p. 12473 - 12476
[3]ACS Catalysis,2017,vol. 7,p. 4655 - 4659

46
[ 84539-34-4 ]
[ 89490-05-1 ]
3-bromo-5-(cyclohex-1-en-1-yl)pyridin-4-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate; In 1,4-dioxane; water; at 130℃; for 1.5h;Inert atmosphere; Microwave irradiation;	Intermediate s:3-bromo-5-{cyclohex-1-en-1-yl)pyridln-4-amine To a stirred and nitrogen degassed solution of <strong>[84539-34-4]3,5-dibromopyridin-4-amine</strong> (CAS 84539-34-4; 2.00 g, 7.94 mmol), potassium carbonate (2.20 g, 15.88 mmol) and (cyclohex-i-en-i-yl)boronic acid (CM 89490-05-1; 1.10 g, 8.73 mmol) in dioxane (26 mL) and water (1.6 mL) was added bis(triphenylphosphine)palladium(1I) dichioride (CAS 13965-03-2; 557 mg, 794 iimol). The reaction mixture was heated under microwave irradiation at 130 C for 1.5 h. The reaction mixture was poured into water and extracted with EtOAc. The combined organics were dried (MgSOJ, filtered and concentrated in vczczw. The crude product was purified by column chromatography (silica, 0-50% EtOAc / petroleum ether) to afford the title compound.?H NMR (400 MHz, DK{SO-d5) 6 ppm i.8 - 1.69 (m, 2 H) 1.69 - 1.78 (m, 2 H) 2.15 (br. S., 4 H) 5.62 - (m, H) 7.78 (s, i H) 8.i6 (s, iH)MS ES: 255

Reference： [1]Patent: WO2015/198045,2015,A1 .Location in patent: Page/Page column 55; 56

47
[ 173772-63-9 ]
[ 89490-05-1 ]
4-chloro-2-(cyclohex-1-en-1-yl)pyridin-3-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 140℃; for 0.5h;Microwave irradiation;	Intermediate 6: 4-chloro-2-(cyclobex-1-en-I-yI)pyfldln-3-anhlne To a stirred solution of 2,4-dichloropyridin-3-amrne (CAS 173772-63-9; 750 mg, 4.60 mmol), potassium carbonate (3.18 g, 23.01 mmol) and (cyclohex-i-en-i-yl)boronie acid (CAS 89490-05-1; 869 mg, 6.go mmol) in dioxane (8 mL) and water (2 mL) was tetrakis(triphenylphosphane) palladium (532 mg, 460 iimol). The reaction mixture was heated under microwave irradiation at 140 C for 30 mm. The reaction mixture was filtered (Celite) and then poured into water and extracted with EtOAc. The combined organics were dried (H-frit) and concentrated in vacuo. The crude product was purified by column chromatography (silica, 0-20% EtOAc / petroleum ether) to afford the title compound.?H NMR (400 MHz, METHANOL-d4) 6 ppm 1.70 - i.8i (m, 2 H) i.8i - 1.90 (m, 2 H) 2.20 - 2.29 (m, 2 H) 2.29 - 2.39 (m, 2 H) 5.9? - 6.09 (m, ill) 7.19 (d, J=s Hz, 1 H) 7.72 (d,J=5Hz,iH)MS ES: 209

Reference： [1]Patent: WO2015/198045,2015,A1 .Location in patent: Page/Page column 56; 57

48
[ 173772-63-9 ]
[ 89490-05-1 ]
3-(benzenesulfonyl)-7-(cyclohex-1-en-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-amine [ No CAS ]

Reference： [1]Patent: WO2015/198045,2015,A1

49
[ 6237-96-3 ]
[ 89490-05-1 ]
4-chloro-6-(cyclohex-1-en-1-yl)-2-ethylpyrimidin-5-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 100.0℃; for 0.666667h;Microwave irradiation;	Intermediate 6: 4-chloro-2-(cyclobex-1-en-I-yI)pyfldln-3-anhlne To a stirred solution of 2,4-dichloropyridin-3-amrne (CAS 173772-63-9; 750 mg, 4.60 mmol), potassium carbonate (3.18 g, 23.01 mmol) and (cyclohex-i-en-i-yl)boronie acid (CAS 89490-05-1; 869 mg, 6.go mmol) in dioxane (8 mL) and water (2 mL) was tetrakis(triphenylphosphane) palladium (532 mg, 460 iimol). The reaction mixture was heated under microwave irradiation at 140 C for 30 mm. The reaction mixture was filtered (Celite) and then poured into water and extracted with EtOAc. The combined organics were dried (H-frit) and concentrated in vacuo. The crude product was purified by column chromatography (silica, 0-20% EtOAc / petroleum ether) to afford the title compoundIntermediate i: 4-chIoro-6-(cyclohcx-1-en-1-yI)-2-ethylpyrirnidin-5- amine mg, 1.27 mmol) in dioxane (io mL) and water (2.5 mL). The reaction mixture was heated under microwave irradiation at 100 C for 40 mm. The crude product was purified by column chromatography (silica, 0-30% EtOAc / petroleum ether) to afford the title compound.?H NMI{ (400 MHz, DMSO-d6) 6ppm ?.17 (t, J=8 Hz, 3 H) 1.59 - 1.75 (m, 4 H) 2.14 - 2.22 (m, 2 H) 2.27- 2.34 (m, 2 H) 2.61 - 2.70 (m, 2 H) 5.14 (s, 2 H) 6.14 (br. s., I H) MS ESi 238

Reference： [1]Patent: WO2015/198045,2015,A1 .Location in patent: Page/Page column 56; 57; 62; 63

50
[ 6502-38-1 ]
[ 89490-05-1 ]
C₂₁H₂₁NO [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%	With pyridine; 1,5-cis,cis-cyclooctadiene; copper diacetate; sodium sulfate; In 1,2-dichloro-ethane; at 25℃; for 18h;Sealed tube;	General procedure: A scintillation vial was charged with oxime 6 (1.0 equiv), alkenylboronic acid 7 (2 equiv), Cu(OAc)2 (10 mol percent), and anhydrous Na2SO4 (8?9 equiv).These solids were diluted with DCE to form a 0.1 M solution of oxime. Pyridine (5 equiv) was added to the resulting slurry via syringe, followed by cyclooctadiene (COD) (1.2equiv). The scintillation vial was then capped with a septum pierced with a ventilation needle and the reaction mixture was stirred at 25 °C for 18 h. DCE and pyridine were removed under reduced pressure and the crude reaction mixture was purified by medium pressure chromatography (2:1; ethyl acetate:hexanes) to give E-8 as a yellowoil or solid. Only the E-isomer of the nitrone was observed and isolated.

Reference： [1]Beilstein Journal of Organic Chemistry,2015,vol. 11,p. 2097 - 2104

51
[ 21067-49-2 ]
[ 89490-05-1 ]
C₂₂H₂₃NO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	With pyridine; 1,5-cis,cis-cyclooctadiene; copper diacetate; sodium sulfate; In 1,2-dichloro-ethane; at 25℃; for 18h;Sealed tube;	General procedure: A scintillation vial was charged with oxime 6 (1.0 equiv), alkenylboronic acid 7 (2 equiv), Cu(OAc)2 (10 mol percent), and anhydrous Na2SO4 (8?9 equiv).These solids were diluted with DCE to form a 0.1 M solution of oxime. Pyridine (5 equiv) was added to the resulting slurry via syringe, followed by cyclooctadiene (COD) (1.2equiv). The scintillation vial was then capped with a septum pierced with a ventilation needle and the reaction mixture was stirred at 25 °C for 18 h. DCE and pyridine were removed under reduced pressure and the crude reaction mixture was purified by medium pressure chromatography (2:1; ethyl acetate:hexanes) to give E-8 as a yellowoil or solid. Only the E-isomer of the nitrone was observed and isolated.

Reference： [1]Beilstein Journal of Organic Chemistry,2015,vol. 11,p. 2097 - 2104

52
[ 154045-43-9 ]
[ 89490-05-1 ]
C₁₉H₁₉NO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	With pyridine; copper diacetate; sodium sulfate; In 1,2-dichloro-ethane; at 25℃; for 18h;Sealed tube;	General procedure: A scintillation vial was charged with oxime 6 (1.0 equiv), alkenylboronic acid 7 (2 equiv), Cu(OAc)2 (10 mol percent), and anhydrous Na2SO4 (8?9 equiv).These solids were diluted with DCE to form a 0.1 M solution of oxime. Pyridine (5 equiv) was added to the resulting slurry via syringe, followed by cyclooctadiene (COD) (1.2equiv). The scintillation vial was then capped with a septum pierced with a ventilation needle and the reaction mixture was stirred at 25 °C for 18 h. DCE and pyridine were removed under reduced pressure and the crude reaction mixture was purified by medium pressure chromatography (2:1; ethyl acetate:hexanes) to give E-8 as a yellowoil or solid. Only the E-isomer of the nitrone was observed and isolated.

Reference： [1]Beilstein Journal of Organic Chemistry,2015,vol. 11,p. 2097 - 2104

53
[ 6502-37-0 ]
[ 89490-05-1 ]
C₂₃H₂₃NO [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	With pyridine; 1,5-cis,cis-cyclooctadiene; copper diacetate; sodium sulfate; In 1,2-dichloro-ethane; at 25℃; for 18h;Sealed tube;	General procedure: A scintillation vial was charged with oxime 6 (1.0 equiv), alkenylboronic acid 7 (2 equiv), Cu(OAc)2 (10 mol %), and anhydrous Na2SO4 (8-9 equiv).These solids were diluted with DCE to form a 0.1 M solution of oxime. Pyridine (5 equiv) was added to the resulting slurry via syringe, followed by cyclooctadiene (COD) (1.2equiv). The scintillation vial was then capped with a septum pierced with a ventilation needle and the reaction mixture was stirred at 25 C for 18 h. DCE and pyridine were removed under reduced pressure and the crude reaction mixture was purified by medium pressure chromatography (2:1; ethyl acetate:hexanes) to give E-8 as a yellowoil or solid. Only the E-isomer of the nitrone was observed and isolated.

Reference： [1]Beilstein Journal of Organic Chemistry,2015,vol. 11,p. 2097 - 2104
[2]Organic Letters,2018,vol. 20,p. 4571 - 4574

54
[ 21921-76-6 ]
[ 89490-05-1 ]
4-(cyclohex-1-en-1-yl)furan-2-carbaldehyde [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
54%		General procedure: Bromoarylaldehyde (1 mmol), aryl or alkenyl-boronicacid (1.2 mmol), and Cs2CO3(2.5 mmol) were dissolved orsuspended in a mixture of 1,4-dioxane (10 mL) and water (5 mL). The resulting mixture was stirred at RT for 5min. Tetrakis (triphenylphosphine) palladium(0) (0.05mmol) was added and the mixture was refluxed for 4?6 h under N2 protection. After cooling to RT, the mixture was dilutedwith CH2Cl2 (10 mL) and the separated aqueous layer wasextracted with CH2Cl2 (3 × 10 mL). The combined organic layers were dried over Na2SO4,filtered, and the solution was concentrated in vacuo to obtain a residue, whichwas purified by silica gel CC using ethyl acetate?petroleum ether gradientelution (1:200?1:4, v/v) to afford the aldehydes.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 1885 - 1888

55
1-(5-bromo-2-methoxypyridin-3-yl)-4-(dimethylamino)-2-(naphthalen-1-yl)-1-phenylbutane-2-ol [ No CAS ]
[ 89490-05-1 ]
1-(5-(cyclohex-1-en-1-yl)-2-methoxypyridine-3-yl)-4-(dimethylamino)-2-(naphthalen-1-yl)-1-phenylbutan-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
49.7%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; water; at 80 - 90℃; for 16h;Inert atmosphere;	1- (5-bromo-2-methoxy-pyridin-3-yl) -4- (dimethylamino) -2- (naphthalen-1-yl) -1-benzyl-2-ol (1.00 g, 1.98 mmol), cyclohex-1-en-1-yl boronic acid (280 mg, 2.18 mmol) 'Pd (dppf) Cl2 (144.88 mg, 198 umol) and potassium acetate (582.95 mg, 5 · 94 mmol) mixed was suspended in 1,4-dioxane (10 mL) and water (2 mL), and purged with nitrogen, and heated to 80~90 ° C was stirred for 16 hours. The reaction was mixed with 20mL water cooling, ethyl acetate (20 mLx2) acetate. The combined organic phase was washed with saturated saline solution (20 mL) was washed, filtered, dried over anhydrous sodium sulfate, and concentrated under reduced pressure by silica gel column chromatography (eluent: petroleum ether / ethyl acetate: 30/1 / 5/1 ) afforded pure 1-(5-(cyclohex-1-en-1-yl)-2-methoxypyridine-3-yl)-4-(dimethylamino)-2-(naphthalen-1-yl)-1-phenylbutan-2-ol (500 mg, 49.7percent yield) as a yellow oil.

Reference： [1]Patent: TW2016/4185,2016,A .Location in patent: Paragraph 0202; 0203

56
[ 446273-59-2 ]
[ 89490-05-1 ]
6-chloro-4-(cyclohex-1-en-1-yl)pyridazin-3-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 110℃; for 5h;	A mixture of 4-bromo-6- chloropyridazin-3-amine (500 mg, 2.42 mmol), cyclohex-1-en-1-ylboronic acid (304 mg, 2.42 mmol), tetrakis(triphenylphosphine)palladium(0) (252 mg, 0.22 mmol) and sodium carbonate (513 mg, 4.84 mmol) in dioxane water (30 mL5 mL) was heated at 110 °C for 5 h. The mixture was concentrated in vacuo, and the residue was diluted with aqueous hydrochloric acid (1 N, 20mL) before being washed with ethyl acetate (3 x 10 mL). The separated aqueous layer was neutralized with sodium carbonate and extracted with methylene chloride (3 x 20 mL). The combined organic layers were washed with brine, dried over sodium sulfate and concentrated to provide the crude title compound (350 mg, 69percent yield) as yellow solid.

Reference： [1]Patent: WO2016/138114,2016,A1 .Location in patent: Page/Page column 146

57
[ 2044-08-8 ]
[ 1195-66-0 ]
[ 89490-05-1 ]

Yield	Reaction Conditions	Operation in experiment
81%	With iodine; magnesium; In tetrahydrofuran; at 40 - 55℃;Inert atmosphere;	Under the protection of nitrogen, adding magnesium metal in the reaction bottle 8.0g (0.33mol) and several grain of iodines, prior to dropping funnel in the uniformly mixed methoxy boronic acid frequency that alcohol ester 56.9g (0.36mol), cyclohexene-1-polybromide 48.3g (0.3mol) and anhydrous tetrahydrofuran 300 ml, the temperature rising to outside bath 40-45 degrees, to a first 25 ml mixed solution, after color treats the iodine triggered evanishment standard, the oven-keeping 40-55 degrees between the completion of the dropping of the remaining mixed solution, then subsequently gradually heated up to reflow to continue reaction 2-3 hours, disappearance of the raw material after detection GC, to the reaction liquid 0-10 degree, slowly adding saturated NH4Cl quenching, adjusting for PH 5-6, separating the organic layer, the water layer using MTBE 150 ml extraction a, combined with the organic layer, the saturated salt water washing, solvent evaporation to dryness of the organic layer is concentrated under reduced pressure, then replace the high vacuum pump, collecting 80-83 °C fraction, get colorless transparent liquid 50.5g, yield 81percent

Reference： [1]Patent: CN104788481,2016,B .Location in patent: Paragraph 0024

58
[ 116265-10-2 ]
[ 89490-05-1 ]
C₁₇H₁₈ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
> 99%	With potassium phosphate; (NC5H3(N2C7H4(CH2)3CH3)2)NiBr(1+)*Br(1-)=Ni(NC5H3(N2C7H4(CH2)3CH3)2)Br2; triphenylphosphine; In 1,4-dioxane; at 80℃; for 24h;Schlenk technique;	General procedure: To a 50mL Schlenk tube containing benzylic ammonium iodide (0.5mmol), arylboronic acid (2.0mmol), K3PO4 (2.25mmol), castalyst (5mol%) and PPh3 (20mol%) were added and the tube was purged with N2 for 3 times. Then 1,4-dioxane (2.0mL), subsequently, was introduced to the tube. The resulted mixture was allowed to stir for 24h at 80C under atmosphere of N2. After the completion of the reaction, the resulting mixture was filtered through a Celite pad and concentrated under the vacuum and directly purified by flash chromatography to give the desired product.

Reference： [1]Chinese Chemical Letters,2017,vol. 28,p. 350 - 353

59
ethyl 2-bromo-5-morpholinothiazole-4-carboxylate [ No CAS ]
[ 89490-05-1 ]
C₁₆H₂₂N₂O₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In N,N-dimethyl-formamide; at 100℃;	A solution of ethyl 2-bromo-5-morpholinothiazole-4-carboxylate, prepared in Example 385,(700 mg, 2.19 mmol), cyclohexenylboronic acid (303 mg, 2.41 mmol), K2C03 (604 mg, 4.38mmol) and Pd(dppf)Cl2 (160 mg, 0.2 19 mmol) was dissolved in DMF (5 mL), then themixture was stirred at 100 C overnight. It was concentrated, and purified by silica gelchromatography with PE:EA=5:1 to obtain a yellow oil (571 mg, 81%). ESI MS m/z = 322.6 [M+Hj .
81%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In N,N-dimethyl-formamide; at 100℃;	A solution of ethyl 2-bromo-5-morpholinothiazole-4-carboxylate, prepared in Example 385, (700 mg, 2.19 mmol), cyclohexenylboronic acid (303 mg, 2.41 mmol), K2CO3 (604 mg, 4.38 mmol) and Pd(dppf)Cl2 (160 mg, 0.219 mmol) was dissolved in DMF (5 mL), then the mixture was stirred at 100°C overnight. It was concentrated, and purified by silica gel chromatography with PE:EA=5:1 to obtain a yellow oil (571 mg, 81percent). ESI MS m/z = 322.6 [M+H]+.

Reference： [1]Patent: WO2017/15449,2017,A1 .Location in patent: Page/Page column 301
[2]Patent: WO2019/67864,2019,A1 .Location in patent: Page/Page column 275

60
[ 99548-55-7 ]
[ 89490-05-1 ]
methyl 4-(cyclohexen-1-yl)-2-methylbenzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79.6%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In toluene; at 120℃; for 2h;Inert atmosphere;	A mixture of methyl 4-bromo-2-methylbenzoate (50.0 mg, 0.22 mmol), 1,1?-bis(diphenylphosphino)ferrocene palladium dichloride (16.0 mg, 0.02 mmol), potassium carbonate (60.3 mg, 0.44 mmol) and <strong>[89490-05-1]1-cyclohexen-1-yl boronic acid</strong> (41.2 mg, 0.33 mmol) in toluene (5 mL) was stirred at 120 °C for 2 h under N2 and evaporated to dryness. The residue was taken up in EtOAc (20 mL), washed with water (20 mL x 2) and brine (20 mL), dried over MgSO4 and concentrated. The residue was purified by flash column chromatography (5percentEtOAc in petroleum ether, Rf = 0.7) to afford methyl 4-(cyclohexen-1-yl)-2-methylbenzoate (40 mg, 79.6percent yield) as a colorless oil. ?H NMR (400 MHz, CDC13) 7.88 (d, I = 8.8 Hz, 1H), 7.28- 7.23 (m, 2H) , 6.23-6.21 (m, 1H), 3.88 (s, 3H), 2.61 (s, 3H), 2.41 - 2.39 (m, 2H), 2.23-2.21 (m, 2H), 1.80-1.77 (m, 2H), 1.68-1.65 (m, 2H).

Reference： [1]Patent: WO2017/84630,2017,A1 .Location in patent: Paragraph 00947

61
[ 585-79-5 ]
[ 89490-05-1 ]
[ 5369-21-1 ]

Yield	Reaction Conditions	Operation in experiment
74%		A solution of l-bromo-3-nitro-benzene (2.50 g, 12.4 mmol), cyclohexen-1-ylboronic acid (1.56 g, 12.4 mmol), Pd(dppf)Cl2(505 mg, 0.619 mmol)), and Na2C03(2.62 g, 24.8 mmol) in dioxane (50 mL) and H20 (5 mL) was stirred at 110 °C overnight. The reaction mixture was concentrated to dryness and the residue was purified by flash column chromatography to give the intermediate as a yellow solid. To the intermediate in EtOH (50 mL) at rt was added Pd/C (1.0 g). The mixture was flushed with H2(2X) and stirred at rt for 16 h. The reaction mixture was filtered and the filtrate was concentrated to dryness to give the title compound (1.6 g, 74percent yield), which was used without further
74%		A solution of 1-bromo-3-nitro-benzene (2.50 g, 12.4 mmol) , cyclohexen-1-ylboronic acid (1.56 g, 12.4 mmol) , Pd (dppf) Cl2(505 mg, 0.619 mmol) ) , and Na2CO3(2.62 g, 24.8 mmol) in dioxane (50 mL) and H2O (5 mL) was stirred at 110 overnight. The reaction mixture was concentrated to dryness and the residue was purified by flash column chromatography to give the intermediate as a yellow solid. To the intermediate in EtOH (50 mL) at rt was added Pd/C (1.0 g) . The mixture was flushed with H2(2X) and stirred at rt for 16 h. The reaction mixture was filtered and the filtrate was concentrated to dryness to give the title compound (1.6 g, 74yield) , which was used without further

Reference： [1]Patent: WO2017/100668,2017,A1 .Location in patent: Page/Page column 540
[2]Patent: WO2018/103058,2018,A1 .Location in patent: Page/Page column 540

62
[ 23056-36-2 ]
[ 89490-05-1 ]
2-cyclohexylpyridin-4-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%		A solution of 2-chloro-4-nitropyridine (2.50 g, 15.8 mmol), cyclohexen-1-ylboronic acid (2.38 g, 18.9 mmol), Pd(dppf)Cl2(0.643 g, 0.788 mmol), and Na2C03 (3.34 g, 31.5 mmol) in dioxane (50 mL) and Eta2Omicron (5 mL) was stirred at 110 °C overnight. The reaction was concentrated to dryness and the residue was purified by flash column chromatography to give a yellow solid. The yellow solid was dissolved in EtOH (100 niL) at rt and Pd/C (500 mg) was added. The mixture was flushed with H2(2x) and was stirred at rt for 16 h. The reaction was filtered and concentrated to dryness to give the title compound (2.0 g, 72percent yield), which was used in the next step without further purification.

Reference： [1]Patent: WO2017/100668,2017,A1 .Location in patent: Page/Page column 641; 642

63
[ 1320288-30-9 ]
[ 89490-05-1 ]
2-chloro-4-(cyclohex-1-en-1-yl)-6-methoxy-7-[3-(pyrrolidin-1-yl)propoxy]quinazoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,4-dioxane; water; at 60℃; for 7h;Inert atmosphere;	Into a 100-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed 2,4-dichloro-6-methoxy-7-[3-(pyrrolidin-l- yl)propoxy] quinazoline (300 mg, 0.84 mmol, 1 equiv), (cyclohex-l-en-l-yl)boronic acid (116 mg, 0.92 mmol, 1.1 equiv), Pd(dppf)Cl2 dichloromethane (69 mg, 0.10 equiv), sodium carbonate (179 mg, 1.69 mmol, 2.00 equiv), dioxane (16 mL), water(4 mL). The resulting solution was stirred for 7 h at 60 °C in an oil bath. The solids were filtered out. The resulting mixture was concentrated under vacuum. The crude product (350 mg) was purified by Flash HPLC MeOH. This resulted in 220 mg (64percent) of the title compound as yellow oil. Analytical Data: LC-MS: (ES, m/z): RT = 1.08 min, LCMS 53: m/z = 402.0 [M+l]. lH NMR (400 MHz, Methanol-^) delta 7.47 (s, 1H), 7.25 (s, 1H), 6.25 - 6.22 (m, 1H), 4.29 (t, J= 6.1 Hz, 2H), 3.98 (s, 3H), 2.82 - 2.74 (m, 2H), 2.67 - 2.60 (m, 4H), 2.56 - 2.49 (m, 2H), 2.39 - 2.20 (m, 2H), 2.17 - 2.10 (m, 2H), 1.97 - 1.78 (m, 8H).

Reference： [1]Patent: WO2017/181177,2017,A1 .Location in patent: Paragraph 01323-01326

64
[ 210539-04-1 ]
[ 89490-05-1 ]
6-benzyl-2-(cyclohexen-1-yl)-7,8-dihydro-5H-1,6-naphthyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68.00%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; cesium fluoride; In 1,4-dioxane; water; at 110℃; for 12h;Inert atmosphere;	6-Benzyl-2-chloro-7,8-dihydro-5H-1,6-naphthyridine (200.00 mg, 772.95 mumol, 1.00 eq), cyclohexene-1-yl boronic acid (146.04 (1.65 mmol, 1.50 eq), Pd(dppf)Cl2 (56.56 mg, 77.30 mumol, 0.10 eq) and cesium fluoride (234.82 mg, 1.55 mmol, 2.00 eq) were dissolved in dioxane (4.00 mL) and water (0.4 mL), and then the mixture was stirred at 110 °C for 12 hours under the nitrogen gas atmosphere. The reaction mixture was concentrated under reduced pressure, water (10 mL) was added to the residue, and extracted with ethyl acetate (20 mL). The combined organic layers were washed with brine (10 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was separated and purified by silica gel chromatography (SiO2, petroleum ether / ethyl acetate = 20/1 to 10: 1) to deliver 6-benzyl-2-(cyclohexen-1-yl)-7,8-dihydro-5H-1,6-naphthyridine (160.00 mg, 525.57 mumol, 68.00percent yield) as a yellow solid. 1H NMR (300MHz, CDCl3) delta 7.36-7.11 (m, 6H), 7.05-6.99 (m, 1H), 6.54 (s, 1H), 3.64 (s, 2H), 3.53 (s, 2H), 3.01-2.92 (m, 2H), 2.83-2.73 (m, 2H), 2.39 (br. s., 2H), 2.17 (d, J= 6.2 Hz, 2H), 1.77-1.66 (m, 2H), 1.65-1.55 (m, 2H).

Reference： [1]Patent: EP3252059,2017,A1 .Location in patent: Paragraph 0521-0523

65
[ 1017781-60-0 ]
[ 89490-05-1 ]
C₁₃H₁₈N₂OS [ No CAS ]

Reference： [1]Chemical Biology and Drug Design,2018,vol. 91,p. 172 - 180

66
3-((5'-bromo-2'-(2-trityl-2H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl)methyl)-2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridine [ No CAS ]
[ 89490-05-1 ]
2-ethyl-5,7-dimethyl-3-((6'-(2-trityl-2H-tetrazol-5-yl)-2",3",4",5"-tetrahydro-[1,1':3',1"-terphenyl]-4-yl)methyl)-3H-imidazo[4,5-b]pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate; In ethanol; water; toluene; at 120℃; for 0.5h;Microwave irradiation; Inert atmosphere; Sealed tube;	To a microwave vial containing PdCl2(dppf) (3.00 mg, 4.11 mumol) and cyclohex-l-en-1- ylboronic acid (10.34 mg, 0.082 mmol) was added a solution of Intermediate 55c (30 mg, 0.041 mmol) in toluene (1 mL) followed by ethanol (250 mu) and tripotassium phosphate (2 M aq, 51.3 muL, 0.103 mmol). N2 was sparged through the reaction mixture for 5 min before the vial was sealed and heated at 120 °C in the microwave for 30 min. The solution was then filtered over a pad of Celite/MgS04 before being concentrated in vacuo. This crude residue was purified by column chromatography (ISCO, 12g silica gel column, gradient of 0 to 100percent EtOAc in hexanes) to give Intermediate 71a (25 mg, 0.034 mmol, 83 percent yield) as an off-white solid. LC-MS (Method A2) RT = 1.22 min, MS (ESI) m/r. 732.3 (M+H)+.

Reference： [1]Patent: WO2018/5591,2018,A1 .Location in patent: Page/Page column 158-159

67
(R)-3-bromo-6-((4-hydroxy-1-(4,4,4-trifluoro-3-phenylbutanoyl)piperidin-4-yl)methyl)-2-methyl-2H-pyrazolo[4,3-d]pyrimidin-7(6H)-one [ No CAS ]
[ 89490-05-1 ]
(R)-3-(cyclohex-1-en-1-yl)-6-((4-hydroxy-1-(4,4,4-trifluoro-3-phenylbutanoyl)piperidin-4-yl)methyl)-2-methyl-2H-pyrazolo[4,3-d]pyrimidin-7(6H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 130℃; for 0.5h;Inert atmosphere; Sealed tube; Microwave irradiation;	A suspension of Intermediate E (50 mg, 0.092 mmol), cyclohex-1-en-1-ylboronic acid (11.6 mg, 0.092 mmol) and potassium phosphate, tribasic (78 mg, 0.369 mmol) in 1 ,4-dioxane (1.5 mL) and water (0.5 mL) in a reaction tube. The reaction mixture was pre-degassed (bubbling nitrogen) for 20 min. Pd(PPh3)4 (10.7 mg, 9.22 muetaiotaomicronIota) was added and the vessel was sealed. The reaction mixture was heated at 130 °C under microwave irradiation for 30 min. The vessel was cooled to RT and the reaction was quenched by the addition of saturated NH4CI(aq) solution. The resulting biphasic mixture was extracted using DCM (x 3) (Phase Separator). The solvents were removed in vacuo and the remaining residue was purified by flash chromatography using a KP-NH column (0-100percent, EtOAc in cyclohexane) to give the title compound (44.5 mg, 88percent) as a white solid. LCMS (Method A): RT = 1.45 min, m/z = 544 [M+H]+. 1 H NMR (400 MHz, CDCI3): delta 7.67 (d, 1 H), 7.42-27 (m, 5H), 6.09-6.02 (m, 1 H), 4.30 (t, 1 H), 4.20-4.04 (m, 4H), 4.03-3.83 (m, 1 H), 3.72-3.57 (m, 1 H), 3.44-3.28 (m, 2H), 3.03- 2.82 (m, 3H), 2.50-2.39 (m, 2H), 2.36-2.25 (m, 2H), 1.90-1.70 (m, 4H), 1.65-1.43 (m, 2H), 1.33-1.17 (m, 3H), 1.07-0.81 (m, 1 H).

Reference： [1]Patent: WO2018/73602,2018,A1 .Location in patent: Page/Page column 176; 177

68
[ 62802-42-0 ]
[ 89490-05-1 ]
2-(cyclohex-1-en-1-yl)-5-fluoropyrimidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50%	With tetrakis(triphenylphosphine) palladium(0); In water; acetonitrile; at 95℃; for 72h;Inert atmosphere;	A slurry of cyclohexene-1-boronic acid (CombiPhos Catalysts, 4.00 g, 31.8 mmol), sodium carbonate (6.73 g, 63.5 mmol) and 2-chloro-5-fluoro-pyrimidine (3.92 mL, 31.8 mmol) in a mixture of ACN (53 mL) and water (26.5 mL) was deoxygenated with an Ar stream. Tetrakis(triphenylphosphine)palladium (1.84 g, 1.6 mmol) was added and the slurry was again deoxygentaed with an Ar stream. The reaction was heated under Ar at 95 °C for 3d. The reaction mixture was then extracted with DCM (3X). The combined organic layers were dried over anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel chromatography (eluent: 0-50percent DCM in hexanes over a 30 mm period) to provide Example 103.1 (2.8 g, 50percent yield) as a colorless oil. LCMS-ESI (pos.) m/z: 179.1 (M+H)t

Reference： [1]Patent: WO2018/97944,2018,A1 .Location in patent: Paragraph 045; 046; 0248

69
2,4,6-triphenyl‐1-(pyridin-4‐ylmethyl)pyridin-1-ium tetrafluoroborate [ No CAS ]
[ 89490-05-1 ]
4-(cyclohex-1-en-1-ylmethyl)pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
51%	With potassium phosphate; ethanol; 2C2H3O2(1-)C12H8N2(x)H2O*Ni(2+); In 1,4-dioxane; at 60℃; for 24h;Schlenk technique; Inert atmosphere; Sealed tube;	General procedure: To an oven-dried, 25 mL Schlenk flask equipped with a stir bar was added PhenNi(OAc)2·xH2O (20 mg, 0.050 mmol, 5 molpercent), pyridinium salt (1.0 mmol, 1.0 equiv), vinylboronic acid (2.0 mmol, 2.0 equiv), and K3PO4 (722 mg, 3.4 mmol, 3.4 equiv). The flask was fitted with a rubber septum, sealed with parafilm, and then evacuated and refilled with N2 (×3). Dioxane (2.0 mL) was added, followed by EtOH (0.29 mL, 5.0 mmol, 5.0 equiv). The mixture was stirred at 60 °C for 24 h. The mixture was allowed to cool to room temperature, and then filtered through a small pad of Celite. The filter cake was washed with CH2Cl2 (4 × 25 mL), and the filtrate was concentrated. The cross-coupled product was then purified via silica gel chromatography.

Reference： [1]Synthesis,2018,vol. 50,p. 3231 - 3237

70
(1r,4r)-ethyl 4-(4-((6-bromo-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)amino)-1H-pyrazol-1-yl)cyclohexanecarboxylate [ No CAS ]
[ 89490-05-1 ]
(1r,4r)-ethyl 4-(4-((6-(cyclohex-1-en-1-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)amino)-1H-pyrazol-1-yl)cyclohexanecarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%		To a flask was added (1r,4r)-ethyl 4-(4-((6-bromo-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)amino)-1H-pyrazol-1-yl)cyclohexanecarboxylate (13.2 g, 30.4mmol), cyclohex-1-en-1-ylboronic acid (4.60 g, 36.5 mmol) and cesium carbonate (24.8 g, 76mmol). 1,4±1,4-dioxane (80 mL) and water (20 mL) were added. The reaction mixture wasevacuated and purged with N2. PdCl2(PPh3)2 (1.07 g, 1.52 mmol) was then added and mixturewas heated to 90 °C for 5 h and then stirred at ambient temperature for 17 h. Aqueous sodiumbicarbonate solution (200 mL) was added. The resultant mixture was extracted with DCM (2 x200 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated. Tothe resultant residue was added DCM (15 mL). The suspension was filtered and rinsed withDCM. The collected solids were dried to provide 7.51 g of product. The filtrate was concentrated,then purified via flash column chromatography (0±3percent MeOH/DCM) to give additionalproduct. The two lots of product were combined to give (1r,4r)-ethyl 4-(4-((6-bromo-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)amino)-1H-pyrazol-1-yl)cyclohexanecarboxylate (11.8 g, 89percent).MS m/z: 436 (M+H)+. 1H NMR (400 MHz, DMSO-d6) delta 10.13 (s, 1H), 8.14 (d, J = 14.2 Hz,2H), 7.84 (s, 1H), 6.84 (s, 1H), 4.15 (tt, J = 11.6, 3.8 Hz, 1H), 4.11±4.01 (m, 2H), 2.44±2.32 (m,3H), 2.32±2.21 (m, 2H), 2.10 (dd, J = 13.1, 3.6 Hz, 2H), 2.02 (dd, J = 14.0, 3.5 Hz, 2H), 1.83±1.59 (m, 7H), 1.60±1.47 (m, 2H), 1.18 (t, J = 7.1 Hz, 3H).

Reference： [1]PLoS ONE,2018,vol. 13

71
6-bromo-N-(1H-pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-amine [ No CAS ]
[ 141091-37-4 ]
[ 89490-05-1 ]
6-(cyclohex-1-en-1-yl)-N-(1H-pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
46%		A flask was charged with 6-bromo-N-(1H-pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-amine (4.40 g, 15.7 mmol), 2-(cyclohex-1-en-1-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane(5.23 g, 25.1 mmol), PdCl2(dppf) (1.149 g, 1.571 mmol) and potassium phosphate (8.34 g, 39.3mmol). 1,4-dioxane (60 mL) and water (15 mL) were added. The mixture was sparged withnitrogen for 5 min and heated at 90C for 16 h. The reaction mixture was cooled and chargedwith cyclohex-1-en-1-ylboronic acid (0.989 g, 7.85 mmol) and PdCl2(dppf) (0.575 g, 0.785mmol). The flask was degassed and then stirred at 90C overnight. The mixture was diluted withwater (200 mL) and filtered. The precipitate was stirred in MeOH and filtered again. The precipitatewas kept aside. The filtrate was concentrated and the residue was suspended in MeOH andfiltered to give an additional batch of precipitate. The two batches were combined and trituratedwith MeOH:AcOH:THF (4:1:1) to give the title compound (2.02 g, 46percent); 1H NMR (400 MHz,DMSO-d6) delta 10.13 (s, 1H), 8.49 (s, 1H), 8.15 (s, 1H), 8.01 (s, 2H), 6.85 (td, J = 3.9, 1.9 Hz, 1H),2.41 (td, J = 6.1, 2.3 Hz, 2H), 2.26 (qd, J = 5.8, 3.7, 3.3 Hz, 2H), 1.78±1.57 (m, 4H).

Reference： [1]PLoS ONE,2018,vol. 13

72
(1r,4r)-4-(4-((6-bromo-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)amino)-1H-pyrazol-1-yl)cyclohexanol [ No CAS ]
[ 89490-05-1 ]
(1r,4r)-4-(4-((6-(cyclohex-1-en-1-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)amino)-1Hpyrazol-1-yl)cyclohexanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,4-dioxane; water; at 90℃; for 0.75h;Inert atmosphere;	A flask equipped with a mechanical stirrer was charged with (1r,4r)-4-(4-((6-bromo-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)amino)-1H-pyrazol-1-yl)cyclohexanol (83.7 g,221 mmol), cesium carbonate (159 g, 487 mmol) and cyclohex-1-en-1-ylboronic acid (29.8 g,237 mmol). 1,4-Dioxane (506 mL) and water (126 mL) were added. PdCl2(PPh3)2 (6.37 g, 9.07mmol) was added and the reaction mixture was degassed and purged with nitrogen. The reactionmixture was heated to 90C for 45 min and then cooled to ambient temperature overnight.To the reaction mixture was added water (1.4 L). The resultant suspension was stirredfor 30 min, filtered, and washed with water (500 mL) and ethanol (1.2 L). The collected solidwas dried under vacuum to give the title compound (84.1 g, 100percent); MS m/z: 380 (M+H)+. 1HNMR (400 MHz, DMSO-d6) delta 10.12 (s, 1H), 8.49 (s, 1H), 8.21±8.09 (m, 2H), 7.82 (d, J = 0.6Hz, 1H), 6.84 (q, J = 4.2, 3.5 Hz, 1H), 4.62 (d, J = 4.3 Hz, 1H), 4.11 (tt, J = 11.5, 3.9 Hz, 1H),3.48 (tt, J = 10.8, 4.2 Hz, 1H), 2.41 (s, 2H), 2.26 (d, J = 5.8 Hz, 2H), 2.07±1.85 (m, 4H), 1.84±1.57 (m, 6H), 1.43±1.28 (m, 1H).

Reference： [1]PLoS ONE,2018,vol. 13

73
[ 88139-91-7 ]
[ 89490-05-1 ]
(5-(cyclohex-1-en-1-yl)pyridin-2-yl)methanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; palladium diacetate; In tetrahydrofuran; water; at 40℃; for 24h;Inert atmosphere;	To a dry flask was added (5-bromopyridin-2-yl)methanol (1.128 g, 6 mmol), Pd(0Ac)2 (67.36 mg, 0.30 mmol), Sphos (246.4 mg, 0.6 mmol), 1- cyclohexene-l-yl-boronic acid (1.134 g, 9 mmol), K3PO4 (2.547 g, 12 mmol) . The mixture was backflushed with argon (3X), and 55 ml THF and 0.22 ml water were added. The mixture was stirred at 40 °C for 24 h. The reaction mixture was poured onto water and extracted with EtOAc (3X). The combined organic layer was washed with brine, dried with Na2S04, concentrated under vacuum and purified by chromatography providing (5-(cyclohex-l-en-l-yl)pyridin-2-yl)methanol (1.08 g, 95percent yield) as a yellowish solid. NMR (300 MHz, cdch) delta 8.54 (s, 1H), 7.65 (dd, J= 8.1, 2.2 Hz, 1H), 7.22 (d, J= 8.1 Hz, 1H), 6.20 - 6.10 (m, 1H), 4.74 (s, 2H), 2.44 - 2.33 (m, 2H), 2.27 - 2.17 (m, 2H), 1.85 - 1.74 (m, 2H), 1.73 - 1.62 (m, 2H).

Reference： [1]Patent: WO2018/136935,2018,A1 .Location in patent: Paragraph 00650; 00652

74
[ 33332-25-1 ]
[ 89490-05-1 ]
methyl 5-(cyclohex-1-en-1-yl)pyrazine-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%	With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; palladium diacetate; In tetrahydrofuran; water; at 40℃; for 15h;Inert atmosphere;	To a solution of methyl 5-chloropyrazine-2-carboxylate (601 mg, 3.48 mmol) in THF (11.6 mL) was added 1-cyclohexene-l-yl-boronic acid (656 mg, 5.21 mmol), K3PO4 (1.47 g, 6.91 mmol), Pd(OAc)2 (39.2 mg, 0.175 mmol), SPhos (144 mg, 0.350 mmol) and H2O (0.13 mL, 7.2 mmol) at room temperature. After stirring for 15 h at 40 °C, the reaction was quenched by adding water. The crude products were extracted with EtOAc (3X), and the combined organic extracts were washed with brine, dried (MgS04), and concentrated in vacuo. The residue was purified by flash column chromatography (hexane/EtOAc = 9/1 to 4/1) to afford methyl 5-(cyclohex-l-en-l-yl)pyrazine-2-carboxylate (736 mg, 97percent) as a pale yellow solid. NMR (300 MHz, CDCh) delta 9.21 (d, J= 1.2 Hz, 1H), 8.81 (d, J= 1.2 Hz, 1H), 6.98-7.01 (m, 1H), 4.05 (s, 3H), 2.55-2.60 (m, 2H), 2.34-2.38 (m, 2H), 1.81-1.89 (m, 2H), 1.70-1.77 (m, 2H).

Reference： [1]Patent: WO2018/136935,2018,A1 .Location in patent: Paragraph 00662; 00665; 00762

75
[ 97483-77-7 ]
[ 89490-05-1 ]
5-(cyclohex-1-en-1-yl)-2-picolinonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%	With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; palladium diacetate; In 1,4-dioxane; water; at 115℃; for 18h;Inert atmosphere;	In a dry flask under argon was added 5-bromo-2-cyanopyridine (1.83 g, 10 mmol), SPhos (410 mg, 1.0 mmol), cyclohexene-l -yl boronic acid (1.76 g, 14 mmol) and potassium phosphate tribasic (6.37 g, 30 mmol). The flask flushed with argon. Dioxane (30 mL) and water (4 mL) were added and the mixture was degassed with vacuum and backflushed with argon. Pd(OAc)2 (112 mg, 0.5 mmol) was added and the reaction was degassed again. The reaction mixture was stirred at 115 °C for 18 h. The crude reaction mixture was cooled, poured onto water and extracted with EtOAc (3X). The organic layers were washed with water and then brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by chromatography (0-20percent EtOAc in hexanes) followed by re-purification by chromatography (5-8percent EtOAc/ hexanes) provided 5-(cyclohex-l-en-l-yl)picolinonitrile (1.22 g, 65percent yield). NMR (300 MHz, Chloroform-c delta 8.75 (d, J= 2.2 Hz, 1H), 7.76 (dd, J= 8.2, 2.2 Hz, 1H), 7.64 (d, J= 8.2 Hz, 1H), 6.43 - 6.30 (m, 1H), 2.48 - 2.35 (m, 2H), 2.35 - 2.23 (m, 2H), 1.92 - 1.78 (m, 2H), 1.77 - 1.66 (m, 2H).

Reference： [1]Patent: WO2018/136935,2018,A1 .Location in patent: Paragraph 00694; 00696

76
[ 221295-04-1 ]
[ 89490-05-1 ]
5-(cyclohex-1-en-1-yl)pyrazine-2-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; palladium diacetate; In 1,4-dioxane; water; at 95℃;Inert atmosphere;	In a dry flask under argon was added <strong>[221295-04-1]2-bromo-5-cyanopyrazine</strong> (1.84 g, 10 mmol), SPhos (410 mg, 1.0 mmol), cyclohexene-l-yl boronic acid (1.76 g, 14 mmol) and potassium phosphate tribasic (6.37 g, 30 mmol). The flask flushed with argon. Dioxane (30 mL) and water (4 mL) were added and the mixture was degassed with vacuum and backflushed with argon. Pd(OAc)2 (1 12 mg, 0.5 mmol) was added and the reaction was degassed again. The reaction mixture was stirred at 95 C for overnight. The crude reaction mixture was cooled, poured onto water and extracted with EtOAc (3X). The organic layers were washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by chromatography (80: 15:5 hexane: DCM: EtOAc eluent) provided 5- (cyclohex-l-en-l-yl)pyrazine-2-carbonitrile (1.3 g, 68%). NMR (300 MHz, Chloroform- delta 8.87 - 8.70 (m, 2H), 7.10 - 6.98 (m, 1H), 2.61 - 2.49 (m, 2H), 2.43 - 2.31 (m, 2H), 1.93 - 1.79 (m, 2H), 1.78 - 1.68 (m, 2H).

Reference： [1]Patent: WO2018/136935,2018,A1 .Location in patent: Paragraph 00705; 00707

77
methyl (R)-2-(benzyloxy)-4-(N-((5-bromopyridin-2-yl)methyl)-1-((perfluorophenyl)sulfonyl)azetidine-2-carboxamido)benzoate [ No CAS ]
[ 89490-05-1 ]
(R)-2-(benzyloxy)-4-(N-((5-(cyclohex-1-en-1-yl)pyridin-2-yl)methyl)-1-((perfluorophenyl)sulfonyl)azetidine-2-carboxamido)benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%	With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; palladium diacetate; In tetrahydrofuran; water; at 40℃; for 20h;Inert atmosphere; Sealed tube;	Methyl (R)-2-(benzyloxy)-4-(N-((5-bromopyridin-2-yl)methyl)-l-((perfluorophenyl)sulfonyl)azetidine-2-carboxamido)benzoate (354.6 mg, 0.479 mmol), palladium acetate (5.37 mg), SPhos (19.6 mg), cyclohex-l-en-l-ylboronic acid (90.4 mg), potassium phosphate (203 mg) and HPLC quality water (17 mg) were mixed under N2. The mixture was further thoroughly flushed with N2, capped, and a N2 balloon was set. THF (7.2 mL) was added through a septum. The mixture was stirred at 40 °C for 20 h. Water was added and the mixture was extracted with EtOAc (2 x). The extract was washed with brine, dried (Na2S04) and concentrated. Purification by S1O2 flash column (85: 15 Hexane/EtOAc) gave methyl (R)-2-(benzyloxy)-4-(N-((5-(cyclohex-l-en-l-yl)pyridin-2-yl)methyl)-l-((perfluorophenyl)su lfonyl)azetidine-2-carboxamido)benzoate (194 mg, 55percent yield) as a white solid. MS (ESI): [M+H]+ m/z 742.2

Reference： [1]Patent: WO2018/136935,2018,A1 .Location in patent: Paragraph 00737; 00742

78
[ 89581-38-4 ]
[ 89490-05-1 ]
methyl 5-(cyclohex-1-en-1-yl)pyrimidine-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; palladium diacetate; In tetrahydrofuran; water; at 40℃; for 14h;Inert atmosphere;	General procedure: To a solution of methyl 5-chloropyrazine-2-carboxylate (601 mg, 3.48 mmol) in THF (11.6 mL) was added 1-cyclohexene-l-yl-boronic acid (656 mg, 5.21 mmol), K3PO4 (1.47 g, 6.91 mmol), Pd(OAc)2 (39.2 mg, 0.175 mmol), SPhos (144 mg, 0.350 mmol) and H2O (0.13 mL, 7.2 mmol) at room temperature. After stirring for 15 h at 40 C, the reaction was quenched by adding water. The crude products were extracted with EtOAc (3X), and the combined organic extracts were washed with brine, dried (MgS04), and concentrated in vacuo. The residue was purified by flash column chromatography (hexane/EtOAc = 9/1 to 4/1) to afford methyl 5-(cyclohex-l-en-l-yl)pyrazine-2-carboxylate (736 mg, 97%) as a pale yellow solid. NMR (300 MHz, CDCh) delta 9.21 (d, J= 1.2 Hz, 1H), 8.81 (d, J= 1.2 Hz, 1H), 6.98-7.01 (m, 1H), 4.05 (s, 3H), 2.55-2.60 (m, 2H), 2.34-2.38 (m, 2H), 1.81-1.89 (m, 2H), 1.70-1.77 (m, 2H). Preparation by a similar procedure to Example 110, step 2, starting from <strong>[89581-38-4]methyl 5-bromopyrimidine-2-carboxylate</strong> to obtain methyl 5-(cyclohex-l-en-l-yl)pyrimidine-2-carboxylate. NMR (300 MHz, CDCh) delta 8.91 (s, 2H), 6.42-6.44 (m, 1H), 4.09 (s, 3H), 2.43-2.48 (m, 2H), 2.28-2.34 (m, 2H), 1.84-1.88 (m, 2H), 1.71-1.76 (m, 2H).

Reference： [1]Patent: WO2018/136935,2018,A1 .Location in patent: Paragraph 00665; 00762; 00770; 00773

79
7-chloro-3-(2,6-dimethylphenyl)-2-methylpyrazolo[1,5-a]pyrimidine-5-carboxylic acid methyl ester [ No CAS ]
[ 89490-05-1 ]
7-cyclohex-1-enyl-3-(2,6-dimethylphenyl)-2-methylpyrazolo[1,5-a]pyrimidine-5-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
67%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 90℃;Inert atmosphere;	[0679] To a solution of 7-chloro-3-(2,6-dimethyl-phenyl)-2-methyl-pyrazolo[l,5-a] pyrimidine-5-carboxylic acid methyl ester (343 mg, 1.0 mmol) and cyclohex-l-enyl boronic acid (189 mg, 1.5 mmol) in dioxane/H20 (30 mL + 10 mL) were added Pd(dppf)Cl2 (732 mg, 0.1 mmol) and K2C03 (552 mg, 4.0 mmmol). The resulting mixture was degassed and refilled with N2 for 3 times and stirred at 90 °C overnight. Then the reaction mixture was concentrated in vacuum to give an aqueous residue, which was extracted with EtOAc (20 mL x3). The combined organic layers were concentrated to give a crude product, which was purified by a reversed-phase column (B from 5-95, A: H20, B: ACN) to afford 7-cyclohex-l- enyl-3-(2,6-dimethyl-phenyl) -2-methyl-pyrazolo[l,5-a]pyrimidine-5-carboxylic acid (242 mg, yield: 67percent) as a yellow solid. [0680] 1HNMR (400 MHz, DMSO-6): delta = 7.22 (s, 1H), 7.20 (dd, J = 8.8, 6.0 Hz, 1H), 7.17-7.12 (m, 3H), 2.66-2.58 (m, 2H), 2.37-2.29 (m, 2H), 2.16 (s, 3H), 1.94 (s, 6H), 1.83- -1.66 (m, 2H). MS: m/z 361.9 (M+H+).

Reference： [1]Patent: WO2019/32720,2019,A1 .Location in patent: Paragraph 0678-0680

80
6-chloro-N2,N4-bis((R)-1,1,1-trifluoropropan-2-yl)-1,3,5-triazine-2,4-diamine [ No CAS ]
[ 89490-05-1 ]
6-(cyclohex-1-en-1-yl)-N2,N4-bis((R)-1,1,1-trifluoropropan-2-yl)-1,3,5-triazine-2,4-diamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90.4%	With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,4-dioxane; water; at 100℃; for 16h;Inert atmosphere;	In the reaction flask, under the protection of nitrogen, intermediate I-3 (150 mg, 0.44 mmol), cyclohex-1-en-1-ylboronic acid (85 mg, 0.66 mmol),Cesium carbonate (290 mg, 0.88 mmol), Pd(PPh3)4 (26 mg, 0.022 mmol), 1,4-dioxane (10 mL) and water (2 mL).Heat to 100 ° C and stir for 16 hours.After the reaction is completed, it is cooled to room temperature, concentrated, and flashed.Purified by column chromatography (petroleum ether / ethyl acetate)A white solid (154 mg, yield 90.4percent) was obtained.

Reference： [1]Patent: WO2019/47909,2019,A1 .Location in patent: Page/Page column 89
[2]Patent: CN109467538,2019,A .Location in patent: Paragraph 0351; 0604-0607

81
[ 70258-18-3 ]
[ 89490-05-1 ]
2-chloro-5-(cyclohexenylmethyl)pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In water; acetonitrile; at 50℃;Inert atmosphere;	To a solution of 2-chloro-5-(chloromethyl)pyridine (6.38 g, 39.65 mmol), cyclohexenylboronic acid (5 g, 39.65 mmol) and potassium carbonate (1 1 g, 79.3 mmol) in water (30 ml_) and acetonitrile (120 ml_) was added [1 ,1 '-b/s(diphenylphosphino)ferrocene]palladium(ll) dichloride dichloromethane adduct (3.23 g, 3.97 mmol) under nitrogen. The reaction mixture was heated to 50 C and stirred for 1 h before volatiles were removed under reduced pressure. The aqueous layer was extracted with dichloromethane (50 ml_). The combined organic layers were collected, dried over sodium sulfate, filtered and concentrated. The residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate = 10/1 ) to offer 2-chloro-5-(cyclohexenylmethyl)pyridine (5.3 g, 25.6 mmol, 65%) as a white solid. LCMS (ESI) m/z: 208.1 [M+H]+.

Reference： [1]Patent: WO2019/183587,2019,A1 .Location in patent: Page/Page column 139; 143-144

82
[ 1914946-33-0 ]
[ 89490-05-1 ]
[ 2380257-54-3 ]

Yield	Reaction Conditions	Operation in experiment
73%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate In 1,4-dioxane; water at 90℃; for 3h; Inert atmosphere;	31.1; 32.1 Step 1: Step 1: Preparation of ethyl 5-cyclohexenylisoxazole-3-carboxylate The mixture of ethyl 5-bromoisoxazole-3-carboxylate (1.5 g, 6.81 mmol) in 1,4-dioxane (30 mL) and water (10 mL) under nitrogen was added cyclohexenylboronic acid (1.02 g, 8.17 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.497 g, 0.68 mmol) and cesium carbonate (6.63 g, 20.4 mmol). The mixture was heated at 90° C. for 3 h then cooled to room temperature. The reaction mixture was diluted with water (20 mL) and extracted with ethyl acetate (20 mL2). The combined organic layers were washed with water (20 mL2) and brine (20 mL*2), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography (silica, petroleum ether/ethyl acetate=20/1) to give ethyl 5-cyclohexenylisoxazole-3-carboxylate (1.1 g, 4.97 mmol, 73%) as a yellow oil. LCMS (ESI) m/z: 222.1 [M+H]+.

Reference： [1]Current Patent Assignee: YUMANITY THERAPEUTICS INC - US2019/330198, 2019, A1 Location in patent: Paragraph 0751; 0758

83
[ 89490-05-1 ]
[ 391-53-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: tetrakis-(triphenylphosphine)-palladium; potassium carbonate / lithium hydroxide monohydrate; tetrahydrofuran / 20 h / 85 °C / Inert atmosphere 2: [4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridine-κN1,κN1′]bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-κN]phenyl-κC]iridium hexafluorophosphate; palladium (II) chloride; triphenylphosphine / 1,4-dioxane / 60 °C / Inert atmosphere; Irradiation

Reference： [1]Qu, Zhonghua; Ji, Xiaochen; Tang, Shi; Deng, Guo-Jun; Huang, Huawen [Organic Letters, 2022, vol. 24, # 39, p. 7173 - 7177]

84
[ 53848-17-2 ]
[ 89490-05-1 ]
[ 6510-65-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: potassium carbonate; bis-triphenylphosphine-palladium(II) chloride / N,N-dimethyl-formamide; water / 80 °C / Inert atmosphere 2: iron(III) chloride; 2-oxoindole / N,N-dimethyl acetamide / 100 °C

Reference： [1]Wang, Zheng-Lin; Zhang, Yun-Hao; Huang, Jun-Yu; Zhou, Jian; Yu, Ya-Qin; Feng, Dexin; Xu, Da-Zhen [Green Chemistry, 2023]

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CAS No. :	89490-05-1	MDL No. :	MFCD02179497
Formula :	C₆H₁₁BO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	XZWQKJXJNKYMAP-UHFFFAOYSA-N
M.W :	125.96	Pubchem ID :	3862902
Synonyms :

Num. heavy atoms :	9
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.67
Num. rotatable bonds :	1
Num. H-bond acceptors :	2.0
Num. H-bond donors :	2.0
Molar Refractivity :	37.5
TPSA :	40.46 Å²

GI absorption :	High
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) :	-6.42 cm/s

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	0.92
Log Po/w (WLOGP) :	0.5
Log Po/w (MLOGP) :	0.07
Log Po/w (SILICOS-IT) :	-0.63
Consensus Log Po/w :	0.17

[ CAS No. 89490-05-1 ] {[proInfo.proName]}

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[ 89490-05-1 ] Synthesis Path-Upstream 1~5

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[ 89490-05-1 ]

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Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Log S (ESOL) :	-1.13
Solubility :	9.24 mg/ml ; 0.0734 mol/l
Class :	Very soluble
Log S (Ali) :	-1.36
Solubility :	5.56 mg/ml ; 0.0441 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-0.15
Solubility :	89.8 mg/ml ; 0.713 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.83

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H332-H335	Packing Group:	N/A
GHS Pictogram:

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P378
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P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
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P337 + P313	IF eye irritation persists: Get medical advice/attention.
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[ CAS No. 89490-05-1 ] {[proInfo.proName]}

Quality Control of [ 89490-05-1 ]

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[ 89490-05-1 ] Synthesis Path-Upstream 1~5

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[ 89490-05-1 ]