118650-08-1|Methyl 2-(5-bromopyridin-3-yl)acetate| Ambeed

Structure of 118650-08-1

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Quality Control of [ 118650-08-1 ] Purity: 95% SDS Specification

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Product Details of [ 118650-08-1 ]

CAS No. :	118650-08-1
Formula :	C₈H₈BrNO₂
M.W :	230.06
SMILES Code :	COC(=O)CC1=CC(Br)=CN=C1
MDL No. :	MFCD10000065

Safety of [ 118650-08-1 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Application In Synthesis of [ 118650-08-1 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Downstream synthetic route of [ 118650-08-1 ]

[ 118650-08-1 ] Synthesis Path-Downstream 1~35

1
[ 108-86-1 ]
[ 118650-08-1 ]
[ 597584-53-7 ]

References: [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 3709 - 3727.

2
[ 39891-12-8 ]
[ 18107-18-1 ]
[ 118650-08-1 ]

Yield	Reaction Conditions	Operation in experiment
72%	In methanol; diethyl ether; toluene; at 20℃; for 0.166667h;	A 2.0 M solution of trimethylsilyldiazomethane in ether (10.3 mL, 20.5 mmol) was added dropwise to a solution of (5-bromo-pyridin-3-yl)-acetic acid (4.04 g, 18.7 mmol) in toluene (17.3 mL) and methanol (11.5 mL), and the mixture was stirred at room temperature for 10 minutes. The reaction solution was concentrated under reduced pressure. The residue was purified by silica gel chromatography (hexane:ethyl acetate = 1:3) to give the title compound (3.12 g, 72%). 1H-NMR (chloroform-d): 3.63 (2H, s), 3.73 (3H, s), 7.81 (1H, s), 8.44 (1H, s), 8.60 (1H, s).
		To a cooled (0 C) solution of (5-bromo-3-pyridinyl)acetic acid (1.00 g, 4.63 mmol) in diethyl ether (17 mL) and methanol (11 mL) was added a solution of(trimethylsilyl)diazomethane in diethyl ether (2.0 M, 4.6 ml, 9.3 mmol). The reaction was warmed to room temperature and then quenched by the dropwise addition of acetic acid. Once gas evolution ceased, the solution was concentrated under reduced pressure. The resulting material was diluted with ethyl acetate and washed with water and saturated aqueous sodium chloride solution. The organic layers were combined, dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification by flash chromatography on silica gel (20 - 80% ethyl acetate in hexanes) provided the title compound: LCMS m/z 231.66 [M + 2 + H]+; 1H NMR (500 MHz, CD3OD) delta 7.01 (s, 1 H), 6.88 (s, 1 H), 6.45 (s, 1 H), 2.21 (s, 2 H), 2.17 (s, 3 H).

References: [1]Patent: EP1894911,2008,A1 .Location in patent: Page/Page column 57.
[2]Patent: WO2012/148808,2012,A1 .Location in patent: Page/Page column 99; 100.

3
[ 67-56-1 ]
[ 39891-12-8 ]
[ 118650-08-1 ]

Yield	Reaction Conditions	Operation in experiment
88%	With thionyl chloride;Reflux;	Compound 2-(5-bromopyridin-3-yl)acetic acid (1 ,15 g, 69.8 mmol) in MeOH (180 mL) was added SOCI2 (15 mL). The resulting mixture was refluxed overnight. After the reaction is completed, the volatile was removed in vaccuo. The residue was partitioned between ethyl acetate (100 mL) and water (20 mL). The organic layer was washed with saturated NaHCO3 (30 mL x 3), brine (20 mL x 2) and dried over Na2SO4. After filtration and evaporation of the solvent, 14g of A034-2 was obtained as a yellow solid in 88% yield.
77%	With hydrogenchloride; In 1,4-dioxane; at 50℃;	Step 1 : 2-(5-bromopyridin-3-yl)acetic acid (500 mg, 2.31 mmol) was dissolved in MeOH (30 mL). HCI (4M in dioxane) (10 mL) was added and the mixture was heated overnight at 50 C. The mixture was concentrated to dryness. The oil was Ex.12a partitioned between EtOAc and sat. NaHCO3 solution. The organic layer was dried over MgSO4, filtered and the solution was concentrated to dryness. The resulting oil was purified by column chromatography on silica gel eluting with a gradient of Heptane/EtOAc from [100:0] to [50:50]. The product fractions were combined and concentrated to dryness to afford methyl 2-(5-bromopyridin-3- yl)acetate Ex.12a (412 mg, 77%) as colorless oil.
	With thionyl chloride; at 0℃; for 2h;	To a suspension of 2-(5-bromopyridin-3~yl)acetic acid (5 g, 23.14 mmol) in MeOH (100 ml) was added thionyl chloride (1.858 mL, 25.5 mmol) at O 0C, and the mixture was stirred at O 0C for 2h. The mixture was concentrated in vacuo, re-dissolved in DCM (100 mL) and MeOH (10 mL), and saturated NaHCO3 in water (5 mL) was added, followed with NaHCO3 (10 g). To the mixture was added silica gel (10 g) and the mixture was concentrated. The residue was purified by silica chromatography eiuting with 0-50% EtOAc-heptane to give methyl 2-(5-bromopyridin-3-yl)acetate. 1H NMR (400 MHz, DMSO-dbeta) delta ppm 3.64 (s, 3 H), 3.80 (s, 2 H), 8.01 (dd, J=2.0 Hz. 1 H), 8.48 (d, J=1.8 Hz, 1 H), 8.61 (d, J-2.3 Hz, 1 H).

	With thionyl chloride; at 0℃; for 2h;Inert atmosphere; Reflux;	To a solution of (5-bromo-pyridin-3-yl)-acetic acid (4.2 g, 20 mmol) in methanol (50 mL) was added thionyl chloride (4.4 mL, 60 mmol) slowly at 0C. After the addition, the reaction mixture was warmed up and heated to reflux temperature for 2 hours. After cooling back to room temperature, the reaction mixture was concentrated in vacuo and the residue was re-dissolved in EtOAc (250 mL) and washed with aq. NaHC03 solution and brine. The organic layer was dried over Na2S04, filtered and concentrated in vacuo to give a crude product (4.6 g, quant.) as light yellow solid. MS: 230.1 & 232.0 (M+H+).
	With thionyl chloride; at 0℃; for 2h;Reflux;	[A] (5-Bromo-pyridin-3-yl)-acetic acid methyl ester To a solution of (5-bromo-pyridin-3-yl)-acetic acid (4.2 g, 20 mmol) in methanol (50 mL) was added thionyl chloride (4.4 mL, 60 mmol) slowly at 0 C. After the addition, the reaction mixture was warmed up and heated to reflux temperature for 2 hours. After cooling back to room temperature, the reaction mixture was concentrated in vacuo and the residue was re-dissolved in EtOAc (250 mL) and washed with aq. NaHCO3 solution and brine. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo to give a crude product (4.6 g, quant.) as light yellow solid. MS: 230.1 & 232.0 (M+H+).

References: [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 1850 - 1864.
[2]Patent: WO2014/154726,2014,A1 .Location in patent: Page/Page column 76.
[3]Patent: WO2018/138356,2018,A1 .Location in patent: Page/Page column 35; 45.
[4]Patent: WO2010/130796,2010,A1 .Location in patent: Page/Page column 113.
[5]Patent: WO2013/79452,2013,A1 .Location in patent: Page/Page column 290.
[6]Patent: US2013/143863,2013,A1 .Location in patent: Paragraph 1161; 1162.

4
[ 2979-48-8 ]
[ 118650-08-1 ]
[ 936371-69-6 ]

References: [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 1850 - 1864.

5
[ 118650-08-1 ]
2-(5-bromopyridin-3-yl)-1-(furan-2-yl)ethanone [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 1850 - 1864.

6
[ 118650-08-1 ]
[ 597584-55-9 ]

References: [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 3709 - 3727.

7
[ 118650-08-1 ]
[ 597584-56-0 ]

References: [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 3709 - 3727.

8
[ 118650-08-1 ]
[ 597584-54-8 ]

References: [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 3709 - 3727.

9
[ 118650-08-1 ]
N-(cyanomethyl)-4-methyl-2-(5-phenylpyridin-3-yl)pentanamide trifluoroacetate [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 3709 - 3727.

10
[ 927436-07-5 ]
[ 118650-08-1 ]
{5-[4-(2'-fluoro-2-trifluoromethyl-biphenyl-4-yloxymethyl)-phenyl]-pyridin-3-yl}-acetic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium fluoride;palladium diacetate; CyJohnPhos; In 1,4-dioxane; at 130℃; for 12h;	Step 3: To a round-bottom flask containing <strong>[118650-08-1](5-bromo-pyridin-3-yl)-acetic acid methyl ester</strong> (40 mg, 0.17 mmol), 2-[4-(2'-fluoro-2-trifluoromethyl-biphenyl-4- yloxymethyl)-phenyl]-4,4,5,5-tetramethyl-[l,3,2]dioxaborolane 13 (80 mg, 0.17 mmol), palladium acetate (6 mg, 0.026 mmol), 2-(dicyclohexylphosphino)biphenyl (18 mg, 0.051 mmol) and potassium fluoride (30 mg, 0.051 mmol) is added anhydrous 1,4-dioxane (2 ml). The flask is purged with argon and sealed. The mixture is stirred at 13O0C for 12 hours and then cooled to ambient temperature before water (5 ml) is added. The mixture is extracted with EtOAc (10 ml x 2), dried over MgSO4, and concentrated. The residue is purified by silica gel column chromatography (EtOAc/Hexane, gradient) to give {5-[4-(2'-fluoro-2- trifluoromethyl-biphenyl-4-yloxymethyl)-phenyl]-pyridin-3-yl} -acetic acid methyl ester 14: LC-MS m/z: 496.0 (M+l).

References: [1]Patent: WO2007/24922,2007,A1 .Location in patent: Page/Page column 27; 28.

11
[ 186581-53-3 ]
[ 39891-12-8 ]
[ 118650-08-1 ]

Yield	Reaction Conditions	Operation in experiment
	In methanol; at 20℃; for 0.0833333h;	To a solution of (5-bromopyridin-3-yl)acetic acid in methanol (0.1 M) was added a slight excess of a solution of diazomethane in ether at room temperature. After stirring for 5 min, solvents and residual diazomethane were removed under reduced pressure to afford the title compound

References: [1]Patent: WO2008/46226,2008,A1 .Location in patent: Page/Page column 52.

12
[ 73183-34-3 ]
[ 118650-08-1 ]
methyl [5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl]acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In N,N-dimethyl-formamide; at 100℃; for 18h;	A mixture of methyl (5-bromopyridine-3-yl)acetate [from example 24, step 1], bis(pinacolato)diboron (1.25 equiv.), potassium acetate (3 equiv.), palladium (II) dichloride (dppf) (0.1 equiv.) in DMF (0.4 M) was heated, under nitrogen, at 100 0C for 18 h. The reaction mixture was then filtered over celite and washed with dichloromethane. The filtrate was concentrated under reduced pressure and the crude residue was taken in heptane. The solid was filtered off and the filtrate containing the title compound was concentrated without further purification

References: [1]Patent: WO2008/46226,2008,A1 .Location in patent: Page/Page column 59.

13
[ 1020658-44-9 ]
[ 118650-08-1 ]
[ 1020658-27-8 ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of <strong>[118650-08-1]methyl (5-bromopyridin-3-yl)acetate</strong> (1 equiv.) and 5-(4,4,5,5- tetramethyl- 1 ,3 ,2-dioxaborolan-2-yl)-2- {4-[2-(trifluoromethyl)phenoxy]piperidin- 1 -yl} pyridine (prepared as described in example 1, step 3) (1.4 equiv.) in DMF (0.045 M), 2N aqueous sodium carbonate solution (3.3 equiv.) and tetrakis(triphenylphosphine)palladium(0) (O.I equiv.) were added. The reaction mixture was then stirred overnight at 100 0C. After cooling, the mixture was diluted with water and washed with ethyl acetate. The aqueous layer was then acidified with a saturated NH4Cl aqueous solution and the product was extracted twice with ethyl acetate. The combined organic layers were dried over MgStheta4, filtered and concentrated to afford the title compound. MS: m/z 458.1 (ESI+)

References: [1]Patent: WO2008/46226,2008,A1 .Location in patent: Page/Page column 52.

14
[ 917026-59-6 ]
[ 118650-08-1 ]
[ 917026-60-9 ]

Yield	Reaction Conditions	Operation in experiment
73%	With potassium phosphate;dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; palladium diacetate; In water; toluene; at 100℃; for 2h;	(5-Bromo-pyridin-3-yl)acetic acid methyl ester (Example 24-(2); 28.6 mg, 0.124 mmol), palladium acetate (1.8 mg, 0.008 mmol), 2-dicyclohexylphosphino-2',6'-dimethoxy-1,1'-biphenyl (7.0 mg, 0.017 mmol), potassium phosphate (53 mg, 0.249 mmol) and water (0.2 mL) were added to a solution of 1-(4-{1-ethyl-1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propyl}-2-methyl-phenoxy)-3,3-dimethyl-butan-2-one (Example 143-(4); 39.7 mg, 0.083 mmol) in toluene (2 mL). After replacement with nitrogen, the mixture was stirred at 100C for two hours. The reaction mixture was then poured into a saturated aqueous sodium bicarbonate solution, followed by extraction with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (hexane:ethyl acetate = 1:1) to give the target compound as a colorless oil (30.4 mg, 73%). 1H-NMR (chloroform-d): 0.64 (6H, t, J=7.26Hz), 1.25 (9H, s), 2.10 (4H, q, J=7.25Hz), 2.25 (3H, s), 3.69 (2H, s), 3.72 (3H, s), 4.84 (2H, s), 6.52 (1H, d, J=8.57Hz), 6.90-6.94 (2H, m), 7.26 (2H, d, J=8.24Hz), 7.47 (2H, d, J=8.24Hz), 7.81 (1H, m), 8.46 (1H, d, J=1.82Hz), 8.75 (1H, d, J=1.98Hz).

References: [1]Patent: EP1894911,2008,A1 .Location in patent: Page/Page column 208.

15
[ 917022-88-9 ]
[ 118650-08-1 ]
[ 917025-49-1 ]

Yield	Reaction Conditions	Operation in experiment
72%	With potassium phosphate;tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 140℃; for 0.166667h;Irradiation;	A solution of 2-(4-{1-ethyl-1-[3-methyl-4-(4,4,4-trifluoro-3-methoxymethoxy-3-trifluoromethyl-1-butynyl)-phenyl]-propyl}-2-methyl-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (Example 25-(4); 47.7 mg, 0.1 mmol), (5-bromo-pyridin-3-yl)acetic acid methyl ester (Example 24-(2); 26.8 mg, 0.11 mmol), tetrakistriphenylphosphine palladium (12.5 mg, 0.0108 mmol) and potassium phosphate (24.7 mg, 0.11 mmol) in N,N-dimethylformamide (0.25 mL) was stirred with microwave heating at 140C for 10 minutes. The reaction mixture was filtered through cotton plug, and the mixture was purified by silica gel chromatography (40% ethyl acetate/hexane) to give the title compound (36.0 mg, 72%). 1H-NMR (chloroform-d): 0.65 (t, 6H, J=7.3Hz), 2.12 (q, 4H, J=7.4Hz), 2.23 (s, 3H), 2.42 (s, 3H), 3.48 (s, 3H), 3.68 (s, 2H), 3.73 (d, 3H, J=2.9Hz), 5.16 (s, 2H), 7.01-7.04 (m, 3H), 7.09-7.11 (m, 2H), 7.41 (d, 1H, J=8.1Hz), 7.62 (t, 1H, J=2.0Hz), 8.47 (d, 1H, J=1.8Hz), 8.51 (d, 1H, J=1.8Hz).

References: [1]Patent: EP1894911,2008,A1 .Location in patent: Page/Page column 126.

16
[ 917022-89-0 ]
[ 118650-08-1 ]
[ 917025-41-3 ]

Yield	Reaction Conditions	Operation in experiment
17%	With potassium phosphate;dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; palladium diacetate; In water; toluene; at 100℃; for 1h;	A solution of palladium acetate (1.4 mg, 0.00623 mmol), 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl (5.3 mg, 0.0124 mmol) and potassium phosphate (27.6 mg, 0.1246 mmol) in water (0.020 mL) and toluene (0.100 mL) was stirred for three minutes. Then, a solution of (5-bromo-pyridin-3-yl)acetic acid methyl ester (Example 24-(2); 15.2 mg, 0.0659 mmol) and (E)-4-(4-{1-ethyl-1-[3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2] dioxaborolan-2-yl) - phenyl]-propyl}-2-methyl-phenyl)-1,1,1-trifluoro-2-trifluoromethyl-3-buten-2-ol (Example 26-(5); 26.9 mg, 0.0471 mmol) in toluene (0.12 mL) was added, and the mixture was stirred in a nitrogen atmosphere at 100C for one hour. After filtration through cotton plug, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography (hexane/ethyl acetate = 3/2) to give the title compound (5.0 mg, 17%). 1H-NMR (chloroform-d): 0.65 (t, 6H, J=7.2Hz), 1.60 (brs, 1H), 2.12 (q, 4H, J=7.2Hz), 2.24 (s, 6H), 3.69 (s, 2H), 3.73 (s, 3H), 6.16 (d, 1H, J=15.6Hz), 6.97-7.05 (m, 5H), 7.36-7.43 (m, 2H), 7.66 (s, 1H), 8.43 (d, 1H, J=6.9Hz).

References: [1]Patent: EP1894911,2008,A1 .Location in patent: Page/Page column 119-120.

17
[ 917022-91-4 ]
[ 118650-08-1 ]
[ 917025-52-6 ]

Yield	Reaction Conditions	Operation in experiment
71%	With potassium phosphate;tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 140℃; for 0.166667h;Irradiation;	A solution of (E)-3-ethyl-1-(4-{1-ethyl-1-[3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propyl}-2-methyl-phenyl)-1-penten-3-ol (Example 28; 49.3 mg, 0.1 mmol), (5-bromo-pyridin-3-yl)acetic acid methyl ester (Example 24-(2); 34.7 mg, 0.15 mmol), tetrakistriphenylphosphine palladium (16.2 mg, 0.014 mmol) and potassium phosphate (31.9 mg, 0.15 mmol) in N,N-dimethylformamide (0.27 mL) was stirred with microwave heating at 140C for 10 minutes. The reaction mixture was filtered through cotton plug, and the mixture was purified by silica gel chromatography (40% ethyl acetate/hexane) to give the title compound (37.1 mg, 71%). 1H-NMR (chloroform-d): 0.66 (t, 6H, J=7.3Hz), 0.92 (t, 6H, J=7.5Hz), 1.65 (q, 4H, J=7.5Hz), 2.12 (q, 4H, J=7.3Hz), 2.24 (s, 3H), 2.34 (s, 3H), 3.68 (s, 2H), 3.72 (s, 3H), 6.03 (d, 1H, J=15.7Hz), 6.76 (d, 1H, J=15.7Hz), 6.97-6.99 (m, 2H), 7.05-7.10 (m, 3H), 7.33 (d, 1H, J=8.1Hz), 7.62 (t, 1H, J=2.2Hz), 8.46 (d, 1H, J=2.2Hz), 8.52 (d, 1H, J=2.2Hz).

References: [1]Patent: EP1894911,2008,A1 .Location in patent: Page/Page column 128-129.

18
[ 917022-92-5 ]
[ 118650-08-1 ]
[ 917025-88-8 ]

Yield	Reaction Conditions	Operation in experiment
92%	With potassium phosphate;tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 85 - 94℃; for 3h;	Degassed N,N-dimethylformamide (0.37 mL) was added to 3-ethyl-1-(4-{1-ethyl-1-[3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propyl}-2-methyl-phenyl)-pentan-3-ol (Example 29; 30.6 mg, 0.0621 mmol), (5-bromo-pyridin-3-yl)acetic acid methyl ester (Example 24-(2); 21.1 mg, 0.0917 mmol), tetrakis(triphenylphosphine)palladium (0) (9.0 mg, 0.0078 mmol) and potassium phosphate (29.4 mg, 0.138 mmol). After replacement with nitrogen, the mixture was heated while stirring at an external temperature of 85 to 94C for three hours. Water was added to the reaction mixture, followed by extraction with diethyl ether. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel chromatography (hexane/ethyl acetate = 1/1) to give the title compound (29.5 mg, 92%). 1H-NMR (chloroform-d): 0.66 (t, 6H, J=7.4Hz), 0.93 (t, 6H, J=7.5Hz), 1.57 (q, 4H, J=7.5Hz), 1.68 (m, 2H), 2.12 (q, 4H, J=7.4Hz), 2.25 (s, 3H), 2.30 (s, 3H), 2.59 (m, 2H), 3.68 (s, 2H), 3.73 (s, 3H), 6. 93-7. 11 (m, 6H), 7.62 (dd, 1H, J=2.1, 1.8Hz), 8.46 (d, 1H, J=2.1Hz), 8.52 (d, 1H, J=1.8Hz).

References: [1]Patent: EP1894911,2008,A1 .Location in patent: Page/Page column 159.

19
[ 917022-93-6 ]
[ 118650-08-1 ]
[ 917025-80-0 ]

Yield	Reaction Conditions	Operation in experiment
83%	With potassium phosphate;tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 140℃; for 0.166667h;Irradiation;	A solution of 1-(4-{1-ethyl-1-[3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propyl}-2-methyl-phenoxy)-3,3-dimethyl-butan-2-one (Example 30-(2); 0.06 g, 0.12 mmol), (5-bromo-pyridin-3-yl)acetic acid methyl ester (Example 24-(2); 42.0 mg, 0.18 mmol), tetrakistriphenylphosphine palladium (19.6 mg, 0.017 mmol) and potassium phosphate (38.7 mg, 0.18 mmol) in N,N-dimethylformamide (0.3 mL) was stirred with microwave heating at 140C for 10 minutes. The reaction mixture was filtered through cotton plug, and the mixture was purified by silica gel chromatography (40% ethyl acetate/hexane) to give the title compound (52.8 mg, 83%). 1H-NMR (chloroform-d): 0.64 (t, 6H, J=7.1Hz), 1.25 (s, 9H), 2.08 (q, 4H, J=7.2Hz), 2.23 (s, 3H), 2.26 (s, 3H), 3.68 (s, 2H), 3.72 (s, 3H), 4.85 (s, 2H), 6.52 (d, 1H, J=8.1Hz), 6.92-6.96 (m, 2H), 7.04-7.10 (m, 3H), 7.62 (s, 1H), 8.47 (s, 1H), 8.52 (s, 1H).

References: [1]Patent: EP1894911,2008,A1 .Location in patent: Page/Page column 152.

20
[ 917022-94-7 ]
[ 118650-08-1 ]
[ 917025-77-5 ]

Yield	Reaction Conditions	Operation in experiment
62%	With potassium phosphate;tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 140℃; for 0.166667h;Irradiation;	A solution of 1-{4-{1-ethyl-1-[3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propyl}-2-methyl-phenoxy)-3,3-dimethyl-butan-2-ol (Example 31; 0.06 g, 0.12 mmol), (5-bromo-pyridin-3-yl)acetic acid methyl ester (Example 24-(2); 41.8 mg, 0.18 mmol), tetrakistriphenylphosphine palladium (19.5 mg, 0.0169 mmol) and potassium phosphate (38.6 mg, 0.18 mmol) in N,N-dimethylformamide (0.3 mL) was stirred with microwave heating at 140C for 10 minutes. The reaction mixture was filtered through cotton plug, and the residue was purified by silica gel chromatography (50% ethyl acetate/hexane) to give the title compound (39.5 mg, 62%). 1H-NMR (chloroform-d): 0.64 (t, 6H, J=7.0Hz), 1.01 (s, 9H), 2.09 (q, 4H, J=7.0Hz), 2.20 (s, 3H), 2.24 (s, 3H), 3.68 (s, 2H), 3.70 (d, 1H, J=8.4Hz), 3.72 (s, 3H), 3.87 (t, 1H, J=8.4Hz), 4.10 (d, 1H, J=8.4Hz), 6.73 (d, 1H, J=8.4Hz), 6.95-7.00 (m, 2H), 7.04-7.10 (m, 3H) 7.63 (s, 1H), 8.46 (s, 1H), 8.52 (s, 1H).

References: [1]Patent: EP1894911,2008,A1 .Location in patent: Page/Page column 149.

21
[ 917024-88-5 ]
[ 118650-08-1 ]
[ 917025-65-1 ]

Yield	Reaction Conditions	Operation in experiment
67%	With potassium phosphate;tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 140℃; for 0.166667h;Irradiation;	A solution of 2-(4-{1-ethyl-1-[3-methyl-4-(1-trimethylsilanyloxy-cyclopentylethynyl)-phenyl]-propyl}-2-methyl-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (Example 32-(4); 54.1 mg, 0.0968 mmol), (5-bromo-pyridin-3-yl)acetic acid methyl ester (Example 24-(2); 33.4 mg, 0.14 mmol), tetrakistriphenylphosphine palladium (15.6 mg, 0.0135 mmol) and potassium phosphate (30.8 mg, 0.14 mmol) in N,N-dimethylformamide (0.27 mL) was stirred with microwave heating at 140C for 10 minutes. The reaction mixture was filtered through cotton plug, and the mixture was purified by silica gel chromatography (45% ethyl acetate/hexane) to give the title compound (38.2 mg, 67%). 1H-NMR (chloroform-d): 0.22 (s, 9H), 0.64 (t, 6H, J=7.3Hz), 1.72-1.86 (m, 4H), 1.95-2.06 (m, 4H), 2.11 (q, 4H, J=7.3Hz), 2.23 (s, 3H), 2.39 (s, 3H), 3.68 (s, 2H), 3.72 (s, 3H), 6.96-7.10 (m, 5H), 7.30 (d, 1H, J=8.1Hz), 7.62 (s, 1H), 8.47 (s, 1H), 8.52 (s, 1H).

References: [1]Patent: EP1894911,2008,A1 .Location in patent: Page/Page column 140.

22
[ 917022-96-9 ]
[ 118650-08-1 ]
[ 917025-56-0 ]

Yield	Reaction Conditions	Operation in experiment
78%	With potassium phosphate;tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 140℃; for 0.166667h;Irradiation;	A solution of 1-[(E)-2-(4-{1-ethyl-1-[3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propyl}-2-methyl-phenyl)-vinyl]-cyclopentanol (Example 33-(3); 0.05 g, 0.10 mmol), (5-bromo-pyridin-3-yl)acetic acid methyl ester (Example 24-(2); 35.3 mg, 0.15 mmol), tetrakistriphenylphosphine palladium (16.5 mg, 0.0143 mmol) and potassium phosphate (32.6 mg, 0.15 mmol) in N,N-dimethylformamide (0.3 mL) was stirred with microwave heating at 140C for 10 minutes. The reaction mixture was filtered through cotton plug, and the mixture was purified by silica gel chromatography (40% ethyl acetate/hexane) to give the title compound (41.0 mg, 78%). 1H-NMR (chloroform-d): 0.65 (t, 6H, J=7.0Hz), 1.72-1.86 (m, 6H), 1.91-1.99 (m, 2H), 2.12 (q, 4H, J=7.1Hz), 2.23 (s, 3H), 2.34 (s, 3H), 3.68 (s, 2H), 3.72 (s, 3H), 6.28 (d, 1H, J=16.8Hz), 6.85 (d, 1H, J=16.1Hz), 6.98-7.02 (m, 2H), 7.05-7.10 (m, 3H), 7.36 (d, 1H, J=8.4Hz), 7.62 (s, 1H), 8.46 (s, 1H), 8.52 (s, 1H).

References: [1]Patent: EP1894911,2008,A1 .Location in patent: Page/Page column 132.

23
[ 917024-90-9 ]
[ 118650-08-1 ]
[ 917025-91-3 ]

Yield	Reaction Conditions	Operation in experiment
72%	With potassium phosphate;tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 95℃; for 3h;	2-[4-(1-ethyl-1-{3-methyl-4-[2-(1-trimethylsilanyloxy-cyclopentyl)-ethyl]-phenyl}-propyl)-2-methyl-phenyl]-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (Example 34-(1); 35.7 mg, 0.063 mmol), (5-bromo-pyridin-3-yl)acetic acid methyl ester (Example 24-(2); 19.0 mg, 0.082 mmol), tetrakis(triphenylphosphine)palladium (0) (9.2 mg, 0.080 mmol), potassium phosphate (26.3 mg, 0.124 mmol) and N,N-dimethylformamide (0.38 mL) were placed in a reaction vessel and stirred in a nitrogen atmosphere at 95C for three hours. A saturated aqueous ammonium chloride solution (0.1 mL) and water (0.1 mL) were added to the reaction mixture, followed by extraction with diethyl ether. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (hexane only to hexane/ethyl acetate = 3/1) to give the title compound (26.8 mg, 72%). 1H-NMR (chloroform-d): 0.15 (s, 9H), 0.65 (t, 6H, J=7.3Hz), 1.58 (m, 4H), 1.75-1.81 (m, 6H), 2.11 (q, 4H, J=7.3Hz), 2.24 (s, 3H), 2.28 (s, 3H), 2.64-2.70 (m, 2H), 3.68 (s, 2H), 3.72 (s, 3H), 6.93-7.10 (m, 6H), 7.62 (dd, 1H, J=2.0, 2.1Hz), 8.46 (d, 1H, J=2.1Hz), 8.52 (d, 1H, J=2.0Hz).

References: [1]Patent: EP1894911,2008,A1 .Location in patent: Page/Page column 162-163.

24
[ 917022-98-1 ]
[ 118650-08-1 ]
[ 917025-73-1 ]

Yield	Reaction Conditions	Operation in experiment
62%	With potassium phosphate;tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 140℃; for 0.166667h;Irradiation;	A solution of 2-(4-{1-ethyl-1-[3-methyl-4-(1-trimethylsilanyloxy-cyclohexylethynyl)-phenyl]-propyl}-2-methyl-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (Example 35-(4); 57.6 mg, 0.10 mmol), (5-bromo-pyridin-3-yl)acetic acid methyl ester (Example 24-(2); 30.1 mg, 0.13 mmol), tetrakistriphenylphosphine palladium (14.1 mg, 0.0122 mmol) and potassium phosphate (27.8 mg, 0.13 mmol) in N,N-dimethylformamide (0.27 mL) was stirred with microwave heating at 140C for 10 minutes. The reaction mixture was filtered through cotton plug, and the mixture was purified by silica gel chromatography (45% ethyl acetate/hexane) to give the title compound (37.3 mg, 62%). 1H-NMR (chloroform-d): 0.23 (s, 9H), 0.65 (t, 6H, J=7.1Hz), 1.54-1.69 (m, 8H), 1.93-2.02 (m, 2H), 2.11 (q, 4H, J=7.1Hz), 2.24 (s, 3H), 2.41 (s, 3H), 3.68 (s, 2H), 3.72 (s, 3H), 6.96-7.11 (m, 5H), 7.30 (d, 1H, J=8.1Hz), 7.62 (d, 1H, J=1.8Hz), 8.47 (s, 1H), 8.52 (2, 1H).

References: [1]Patent: EP1894911,2008,A1 .Location in patent: Page/Page column 146.

25
[ 917022-99-2 ]
[ 118650-08-1 ]
[ 917025-62-8 ]

Yield	Reaction Conditions	Operation in experiment
91%	With potassium phosphate;tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 140℃; for 0.166667h;Irradiation;	A solution of 1-[(E)-2-(4-{1-ethyl-1-[3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propyl}-2-methyl-phenyl)-vinyl]-cyclohexanol (Example 36-(3); 0.05 g, 0.0994 mmol), (5-bromo-pyridin-3-yl)acetic acid methyl ester (Example 24-(2); 34.3 mg, 0.14 mmol), tetrakistriphenylphosphine palladium (16.0 mg, 0.0139 mmol) and potassium phosphate (31.7 mg, 0.14 mmol) in N,N-dimethylformamide (0.27 mL) was stirred with microwave heating at 140C for 10 minutes. The reaction mixture was filtered through cotton plug, and the mixture was purified by silica gel chromatography (40% ethyl acetate/hexane) to give the title compound (47.8 mg, 91%). 1H-NMR (chloroform-d): 0.65 (t, 6H, J=7.0Hz), 1.30-1.36 (m, 2H), 1.54-1.64 (m, 4H), 1.65-1.75 (m, 4H), 2.12 (q, 4H, J=7.3Hz), 2.23 (s, 3H), 2.33 (s, 3H), 3.68 (s, 2H), 3.72 (s, 3H), 6.22 (d, 1H, J=16.1Hz), 6.83 (d, 1H, J=16.1Hz), 6.98-7.01 (m, 2H), 7.05-7.09 (m, 3H), 7.36 (d, 1H, J=8.1Hz), 7.62 (s, 1H), 8.47 (s, 1H), 8.52 (s, 1H).

References: [1]Patent: EP1894911,2008,A1 .Location in patent: Page/Page column 137-138.

26
[ 917023-02-0 ]
[ 118650-08-1 ]
[ 917025-99-1 ]

Yield	Reaction Conditions	Operation in experiment
24%	With potassium phosphate;dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; palladium diacetate; In water; toluene; at 100℃; for 2.5h;	(5-Bromo-pyridin-3-yl)acetic acid methyl ester (Example 24-(2); 30 mg, 0.149 mmol), palladium acetate (2.2 mg, 0.010 mmol), 2-dicyclohexylphosphino-2',6'-dimethoxy-1,1'-biphenyl (8.2 mg, 0.020 mmol), potassium phosphate (63 mg, 0.297 mmol) and water (0.2 mL) were added to a solution of (E)-1-(4-{1-[3,5-dimethyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1-ethyl-propyl}-2-methyl-phenyl)-3-ethyl-1-penten-3-ol (Example 38-(6); 50 mg, 0.099 mmol) in toluene (2 mL). After replacement with nitrogen, the mixture was stirred at 100C for 2.5 hours. The reaction mixture was then poured into a saturated aqueous sodium bicarbonate solution, followed by extraction with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (hexane:ethyl acetate = 1:1) to give the target compound as a colorless oil (12.5 mg, 24%). 1H-NMR (chloroform-d): 0.66 (6H, t, J=7.26Hz), 0.93 (6H, t, J=7.25Hz), 1.65 (4H, q, J=7.34Hz), 1.98 (6H, s), 2.11 (4H, q, J=7.42Hz), 2.35 (3H, s), 3.68 (2H, s), 3.72 (3H, s), 6.03 (1H, d, J=15.99Hz), 6.76 (1H, d, J=16.00Hz), 6.91 (2H, s), 6.97-7.01 (2H, m), 7.33 (1H, d, J=7.91Hz), 7.49 (1H, s), 8.35 (1H, d, J=2.14Hz), 8.47 (1H, d, J=2.14Hz).

References: [1]Patent: EP1894911,2008,A1 .Location in patent: Page/Page column 169-170.

27
[ 917023-03-1 ]
[ 118650-08-1 ]
[ 917026-02-9 ]

Yield	Reaction Conditions	Operation in experiment
88%	With potassium phosphate;tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 140℃; for 0.166667h;Irradiation;	A solution of (E)-3-ethyl-1-(4-{1-ethyl-1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propyl}-2-methyl-phenyl)-1-penten-3-ol (Example 39-(5); 50.0 mg, 0.10 mmol), (5-bromo-pyridin-3-yl)acetic acid methyl ester (Example 24-(2); 36.2 mg, 0.15 mmol), tetrakistriphenylphosphine palladium (16.8 mg, 0.0146 mmol) and potassium phosphate (33.4 mg, 0.15 mmol) in N,N-dimethylformamide (0.30 mL) was stirred with microwave heating at 140C for 10 minutes. The reaction mixture was filtered through cotton plug, and the residue was purified by silica gel chromatography (40 to 50% ethyl acetate/hexane) to give the title compound (46.5 mg, 88%). 1H-NMR (chloroform-d): 0.66 (t, 6H, J=7.1Hz), 0.92 (t, 6H, J=7.5Hz), 1.64 (q, 4H, J=7.6Hz), 2.13 (q, 4H, J=7.3Hz), 2.32 (s, 3H), 3.69 (s, 2H), 3.72 (s, 3H), 6.02 (d, 1H, J=16.1Hz), 6.75 (d, 1H, J=15.7Hz), 6.98 (brs, 2H), 7.26-7.34 (m, 3H), 7.47 (d, 2H, J=8.4Hz), 7.81 (s, 1H), 8.46 (d, 1H, J=1.8Hz), 8.76 (d, 1H, J=1.8Hz).

References: [1]Patent: EP1894911,2008,A1 .Location in patent: Page/Page column 172-173.

28
[ 917025-83-3 ]
[ 118650-08-1 ]
[ 917025-84-4 ]

Yield	Reaction Conditions	Operation in experiment
80%	With potassium phosphate;tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 85 - 95℃; for 3h;	Degassed N,N-dimethylformamide (0.37 mL) was added to 2-(4-{1-ethyl-1-[3-methyl-4-(4,4,4-trifluoro-3-methoxymethoxy-3-trifluoromethyl-butyl)-phenyl]-propyl}-2-methyl-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (Example 108-(1); 38.4 mg, 0.0623 mmol), (5-bromo-pyridin-3-yl)acetic acid methyl ester (Example 24-(2); 19.9 mg, 0.0865 mmol), tetrakis(triphenylphosphine)palladium (0) (9.0 mg, 0.0078 mmol) and potassium phosphate (28.2 mg, 0.133 mmol). After replacement with nitrogen, the mixture was heated while stirring at an external temperature of 85 to 95C for three hours. Water was added to the reaction mixture, followed by extraction with diethyl ether. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel chromatography (hexane/ethyl acetate = 2/1) to give the title compound (32 mg, 80%). 1H-NMR (chloroform-d): 0.66 (t, 6H, J=7.4Hz), 2.12 (q, 4H, J=7.4Hz), 2.25 (m, 2H), 2.25 (s, 3H), 2.29 (s, 3H), 2.82 (m, 2H), 3.51 (s, 3H), 3.68 (s, 2H), 3.73 (s, 3H), 5.00 (s, 2H), 6.95-7.11 (m, 6H), 7.63 (dd, 1H, J=2.1, 1.8Hz), 8.47 (d, 1H, J=2.1Hz), 8.52 (d, 1H, J=1.8Hz).

References: [1]Patent: EP1894911,2008,A1 .Location in patent: Page/Page column 156.

29
[ 917026-30-3 ]
[ 118650-08-1 ]
[ 917026-37-0 ]

Yield	Reaction Conditions	Operation in experiment
91%	With potassium phosphate;dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; palladium diacetate; In water; toluene; at 100℃; for 3.5h;	(5-Bromo-pyridin-3-yl)acetic acid methyl ester (Example 24-(2); 40 mg, 0.173 mmol), palladium acetate (2.7 mg, 0.012 mmol), 2-dicyclohexylphosphino-2',6'-dimethoxy-1,1'-biphenyl (9.9 mg, 0.024 mmol), potassium phosphate (74 mg, 0.348 mmol) and water (0.2 mL) were added to a solution of 4-(4-{1-ethyl-1-[3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propyl}-2-methyl-phenylethynyl)-4-trimethylsilanyloxy-tetrahydro-pyran (Example 130-(4); 66.4 mg, 0.116 mmol) in toluene (3 mL). After replacement with nitrogen, the mixture was stirred at 100C for 3.5 hours. The reaction mixture was then poured into a saturated aqueous sodium bicarbonate solution, followed by extraction with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (hexane:ethyl acetate = 1:1) to give the target compound as a colorless oil (62.9 mg, 91%). 1H-NMR (chloroform-d): 0.25 (9H, s), 0.65 (6H, t, J=7.25Hz), 1.88-2.01 (4H, m), 2.12 (4H, q, J=7.42Hz), 2.24 (3H, s), 2.42 (3H, s), 3.63 (2H, s), 3.70-3.78 (2H, m), 3.73 (3H, s), 3.85-3.92 (2H, m), 6.98-7.11 (5H, m), 7.31 (1H, d, J=8.08Hz), 7.62 (1H, s), 8.47 (1H, d, J=2.14Hz), 8.51 (1H, d, J=1.97Hz).

References: [1]Patent: EP1894911,2008,A1 .Location in patent: Page/Page column 190-191.

30
[ 917026-35-8 ]
[ 118650-08-1 ]
[ 917026-39-2 ]

Yield	Reaction Conditions	Operation in experiment
48%	With potassium phosphate;dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; palladium diacetate; In water; toluene; at 100℃; for 3h;	(5-Bromo-pyridin-3-yl)acetic acid methyl ester (Example 24-(2); 39 mg, 0.171 mmol), palladium acetate (2.5 mg, 0.011 mmol), 2-dicyclohexylphosphino-2',6'-dimethoxy-1,1'-biphenyl (9.0 mg, 0.022 mmol), potassium phosphate (73 mg, 0.342 mmol) and water (0.2 mL) were added to a solution of 4-[(E)-2-(4-{1-ethyl-1-[3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propyl}-2-methyl-phenyl)-vinyl]-tetrahydro-pyran-4-ol (Example 131-(3); 57.4 mg, 0.114 mmol) in toluene (2 mL). After replacement with nitrogen, the mixture was stirred at 100C for three hours. The reaction mixture was then poured into a saturated aqueous sodium bicarbonate solution, followed by extraction with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (hexane:ethyl acetate = 1:1) to give the target compound as a colorless oil (29.1 mg, 48%). 1H-NMR (chloroform-d): 0.66 (6H, t, J=7.26Hz), 1.63 (2H, m), 1.85-1.97 (2H, m), 2.10 (4H, q, J=7.25Hz), 2.23 (3H, s), 2.33 (3H, s), 3.68 (2H, s), 3.72 (3H, s), 3.80-3.87 (4H, m), 6.20 (1H, d, J=15.99Hz), 6.85 (1H, d, J=16.16Hz), 6.96-7.08 (5H, m), 7.35 (1H, d, J=8.57Hz), 7.62 (1H, m), 8.46 (1H, d, J=2.14Hz), 8.51 (1H, d, J=1.98Hz).

References: [1]Patent: EP1894911,2008,A1 .Location in patent: Page/Page column 191-192.

31
[ 917026-46-1 ]
[ 118650-08-1 ]
[ 917026-49-4 ]

Yield	Reaction Conditions	Operation in experiment
79%	With potassium phosphate;dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; palladium diacetate; In water; toluene; at 110℃; for 2h;	(5-Bromo-pyridin-3-yl)acetic acid methyl ester (Example 24-(2); 58 mg, 0.25 mmol), palladium acetate (3.8 mg, 0.017 mmol), 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl (14 mg, 0.034 mmol), potassium phosphate (108 mg, 0.51 mmol) and water (0.4 mL) were added to a solution of 2-(4-{1-ethyl-1-[3-methyl-4-(4-trimethylsilanyloxy-tetrahydro-thiopyran-4-ylethynyl)-phenyl]-propyl}-2-methyl-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (Example 136-(4); 100 mg, 0.17 mmol) in toluene (4 mL). The mixture was stirred in a nitrogen stream at 110C for two hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (hexane:ethyl acetate = 1:3) to give the title compound (82 mg, 79%). 1H-NMR (chloroform-d): 0.23 (s, 9H), 0.65 (t, 6H, J=7.3Hz), 1.96-2.06 (m, 2H), 2.12 (q, 4H, J=7.3Hz) 2.16-2.24 (m, 2H), 2.24 (s, 3H), 2.41 (s, 3H), 2.7-2.8 (m, 2H), 2.8-2.9 (m, 2H), 3.67 (s, 2H), 3.72 (s, 3H), 6.96-7.12 (m, 5H), 7.30 (d, 1H, J=8.0Hz), 7.60-7.64 (m, 1H), 8.47 (d, 1H, J=1.8Hz), 8.52 (d, 1H, J=1.8Hz).

References: [1]Patent: EP1894911,2008,A1 .Location in patent: Page/Page column 199.

32
[ 917026-53-0 ]
[ 118650-08-1 ]
[ 917026-55-2 ]

Yield	Reaction Conditions	Operation in experiment
38%	With potassium phosphate;dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; palladium diacetate; In water; toluene; at 110℃; for 2h;	(5-Bromo-pyridin-3-yl)acetic acid methyl ester (Example 24-(2); 35 mg, 0.14 mmol), palladium acetate (2.2 mg, 0.01 mmol), 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl (7.9 mg, 0.019 mmol), potassium phosphate (61 mg, 0.29 mmol) and water (0.2 mL)were added to a solution of 4-[(E)-2-(4-{1-ethyl-1-[3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propyl}-2-methyl-phenyl)-vinyl]-tetrahydro-thiopyran-4-ol (Example 138-(3); 50 mg, 0.096 mmol) in toluene (2 mL). The mixture was stirred in a nitrogen stream at 110C for two hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (hexane:ethyl acetate = 1:2) to give the title compound (20 mg, 38%). 1H-NMR (chloroform-d): 0.65 (t, 6H, J=7.0Hz), 1.9-2.0 (m, 4H), 2.12 (q, 4H, J=7.0Hz) 2.24 (s, 3H), 2.33 (s, 3H), 2.46-2.54 (m, 2H), 3.0-3.12 (m, 2H), 3.68 (s, 2H), 3.73 (s, 3H), 6.18 (d, 1H, J=15.8Hz), 6.83 (d, 1H, J=15.8Hz), 6.98-7.12 (m, 5H), 7.34 (d, 1H, J=8.8Hz), 7.62 (brs, 1H), 8.47 (brs, 1H), 8.52 (brs, 1H).

References: [1]Patent: EP1894911,2008,A1 .Location in patent: Page/Page column 203.

33
[ 917024-80-7 ]
[ 118650-08-1 ]
[ 917025-23-1 ]

Yield	Reaction Conditions	Operation in experiment
76%	With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In water; N,N-dimethyl-formamide; at 76 - 84℃; for 5.5h;	A solution of t-butyl-(1-{2-[4-(1-ethyl-1-{4-[4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl]-3-methyl-phenyl}-propyl)2-methyl-phenyl]-ethyl}-2,2-dimethyl-propoxy)dimethylsilane (Example 24-(1); 22.0 mg, 0.036 mmol) in N,N-dimethylformamide (0.3 mL) was added to 5-bromopyridine-3-acetic acid methyl ester (Example 24-(2); 19.2 mg, 0.083 mmol) and a [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium (II), dichloromethane complex (1:1) (3.2 mg, 0.0039 mmol). After replacement with nitrogen, the mixture was heated while stirring at an external temperature of 76 to 84C for five hours and 30 minutes. Water was added to the reaction mixture, followed by extraction with ether. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel chromatography (hexane/ethyl acetate = 4/1) to give the title compound (17.2 mg, 76%). 1H-NMR (chloroform-d): 0.08 (s, 3H), 0.12 (s, 3H), 0.66 (t, 6H), 0.89 (s, 9H), 0.94 (s, 9H), 1.57 (m, 1H), 1.79 (m, 1H), 2.12 (q, 4H), 2.15 (s, 3H), 2.25 (s, 3H), 2.43 (m, 1H), 2.78 (m, 1H), 3.35 (dd, 1H), 3.68 (s, 2H), 3.73 (s, 2H), 6.93-7.11 (m, 6H), 7.62 (t, 1H), 8.46 (d, 1H), 8.52 (d, 1H).

References: [1]Patent: EP1894911,2008,A1 .Location in patent: Page/Page column 57-58.

34
[ 917024-83-0 ]
[ 118650-08-1 ]
[ 917024-84-1 ]

Yield	Reaction Conditions	Operation in experiment
83%	With potassium phosphate;tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 81 - 92℃; for 3h;	Degassed N,N-dimethylformamide (0.12 mL) was added to t-butyl-(1-{2-[4-(1-ethyl-1-{4-[4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl]-3-methyl-phenyl}-propyl)-2-methyl-phenyl]-ethyl}-2,2-dimethyl-propoxy)dimethylsilane (Example 23-(1); 11.0 mg, 0.0181 mmol), (5-bromo-pyridin-3-yl)acetic acid methyl ester (Example 24-(2); 6.3 mg, 0.027 mmol), tetrakis(triphenylphosphine)palladium (0) (2.6 mg, 0.0022 mmol) and potassium phosphate (9.0 mg, 0.042 mmol). After replacement with nitrogen, the mixture was heated while stirring at an external temperature of 81 to 92C for three hours. Water was added to the reaction mixture, followed by extraction with diethyl ether. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel chromatography (hexane/dichloromethane = 3/1) to give the title compound (9.5 mg, 83%). 1H-NMR (chloroform-d): 0.08 (s, 3H), 0.12 (s, 3H), 0.66 (t, 6H, J=7.4Hz), 0.89 (s, 9H), 0.94 (s, 9H), 1.57 (m, 1H), 1.79 (m, 1H), 2.12 (q, 4H, J=7.4Hz), 2.15 (s, 3H), 2.25 (s, 3H), 2.43 (m, 1H), 2.78 (m, 1H), 3.35 (dd, 1H, J=7.0, 3.0Hz), 3.68 (s, 2H), 3.73 (s, 3H), 6.93-7.11 (m, 6H), 7.62 (t, 1H, J=2.0Hz), 8.46 (d, 1H, J=2.0Hz), 8.52 (d, 1H, J=2.0Hz).

References: [1]Patent: EP1894911,2008,A1 .Location in patent: Page/Page column 102-103.

35
[ 1219936-10-3 ]
[ 118650-08-1 ]
[ 1219936-11-4 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 80℃; for 12h;Inert atmosphere;	Step 4: Ethyl-[2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-5-trifluoromethyl-benzyl]-carbamic acid tert-butyl ester (1.0 g, 2.33 mmol), <strong>[118650-08-1](5-bromo-pyridin-3-yl)-acetic acid methyl ester</strong> (0.535 g, 2.33 mmol), potassium carbonate (0.807 g, 5.8 mmol), and tetrakis(triphenylphosphine)palladium(0) (0.100 g, 0.09 mmol) were combined in DME (8 mL) and H2O (4 mL). The solution was purged with N2, and then the reaction was stirred at 80 C. for 12 hours. The mixture was partitioned between EtOAc and H2O, and the aqueous layer was extracted with EtOAc. The combined organic layers were dried over MgSO4, filtered, and concentrated, and the residue was purified by silica gel chromatography to give (5-{2-[(N-tert-butoxycarbonyl-N-ethyl-amino)-methyl]-4-trifluoromethyl-phenyl}-pyridin-3-yl)-acetic acid methyl ester.

References: [1]Patent: US2010/81673,2010,A1 .Location in patent: Page/Page column 13.

Historical Records

Technical Information

• Acyl Group Substitution • Alkyl Halide Occurrence • Bouveault-Blanc Reduction • Catalytic Hydrogenation • Complex Metal Hydride Reductions • Ester Cleavage • General Reactivity • Grignard Reaction • Hiyama Cross-Coupling Reaction • Kinetics of Alkyl Halides • Kumada Cross-Coupling Reaction • Preparation of Amines • Reactions of Alkyl Halides with Reducing Metals • Reactions of Amines • Reactions of Dihalides • Reactions with Organometallic Reagents • Specialized Acylation Reagents-Carbodiimides and Related Reagents • Stille Coupling • Substitution and Elimination Reactions of Alkyl Halides • Suzuki Coupling

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CAS No.: 118650-08-1

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CAS No.: 118650-08-1

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[ 118650-08-1 ] Synthesis Path-Downstream 1~35

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