Name: 89878-14-8|3-(Diethylboryl)pyridine|97%
Brand: Ambeed
SKU: A163979
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1
[ 109-09-1 ]
[ 89878-14-8 ]
[ 581-50-0 ]

Reference： [1]Synthesis,1984,p. 936 - 938

2
[ 109-04-6 ]
[ 89878-14-8 ]
[ 581-50-0 ]

Reference： [1]Synthesis,1984,p. 936 - 938

3
[ 625-92-3 ]
[ 89878-14-8 ]
[ 15862-22-3 ]

Yield	Reaction Conditions	Operation in experiment
33%	With potassium hydroxide; tetrabutylammomium bromide;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; ethyl acetate;	3-Bromo-5-(3-pyridyl)pyridine STR35 Tetrakis(triphenylphosphine)palladium (915 mg; 0.75 mM) was added to a solution of 3,5-dibromopyridine (4.74 g, 20 mM) in 75 mL of tetrahydrofuran. After stirring for 5 minutes tetra-n-butylammonium bromide (483 mg; 1.5 mM), finely powdered potassium hydroxide (2.52 g; 45 mM) and 3-pyridyldiethylborane (2.2 g; 15 mM) were added and the resulting reaction mixture was heated to reflux for 2 hours. The reaction mixture was cooled, diluted with 100 mL of ethyl acetate and washed with 10*25 mL of saturated sodium chloride solution and dried over anhydrous magnesium sulfate. Solvent removal gave the crude product which was chromatographed on silica gel using ethyl acetate to give the desired product as a solid, boiling at 135-6 C./~1 mm in 33% yield.

Reference： [1]Chemical and Pharmaceutical Bulletin,1985,vol. 33,p. 4755 - 4763
[2]Patent: US5409920,1995,A

4
[ 626-05-1 ]
[ 89878-14-8 ]
[ 106047-28-3 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium hydroxide; tetrabutylammomium bromide;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; for 3h;Heating / reflux;	Step 1 2-bromo-6-(3-pyridyl)pyridine This compound was prepared by version of the method described in the document (Chem. Pharm. Bull., 1985, 33(11), 4755-4763.). To 40 ml of tetrahydrofuran, 1.76 g of diethyl(3-pyridyl)borane, 5.92 g of 2,6-dibromopyridine, 1.99 g of tetra-n-butylammonium bromide, 692 mg of tetrakis(triphenylphosphine)palladium (0) and 1.87 g of ground potassium hydroxide were added in turn and the mixture was heated at reflux for three hours under an argon atmosphere. After air cooling, the reaction solution was diluted with ethyl acetate and insolubles were removed by filtration. The solvent in the filtrate was distilled off under reduced pressure and ethyl acetate and saturated saline were added to the residue to separate the aqueous layer. The organic layer was dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography to obtain 1.26 g of the objective compound as a pale yellow crystal. 1H-NMR(CDCl3)delta: 7.34-7.51(2H, m), 7.62-7.75(2H, m), 8.34(1H, dt), 8.67(1H, dd), 9.17(1H, d)

Reference： [1]Chemical and Pharmaceutical Bulletin,1985,vol. 33,p. 4755 - 4763
[2]Patent: EP1533304,2005,A1 .Location in patent: Page/Page column 22

5
[ 104-92-7 ]
[ 89878-14-8 ]
[ 5958-02-1 ]

Reference： [1]Heterocycles,1984,vol. 22,p. 265 - 268

6
[ 557-93-7 ]
[ 89878-14-8 ]
[ 15825-89-5 ]

Reference： [1]Heterocycles,1984,vol. 22,p. 2475 - 2478

7
[ 577-19-5 ]
[ 89878-14-8 ]
[ 4253-80-9 ]

Yield	Reaction Conditions	Operation in experiment
28%	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In tetrahydrofuran; for 4h;Heating / reflux;	To a mixture consisting of 1-BROMO-2-NITROBENZENE (2.12 g, 8.7 mmol), diethyl (3- pyridyl) borane (1.47 g, 10.0 MMOL), and bis (triphenylphosphine) palladium (II) CHLORIDE (913 mg, 1.3 MMOL) in tetrahydrofuran (40 MIL), sodium carbonate (4.24 g, 40.0 mmol) was added, and the resulting reaction mixture was heated at reflux for 4 hours. Water (40 ML) was added to the cooled reaction mixture which was then extracted with three 25 ml portions of ethyl acetate. The combined organic extracts were dried (anhydrous sodium sulfate) and concentrated in vacuo to afford a tacky residue. Flash chromatography of the entire sample (silica gel, 47-61 micron mesh; elution initially with methylene chloride and finally with methylene chloride/methanol = 98: 2 in volume) afforded the title compound as a viscous amber oil (713 MG, 41 % YIELD). Subsequent eluent contained less pure product which was further purified by a similar flash chromatography, eluting with methylene chloride/methanol = 99: 1 in volume, thus affording an additional 488 mg (28% yield) of the purified title compound, again as a viscous amber oil. MS m/z 200 (M+ 1). 'H NMR (400 MHz, CD13) delta 8.65 (1H, M), 8.58 (1 H, m), 7.99 (1 H, m), 7.60-7. 73 (2H, overlapping multiplets), 7.56 (1 H, m), 7.43 (1 H, m), 7.36 (1 H, m) ppm.

Reference： [1]Heterocycles,1984,vol. 22,p. 265 - 268
[2]Patent: WO2004/43929,2004,A1 .Location in patent: Page 55

8
[ 619-42-1 ]
[ 89878-14-8 ]
[ 90395-47-4 ]

Yield	Reaction Conditions	Operation in experiment
45%	With potassium hydroxide; tetrabutylammomium bromide; water;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; for 2h;Heating / reflux;	Methyl 4-bromobenzoate (5.04 g) and diethyl-3-pyridylborane (Chem. Pharm. Bull., 33, 4755(1985) (2.30 g) were dissolved in tetrahydrofuran (100 ml). Under an argon atmosphere, tetrabutylammonium bromide (2.51 g), potassium hydroxide (2.63 g), tetrakis(triphenylphosphine) palladium (0) (1.8 g) and water (1 ml) were added to the resulting solution, followed by heating under reflux for 2 hours. After ice cooling, an aqueous solution of ammonium chloride and ethyl acetate were added to the reaction mixture. The organic layer thus separated was dried over anhydrous magnesium sulfate. The residue obtained by distilling off the solvent was purified by chromatography (hexane:ethyl acetate = 1:1) on a silica gel column. The solvent was then distilled off. Methanol and ethanolic 1N hydrochloric acid were added to the residue. The solvent was distilled off again. Tetrahydrofuran was added to the residue. The precipitate thus formed was collected by filtration and dried, whereby the title compound (1.76 g, 45%) was obtained as a colorless solid.1H-NMR(DMSO-d6) delta: 3.91 (3H, s), 8.0-8.1(3H,m), 8.1-8.15 (2H, m), 8.75-8.85 (1H, m), 8.85-8.95 (1H, m), 9.25-9.3 (1H, m).

Reference： [1]Heterocycles,1984,vol. 22,p. 265 - 268
[2]Patent: EP1577302,2005,A1 .Location in patent: Page/Page column 125-126

9
[ 99-90-1 ]
[ 89878-14-8 ]
[ 90395-45-2 ]

Reference： [1]Heterocycles,1984,vol. 22,p. 265 - 268

10
[ 89878-14-8 ]
[ 106047-29-4 ]
[ 106047-30-7 ]

Reference： [1]Chemical and Pharmaceutical Bulletin,1985,vol. 33,p. 4755 - 4763

11
[ 15177-57-8 ]
[ 89878-14-8 ]
5-Chloro-3,3'-bipyridine 1-oxide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate 1.) THF, r.t., 5 min, 2.) reflux, 12 h; Yield given. Multistep reaction;

Reference： [1]Zoltewicz, John A.; Cruskie, Michael P.; Dill, Carlton D. [Journal of Organic Chemistry, 1995, vol. 60, # 1, p. 264 - 267]

12
[ 15177-57-8 ]
[ 89878-14-8 ]
3,3':5',3"-Terpyridine 1'-oxide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate 1.) THF, r.t., 5 min, 2.) reflux, 12 h; Yield given. Multistep reaction;

Reference： [1]Zoltewicz, John A.; Cruskie, Michael P.; Dill, Carlton D. [Journal of Organic Chemistry, 1995, vol. 60, # 1, p. 264 - 267]

13
[ 34896-80-5 ]
[ 89878-14-8 ]
3-(3-methanesulfonylphenyl)-pyridine [ No CAS ]

Reference： [1]Tetrahedron Letters,1994,vol. 35,p. 9063 - 9066
[2]Organic Process Research and Development,2003,vol. 7,p. 385 - 392

14
[ 6271-78-9 ]
[ 89878-14-8 ]
[ 164074-61-7 ]

Reference： [1]Tetrahedron,1995,vol. 51,p. 3103 - 3114

15
[ 115375-60-5 ]
[ 89878-14-8 ]
[ 154229-18-2 ]

Yield	Reaction Conditions	Operation in experiment
95%	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In tetrahydrofuran; at 65℃; for 4h;Reflux;	Diethyl(3-pyridyl)borane (35g) was added to a stirred solution of Compound of formula (III) ( lOOg, 0.216 moles) in THF (800 ml) containing Pd(PPh3)2Cl2 catalyst (0.6g, 0.00085 moles). An aqueous solution of sodium carbonate (82.4g, 0.778 moles) was then added and the reaction mixture was heated to reflux temperature (about 65C) under stirring. Maintained the reaction for 4 hours and its completion was checked by TLC. The reaction mixture was cooled to room temperature and partitioned between Ethylacetate(400 ml) and water. The organic layer was washed thrice with brine solution and concentrated under reduced pressure at 45-55C. The degassed oily mass was stirred in Methanol (800 ml) and was heated at 45-55C after adding charcoal to it. The precipitated solid along with charcoal was filtered and washed with Methanol (200 ml). Water (450 ml) was slowly added to the filtrate at 40-50C under stirring. The resulting suspension was maintained at 20-25C for 3 hours and filtered the solid. Filtered solid was washed with water and dried under reduced pressure at 55-65C to obtain crude Abiraterone acetate. ? Yield : 80 g, 95% Th. ? Chromatographic (HPLC ) purity 95.7%
94%	With bis-triphenylphosphine-palladium(II) chloride; sodium hydrogencarbonate; In tetrahydrofuran; water; at 60℃; for 1h;	Compound 3 (2 g, 4.3 mmol) was added to a round-bottomed flask and dissolved in a mixture of THF (29 mL, 0.15 M) and saturated aqueous sodium bicarbonate (8.6 mL, 8.6 mmol). Bis(triphenylphosphine)palladium(II) dichloride (301 mg, 0.43 mmol) and diethyl (3-pyridyl)borane (691 mg, 4.73 mmol) were added. A condenser was attached, and the mixture heated to 60 C. for 1 h. The THF was removed under an N2 stream, and water was added. The mixture was extracted with chloroform, washed with brine, and dried over NaSO4. The crude material was purified by automatic purification (40 g silica, 10% to 30% to 50% EtOAc/hexanes) to yield 1.63 g of white solid (94%). The analytical data matched reported values, such as in Potter, G. A.; Barrie, S. E.; Jarman, M.; Rowlands, M. G. Novel Steroidal Inhibitors of Human Cytochrome P45017alpha-Hydroxylase-C17,20-lyase): Potential Agents for the Treatment of Prostatic Cancer. J. Med. Chem. 1995, 38, 2463-2471.
90%	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In tetrahydrofuran; water; for 18h;Inert atmosphere; Reflux;	A suspension of compound 17 (3.6 g, 7.78 mmol), diethyl-3-pyridylborane (1.37 g, 9.34 mmol), bis(triphenylphosphine)palladium (II) chloride (54 mg, 0.077 mmol) in THF (35 mL) was added to an aqueous solution of sodium carbonate (2 M, 10 mL). The mixture was refluxed for 18 h under N2. The reaction was concentrated under reduced pressure, and the residue was extracted with ethyl acetate. The organic phase was washed with brine, dried over Na2S04, and concentrated under reduced pressure. Compound 18 was purified by flash column chromatography on silica gel (hexanes to 50% ethyl acetate in hexanes), yield: 90%. 1H NMR (400 MHz, CDCI3) delta: 8.47 (d, J=4 Hz, 1H), 7.68-7.62 (m, 1H), 7.25-7.20 (m, 1H), 5.95 (bs, 1H), 5.48-5.38 (d, 1H, 3.6 Hz), 4.69-4.56 (m, 1H), 2.44-2.22 (m, 4H), 2.16-2.0 (m, 8H), 1.96-1.44 (m, 15H), 1.30-1.00 (m, 11H) ppm. 13C NMR (100 MHz, CDC13) delta: 170.82, 151.89, 148.14, 148.08, 140.26, 133.95, 129.49,123.28, 122.54, 77.52, 77.27, 77.01, 74.10, 57.70, 50.50, 47.56, 38.37, 37.15, 37.01, 35.42, 32.02, 31.73, 30.63, 27.98, 21.70, 21.04, 19.48, 16.82 ppm.

	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In tetrahydrofuran; water; for 1h;Inert atmosphere; Reflux;	Trifluoromethanesulphonic anhydride (235 g) is dropped into a solution of prasterone acetate (250 g) in methylene chloride (5 L), maintaining the emperature between - 5C and 0C, and anhydrous sodium carbonate (80 g) is added in portions. The mixture is stirred for 4h at 0-5C. Cold water (2.5 L) is added and the organic phase is separated and washed with a 10% sodium chloride aqueous solution. The mixture is treated with decolourising carbon (120 g), and then concentrated under vacuum to obtain an oily residue (about 355 g). The vinyl triflate thus obtained is taken up with tetrahydrofuran (3.0 L), and <strong>[89878-14-8]diethyl(3-pyridyl)boran</strong>e (100 g), bis(triphenylphosphine)palladium II chloride (3.3 g) and a 2M sodium carbonate aqueous solution (900 mL) are loaded in succession in an inert gas environment. The resulting mixture is refluxed for about 1 h, then cooled to room temperature, and ethyl acetate (2.5 L) and water (2.5 L) are added. The aqueous phase is back-extracted with ethyl acetate (1.4 L), and the combined organic phases are treated with decolourising carbon (about 100 g), and then concentrated under vacuum to obtain crude abiraterone acetate as an oil (304 g; purity about 92%; assay 52%).
	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In 2-methyltetrahydrofuran; water; at 20 - 80℃; for 2.15h;Inert atmosphere;	Compound (5) (10 g, 19.26 mmol) was charged into a 100 ml three-neck flask along with 3-(diethylboryl)pyridine (2.83 g, 19.26 mmol), Pd(PPh3)2Cl2 (0.135 g, 0.193 mmol) and sodium carbonate (2.042 g, 19.26 mmol). The flask was filled with argon and 2-methyltetrahydrofuran (100 ml) was added. The reaction mixture (RM) was stined at ambient temperature until all the organics dissolved (ca. 2 min). Then water (60.0 ml) was added, the RM immersed in a preheated (80 C) oil bath and heated. The RM reached reflux temperature (70 C) in ca. 27 min. After about 1 hour and 40 min the heating was stopped. RM was allowed to cool to RT and the aqueous layer was removed. The organic layer was washed with 100 ml of water, 50 ml of 0.25M Na2S2O5, 100 ml of water and 50 ml of brine, dried over MgSO4 and filtered through Celite. During the work-up the RM containing abiraterone3-acetate (1) was diluted with a total of ca. 60 ml of 2-methyltetrahydrofuran (washings of separation funnel, filter cake, etc.) to a final volume of ca. 150 ml.
15.68 g	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In tetrahydrofuran; water; at 66℃; for 3.5h;	In a 500 ml three-necked flask compound (5) (20.18 g, 43.6 mmol) was dissolved withstirring in tetrahydrofuran (200 ml) to give a purple solution. To the resulting solution was added3-(diethylboryl)pyridine (8.27 g, 56.2 mmol), mono(bis(triphenylphosphonio)palladium(IV)) dichloride (0.58 g, 0.826 mmol) and sodium carbonate (18.50 g, 175 mmol) as an aqueoussolution (40 ml). The resulting red/brown solution was heated on an oil bath to 66C for 90 min.TLC after 3.5hr showed complete conversion of the triflate. The mixture was then allowed tocool to room temperature, was diluted with water (200 ml) and ethyl acetate (150 ml) and stirred for 5 minutes. The organic phase was separated and the aqueous phase was extracted once withethyl acetate (150 ml). The combined organic layers were dried (sodium sulfate), filtered, andconcentrated to a volume of 50 ml. The solution was diluted with methanol (150 ml) andconcentrated again to a volume of 100 ml. The resulting light brown suspension was stirred overthe weekend and then was filtered off. The filtrate was concentrated to a brown oily residue togive 15.68 g of crude abiraterone-3-acetate (1), which was purified as known in the art viacrystallization of an acid addition salt there of, and conversion of the salt to give abiraterone-3-acetate as a beige solid with a purity of 98.52%.
	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In tetrahydrofuran; water; at 25 - 80℃; for 6h;Inert atmosphere;	Example 1 : Preparation of abiraterone Dehydroepiandrosterone-3-acetate (200 gm) was dissolved in methylene chloride (2000 ml) at 0 to 5C and then added trifluoromethanesulfonic anhydride (256 gm). To the contents were added a solution of tetramethylethylenediamine (57 gm) in methylene chloride (500 ml) slowly for 30 minutes at 0 to 5C and stirred for 3 hours. The temperature of the reaction mass was raised to room temperature and then added water (3000 ml). The layers were separated and the aqueous layer was extracted with methylene chloride. Combined organic layers were dried with sodium sulfate and then concentrated to obtain a residual mass. The residual mass obtained was dissolved in tetrahydrofuran (2000 ml) and then added <strong>[89878-14-8]diethyl(3-pyridyl)boran</strong>e (76 gm) at room temperature. The reaction mass was stirred for 30 minutes and then added bis(triphenylphosphine)palladium(II) chloride (2.5 gm), and stirred for 30 minutes. A solution of sodium carbonate (205 gm) in water (1000 ml) added to the reaction mass under nitrogen atmosphere. The reaction mass was stirred for 30 minutes at room temperature and then heated to 80 C. The reaction mass was maintained for 5 hours 30 minutes at 80C and then cooled to room temperature. Water (3000 ml) and ethyl acetate (2000 ml) was added to the reaction mass and then the layers were separated. The aqueous layer was extracted with ethyl acetate. Combined organic layers were dried with sodium sulfate and then concentrate to obtain a residual mass. The residual mass obtained was dissolved in methanol (2400 ml) and then added sodium hydroxide solution (10%; 500 ml). The contents were heated to 80C and maintained for 2 hours. The reaction mass was then cooled to room temperature and then added water (1200 ml). The reaction mass was then cooled to 15 to 20C and pH was adjusted to 5.5 with hydrochloric acid (2N). To the reaction mass was added methylene chloride (3000 ml) and the separated aqueous layer was extracted with methylene chloride. Combined organic layers were dried with sodium sulfate and then concentrate to obtain a residual solid. To the residual solid was added toluene (1600 ml) and then heated to 90C for 15 minutes. The solution was then cooled to room temperature and stirred for 3 hours. The contents were further cooled to 0 to 5C, stirred for 30 minutes and filtered. The solid obtained was then dried to obtain 125 gm of abiraterone.
65 kg	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In tetrahydrofuran; water; at 20℃; for 1.5h;Reflux; Large scale;	EXAMPLE 2This example illustrates a preparation of abiraterone acetate (I) on an industrial scale starting from prasterone acetate (Ill) according to the invention.51 kg of potassium tert-butylate in THF (760 kg) and prasterone acetate (100 kg) are stirred at a temperature below -70 C. Then N-(2-pyridyl)-bis(trifluoromethanesulfonimide) (1 33 kg) is added maintaining the stirring for 2 hours at a temperature between -70 and -80 C.The cold solution is poured onto a biphasic solution consisting of isopropyl acetate(360 kg) and a 10% ammonium chloride aqueous solution.The phases are separated and the organic phase is first washed with an aqueoussolution of ammonium chloride, then with 450 kg 10% sodium acetate aqueoussolution, and eventually with an aqueous solution of sodium chloride.A part of the solvent is distilled off at reduced pressure obtaining the precipitation of a solid which is eliminated by filtration. The residual solution is then distilled until obtaining an oil which is crystallized from the mixture methanol/triethylamine. The sample obtained after drying (112 kg) verified in HPLC (A = 220 nm) against anauthentic sample is intermediate (II) with 98.14% titer.112 kg of intermediate (II) is dissolved in THF (1079 kg), then bis(triphenylphosphinepalladium(l l)dichloride Pd(P Ph3)2C12 (3.2 kg), diethyl(pyridyl)borane (129.3 kg) and an aqueous solution of sodium carbonate are added under stirring at 20-25 00.Reflux is kept for 1 hour (TLC check), further 400 g of bis(triphenylphosphinepalladium(l l)dichloride Pd(PPh3)2C12 is added, obtaining complete transformation (TLC check) after further 30 minutes of reaction. Cooling down to 20-25 C is performed, the phases are separated by washing the organic phase with an aqueous solution of sodium chloride.The organic phase is then distilled until obtaining a dark oil which is then solubilized with methanol, recovering by fractional crystallization the excess diethyl(pyridyl)borane.Methanol is eliminated by distillation, the residue is dissolved in isopropyl acetate, then the solution is filtered after treatment with decolorising carbon and silica gel.The solution, adjusted at T = 20 ± 5 00 is then treated with oxalic acid dihydrate (60 kg).Stirring is performed at T = 20 ± 5 00 for 8 hours and then the solid is filtered and washed with isopropyl acetate.The abiraterone acetate oxalate obtained is stirred at a temperature between 0 and 500 with methylene chloride (880 kg) and an aqueous solution of sodium bicarbonate.The phases are separated and the organic phase is distilled.The solid obtained is dissolved in isopropyl acetate, then treated with Quadrasil(registered trademark of Johnson Matthey Finland Oy) for 6 hours, for the removal of the catalyst; the Quadrasil scavengers, sold by Sigma-Aldrich, consist of porous silica beads having defined pore size, wherein the silica surface is functionalised with metal binders, and allow a quick and effective removal of traces of metals fromaqueous or organic solutions.After filtration, a part of the solvent is distilled off, cooling down to 0 ± 5 00 is performed obtaining the crystallisation of the product.The abiraterone acetate obtained after drying (65 kg) meets the specifications reported in the corresponding chapter of the European Pharmacopoeia.
		b) Into a reaction bottle was added 0.42 g of bis(triphenylphosphine)palladium(II) chloride and 14.7 g of diethyl-(3-pyridyl) borane, and then vacuumized under argon. 47.3 g of brownish black oil obtained in step a) was dissolved in 400 mL of tetrahydrofuran, and the tetrahydrofuran solution was added into the aforesaid reaction bottle. The mixture was stirred at room temperature for 5 min, and then 225 mL of 17wt% aqueous solution of sodium carbonate was added and stirred for another 5 min at room temperature. After that, the bottle was placed in an oil-bath, and the reaction was refluxed for 4-5 hours. The reaction was monitored by TLC till the conversion was complete. The reaction mixture was cooled to room temperature, 400 mL of ethyl acetate and 400 mL of water were added, and layers were separated. The ethyl acetate phase was collected and the aqueous phase was extracted twice with 200 mL of ethyl acetate. The ethyl acetate phases were combined, dried over anhydrous sodium sulfate and then filtered by suction. The filtrate was concentrated to obtain 44.2 g of brownish black oil. 145 mL of methanol was added into the obtained 44.2 g of brownish black oil and then warmed gently by hair drier till the oil was dissolved. The solution was standing at room temperature and great amount of solids precipitated. After 2 hours, the mixture was filtered by suction. The filtrate was washed with a little ice methanol and concentrated to obtain 41.4 g of brownish black foamy solid, i.e. crude abiraterone acetate, in HPLC purity of 75.29%. See figure 1 and table 1 (processing channel: W2498ChA 210 nm).
	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In tetrahydrofuran; water;Reflux; Inert atmosphere;	Into a reaction bottle was added 0.42 g of bis(triphenylphosphine)palladium(II) chloride and 14.7 g of diethyl-(3-pyridyl) borane, and then vacuumized under argon. 47.3 g of brownish black oil obtained in step a) was dissolved in 400 mL of tetrahydrofuran, and the tetrahydrofuran solution was added into the aforesaid reaction bottle. The mixture was stirred at room temperature for 5 min, and then 225 mL of 17 wt % aqueous solution of sodium carbonate was added and stirred for another 5 min at room temperature. After that, the bottle was placed in an oil-bath, and the reaction was refluxed for 4-5 hours. The reaction was monitored by TLC till the conversion was complete. The reaction mixture was cooled to room temperature, 400 mL of ethyl acetate and 400 mL of water were added, and layers were separated. The ethyl acetate phase was collected and the aqueous phase was extracted twice with 200 mL of ethyl acetate. The ethyl acetate phases were combined, dried over anhydrous sodium sulfate and then filtered by suction. The filtrate was concentrated to obtain 44.2 g of brownish black oil. 145 mL of methanol was added into the obtained 44.2 g of brownish black oil and then warmed gently by hair drier till the oil was dissolved. The solution was standing at room temperature and great amount of solids precipitated. After 2 hours, the mixture was filtered by suction. The filtrate was washed with a little ice methanol and concentrated to obtain 41.4 g of brownish black foamy solid, i.e. crude abiraterone acetate, in HPLC purity of 75.29%.
	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In tetrahydrofuran; water; for 2h;Inert atmosphere; Reflux;	In an inert gas environment, <strong>[89878-14-8]diethyl(3-pyridyl)boran</strong>e (7.5 g), bis(triphenylphosphine)palladium II dichloride (333 mg) and a 2M aqueous solution of sodium carbonate (80 mL) are added to a solution of prasterone acetate triflate prepared as described in example 4 (21.5 g) in tetrahydrofuran (306 mL) The resulting mixture is heated to reflux for about 2 h, then cooled to room temperature, and water (215 mL) and ethyl acetate (215 mL) are added. The phases are separated and the organic phase is treated with decolourising carbon. The decolourised organic phase is concentrated under vacuum to obtain crude Abiraterone acetate as oil (Abiraterone acetate content about 17 g).
496.5 g	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In tetrahydrofuran; water; for 2h;Reflux;	To the above tetrahydrofuran solution were added successively 4.5g (6.4mmol) bis triphenylphosphine palladium dichloride, 120g (0.82mol) of <strong>[89878-14-8]diethyl(3-pyridyl)boran</strong>e, 356g (3.36mol) of sodium carbonate and 1600mL water the mixture was stirred at reflux for 2 hours. Then was added 1.5 L of water, 1.8L of ethyl acetate, stirred well, separated, and the aqueous layer extracted with ethyl acetate, the combined organic phases were washed with 600mL water and 600mL saturated brine, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated to dried to give 496.5g of brown crude oil. HPLC showed a purity of 82.15%, impurity greater than 1% of the 6.
	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In tetrahydrofuran; at 80℃;	AB-2(280g)THF(2L)Pd(PPh3)2Cl2(3.7g), Diethyl- (3-pyridyl) borane (96 g) and 2M Na2CO3 (1L). Heated to an external temperature of 80 C and carried out reaction for 4 ~ 5h. then allowed to stand to separate liquid , the lower aqueous phase extracted with ethyl acetate (1L), the upper organic phase was distilled off to remove most of the THF then added ethyl acetate (2L), and the combined organic layers were washed successively with 2 L of water and brine, and dried over anhydrous sodium sulfate. Rotary evaporation to obtain 260g of black oil product (abiraterone acetate Crude product).

Reference： [1]Patent: WO2014/207762,2014,A1 .Location in patent: Page/Page column 17
[2]Patent: US2016/31929,2016,A1 .Location in patent: Paragraph 0100
[3]Patent: WO2016/144871,2016,A1 .Location in patent: Page/Page column 47
[4]Journal of Medicinal Chemistry,1995,vol. 38,p. 2463 - 2471
[5]Journal of Medicinal Chemistry,2018,vol. 61,p. 4946 - 4960
[6]Patent: WO2014/64032,2014,A1 .Location in patent: Page/Page column 7; 12
[7]Patent: WO2014/71984,2014,A1 .Location in patent: Page/Page column 16
[8]Patent: WO2014/75978,2014,A1 .Location in patent: Page/Page column 11; 12
[9]Patent: WO2014/102833,2014,A2 .Location in patent: Page/Page column 6; 7
[10]Patent: WO2015/14686,2015,A1 .Location in patent: Page/Page column 9; 10; 11
[11]Patent: EP2860187,2015,A1 .Location in patent: Paragraph 0046
[12]Patent: US2015/133652,2015,A1 .Location in patent: Paragraph 0057
[13]Patent: US2015/337007,2015,A1 .Location in patent: Paragraph 0034
[14]Patent: CN102731605,2016,B .Location in patent: Paragraph 0008; 0026
[15]Patent: CN103059090,2016,B .Location in patent: Paragraph 0030; 0033-0034

16
[ 619-58-9 ]
[ 89878-14-8 ]
[ 4385-75-5 ]

Reference： [1]Journal of Organic Chemistry,1996,vol. 61,p. 5169 - 5171

17
[ 32138-69-5 ]
[ 89878-14-8 ]
[ 154229-19-3 ]

Yield	Reaction Conditions	Operation in experiment
74.1%	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In ethanol; water; at 70 - 75℃; for 22h;	40 g of compound VIII, dissolved in 1200 ml of ethanol, 15.5 g of diethyl (3-pyridyl) borane, 720 mg of bis (triphenylphosphine) palladium dichloride, and 53.6 g of sodium carbonate were added to 240 ml of water The solution was heated to 70-75 C for 22 hours. The mixture was cooled and filtered. The filtrate was concentrated under reduced pressure. The mixture was stirred at room temperature with 1200 ml of water and filtered to give crude IX. HPLC purity: 86.1% X 0.9%.The crude cake was stirred at about 65 C for 1 hour, cooled and filtered. The filter cake was dried under reduced pressure at about 50 C to give Compound IX 26 g; HPLC purity: 98.6%, containing impurities X0.5% ; Yield: 74.1%.
72.1%	With bis-triphenylphosphine-palladium(II) chloride; In tetrahydrofuran; for 24h;Reflux; Autoclave; Large scale;	100L in the reaction kettle, by adding KOH (3.36 kg, 60 . 0mol) and 32 kg water stirring dissolves clear, adding THF32L, 17-iodo-androst -5,16-diene -3 beta- mellow vinegar ester (7.96 kg, 20 . 0mol), b (triphenylphosphine) palladium chloride [Pd (PPh3)2Cl2] (140g, 0.2mol), diethyl (3-pyridyl) borane (2.94 kg, 20 . 0mol) heating to reflux, stirring for 24 hours. Decompression concentrating reaction solution, removing THF, precipitating a large amount of solid. Then added to the reaction kettle 80L water, continue to stir 20 minutes. Centrifugal separation to obtain a large number of light gray color solid, solid to pH7-8 eluviation of a large amount of water, the resulting solid for 50-60 C drying, to crude abiraterone 7.23 kg. 2.1 purification of crude abiraterone 1 produced in the added to crude abiraterone 200L in the reaction kettle, add isopropanol 145L, heating and stirring, to be completely dissolve, then adding activated carbon 723g reflux decolourizations and a half hours, to take advantage of heat filtering, removing the activated carbon. Adding the filtrate 70L water, stirring separating out crystal, when the system is cooled to the room temperature to continue stirring 2 hours, and then cooling to-5-5 C stirring 8 hours. Centrifugal drying, with 10L freezing of isopropanol and water mixed solution (volume ratio of 1:1) washing the filter cake, getting white crystalline solid, for 50-60 C vacuum drying 5 hours, shall be abiraterone 5.74 kg, yield quality of 72.1%.
71.2%	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In tetrahydrofuran; water; at 80℃;Inert atmosphere;	At room temperature, under nitrogen protection, a mixed solution of tetrahydrofuran (30 mL) and water (10 mL) was added to a mixture of 17-iodoandrost-5,16-diene-3beta-alcohol (2.00 g, 5.02 mmol), 3-diethylboranylpyridine (900 mg, 6.02 mmol), bis(triphenylphosphine)palladium (II) chloride (180 mg, 0.26 mmol), and sodium carbonate (2.12 g, 20.08 mmol). The reaction solution was kept at 80C overnight (16 hrs). After cooled to room temperature, the reaction was quenched with water (25 mL), and filtered through celite, and the filtrate was extracted with ethyl acetate (60 mL x 3). The organic layers were combined, washed with brine (60 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure, and the concentrate was purified by column chromatography (eluent: PE/EtOAc (v/v) = 1/1) to give 1.25 g of a pale yellow solid, yield: 71.2%, purity: 96.25%, LC -MS (APCI): m/z = 350.1 (M+1)+. 1H NMR (300 MHz, MeOD-d4) (delta/ppm) 8.54 (s, 1H), 8.40 (d, J=4.0 Hz, 1H), 7.86 (d, J=8.1 Hz, 1H), 7.39 (dd, J=7.8, 4.9Hz, 1H), 6.10(s, 1H), 5.41 (d, J=5.0Hz, 1H), 3.49-3.37 (m, 1H), 2.36-2.21 (m, 3H), 2.17 - 2.00 (m, 3H), 1.95-1.78 (m, 3H), 1.76-1.62 (m, 4H), 1.56-1.44 (m, 2H), 1.15-1.06 (m, 8H).

	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In tetrahydrofuran; water; for 50h;Inert atmosphere; Reflux;	17-Iodoandrosta-5, 16-dien-3 -ol [Organic Preparations and Procedures Int., 29, 123- 134 (1997)] (90 g) in tetrahydrofuran (1.0 L), in an inert gas environment, is added with diethyl(3-pyridyl)borane (40 g), bis(triphenylphosphine)palladium II chloride (1.5 g) and a 2M sodium carbonate aqueous solution (450 mL). The resulting mixture is refluxed until the reaction is complete (about 50 h), then cooled to room temperature, and tetrahydrofuran (1 L) is added. The organic phase is separated and washed with a 5% sodium chloride aqueous solution, then dried over magnesium sulphate. The residue is then concentrated under vacuum, and the concentrate is taken up in tert-butyl methyl ether (about 600 mL) to obtain a sandy solid, which is isolated by filtration (at 0-5 C) and dried under vacuum at 40C for 16 h. The crude abiraterone thus obtained (about 64 g) is taken up in methylene chloride (350 mL), and the resulting mixture, cooled to a temperature of -5 to 0C, is added with acetic anhydride (130 mL) and then with triethylamine (190 mL), maintaining the temperature at -5 to 0C. The mixture is stirred at room temperature for about 25 h, then washed with water and concentrated under vacuum, taking up the residue in acetone (250 mL). The resulting solid is isolated by filtration (at 0-5C) and dried under vacuum at 40C for 16 h (about 46 g; purity: 82.5%; assay: about 73%). A second fraction of crude abiraterone acetate, as an oil, is obtained by concentration of the mother liquor under vacuum (54 g, purity: 74%, assay: about 45%).
81.5 g		(3f)-l7-iodo-androsta-5,16-dien-3-ol compound of formula-2 (100 gin) was added to a mixture of tetrahydrofuran (700 ml) and methanol (500 ml) at 25-30C and stirred the reaction mixture for 10 mm at the same temperature. 3-(diethylboryl)pyridune compound of formula-3 (42.5 gm) and Pd(PPh3)2C12 (2 gin) were added to the reaction mixture at 25-30Cand stirred for 10 mm at the same temperature. Aq.sodium carbonate solution (prepared by dissolving 148.5 gm of sodium carbonate in 700 ml of water) was slowly added to the reaction mixture at 25-30C. Heated the reaction mixture to 60-70C and stirred for 2 brs at the same temperature. After completion of the reaction, reduced the temperature of the reaction mixture to 25-30C. Dichioromethane and water were added to the reaction mixtureat 25-30C and stirred for 10 miii at the same temperature. Both the organic and aqueous layers were separated and the aqueous layer was extracted with dichioromethane. Combined the organic layers and dried over sodium sulfate. Charcoal (20 gm) was added to the organic layer at 25-30C and stirred for 2 hrs at the same temperature. Filtered the reaction mixture through hyflow bed and washed the hyflow bed with dichloromethane. Distilled off the solvent completely from the filtrate and co-distilled with ethyl acetate. Cooled the obtainedcompound to 25-30C, ethyl acetate (150 ml) was added and stirred the reaction mixture for10 mm at the same temperature. Pet ether (1500 ml) was added to the reaction mixture at25-30C and stirred for 15 mm at the same temperature. Further cooled the reaction mixture to 0-5C and stirred for 1 hr at the same temperature. Filtered the precipitated solid, washed with pet ether and then dried to get the title compound.Yield: 81.5 gm; Purity by HPLC: 99.36%; Water content by KFR: 0.5% w/w.
30 g	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In tetrahydrofuran; methanol; water; at 60 - 65℃; for 10h;	A 2 lit round bottom flask fitted with a mechanical stirrer, thermometer socket was charged 30% methanol and tetrahydrofuran (1 lit), 17-Iodo-androsta-5,16-diene-3 -ol of Formula III (50 gm), aqueous sodium carbonate (53.2 gm dissolved in 300 ml water), bis (triphenyl phosphine)Pd (II) chloride (1.75 gm) and diethyl (3- pyridyl)borane (18.45 gm) at 25-30C and heated to 60-65C and stirred for 10 hr at same temperature. After completion of the reaction, cooled the reaction mass to 25- 35C and charged reaction mass in to 10% methanol in water (2.5 lit) at same .temperature and stirred for 2 hr at same temperature. Filtered the obtained solids and washed with water (100 ml); wet wt: 60 gm. The XRPD is set forth in Figure- 1 Palladium recovery: To a '2 lit round bottom flask charged 2-methoxy ethanol (1250 ml) and above wet compound (60 gm) at 25-35C and allowed to stir for 10 min. The reaction mass temperature was raised to 85-90C and allowed to stir for 2 hrs. Reaction mass cooled to 60-65 C and filtered to obtain palladium metal, distilled the obtained filterate up to 2 volumes remains in the flask under vacuum at 60-65C. Cooled the reaction mass to 25-35 C and stirred for 1 hr at same temperature. Filtered the obtained solids and washed with 2-methoxy ethanol (50 ml); wt: 35 gm. Purity by HPLC: 98% - - The XRPD is set forth in Figure-2- Purification of abiraterone: To a 2 lit round bottom flask charged the above obtained wet compound (35 gm) and tetrahydrofuran (800 ml) at 25-35C and heated to reflux. Filtered the clear solution through micron filter and distilled out the reaction mass to 2 volumes remains in the . flask at 45-50C. Cooled the reaction mass to 25-35C and stirred for 1 hr at same temperature. Filtered the obtained solids and washed with tetrahydrofuran (25 ml) and dryed under vacuum for lhr and dryed under vacuum at 45-50C for 6 hr to obtain pure abiraterone. Yield: 30 gm Purity by HPLC: 99.5% The XRPD is set forth in Figure-3.
39.2 kg	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In 1-methyl-pyrrolidin-2-one; at 70 - 80℃;Large scale;	The 110L NMP was added to the 3L three-necked flask with stirring followed by adding 7.5kg 17-iodoandrosta-5,16-dien-3beta-ol, 132g bis(triphenylphosphine)palladium chloride and 29.6kg diethyl (3-pyridyl)borane, and finally adding 500L 2mol / L Na2CO3 solution. Maintain the internal temperature of about 70-80 C, TLC monitored the reaction was complete. The reaction was cooled to room temperature, the reaction mixture was added to 220 L of water, stirred for 30min, filtered, washed with water. Blast drying, abiraterone was 39.2kg.
	With potassium phosphate; palladium on activated charcoal; In N,N-dimethyl-formamide; at 90℃; for 6h;	In 1000 ml of the magneton with stirring, of the reflux condensation tube of three compounds are added to a reaction flask 17 - iodine male steroid - 5, 16 - diene - 3 beta - hydroxy 39.8 g (0.10 muM, 1.0 equiv), diethyl (3 - pyridyl) borane 16.2 g (0.11 muM, 1.1 equiv), palladium/carbon (to palladium) 0.106 g (0.001 muM, 0 . 01 equiv), adding phosphoric acid potassium 31.8 g (0.15 muM, 1.5 equiv), adding N, N - dimethyl formamide 500 ml as the solvent, nitrogen replacement heating to 90 C reaction 6 hours. After the reaction, distilled under reduced pressure (the distillation temperature is 90 C, vacuum degree is -0.08 mpa) to remove the solvent, by adding dichloromethane 500 ml and triethylamine 11.1 g (0.11 muM, 1.1 equiv) solution, adding 4 - dimethyl aminopyridine 0.62 g (0.005 muM, 0 . 05 equiv) as catalyst, lowering the temperature to 0 C, slowly dropping vinegar anhydride 15.3 g (0.15 muM, 1.5 equiv), the end of the [...], raising the temperature to 25 C after three hours to continue the reaction after the palladium/carbon catalyst filter recovery, organic layer is 500 ml water, 500 mL1N sodium bicarbonate solution and then concentrated under reduced pressure (the distillation temperature is 30 C, vacuum degree is -0.07 mpa) to dry, adding 120 g acetone heating [...] after two hours the temperature slowly to 0 C to crystallize, get acetate 30.7 g, purity of 99.3%, the molar yield is 78.0%,

Reference： [1]Patent: CN103172690,2016,B .Location in patent: Paragraph 0097 - 0099
[2]Patent: CN105503992,2016,A .Location in patent: Paragraph 0012; 0087; 0089; 0090
[3]Patent: EP3392261,2018,A1 .Location in patent: Paragraph 0081
[4]Organic Preparations and Procedures International,1997,vol. 29,p. 123 - 128
[5]Patent: WO2014/64032,2014,A1 .Location in patent: Page/Page column 8
[6]Patent: WO2014/188445,2014,A1 .Location in patent: Page/Page column 19; 20
[7]Patent: WO2015/102022,2015,A2 .Location in patent: Page/Page column 29; 30; 31; 32
[8]Patent: CN103665085,2016,B .Location in patent: Paragraph 0036; 0037; 0039
[9]Patent: CN109705186,2019,A .Location in patent: Paragraph 0033-0035

18
[ 91934-55-3 ]
[ 89878-14-8 ]
[ 219843-76-2 ]

Yield	Reaction Conditions	Operation in experiment
90%	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In tetrahydrofuran; water; for 18h;Inert atmosphere; Reflux;	00116] A suspension of compound 2 (2 g, 4.30 mmol), diethyl-3-pyridylborane (758.5 mg, 5.48 mmol), bis(triphenylphosphine)palladium (II) chloride (30 mg, 0.043 mmol) in THF (20 mL) was added to an aqueous solution of sodium carbonate (2 M, 7.5 mL). The mixture was refluxed for 18 h under N2. The reaction was concentrated under reduced pressure, and the residue was extracted with ethyl acetate; the organic phase was washed with brine, dried over Na2S04 and concentrated under reduced pressure. Compound 3 was purified by flash column chromatography on silica gel (hexanes to 50% ethyl acetate in hexanes), yield: 90%. 1H NMR (400 MHz, CDC13) delta: 8.6 (s, 1H), 8.5 (d, J = 4.8 Hz, 1H), 7.7 (d, J = 7.6 Hz, 1H), 7.3 (dd, Jl= 4.8 Hz and J2= 7.6 Hz, 1H), 6.0 (s, 1H), 4.7 (bs, 1H), 2.24 (d, 1H), 2.0-0.9 (m, 16H), 1.0 (s, 3H), 0.98 (s, 3H) ppm. 13C NMR (100 MHz, CDCI3) delta: 170.6, 151.7, 147.8, 143.7, 140.8, 133.6, 129.1, 122.9, 69.9, 21.5, 11.3, 9.1 ppm.

Reference： [1]Journal of Medicinal Chemistry,1998,vol. 41,p. 5375 - 5381
[2]Patent: WO2016/144871,2016,A1 .Location in patent: Page/Page column 42

19
[ 98519-65-4 ]
[ 89878-14-8 ]
7-chloro-4-pyridin-3-yl-quinoline [ No CAS ]

Reference： [1]Organic letters,2000,vol. 2,p. 879 - 882

20
[ 89878-14-8 ]
[ 79606-46-5 ]
[ 288093-12-9 ]

Reference： [1]Archiv der Pharmazie,2000,vol. 333,p. 145 - 153

21
[ 89878-14-8 ]
[ 171288-01-0 ]
5,6-dihydro-4H-[2,3']bipyridinyl-1-carboxylic acid tert-butyl ester [ No CAS ]

Reference： [1]Organic Letters,2000,vol. 2,p. 1241 - 1242

22
[ 89878-14-8 ]
[ 5728-20-1 ]
[ 131986-28-2 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate;tetrakis(triphenylphosphine)palladium (0); In toluene;	3-Chloro-4-(pyrid-3-yl)-1,2,5-thiadiazole 2 mL of a 1M aqueous solution of K2CO3 (0.002 mol), 0.147 g (0.001 mol) of diethyl(3-pyridyl)borane and 0.057 g (0.00005 mol) of tetrakis(triphenylphosphine)palladium(0) were added to a solution of 0.155 g (0.001 mol) of <strong>[5728-20-1]<strong>[5728-20-1]3,4-dichloro-1,2,5-thiadiazol</strong>e</strong> in 4 mL of toluene under nitrogen and heated at reflux with vigorous stirring for 24 h. The organic phase was decanted and the aqueous phase was re-extracted with diethyl ether. The combined organic phases were dried over magnesium sulfate and concentrated. The oily residue was purified by chromatography on silica gel (eluant: cyclohexane/ethyl acetate 80/20) to produce 0.035 g (18%) of 3-chloro-4-(pyrid-3-yl)-1,2,5-thiadiazole in the form of a colorless oil which crystallizes slowly (melting point: 45 C.).

Reference： [1]Heterocycles,2003,vol. 60,p. 29 - 45
[2]Patent: US6620940,2003,B1

23
[ 20986-40-7 ]
[ 89878-14-8 ]
[ 484673-69-0 ]

Yield	Reaction Conditions	Operation in experiment
82%		To a solution of 5-bromo-nicotinic acid ethyl ester (1 eq) in THF was added diethyl (3-pyridyl) borane (2 eq), tetrakis (triphenylphosphine) palladium (10%), potassium carbonate (3 eq) and H20. The solution was left stirring in a 80C oil bath for 60 hours. Upon cooling, the reaction was filtered and concentrated. The crude solid was treated with 3 N HCl and ethyl acetate. Once the aqueous layer was seperated, it was added to ethyl acetate and the whole was treated with sodium bicarbonate under vigorous stirring to obtain an approximate basic pH 7. The organic phase was seperated and washed with NACI (sat. ), dried over sodium sulfate, filtered, and concentrated to give [3, 3'] bipyridinyl-5-COOH ethyl ester (82%). MH+ (229)

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 1730 - 1743
[2]Patent: WO2004/96822,2004,A2 .Location in patent: Page 255

24
[ 62856-42-2 ]
[ 89878-14-8 ]
3-(4-<i>p</i>-tolylethynyl-phenyl)-pyridine [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2006,vol. 45,p. 6488 - 6491

25
[ 18982-54-2 ]
[ 89878-14-8 ]
[ 857284-03-8 ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 1925 - 1932

26
[ 89878-14-8 ]
[ 134363-45-4 ]

Reference： [1]Journal of Medicinal Chemistry,1994,vol. 37,p. 4357 - 4362

27
Et₂ [ No CAS ]
[ 32138-69-5 ]
[ 89878-14-8 ]
[ 154229-19-3 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;	(c) 17-(3-Pyridyl)androsta-5,16-dien-3beta-ol diethyl(3-pyridyl)borane (3.23g, 22 mmol) from Aldrich Chemical Co. Ltd. was added to a stirred solution of 17-iodo-androsta-5,16-dien-3beta-ol (7.96g, 20 mmol) in THF (120ml) containing bis(triphenylphosphine)palladium (II) chloride (140mg. 0.2 mmol). An aqueous solution of sodium carbonate (2M, 50ml) was then added and the mixture heated, with stirring, by an oil bath at 80C for 48h, and allowed to cool. The mixture was partitioned between Et2 and water the organic phase was separated, dried (Na2O3 and twice concentrated from Et2 by evaporation to remove THF (with Et2). The residual solid was then washed with Et2 (100ml), the Et2 solution decanted off, and the remaining white solid recrystallized from toluene (3.94g, 56%). Notes

Reference： [1]Patent: EP721461,1999,B1

28
[ 591-20-8 ]
[ 89878-14-8 ]
[ 93851-31-1 ]

Yield	Reaction Conditions	Operation in experiment
88 - 92%		3-bromophenol (49.42g, 285.66 mmol) and diethyl- (3-pyridyl) borane (40. 00g, 272.05 mmol) were dissolved in 945 mL of a 4: 2: 1 mixture OF THF/H2O/ETHANOL IN a 2 L round bottom flask equipped with a magnetic stirrer. Sodium carbonate (57.7g, 544.11 MMOL) ARID tetrakis (TRIPHENYLPHOSPHINE) PALLADIUM (0) (3.14g, 2.72 mmol) was added and the mixture was heated at reflux for 2 h then cooled to ambient temperature and stirred an additional 18 h. The mixture was diluted with 400 mL water and extracted with ethyl acetate (3 x 500 mL). The organic phases were combined and dried over anhydrous sodium sulfate, filtered and concentrated to a volume of 1 L. The organic solution was diluted with 500 mL water and made acidic with 12N HCI. The layers were separated and the organic phase extracted with water (2 x 300 mL). The acidic extractions were combined and made basic with 5N aqueous sodium hydroxide. This basic layer was extracted with diethyl ether (3 x 500 mL) and the extracts were combined, washed with 500 mL brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to yield 40. 91 G (88%) of 3- (3-hydroxyphenyl) pyridine as a pale yellow oil which crystallized on standing. LC-MS 172.1 (M + H) +. 'H NMR (400 MHz, CD30D) 8 8.74 (d, 1 H), 8.49 (dd, 1 H), 8.04 (dd, 1 H), 7.49 (dt, 1 H), 7.30 (t, 1 H), 7.09 (dd, 1 H), 7.04 (t, 1H), 6.84 (dd, 1 H).; A mixture of 3-pyridin-3-yl-phenol (5.14 g, 30.0 MMOL), ethyl 2- bromoisobutyrate (26.3 g, 135.0 MMOL), and K2CO3 (18.7 g, 135.0 mmol) in anhydrous DMF (60 mL) was heated at 95 C under nitrogen for 5 h. After cooling, brine (200 mL) was added and the mixture was extracted with ethyl acetate (250 mL). The separated organic layer was washed with brine, filtered, and concentrated. The oil residue was taken up in 80 mL of 3 M HCI, stirred for 15 min, diluted with brine (100 mL), and extracted with ethyl acetate (2 x 150 mL). The separated aqueous layer was cooled in ice/water bath, adjusted to pH 10 with solid Na2CO3, and extracted with ethyl acetate (2 x 200 mL). The organic extract was dried over sodium sulfate and concentrated to afford 6.70 g (78%) of 2-methyl-2- (3-pyridin-3-yl- phenoxy) -propionic acid ethyl ester as a light brown oil :'H NMR (CDCI3) 8 1. 22 (t, 3H), 1.61 (s, 6H), 4.22 (q, 2H), 6.82 (dd, 1 H), 7.08 (s, 1 H), 7.20 (dd, 1 H), 7.38 (m, 2H), 7.81 (dd, 1 H), 8.59 (br s, 1 H), 8.80 (br s, 1 H); MS M/Z (relative intensity) 285 (M+, 11), 212 (22), 171 (100).

Reference： [1]Patent: WO2004/48334,2004,A1 .Location in patent: Page 106

29
[ 2398-37-0 ]
[ 89878-14-8 ]
[ 4373-67-5 ]

Yield	Reaction Conditions	Operation in experiment
99%	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In tetrahydrofuran; water; for 4h;Heating / reflux;	3-bromo ANISOTE (17.4g, 93.03 mmol) was dissolved in 650 mL tetrahydrofuran and 210 mL water in a 2L round bottom flask equipped with a magnetic stirrer. Diethyl- (3-pyridyl) borane (15. 73g, 106.99 MMOL), sodium carbonate (44.4g, 418.64 mmol) and dichlorobis (triphenylphosphine) palladium (II) (9.8g, 13.95 mmol) were added and the mixture heated at reflux for 4 h then cooled to ambient temperature. The mixture was diluted with 300 mL water and extracted with diethyl ether (2 x 300 mL). The extracts were combined and dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resultant oil was purified by flash chromatography (1: 1 ethyl acetate/hexanes). Product fractions were concentrated under reduced pressure to yield 17.75g (99%) of the desired compound as a pale yellow oil. MS (APCI) 186.1 (M + H) +. 1H NMR (400 MHz, CDCI3) 8 8. 85 (d, 1 H), 8.60 (d, 1 H), 7.92 (dd, 1 H), 7.39 (m, 2H), 7.13 (dd, 1H), 7.08 (t, 1H), 6.94 (dd, 1H), 3.85 (s, 3H).

Reference： [1]Patent: WO2004/48334,2004,A1 .Location in patent: Page 101-102

30
[ 60956-26-5 ]
[ 89878-14-8 ]
[ 4373-62-0 ]

Yield	Reaction Conditions	Operation in experiment
74%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; for 18h;Heating / reflux;	2-Nitro-4-bromotoluene (8.74 g, 40.46 mmol) was dissolved in 75 mL dioxane and 25 mL water to which was added diethyl- (3-pyridyl) borane (5.95 g, 40.46 MMOL), sodium carbonate (8.58g, 80.91 mmol) and tetrakis (TRIPHENYLPHOSPHINE PALLADIUM (0) (0.94 g, 0.81 MMOL). The mixture was heated at reflux for 18 h then cooled to ambient temperature. The mixture was diluted with 600 mL water and extracted with diethyl ether (2 x 300 mL). The organic phases were combined and extracted with 0.3 N HCI (3 x 200 mL). The acidic extractions were combined and made basic with 5N aqueous sodium hydroxide. This basic layer was extracted with diethyl ether (2 x 300 mL) and the extracts were combined and dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to yield 6.39 g (74%) of 2-NITRO-4- (3- pyridyl) toluene as a brown oil. MS (LC-MS) 215.1 (M + H) +. 'H NMR (400 MHz, CDCI3) 8 8.87 (d, 1 H), 8.66 (d, 1 H), 8.20 (d, 1 H), 7.92 (d, 1 H), 7.73 (dd, 1 H), 7.44 (m, 2H), 2.66 (s, 3H). A 500 mL hydrogenation vessel was charged with 0.64g PLATINUM (II) oxide and purged with nitrogen. 2-Nitro-4- (3-pyridyl) toluene (19.57g, 81.10 mmol) was added as a solution in 150 mL acetic acid. The suspension was hydrogenated at 45 psi for 18 h. The catalyst was filtered through celite and the filter plug was washed with 300 mL ethyl acetate. The filtrate was concentrated under reduced pressure. The resultant oil was taken up in 300 mL water and made basic with 5N aqueous sodium hydroxide. This basic layer was extracted with ethyl acetate (2 x 300 mL) and the extracts were combined and dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to yield 5.38 g (95%) of 2-amino- 4- (3-PIPERIDINYLL) TOLUENE as a brown oil. MS (LC-MS) 191.2 (M + H) . 'H NMR (400 MHz, CDCI3) 8 6.97 (d, 1 H), 6.56 (dd, 1 H), 6.54 (d, 1 H), 3.57 (brs, 1H), 3.12 (dd, 2H), 2.61 (m, 3H), 2.13 (s, 3H), 1, +95 (brs, 2H), 1.75 (m, 1H), 1. 57 (m, 2H). 2-Amino-4- (3-piperidinyl) toluene (1.25 g, 6.57 mmol) was dissolved in 25 mL tetrahydrofuran. 1 N sodium hydroxide (13.14 mL, 13.14 mmol) was added followed by dibenzyl-dicarbonate (1.88 g, 6.57 MMOL). The reaction was stirred for 2 h at ambient temperature then diluted with 200 mL diethyl ether and washed with 200 mL water. The ORGARFHPHASE was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resultant oil was flash chromatographed with 20% ethyl acetate/hexanes to yield 1.414 g (66%) of the desired 3- (3-AMINO-4- methyl-phenyl)-piperidine-1-carboxylic acid benzyl ester as a clear oil. MS (LC-MS) 325.2 (M + H) +. 'H NMR (400 MHz, DMSO-D6) 8 7.34 (m, 5H), 6.81 (d, 1 H), 6.45 (s, 1 H), 6.32 (d, 1 H), 5.06 (s, 2H), 4.02 (m, 2H), 2.76 (brm, 1H), 2.41 (t, 1 H), 1.97 (s, 3H), 1.82 (d, 2H), 1.69 (d, 1 H), 1.54 (q, 1 H), 1.44 (t, 1 H). 3- (3-AMINO-4-METHYL-PHENYL)-PIPERIDINE-1-CARBOXYLIC acid benzyl ester (470 mg, 1.45 mmol) was dissolved in 10 mL CH2CI2 and cooled to 0C. Triethylamine (0.4 mL, 2.90 mmol) was added followed by dropwise addition of trifluoromethane sulfonic anhydride (0.24 mL, 1.45 mmol) and the reaction stirred for 0.5 h at 0C. The mixture was concentrated under reduced pressure and taken up in 50 mL water. The aqueous suspension was made acidic with 1 N HCI and extracted with 50 mL ethyl acetate. The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resultant oil was flash chromatographed with 15% methanol/chloroform (1% ammonium hydroxide modifier). The product fractions were combined and concentrated under reduced pressure. The resultant oil was taken up in 50 mL water, made acidic with 1 N HCI and extracted with 50 mL ethyl acetate. The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to yield 403 mg (61 %) of the desired 3- [4-METHYL-3- (TRIFLUORO-METHANESULFONYLAMINO)-PHENYL]- piperidine-1-carboxylic acid benzyl ester as a clear oil. MS (LC-MS) 455.1 (M-H)-. 'H NMR (400 MHz, CD30D) 8 7.35 (m, 5H),. 7.22 (d, 1H),-7. 18 (brs, 2H), 5.13 (s, 2H), 4.15 (d, 2H), 2.89 (brm, 2H), 2.65 (m, 1H), 2.32 (s, 3H), 2.00 (d, 1H), 1.76 (d, 1 H), 1.69 (q, 1 H), 1.58 (t, 1 H). A 250 mL Parr bottle was charged with 80 mg of 10% palladium on carbon (50% water) and covered with 10 mL ethanol. 3- [4-methyl-3- (TRIFLUOROMETHANESULFONYLAMINO)-PHENYL]-PIPERIDINE-1-CARBOXYLIC acid benzyl ester (403 mg, 0.88 mmol) was dissolved in 20 mL ethanol and added to the catalyst suspension. The reaction was hydrogenated at 45 psi for 2 h. Water (50 mL) was added to dissolve the white precipitate and the catalyst was filtered through a celite plug. The filter cake was washed with 200 mL 25% WATER/ETHANOL and the filtrate concentrated under reduced pressure to yield 275 mg (97%) of c, c, C-TRIFLUORO-N- (2- methyl-5-piperidin-3-yl-phenyl)-methanesulfonamide as a white crystalline solid. MS (LC-MS) 323.2 (M + H) +. 'H NMR (400 MHz, DMSO-D6) 8...

Reference： [1]Patent: WO2004/48334,2004,A1 .Location in patent: Page 172-175

31
[ 683240-54-2 ]
[ 89878-14-8 ]
[ 683240-57-5 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; at 200℃; for 0.666667h;Microwave irradiation;	Example 10 [4-PYRIDIN-3-YL-6-TRIFLUOROMETHYL-2- [4- (3-TRIFLUOROMETHYLPYRIDIN-2-YL)] piperazin- [1-YL]-1 H-BENZOIMIDAZOLE.] A mixture of [4-BROMO-6-TRIFLUOROMETHYL-2- [4- (3-TRIFLUOROMETHYLPYRIDIN-2-] yl) [PIPERAZIN-L-YL]-LH-BENZOIMIDAZOLE] (99 mg, 0.2 mmol, Example 7), diethyl (3- pyridyl) borane (37 mg, 0.25 mmol, Aldrich), Pd (PPh3) 4 (23 mg, 0.02 mmol, Aldrich), Na2C03 (32 mg, 0.3 mmol) and dimethoxyethane [(1] mL) was subjected to microwave irradiation at [200 C] with stirring for 40 min. The solvent was removed in vacuo and the residue was purified by silica gel chromatography, eluting with 60% EtOAc/hexane, to give the title compound as a yellow amorphous solid. MS (ESI, pos. ion) [WALZ :] 493 [(M+1).]

Reference： [1]Patent: WO2004/35549,2004,A1 .Location in patent: Page 62

32
[ 89878-14-8 ]
[ 220728-62-1 ]
[ 702683-21-4 ]

Yield	Reaction Conditions	Operation in experiment
99%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; ethanol; water; for 24h;Heating / reflux;	A 500 mL Parr bottle was charged with 2.0 g of 10% palladium on carbon (50% water) and covered with 50 mL ethanol. 2-methyl-5-nitroanisole (10.0 g, 59.8 mmol) was dissolved in 100 mL ethanol and added to the catalyst suspension. The reaction was hydrogenated at 50 psi for 3 h. The catalyst was filtered through a celite plug. The filter cake was washed with 150 mL ethanol and the filtrated concentrated under reduced pressure to yield 8.05g (98%) of 5-amino-2-methylanisole as a clear oil. 'H NMR (400 MHz, CDC13) 8 6. 90 (d, 1 H), 6.23 (m, 2H), 3.78 (s, 3H), 2.11 (s, 3H). 5-amino-2-methylanisole (8.05 g, 58.7 mmol) was dissolved in 244 mL water and 8.1 mL concentrated H2SO4 and cooled to 0C. NAN02 (4.86 g, 70.4 mmol) in 61 mL water was added dropwise with stirring. Reaction was stirred 30 minutes at 0C. Urea (0.70 g, 11.7 mmol) was added and stirring continued for an additional 30 minutes. The pale yellow solution was transferred to a dropping funnel and added slowly to a stirred solution of potassium iodide (19.48 g, 117.4 mmol) in 122 mL water. The solution was stirred at ambient temperature for 1 h after completion of the addition. The reaction was extracted with diethyl ether (3 x 300 mL). The organic extracts were combined and washed with 1 M Na2S203 (2 x 200 mL), dried over NA2SO4, filtered and concentrated under reduced pressure to yield 9.60 g (66%) of 5- iodo-2-methyl anisole as a brown oil. 1H NMR (400 MHz, CDC13) 8 7.19 (dd, 1H), 7.10 (d, 1H), 6.86 (t, 1H), 3.81 (s, 3H), 2.15 (s, 3H). 5-iodo-2-methyl anisole (9.60 g, 38.70 mmol) and diethyl- (3-pyridyl) borane (5.70 g, 38.70 mmol) were dissolved in 60 mL tetrahydrofuran in a 250 mL round bottom flask equipped with a magnetic stirrer. Sodium carbonate (8.20 g, 77.40 mmol) and 30 mL water were added followed by tetrakis (triphenylphosphine) palladium (0) (0.90g, 0.77 mmol) and 15 mL ethanol. The mixture was heated at reflux for 24 h under nitrogen then cooled to ambient temperature. The mixture was diluted with 200 mL water and extracted with diethyl ether (2 x 200 mL). The organic phases were combined and extracted with'N HCI (3 x 150 mL). The acidic extractions were combined and made basic with 5N aqueous sodium hydroxide. This basic layer was extracted with diethyl ether (3 x 150 mL) and the extracts were combined and dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to yield 7. 71G (99%) of 2-methyl-5- (3-pyridyl)- anisole as a brown oil. MS (LC-MS) 200.1 (M + H) +. 'H NMR (400 MHz, CDGI3) 8 8.87 (s, 1 H), 8.60 (d, 1 H), 8.03 (dd, 1 H), 7.50 (m, 1 H), 7.25 (d, 1H), 7.08 (d, 1 H), 7.00 (s, 1 H), 3.92 (s, 3H), 2.27 (s, 3H). A 500 mL L hydrogenation vessel was charged with 0.77 g platinum (II) oxide and purged with nitrogen. 2-methyl-5- (3-pyridyl)-anisole (7.71 g, 38.7 mmol) was added as a solution in 150 mL acetic acid. The suspension was hydrogenated at 45 psi for 18 h. The catalyst was filtered through celite and the filter plug was washed with 200 mL acetic acid. The filtrate was concentrated under reduced pressure. The resultant oil was taken up in 300 mL water and made basic with 5N aqueous sodium hydroxide. This basic layer was extracted with ethyl acetate (2 x 300 mL) and the extracts were combined and dried over anhydrous sodium sulfate,,. filtered and concentrated under reduced pressure. The resultant oil was taken up in 300 mL hot ethanol. L- (+)-tartaric acid (5.81 g, 38.7 mmol) in 50 mL hot ethanol was added into the ethanol solution and was allowed to stir at ambient temperature for 24 h, forming a white precipitate that was collected by filtration. The white solid was recrystallized from hot 5% H2O/ETHANOL (200 mL) to yield 4.88 g (35%) of 5- (3-PIPERIDINYL)-2- methylanisole-L-tartaric acid salt as a white solid. The mother liquors were combined and concentrated under reduced pressure. The resultant oil was taken up in 500 mL diethyl ether and washed with 300 mL saturated aqueous NAHCO3. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resultant oil was taken up in 200 mL hot ethanol. D- (-)-tartaric acid (3.75 g, 25.0 mmol) in 50 mL hot ethanol was added and was allowed to stir at ambient temperature for 48 h, forming a white precipitate that was collected by filtration. The white solid was recrystallized from hot 5% H20/ETHANOL (300 mL) to yield 5.36 g (39%) of 5- (3-PIPERIDINYL)-2-METHYLANISOLE-D-TARTARIC acid salt as a white solid. 'H NMR (400 MHz, DMSOd6) 8 7.06 (d, 1 H), 6.82 (d, 1 H), 6.71 (dd, 1 H), 3.87 (s, 2H), 3.77 (s, 3H), 3.27 (m, 2H), 2.97 (t, 1H), 2.86 (q, 2H), 2.09 (s, 3H), 1.85 (d, 2H), 1.69 (m, 2H). 3- (3-methoxy-4-methylphenyl)-1 H-piperidine-L-tartaric acid salt (4.88 g, 13.73 mmol) was slowly dissolved in hydrobromic acid (50 mL) and the resulting mixture heated at 140 C for 2 h. After cooling to ambient temperature, the hydrobromic acid and water were distilled off and the resulting brown oil was azeotroped with to...

Reference： [1]Patent: WO2004/48334,2004,A1 .Location in patent: Page 159-163

33
[ 56427-54-4 ]
[ 89878-14-8 ]
[ 702682-38-0 ]

Yield	Reaction Conditions	Operation in experiment
97%	With sodium carbonate; DavePhos;palladium diacetate; In tetrahydrofuran; water; for 6.0h;Heating / reflux;	5-chloro-2-methylbenzoic acid (5.04 g, 29.5 mmol) was dissolved in 100 mL ethanol in a 250 mL round bottom flask fitted with a water condenser. 0.5 mL concentrated sulfuric acid was added and the solution heated to reflux. The solution was heated for 48 h and cooled to ambient temperature. The ethanol was removed under reduced pressure. The resultant oil was taken up in 300 mL diethyl ether and washed with saturated aqueous sodium bicarbonate (2 x 300 mL). The organic layer was dried over NA2SO4, filtered and concentrated under reduced pressure to yield 5.12 (87%) of <strong>[56427-54-4]ethyl 5-chloro-2-methylbenzoate</strong> as a clear oil. 'H NMR (400 MHz, CDC13) 8 7.88 (d, 1H), 7.35 (dd, 1H), 7.18 (d, 1H), 4.36 (q, 2H), 2.56 (s, 3H), 1.40 (t, 3H). Ethyl 5-chloro-2-methylbenzoate (16.60 g, 83.56 mmol) and diethyl- (3- pyridyl) borane (13.52 g, 91.92 mmol) were dissolved in 100 mL tetrahydrofuran in a 500 mL round bottom flask equipped with a magnetic stirrer. Sodium carbonate (26.57 g, 250.69 mmol) and 50 mL water were added followed by palladium acetate (0.38g, 1.67 mmol) and (2'-dicyclohexylphosphanyl-biphenyl-2-yl)-dimethyl-amine (AmPhos, 0.92g, 2.51 mmol) and 25 mL ethanol. The mixture was heated at reflux for 6 h then cooled to ambient temperature. The mixture was diluted with 600 mL water and extracted with diethyl ether (2 x 300 mL). The organic phases were combined and extracted with 1 N HCI (3 x 200 mL). The acidic extractions were combined and made basic with 5N aqueous sodium hydroxide. This basic layer was extracted with diethyl ether (3 x 500 mL) and the extracts were combined and dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to yield 19.57g (97%) of ethyl 5- (3-PYRIDYL)-2-METHYLBENZOATE as a brown oil. MS (LC-MS) 242.2 (M + H) +. 'H NMR (400 MHz, CDCI3) 8 8.87 (d, 1H), 8.61 (dd, 1H), 8.13 (d, 1H), 7.95 (dd, 1 H), 7.62 (dd, 1 H), 7.44 (dd, 1 H), 7.37 (d, 1 H), 4.40 (t, 2H), 2.65 (s, 3H), 1.42 (q, 3H). A 500 mL hydrogenation vessel was charged with 2. 0g PLATINUM (II) oxide and purged with nitrogen. Ethyl 5- (3-PYRIDYL)-2-METHYLBENZOATE (19.57g, 81.10 mmol) was added as a solution in 200 mL acetic acid. The suspension was hydrogenated at 45 psi for 18 h. The catalyst was filtered through celite and the filter plug was washed with 200 mL acetic acid. The filtrate was concentrated under reduced pressure. The resultant oil was taken up in 500 mL water and made basic with 5N aqueous sodium hydroxide. This basic layer was extracted with ethyl acetate (2 x 500 mL) and the extracts were combined and dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resultant oil was taken up in 200 mL hot ethanol. L- (+)-tartaric acid (12.17g, 81.1 mmol) was added into the ethanol solution and was allowed to stir at ambient temperature for 48 h, forming a white precipitate that was collected by filtration. The white solid was recrystallized from hot 5% H2O/ETHANOL (300 mL) and then from 350 mL hot 20% H20/ETHANOL to yield 11.25g (35%, 95.8% ee) of (S)-ethyl 5- (3-PIPERIDINYL)-2-METHYLBENZOATE-L-TARTARIC acid salt as a white solid. The mother liquors were combined and concentrated under reduced pressure. The resultant oil was taken up in 300 mL water and made basic with 5N aqueous sodium hydroxide. This basic layer was extracted with ethyl acetate (2 x 300 mL) and the extracts were combined and dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resultant oil was taken up in 200 mL hot ethanol. D- (-)-tartaric acid (6.82g, 45.4 mmol) was added into the ethanol solution and was allowed to stir at ambient temperature for 48 h, forming a white precipitate that was collected by filtration. The white solid was recrystallized from hot 5% H20/ETHANOL (300 mL) and then from 350 mL hot 20% H20/ETHANOL to yield 13. 51g (42%, 100% ee) of (R)-ethyl 5- (3-PIPERIDINYL)-2-METHYLBENZOATE-D-TARTARIC acid salt as a white solid. MS (LC-MS) 248.2 (M + H) +. 1H NMR (400 MHZ, CDCI3) 6 7. 73 (d, 1H), 7.24 (dd, 1H), 7.18 (d, 1H), 4.35 (q, 2H), 3.18 (t, 2H), 2.78 (t, 1H), 2.68 (m, 2H), 2.54 (s, 3H), 2.38 (br, 1H), 2.01 (d, 1H), 1.82 (m, 1 H), 1.64 (6,2H), 1.40 (t, 3H). HPLC analysis: Chiralcel AD, 1 mL/min, 10% ethanol/heptane 0.025% diethylamine, rt = 8.36 min, 9.00 min (R)-Ethyl 5- (3-PIPERIDINYL)-2-METHYLBENZOATE-D-TARTARIC acid (2.02 g, 5.08 mmol) was dissolved in 100 mL ethyl acetate and washed with 100 mL saturated aqueous NAHCO3. The organic phase was dried over NA2SO4 and concentrated under reduced pressure. The resultant oil was taken up in 10 mL toluene and imidazole-1-carboxylic acid 4-trifluoromethyl-benzyl ester (1.37 g, 5.08 mmol) was added. The reaction was stirred for 72 h at room temperature under nitrogen. The reaction was diluted with water (200 mL), acidified with 1 N aqueous hydrochloric acid and extracted with diethyl ether (2 x 150 mL). The organic extracts were combined, dried over anhydrous sodium sulfate, filtered and concentr...

Reference： [1]Patent: WO2004/48334,2004,A1 .Location in patent: Page 147-149

34
[ 5326-34-1 ]
[ 89878-14-8 ]
[ 4373-73-3 ]

Yield	Reaction Conditions	Operation in experiment
65%	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In tetrahydrofuran; water; at 75℃; for 18h;Heating / reflux;	To a well-stirred mixture consisting of 4-bromo-3-nitrotoluene (4.0 g, 18.5 MMOL) in tetrahydrofuran (145 ML), diethyl-3-pyridylborane (3.12 g, 21 mmol), and bis (TRIPHENYLPHOSPHINE) PALLADIUM (II) CHLORIDE (1.94 g, 2.8 mmol), a solution of sodium carbonate (9.8 g, 92.5 MMOL) in water (50 ML) was added. The reaction mixture was heated to 75C for 18 hours. The organic layer of the biphasic mixture was dried (anhydrous sodium sulfate), and the solvent was removed in vacuo to afford an oil (7.0 g). Flash chromatography of the entire sample (silica gel, 47-61 micron mesh; elution with ethyl acetate/hexanes = 1 : 1 in volume) afforded the title compound (2.58 g, 65% yield) as a light yellow foam. TLC Rf (silica gel plates ; elution with ethyl acetate/hexanes = 1 : 1 in volume, UV detection): 0.51. MS m/z 215 (M+1).13C NMR (125 MHz, CDCI3) delta 148. 4,147. 9,140. 3,136. 4,134. 3,133. 9,132. 1,130. 1, 125.2, 123.6, 21.1 ppm

Reference： [1]Patent: WO2004/43929,2004,A1 .Location in patent: Page 51

35
[ 41085-43-2 ]
[ 89878-14-8 ]
[ 695185-41-2 ]

Yield	Reaction Conditions	Operation in experiment
38 - 48%	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In tetrahydrofuran; water; at 75℃; for 18h;Heating / reflux;	To a solution of 2-bromo-3-nitrotoluene 5.0 G (23 MMOL) in tetrahydrofuran (180 ml) ; diethyl-3-pyridyl borane (3.89 g, 26 mmol), bis-triphenylphosphine PALLADIUM (II) CHLORIDE (2.42 G, 3.45 mmol), and a solution of sodium carbonate (12.19 G, 115 MMOL) in water (60 ml) were sequentially added. The resulting well-stirred reaction mixture was then heated at 75C for 18 hours. The separated organic layer was diluted with ethyl acetate (200 mi) and extracted with an equal volume of water. The organic extract was then dried (anhydrous sodium sulfate) and concentrated in vacuo to afford a brown oil (9.4 G). Flash chromatography of the entire sample (silica gel, 47-61 micron mesh; elution with ethyl acetate/hexanes = 1 : 1 in volume) afforded the title compound (2.40 g, 48% yield) as an amber oil. 1HNMR (400 MHz, CDCI3) delta 8.66 (m, 1H), 8.47 (m, 1H), 7.80 (m, 1H), 7.61 (m, 1H), 7.55 (m, 1H), 7.42 (m, 2H), 2.11 (5,3H) ppm. To a mixture consisting of 2-bromo-3-nitrotoluene (5.0 g, 23 MMOL) in tetrahydrofuran (180 ML), diethyl-3-pyridyl borane (3.89 g, 26 mmol), and bis (triphenylphosphine) palladium (II) chloride (2.42 g, 3.45 mmol), a solution of sodium carbonate (12.19 g, 115 MMOL) in water was added. The well-stirred reaction mixture was heated at 75C for 18 hours. The organic and aqueous layers were separated, and the aqueous phase was extracted with ethyl acetate (100 ML). The combined organic extracts were dried (anhydrous sodium sulfate) and concentrated in vacuo to afford an oil (9.6 g). Flash chromatography of the entire sample (silica gel, 41-67 micron mesh; elution with ethyl acetate/hexanes = 1 : 1 in volume) afforded the title compound as a light yellow oil (1.87 g, 38% yield). TLC Rf (silica gel plates ; elution with ethyl acetate/hexanes = 1 : 1 in volume; UV detection): 0.50. MS M/Z 215 (M+1). 13C NMR (125 MHz, CDCI3) delta 171. 4,148. 1,148. 0,139. 6,137. 2,134. 7,133. 0,131. 7, 129.2, 123.9, 122.0, 21. 0 PPM

Reference： [1]Patent: WO2004/43929,2004,A1 .Location in patent: Page 45; 49

36
[ 583-68-6 ]
[ 89878-14-8 ]
[ 695185-44-5 ]

Yield	Reaction Conditions	Operation in experiment
48%	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In tetrahydrofuran; water; at 75℃; for 18h;Heating / reflux;	To a mixture consisting of a tetrahydrofuran (125 ML) solution of 2-bromo-4- methylaniline (2.67 ml, 21 mmol), diethyl-3-pyridyl borane (3.08 g, 24 mmol), and bis (triphenylphosphine) palladium (II) CHLORIDE (2.21 g, 0.32 mmol), an aqueous solution sodium carbonate (11.13 g 10.5 MMOL in 44 ml of water) was added. The well-stirred reaction mixture was heated at 75C for 18 hours. The upper layer of the cooled biphasic mixture was separated, dried (anhydrous sodium sulfate), and then filtered through celite. Solvent removal in vacuo yielded an oil (6.5g). Flash chromatography of the entire sample (silica gel ; elution with methylene chloride/methanol = 95: 5 in volume) afforded the title compound (1.85g, 48% yield) as a colorless amorphous solid. TLC Rf (silica gel plates ; elution with methylene CHLORIDE/METHANOL = 95: 5; UV detection): 0.53. MS M/Z 185 (M+1). 13C NMR (125 MHz, CDCI3) delta 150. 2,148. 5,141. 5,136. 8,135. 6,131. 2,130. 1,128. 4, 124.0, 123.7, 116.3, 20.6 ppm.

Reference： [1]Patent: WO2004/43929,2004,A1 .Location in patent: Page 47

37
7-bromo-3-ethylquinoline [ No CAS ]
[ 89878-14-8 ]
[ 695185-63-8 ]

Yield	Reaction Conditions	Operation in experiment
58%	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In tetrahydrofuran; at 20 - 90℃; for 23h;	To a well-stirred mixture consisting of the title compound of Step 1, this Example (1.40 g, 5.93 mmol), diethyl (3-pyridyl) borane (0.96 g, 6.53 MMOL) and bis (triphenylphosphine) palladium (II) chloride (458 mg, 0.65 MMOL) in tetrahydrofuran (15 ML), a 7.5 ml aqueous solution of sodium carbonate (2.51 g, 23.7 MMOL) was added. The reaction mixture was then STIRRED AT 90C for 5 hours, and then at ambient temperature for 18 hours. The aqueous phase of the biphasic reaction mixture is separated and extracted with an equal volume of ethyl acetate. The solvent of the organic phase of the reaction mixture was removed in vacuo and the residue is extracted with ethyl acetate (25 ML). The combined organic extracts are dried (anhydrous sodium sulfate) and concentrated in vacuo, yielding a dark viscous oil. Flash chromatography of the entire sample (silica gel, 47-61 micron mesh; elution with ethyl acetate) afford the title compound (807 mg, 58% yield) as a viscous yellow syrup. 1H NMR (400 MHz, CDCI3) delta 8. 93 (1H, m), 8.82 (1H, m), 8.62 (1H, m), 8.27 (1H, m), 8.01 (1 H, m), 7.94 (1 H, m), 7.86 (1 H, m), 7.74 (1 H, m), 7.36-7. 49 (2H, overlapping multiplets), 2.84 (2H, q, J = 7.5 Hz), 1.35 (3H, t, J = 7.5 Hz) ppm.

Reference： [1]Patent: WO2004/43929,2004,A1 .Location in patent: Page 64

38
8-bromo-3-ethylquinoline [ No CAS ]
[ 89878-14-8 ]
[ 695185-37-6 ]

Yield	Reaction Conditions	Operation in experiment
35.4%	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In tetrahydrofuran; water; for 4h;Heating / reflux;	To a well-stirred mixture consisting of the title compound from the previous step (2.36 g, 10. 0 MMOL), DIETHYL (3-PYRIDYL) borane (1.67 g, 11.0 mmol), and bis (triphenylphosphine) palladium (II) chloride (913 mg, 1.3 MMOL) in tetrahydrofuran (40 ML), an aqueous solution of sodium carbonate (4.24 g, 40 MMOL in 20 ml water) is added, and the resulting reaction mixture is heated at reflux for 4 hours. Water (50 mi) was added to the well-stirred mixture. The aqueous phase of the biphasic reaction mixture is separated and extracted with three 50 ML portions of ethyl acetate. The solvent of the organic phase of the reaction mixture is removed in vacuo, and the residue is extracted with two 50 ml portions of ethyl acetate. The combined organic extracts are dried (anhydrous sodium sulfate) and concentrated in vacuo, yielding a viscous syrup. Flash chromatography of the entire sample (silica gel, 47-61 micron mesh; elution with ethyl acetate) yielded a pure portion of the title compound (830 mg, 35.4% yield) as a viscous amber syrup and a less pure (judged to be approximately 75% pure by NMR inspection) second portion of the title compound (700 mg), also an amber syrup. MS M/Z 234 (M+1). 'H NMR (400 MHz, CDCI3) delta 8.93 (1H, m), 8.80 (1H, m), 8.63 (1H, m), 8.10 (1H, m), 7.96 (1 H, m), 7.81 (1 H, m), 7.66 (1 H, m), 7.60 (1 H, m), 7.42 (1 H, m), 2.84 (2H, q, J = 7.5 Hz), 1.34 (3H, t, J = 7. 5 HZ) ppm.

Reference： [1]Patent: WO2004/43929,2004,A1 .Location in patent: Page 42-43

39
[ 873-38-1 ]
[ 89878-14-8 ]
[ 695185-48-9 ]

Yield	Reaction Conditions	Operation in experiment
74%	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In tetrahydrofuran; water; at 75℃; for 18h;Heating / reflux;	To a well-stirred mixture consisting of <strong>[873-38-1]2-bromo-4-chloroaniline</strong> (5.0 g, 24 mmol) in tetrahydrofuran (180 ML), diethyl-3-pyridyl borane (4.07 g, 28 MMOL), and bis (TRIPHENYLPHOSOPHINE) PALLADIUM (II) chloride (2.53 g, 3.6 mmol), a solution of sodium carbonate (12.72 g, 120 MMOL) in water (60 ML) was added. The reaction was then heated at 75C for 18 hours. The layers of the biphasic mixture were separated, and the aqueous phase was extracted with an equal volume of ethyl acetate. The combined original reaction organic phase and ethyl acetate extract were dried and concentrated in vacuo to afford an oil (9.4 g). Flash chromatography of the entire sample (silica gel ; initial elution with ethyl acetate/hexanes = 8: 2 in volume followed by elution with pure hexane) afforded the title compound as a colorless oil (3.64 g, 74% yield). TLC Rf (silica gel plates ; elution with ethyl acetate, UV detection): 0.46.

Reference： [1]Patent: WO2004/43929,2004,A1 .Location in patent: Page 53

40
[ 735333-61-6 ]
[ 89878-14-8 ]
[ 735333-63-8 ]

Yield	Reaction Conditions	Operation in experiment
85%	With sodium carbonate;bis(triphenylphosphine)palladium(II)-chloride; In tetrahydrofuran; water; at 20 - 80℃; for 24h;	[0444] To a solution of the title compound from Example 12, Step 1 (207 mg, 0.67 mmol) in 4 ml of THF were added <strong>[89878-14-8]diethyl(3-pyridyl)boran</strong>e (110 mg, 0.75 mmol), bis(triphenylphosphine)palladium(II) chloride (71 mg, 0.01 mmol), and a solution of sodium carbonate (320 mg, 3 mmol) in 2 ml of water. [0445] The resulting mixture was heated at 80 C. for six hours and then stirred at room temperature for 18 hours. Following dilution with 15 ml of water, the mixture was extracted with three 20 ml portions of dichloromethane. The combined organic layers were dried (Na2SO4) and concentrated to an oil. Purification by flash chromatography (40 micron mesh silica gel; elution with methanol: dichloromethane, 5:95 in volume) afforded the title compound as an oil (178 mg, 85% yield). [0446] Mass spectrum: m/z 313 (m+1). [0447] 1H NMR (400 MHz, CDCl3) delta 8.41 (d, 1H, J=1), 8.39 (d, 1H, J=1), 8.01 (s, 1H), 7.92 (s, 1H) 7.40 (m, 5H), 7.08 (m, 5H) 5.26 (s, 1H) ppm.

Reference： [1]Patent: US2004/229874,2004,A1 .Location in patent: Page 22

41
[ 797047-11-1 ]
[ 89878-14-8 ]
[ 797047-12-2 ]

Yield	Reaction Conditions	Operation in experiment
60%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; water; at 70℃;	To a solution of 5-bromo-2-nitro-3-pyrazol-1-yl-phenylamine (200 mg, 0.71 mmol) in THF (8 mL) was added, successively, 3-pyridyl-diethyl borane (157 mg), (tetrakistriphenylphosphine) palladium(0) (84 mg), and sodium carbonate (1.1 mL, 2.2 mmom of 2M aqueous). The resulting mixture was stirred at 70 C. overnight then cooled to room temperature. The reaction mixture was diluted with ethyl acetate (100 mL) and washed with water (50 mL), brine (50 mL), dried (MgSO4) then concentrated in vacuo. The resulting residue was purified by column chromatography over silica gel eluted with a gradient of ethyl acetate:hexanes (1:3, 1:2, 1:0, 2:1, 4:1, 8:1), to afford 120 mg (60%) of the title compound as a yellow solid. 1H NMR (DMSO-d6) delta 6.45 (br,s 2H), 6.55 (t, 1H), 7.1 (s, 1H), 7.25 (s, 1H), 7.55 (m, 1H), 7.7 (s, 1H), 8.1 (dt, 1H), 8.3 (d, 1H), 8.7 (d, 1H), 8.9 (s, 1H).

Reference： [1]Patent: US2004/235886,2004,A1 .Location in patent: Page 69
[2]Journal of Medicinal Chemistry,2008,vol. 51,p. 5243 - 5263

42
[ 159724-30-8 ]
[ 89878-14-8 ]
[ 159725-99-2 ]

Yield	Reaction Conditions	Operation in experiment
38%	With sodium hydrogencarbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water;Heating / reflux;	A mixture of 7-iodo-1-phenyl-5-trifluoromethylbenzimidazole (370mg, 1 mmol), diethyl 3-pyridylborane (220mg, 1. 5mmol), sodium bicarbonate (420mg, 5mmol) and tetrakis (triphenylphosphine) palladium (0) (29mg, 0. 025mmol) in a mixture of water (5ml) and dimethoxyethane (10ml) was stirred at reflux overnight. The cooled reaction mixture was partitioned between ethyl acetate and water, and the organic extract was purified by column chromatography on silica gel eluting with a mixture of dichloromethane and acetone (9: 1, v/v). The product was isolated by removal of solvent from appropriate eluate fractions followed by trituration of the residue with a mixture of water and ethanol. Yield: 130mg (38%), m/z, 340. 1 (M+H) +.

Reference： [1]Patent: WO2005/40131,2005,A1 .Location in patent: Page/Page column 20-21

43
[ 641615-49-8 ]
[ 89878-14-8 ]
[ 641615-50-1 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; water; at 80℃; for 44h;	Step 2 1-methyl-4-nitro-2-[4-(3-pyridyl)pyridin-2-ylamino]benzene To 20 ml of deaerated tetrahydrofuran-water (1:1), 264 mg of 2-[(4-chloro)pyridin-2-ylamino]-1-methyl-4-nitrobenzene obtained in the step 1, 162 mg of <strong>[89878-14-8]diethyl(3-pyridyl)boran</strong>e, 470 mg of potassium carbonate and 173 mg of tetrakis(triphenylphosphine)palladium (0) were added in turn and the mixture was stirred with heating at 80C for 44 hours under an argon atmosphere. The reaction solution was diluted with ethyl acetate to separate the aqueous layer, and then the aqueous layer was further extracted three times with ethyl acetate. The organic layers were combined, washed in turn with water and saturated saline and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography to obtain 247 mg of a crude product. The crude product was crystallized by adding chloroform-methanol and then collected by filtration to obtain 143 mg of the objective compound as an orange crystal. Melting point: 170-173C 1H-NMR(CDCl3)delta: 2.43(3H, s), 6.49(1H, br), 6.99(1H, s), 7.07(1H, dd), 7.41(2H, m), 7.87(2H, m), 8.37(1H, d), 8.68(1H, dd), 8.69(1H, s), 8.86(1H, d)

Reference： [1]Patent: EP1533304,2005,A1 .Location in patent: Page/Page column 21

44
[ 599191-71-6 ]
[ 89878-14-8 ]
[ 599191-72-7 ]

Yield	Reaction Conditions	Operation in experiment
	With cesium fluoride;palladium diacetate; DavePhos; In 1,4-dioxane; at 100℃; for 17h;	900 mg of diethyl-3-pyridylborane, 1.86 g of caesium fluoride, 18.4 mg of palladium acetate and finally 48 mg of 2-dicyclohexylphosphine-2-(N,N-dimethylamino)biphenyl are added to 1.5 g of N-[6-chloro-1-[[2(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide, described previously, in 40 cm3 of dioxane. The mixture is then heated at about 100 C. for 17 hours and then filtered through a sinter funnel and evaporated under reduced pressure (2 kPa; 50 C.). The residue is taken up in 75 cm3 of ethyl acetate and 50 cm3 of distilled water. The organic phase is washed again with 50 cm3 of distilled water and with 50 cm3 of saturated aqueous sodium chloride solution. The organic phase is dried over magnesium sulphate, filtered through a sinter funnel and then evaporated under reduced pressure under the conditions described previously. The residue is purified by chromatography under an argon pressure of 50 kPa, on a column of silica gel (particle size 40-60 mum; diameter 2.5 cm), eluting with a cyclohexane/ethyl acetate mixture (50/50 by volume) and collecting 25 cm3 fractions. The fractions containing the expected product are combined and evaporated under reduced pressure (2 kPa; 50 C.). [0488] After drying (90 Pa; 50 C.), 900 mg of N-[6-(3-pyridyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide are thus obtained in the form of a yellow oil. [0489] 1H NMR spectrum (300 MHz, (CD3)2SO-d6, delta in ppm): -0.09 (s: 9H); 0.84 (broad t, J=8 Hz: 2H); 0.98 (t, J=7.5 Hz: 3H); 1.70 (mt: 2H); 2.43 (t, J=7.5 Hz: 2H); 3.59 (t, J=8 Hz: 2H); 5.76 (s: 2H); 7.52 (dd, J=9 and 2 Hz: 1H); 7.55 (broad dd, J=8.5 and 4.5 Hz: 1H); 7.97 (d, J=9 Hz: 1H); 8.09 (broad s: 1H); 8.20 (ddd, J=8.5-2.5 and 2 Hz: 1H); 8.63 (dd, J=4.5 and 2 Hz: 1H); 9.02 (broad d, J=2.5 Hz: 1H); 10.51 (unresolved peak: 1H).

Reference： [1]Patent: US2004/14802,2004,A1 .Location in patent: Page/Page column 21

45
[ 754214-54-5 ]
[ 89878-14-8 ]
[ 866546-00-1 ]

Yield	Reaction Conditions	Operation in experiment
57%	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,2-dimethoxyethane; water; for 3h;Heating / reflux;	To a solution of 19 (1.77 g, 0.0057 mol), 3-diethylpyridyl borane (1,0 g, 0.0068 mol) in 80 mL of DME, was added PdCl2(Ph3P)2 (320 mg, 0.455 mmol) and aqueous 2M sodium carbonate (8.5 mL, 0.017 mol) under nitrogen. The reaction mixture was refluxed for 3 h. Cooled to rt and diluted with ethyl acetate and washed with brine. The organic layer was dried and concentrated to an oil that was subjected to flash chromatography (30% EtOAc-70% hexanes) to give 1 g (57%) of the desired material 20. 1H NMR CDCl3 8.9 (s, 1H), 8.5 (d, 1H), 8.4 (d, 1H), 8.0 (d, 1H), 7.9 (d, 1H), 7.5 (d, 1H), 7.2 (d, 1H), 6.5 (d, 1H), 0.85 (s, 9H), 0.55 (s, 6H).

Reference： [1]Patent: WO2005/95400,2005,A1 .Location in patent: Page/Page column 333; 334

46
[ 870526-65-1 ]
[ 89878-14-8 ]
[ 870526-75-3 ]

Yield	Reaction Conditions	Operation in experiment
53%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; for 4h;Heating / reflux;	Preparation 18 4-pyridin-3-yl-2-trityl-2H-indazole To a solution of the product of preparation 3 (4.39 g, 10.0 mmol) in toluene (80 mL) and ethanol (50 mL) was added diethyl-(3-pyridyl)-borane (commercially available, 1.47 g, 10.0 mmol), tetrakis(triphenylphosphine)palladium(0) (577 mg, 0.50 mmol) and sodium carbonate (1.59 g, 15.0 mmol as a solution in water 2 mL). The reaction mixture was refluxed for 4 h, then cooled, diluted with ethyl acetate (100 mL) and washed with water (100 mL). The organic layer was separated and the aqueous layer was extracted with EtOAc (2*80 mL). The combined organic layers were dried over Na2SO4 and evaporated to a yellow oil. This was taken up in pentane/EtOAc 1:1 (20 mL) which induced crystallisation. The solvent was evaporated and the solid triturated with hot ethanol and the solid collected on a filter yielding the title compound (2.32 g, 53%) as a cream solid. MS (APCI+)=438 (MH+)

Reference： [1]Patent: US2005/267096,2005,A1 .Location in patent: Page/Page column 27

47
[ 103977-79-3 ]
[ 89878-14-8 ]
[ 100325-56-2 ]

Yield	Reaction Conditions	Operation in experiment
47%	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; water; for 96h;Heating / reflux;	d) 2, 4-Difluoro-3- (pyridin-3-yl) phenylamine; A mixture of <strong>[103977-79-3]3-bromo-2,4-difluorophenylamine</strong> (from Example 2, step b) (12.5 g, 60 mmol), diethyl (3-pyridyl) borane (10.6 g, 72 mmol) and potassium carbonate (16.6 g, 120 mmol) in tetrahydrofuran (150 ml) and water (50 ml) was degassed with nitrogen for 15 min. To this mixture was added tetrakis (triphenylphosphine) palladium (0) (2.1 g, 1.8 mmol) and the reaction was heated at reflux for 4 days. The mixture was cooled to ambient temperature and the majority of the tetrahydrofuran removed on a rotary evaporator. The residue was diluted with water (250 ml), extracted with ethyl acetate (300 ml), the organics were washed with water, brine, dried over anhydrous magnesium sulfate, filtered and pre- adsorbed onto silica. Purification by chromatography [silica gel, 10-50% EtOAc/isohexane (containing 1% triethylamine) ] afforded 5.8 g (47%) of the title compound as a cream-coloured solid : 1H NMR (400 MHz, CDC13) 5 3.69 (2H, br s), 6.72-6. 88 (2H, m), 7.39 (1H, dd, J 8, 5), 7.80 (1H, d, J 8), 8.62 (1H, dd, J 5,1), 8.72 (1H, s).

Reference： [1]Patent: WO2003/93272,2003,A1 .Location in patent: Page/Page column 46

48
[ 625127-09-5 ]
[ 89878-14-8 ]
[ 625127-14-2 ]

Yield	Reaction Conditions	Operation in experiment
100%	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In methanol; water; toluene; at 80℃;	To a solution of diethyl (3-pyridyl) borane (703 mg, 4.782 mmol) and the bromide (Step A, Intermediate 13) (1.5 g, 4.347 mmol) in toluene/methanol (7/3,30 mL) was added sodium carbonate (1.15 g, 10.89 mmol), Pd (PPh3) 2Cl2 (152 mg, 0.217 mmol) and water (6 mL), and the solution was heated at 80 C overnight. The solution was then filtered through celite, concentrated in vacuo, extracted with methylene chloride, washed with 1N sodium hydroxide, dried over sodium sulfate, concentrated in vacuo and purified via MPLC (0-50% ethyl acetate/hexanes) to yield the title compound (1.5 g, 100%).

Reference： [1]Patent: WO2003/93231,2003,A2 .Location in patent: Page/Page column 96

49
[ 364760-20-3 ]
[ 89878-14-8 ]
[ 364760-46-3 ]

Yield	Reaction Conditions	Operation in experiment
81%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane;	EXAMPLE 168 4,5,-Dihydro-1-methyl-8-[4-(3-pyridinyl)phenoxy)-1H-thieno[3,4-g]indazole-6-carboxylic Acid Ethyl Ester: A solution of 8-(4-bromophenoxy)-4,5,-dihydro-1-methyl-1H-thieno[3,4-g]indazole-6-carboxylic acid ethyl ester (2.00 g), <strong>[89878-14-8]diethyl(3-pyridyl)boran</strong>e (0.76 g), tetrakis(triphenylphosphine)palladium (0.26 g), and an aqueous 2 N solution of sodium carbonate (6.6 ml) in dimethoxyethane (60 ml) was heated at reflux for 12 hours under argon atmosphere. The reaction solution was poured into water and extracted with ethyl acetate. The organic layer was washed successively with water and an aqueous, saturated solution of sodium chloride, dried (MgSO4), and then evaporated under reduced pressure to remove the solvent. The thus-obtained, residual oily substance was subjected to chromatography on silica gel. From the fractions eluted with ethyl acetate-hexane (2:1), the title compound (1.61 g, 81%) was obtained as colorless prisms. Melting point: 160-161 C. According to the same manner as that in Example 168, compounds in Examples 169 to 171 were synthesised.

Reference： [1]Patent: US2003/158245,2003,A1

50
[ 656-64-4 ]
[ 89878-14-8 ]
[ 425378-77-4 ]

Yield	Reaction Conditions	Operation in experiment
46%	With potassium carbonate;tetrakis(triphenylphosphine)palladium (0); In 1,2-dimethoxyethane; water;	A mixture of <strong>[656-64-4]3-bromo-4-fluorophenylamine</strong> (7.92 g, 41.7 mmol), diethyl(3-pyridyl)borane (6.74 g, 45.9 mmol), tetrakis(triphenylphosphine)palladium(0) (0.96 g, 0.83 mmol) and potassium carbonate (17.26 g, 125 mmol) in 1,2-dimethoxyethane (30 ml) and water (15 ml) was heated at 80 C. for 20 h. After cooling to ambient temperature the reaction was partitioned between ethyl acetate (500 ml) and water (500 ml). The organics were washed with brine (400 ml), dried (Na2SO4), filtered and concentrated in vacuo. Purification of the residue by flash chromatography (silica gel, 0%-20% EtOAc/CH2Cl2) gave 4-fluoro-3-(pyridin-3-yl)phenylamine (3.64 g, 46%) as a colourless oil that solidified on standing to afford a white solid: 1H NMR (360 MHz, CDCl3) delta 3.65 (2H, s), 6.65-6.72 (2H, m), 6.99 (1H, dd, J 9, 9 Hz), 7.33-7.37 (1H, m), 7.84-7.86 (1H, m), 8.58 (1H, d, J 4 Hz), 8.76 (1H, m).

Reference： [1]Patent: US2003/55060,2003,A1

51
[ 859213-22-2 ]
[ 89878-14-8 ]
[ 859213-23-3 ]

Yield	Reaction Conditions	Operation in experiment
		Step 2 1-methyl-4-nitro-2-[6-(3-pyridyl)pyrimidin-4-ylamino]benzene 2.00 g of 2-[(6-chloro)pyrimidin-4-ylamino]-1-methyl-4-nitrobenzene obtained in the step 1 was dissolved in 80 ml of tetrahydrofuran, 1.22 g of <strong>[89878-14-8]diethyl(3-pyridyl)boran</strong>e and 870 mg of tetrakis(triphenylphosphine)palladium (0) were added in turn, and then the mixture was stirred at room temperature under an argon atmosphere. To the mixture were added 1.27 g of potassium hydroxide and 10 ml of water and then the reaction solution was heated at reflux for 6 hours. The reaction solution was mixed with water, followed by extraction with ethyl acetate three times, and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The crude crystals were washed with ethyl acetate to obtain 1.43 g of the objective compound as brown crystals. Melting point: 187-192C

Reference： [1]Patent: EP1702917,2006,A1 .Location in patent: Page/Page column 34-35

52
[ 60-29-7 ]
[ 32138-69-5 ]
[ 89878-14-8 ]
[ 154229-19-3 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate; In tetrahydrofuran; bis(triphenylphosphine)palladium(II) dichloride;	(c) 17-(3-Pyridyl)androsta-5,16-dien-3beta-ol Diethyl(3-pyridyl)borane (3.23 g, 22 mmol) from Aldrich Chemical Co. Ltd. was added to a stirred solution of 17-iodo-androsta-5,16-dien-3beta-ol (7.96 g, 20 mmol) in THF (120 ml) containing bis(triphenylphosphine)palladium (II) chloride (140 mg, 0.2 mmol). An aqueous solution of sodium carbonate (2M, 50 ml) was then added and the mixture heated, with stirring, by an oil bath at 80 C. for 48 h, and allowed to cool. The mixture was partitioned between Et2 O and water the organic phase was separated, dried (Na2 CO3) and twice concentrated from Et2 O by evaporation to remove THF (with Et2 O). The residual solid was then washed with Et2 O (100 ml), the Et2 O solution decanted off, and the remaining white solid recrystallized from toluene (3.94 g, 56%).

Reference： [1]Patent: US5604213,1997,A

53
petroleum-diethyl ether [ No CAS ]
[ 115375-60-5 ]
[ 89878-14-8 ]
[ 154229-18-2 ]

Yield	Reaction Conditions	Operation in experiment
84%	With sodium carbonate; In tetrahydrofuran; bis(triphenylphosphine)palladium(II)-chloride;	(b) 3beta-Acetoxy-17-(3-pyridyl)androsta-5,16-diene Diethyl(3-pyridyl)borane (3.38 g, 23 mmol) from Aldrich Chemical Co. Ltd. was added to a stirred solution of 3beta-acetoxyandrosta-5,16-dien-17-yl trifluoromethanesulphonate (6.94 g, 15 mmol) in THF (75 ml) containing bis(triphenylphosphine)palladium(II) chloride (0.105 g, 0.15 mmol). An aqueous solution of sodium carbonate (2M, 30 ml) was then added and the mixture heated, with stirring, by an oil bath at 80 C. for 1 h, and allowed to cool. The mixture was partitioned between diethyl ether and water, the ether phase was dried (Na2 CO3), filtered through a short plug of silica, and concentrated. Chromatography, on elution with light petroleum-diethyl ether (2:1), afforded the title compound (4.95 g, 84%) which crystallized from hexane, m.p. 144-145 C., 1 H-NMR(CDCl3) inter alia delta1.05(3H,s, 19-CH3), 1.08(3H,s,18-CH3), 2.04(3H,s,CH3 CO2), 4.60(1H,m,3alpha-H), 5.42(1H,dm, J 4.7 Hz,6-H), 5.99(1H,m,16-H), 7.23(1H,m,Py 5-H) 7.65(1H,m,Py 4-H), 8.46(1H,m,Py 6-H), 8.62(1H,m,Py 2-H). Anal. Calcd: C, 79.75; H, 8.50; N, 3.58. Found: C, 79.78; H, 8.52; N, 3.54%.

Reference： [1]Patent: US5604213,1997,A

54
[ 853-23-6 ]
[ 115375-60-5 ]
[ 89878-14-8 ]
[ 154229-18-2 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In tetrahydrofuran; water; at 80℃; for 5h;	Abiraterone acetate 1; Pd(PPh3)2Cl2 (97 mg, 0.14 mmol, 0.006 eq.), diethyl (3-pyridyl)borane (6.1 lg, 41.5 mmol, 1.7 eq.) and 2M Na2C03 (aq) (55 cm3, 111 mmol, 4.5 eq.) were added consecutively to a stirred solution of the mixture of triflate 3 and ketone 2 (11.20 g, 27.7 mmol assuming all substrate is triflate 3) in THF (130 cm3, 10 vol.). The reaction was heated to 80 C and stirred at this temperature for 5 hours. The reaction was cooled to room temperature and partitioned between ethyl acetate (130 cm3, 11 vol.) and water (130 cm3, 11 vol.). The layers were separated and the aqueous layer extracted with ethyl acetate (65 cm3, 5.5 vol.). The combined organic layers were dried over MgSCU and concentrated under reduced pressure to yield a brown oil. This oil was stirred in MeOH (35 cm3, 3 vol.) and was gently warmed with a hot air gun. A white solid (unreacted diethyl (3-pyridyl)borane) precipitated and was filtered. The filtrate was concentrated under reduced pressure to yield a brown oil (9.54g, 100 % yield). *H NMR showed that this material was a 3 : 1 mixture of abiraterone acetate 1 and ketone 2.

Reference： [1]Patent: WO2006/21776,2006,A1 .Location in patent: Page/Page column 9-11

55
6-bromo-2-(2-[2-(4-methyl-piperazin-1-yl)-phenyl]-ethyl)-3,4-dihydro-2H-isoquinolin-1-one [ No CAS ]
[ 89878-14-8 ]
2-(2-[2-(4-methyl-piperazin-1-yl)-phenyl]-ethyl)-6-pyridin-3-yl-3,4-dihydro-2H-isoquinolin-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With potassium hydroxide; tetrabutylammomium bromide;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; for 2.5h;Heating / reflux;	EXAMPLE 34;2-f2-F2-(4-Methylpiperazin-1-v?phenvnethyl>-6-pyridin-3-yl-3,4-dihydro-2H-isoquinolin-1-one;.Example 32 (0.30 g, 0.70 mmol), <strong>[89878-14-8]3-diethylboranylpyridine</strong> (0.115 g, 0.78 mmol), tetrakis(triphenylphosphine)palladium (0) (80 mg, 0.07 mmol), tetra-n-butylammonium bromide (0.12 g, 0.37 mmol) and freshly ground KOH (0.20 g, 3.56 mmol) in THF (15 mL) were refluxed for 2.5 hrs. The reaction mixture was concentrated and the residue partitioned between EtOAc and water. The organics were washed with brine, dried (MgSO4) and concentrated to an orange oil. Chromatography with 20% MeOH/ EtOAc then 20% MeOH/ EtOAc +0.5% NH4OH gave 0.223 g (75%) of Example 34 as a thick orange oil, the HCI salt had: mp 160-1700C; NMR (DMSO-d6) 11.17 (br s, 1 H), 9.25 (d, J = 1.7 Hz, 1 H), 8.88-8.83(m, 2H), 8.08 (dd, J = 8.3, 5.6 Hz, 1 H), 7.98 (d, J = 8.7 Hz, 1 H), 7.85-7.81 (m, 2H), 7.25-7.17(m, 2H), 7.10 (d, J = 7.1 Hz, 1 H), 7.05 (t, J = 7.5 Hz, 1 H), 3.72 (t, J = 7.7 Hz, 2H), 3.55 (t, J =6.4 Hz, 2H), 3.42 (br d, J = 11.6 Hz, 2H), 3.24-3.00 (m, 6H), 2.96 (t, J = 6.4 Hz, 2H), 2.89 (t, J = 7.7 Hz, 2H), 2.78 (d, J= 4.6 Hz, 3H).

Reference： [1]Patent: WO2006/48727,2006,A1 .Location in patent: Page/Page column 63

56
1-(4-bromophenyl)-3,4,8,9-tetrahydro-6-methoxy-3,3,8,8-tetramethylfuro[2,3-h]isoquinoline [ No CAS ]
[ 89878-14-8 ]
3,4,8,9-Tetrahydro-6-methoxy-3,3,8,8-tetramethyl-1-[4-(3-pyridinyl)phenyl]furo[2,3-h]isoquinoline dihydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	With hydrogenchloride; In 3,4,8,9-Tetrahydro-6-methoxy-3,3,8,8-tetramethyl-1-[2-(4-pyridinyl)phenyl]furo[2,3-h]isoquinoline; ethyl acetate;	EXAMPLE 257 3,4,8,9-Tetrahydro-6-methoxy-3,3,8,8-tetramethyl-1-[4-(3-pyridinyl)phenyl]furo[2,3-h]isoquinoline dihydrochloride By the method similar to that in EXAMPLE 254 and starting from 1-(4-bromophenyl)-3,4,8,9-tetrahydro-6-methoxy-3,3,8,8-tetramethylfuro[2,3-h]isoquinoline and 3-(diethylboryl)pyridine, a free base of the title compound was obtained. This was dissolved in ethyl acetate, combined with 4 M hydrogen chloride/ethyl acetate solution, concentrated under reduced pressure to obtain the title compound. Yield: 84%. Amorphous. 1H NMR (DMSO-d6) delta 1.22 (6H, s), 1.48 (6H, s), 2.29 (2H, s), 3.19 (2H, s), 3.95 (3H, s), 7.13 (1H, s), 7.82 (2H, d, J = 8.4 Hz), 7.92-7.99 (1H, in), 8.16 (2H, d, J = 8.4 Hz), 8.74 (1H, d,J = 7.8 Hz), 8.87 (1H, d, J = 5.0 Hz), 9.31 (1H, s).

Reference： [1]Patent: EP1270577,2003,A1

57
[ 108-36-1 ]
[ 89878-14-8 ]
[ 265644-07-3 ]
[ 4422-32-6 ]

Yield	Reaction Conditions	Operation in experiment
70%	With tetra(n-butyl)ammonium hydroxide; sodium carbonate;tetrakis(triphenylphosphine)palladium (0); In 1,2-dimethoxyethane; diethyl ether; water;	Part A 3-[3-(Tri-n-butylstannanyl)phenyl]Pyridine A mixture of 1,3-dibromobenzene (105.0 g, 0.45 mol), diethyl(3-pyridyl)borane (30.0 g, 0.204 mol) and tetrabutylammonium hydroxide (2 ml of a 40 wt % solution in water) in 1,2-dimethoxyethane (200 ml) and sodium carbonate (100 ml of a 2M solution) was degassed with nitrogen for 15 min before addition of tetrakis(triphenylphosphine)palladium(0) (4.5 g, 3.9 mmol). The mixture was heated at 80 C. for 18 h, cooled to room temperature, diluted with ethyl acetate and extracted with 1M hydrochloric acid (4*250 ml). The combined aqueous phases were made basic with solid sodium hydroxide and then extracted with diethyl ether. The organic layer was washed with water, brine, dried over sodium sulphate and concentrated to give a yellow oil. Purification by silica gel chromatography eluding with isohexane on a gradient of diethyl ether (10% to 50%) gave 3-(3-bromophenyl)pyridine (33.5 g, 70%) as a colourless oil. 1H NMR (400 MHz, CDCl3) deltaH 7.28-7.40 (2H, m), 7.48-7.57 (2H, m), 7.73 (1H, t, J 2), 7.82-7.87 (1H, m), 8.62 (1H, s), 8.80 (1H, s).

Reference： [1]Patent: US2002/188000,2002,A1

58
[ 1067192-68-0 ]
[ 89878-14-8 ]
[ 1067193-13-8 ]

Yield	Reaction Conditions	Operation in experiment
58%	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 100℃; for 16h;	A mixture of 2-(2-bromo-4-m"tro-phenyl)-2-methyl-propionitrile (400 mg; 1.49 mmol), prepared as described in H l(B), diethyl-(3-pyridyl)-borane (328 mg; 2.24 mmol), 2M K2CO3 (1.49 mL; 2.98 mmol) and tetrakis(triphenylphospine)palladium(0) (34 mg; 0.03 mmol) in dioxane (10 mL) was heated at 100C for 16 hours. The solvent was removed under vacuum and the residue taken up with DCM and washed with water. The organic phase was dried over Na2SO4, filtered and evaporated to dryness. The crude compound was purified by ion- <n="177"/>exchange chromatography [SCX, DCM/MeOH (1/1) to MeOH/NH4OH (9/1)], to give the title compound as a yellow solid (234 mg; 58% yield).LCMS (RT): 0.96 min (Method D); MS (ES+) gave m/z: 268.0 (MH+).

Reference： [1]Patent: WO2008/117175,2008,A2 .Location in patent: Page/Page column 175-176

59
[ 1067192-69-1 ]
[ 89878-14-8 ]
[ 1067192-87-3 ]
[ 1067192-86-2 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 110℃; for 20h;	A mixture of 2-(4-amino-2-bromo-phenyl)-2-methyl-propionitrile (157 mg; 0.66 mmol), prepared as described in H l(C), diethyl-(3-pyridyl)-borane (290 mg; 1.96 mmol), 2M K2CO3 (657 uL; 130 mmol) and tetrakis(triphenylphospine)palladium(0) (30 mg; 0.03 mmol) in dioxane (10 mL) was heated at 110C for 20 hours. The solvent was removed under vacuum and the residue taken up with DCM and washed twice with water. The organic phase was dried over Na2SO4, filtered and evaporated to dryness. The crude compound was used in the next step without any further purification. <n="155"/>132(A) LCMS (RT): 1.5 min (Method A); MS (ES+) gave m/z: 238.13 (MH+). 133(A) LCMS (RT): 2.8 min (Method A); MS (ES+) gave m/z: 189.13 (MH+).

Reference： [1]Patent: WO2008/117175,2008,A2 .Location in patent: Page/Page column 153-154

60
[ 13667-12-4 ]
[ 89878-14-8 ]
[ 1064194-22-4 ]

Reference： [1]Journal of the American Chemical Society,2008,vol. 130,p. 14368 - 14369

61
1-{4-amino-2-[1-(4-iodo-benzenesulfonyl)-piperidin-4-ylamino]-thiazol-5-yl}-1-(2,6-difluoro-phenyl)-methanone [ No CAS ]
[ 89878-14-8 ]
1-{4-amino-2-[1-(4-pyridin-3-yl-benzenesulfonyl)-piperidin-4-ylamino]-thiazol-5-yl}-1-(2,6-difluoro-phenyl)-methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
47%		2 TFA The title compound was prepared as follows. According to conditions from BLEICHER, et al, J. Org. CHEM., Vol. 43, pp. 1109-1118 (1998), to a mixture of 1- {4-AMINO-2-T1- (4-IODO- BENZENESULFONYL)-PIPERIDIN-4-YLAMINO]-THIAZOL-5-YL}-1-(2, 6-DIFLUORO-PHENYL)-METHANONE (Example F42 ; 600 mg, 1. 00 MMOL) and K2CO3 (0. 22 g, 2. 5 MMOL) in DME (3. 6 ml) and H20 (1. 6 ml) were added sequentially Pd/C (10% wt, 27 mg), Cul (9. 5 mg) and PPH3 (25 MG). The mixture stirred for a half hour and diethyl (3-pyridyl) borane (0. 37 G, 2. 5 mmol) was added. After heating at 80 C for 4 hours, additional Pd/C, Cul, PPH3, and more diethyl (3- pyridyf) borane (1. 03 G, 6. 95 mmol) were added. After 3 days at 80 C, methanol was added and the mixture was filtered. The filtrate was concentrated and ethyl acetate added. The organic solution was washed with water, separated, dried over MGS04, filtered, and concentrated to give a yellow solid, which was purified via preparative HPLC to afford 0. 26 G of yellow solid in 47% yield. H NMR (DMSO-d6) : 8 8. 99 (s, 1H), 8. 65 (d, 1H, J=4. 9 Hz), 8. 27 (dt, 1H, J=1. 6, 8. 8 Hz), 7. 96 (d, 2H, J=8. 5 Hz), 7. 91 (br, 2H), 7. 76 (d, 2H, J=8. 5 Hz), 7. 62 (dd, 1 H, J=4. 9, 7. 9 Hz), 7. 39 (m, 1H), 7. 05 (dd, 2H, J=7. 6, 8. 2 Hz), 3. 42-3. 39 (m, 2H), 2. 58-2. 45 (m, 2H), 1. 93-1. 79 (m, 2H), 1. 54-1. 38 (m, 2H). LC-ESIMS : (MH+) : 556. Anal. Calcd. for C26H23F2N503S2 * 2. 0 TFA # 0. 5 H20 : C, 45. 46 ; H, 3. 31 ; N, 8. 83 ; S, 8. 09. Found : C, 45. 54 ; H, 3. 54 ; N, 8. 65 ; S, 8. 00

Reference： [1]Patent: WO2004/74283,2004,A1 .Location in patent: Page 126; 127

62
[ 1224436-05-8 ]
[ 89878-14-8 ]
[ 1224434-37-0 ]

Yield	Reaction Conditions	Operation in experiment
50%	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In tetrahydrofuran; water; at 80℃;Inert atmosphere;	To a solution of (4aR,4bS,6aS,9aS,9bR)-1,4a,6a-trimethyl-2-oxo-2,3,4,4a,4b,5,6,6a,9,9a,9b,10-dodecahydro-1H-indeno[5,4-f]quinolin-7-yl trifluoromethanesulfonate (4.3 g, mmol) in THF (100 mL) was added 3-(diethylboryl)pyridine (2.94 g, 20 mmol, 2.0 equiv), (Ph3P)2 PdCl2 (70 mg, 0.1 mmol, 0.01 equiv) and sodium carbonate (4.77 g, 45 mmol, in 40 mL of water). The mixture was degassed and refilled with nitrogen (3×), sealed and heated at 80 C. overnight. The reaction mixture was cooled to room temperature, extracted with DCM (2×), combined, dried (Na2 SO4), concentrated and purified by column chromatography on silica gel (DCM/MeOH, 9.5:0.5) to give (4aR,4bS,6aS,9aS,9bS)-1,4a,6a-trimethyl-7-(pyridin-3-yl)-4,4a,4b,5,6,6a,9,9a,9b,10-decahydro-1H-indeno[5,4-f]quinolin-2(3H)-one (1.8 g, 50%) as a off-white solid. MS calcd for (C24H30N2O+H)+: 363.2; MS found (electrospray): (M+H)+=363.2; 1H NMR (CDCl3, 300 MHz) major characteristic peaks: delta 8.62 (s, 1H), 8.46 (brs, 1H), 7.64 (d, 1H), 7.23 (m, 1H), 6.02 (s, 1H), 5.06 (brs, 1H), 3.13 (s, 3H), 1.10 (s, 3H), 1.06 (s, 3H).

Reference： [1]Patent: US2010/105700,2010,A1 .Location in patent: Page/Page column 42-43

63
[ 174614-35-8 ]
[ 89878-14-8 ]
[ 1224434-39-2 ]

Yield	Reaction Conditions	Operation in experiment
81%	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In tetrahydrofuran; water; at 80℃;Inert atmosphere;	To a solution of (3aS,3bR,9aR,9bS,11aS)-5,9a,11a-trimethyl-7-oxo-3a,3b,4,5,7,8,9,9a,9b,10,11,11a-dodecahydro-3H-cyclopenta[i]phenanthridin-1-yl trifluoromethanesulfonate (4.6 g, 10.6 mmol) in tetrahydrofuran (150 mL) was added diethyl 3-pyridoborane (3.12 g, 2 eq), sodium carbonate (5.06 g, 4.5 eq) in water (30 mL), and bis(triphenylphosphine) palladium chloride (0.75 g, 0.1 eq). The mixture was thoroughly degassed, and heated under nitrogen at 80 C. for overnight. After being filtered through a pad of Celite, the crude product was purified with silica gel column (5% to 10% methanol in dichloromethane) to give (3aS,3bS,9aR,9bS,11aS)-5,9a,11a-trimethyl-1-(pyridin-3-yl)-3b,4,5,8,9,9a,9b,10,11,11a-decahydro-3H-cyclopenta[i]phenanthridin-7(3aH)-one (3.1 g, 81%). MS calcd for (C24H31N2O)+: 362.2; MS found (electrospray): 363.2; 1H NMR (CDCl3, 300 MHz) major characteristic peaks: delta 8.61 (brs, 1H), 8.48 (d, 1H), 7.64 (d, 1H), 7.24 (m, 1H), 5.98 (s, 1H), 5.09 (s, 1H), 2.82 (s, 3H), 1.30 (s, 3H), 1.07 (s, 3H).

Reference： [1]Patent: US2010/105700,2010,A1 .Location in patent: Page/Page column 45-46

64
[ 1224436-12-7 ]
[ 89878-14-8 ]
[ 1224436-13-8 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In tetrahydrofuran; water; at 80℃;Inert atmosphere;	To a solution of (3aS,3bR,9aR,9bS,11aS)-9a,11a-dimethyl-7-oxo-5-((2-(trimethylsilyl)ethoxy)methyl)-3a,3b,4,5,7,8,9,9a,9b,10,11,11a-dodecahydro-3H-cyclopenta[i]phenanthridin-1-yl trifluoromethanesulfonate (13.8 g, 0.021 mmol based previous reaction) in tetrahydrofuran (300 mL) was added diethyl 3-pyridoborane (6.18 g, 2 eq), sodium carbonate (10 g, 4.5 eq) in water (30 mL), and bis(triphenylphosphine) palladium chloride (1.47 g, 0.1 eq). The mixture was thoroughly degassed, and heated under nitrogen at 80 C. for overnight. After being filtered through a pad of Celite, the crude product was purified with silica gel column (5% to 10% methanol in dichloromethane) to give (3aS,3bS,9aR,9bS,11aS)-9a,11a-dimethyl-1-(pyridin-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-3b,4,5,8,9,9a,9b,10,11,11a-decahydro-3H-cyclopenta[i]phenanthridin-7(3aH)-one (7.5 g) as brown sticky solid, which was used for next step reaction without further purification. MS calcd for (C29H42N2O2Si)+: 478.3; MS found (electrospray): 479.3; 1H NMR (CDCl3, 300 MHz) major characteristic peaks: delta 8.60 (brs, 1H), 8.45 (d, 1H), 6.00 (brs, 1H), 5.38 (s, 1H), 4.60 (d, 1H), 4.440 (d, 1H), 1.30 (s, 3H), 0.80 (s, 3H), 0.0 (s, 9H).

Reference： [1]Patent: US2010/105700,2010,A1 .Location in patent: Page/Page column 46

65
[ 1224436-29-6 ]
[ 89878-14-8 ]
[ 1224435-30-6 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In tetrahydrofuran; water; at 80℃;Inert atmosphere;	To a solution of (3aS,3bR,9aR,9bS,11aS)-5-ethyl-9a,11a-dimethyl-7-oxo-3a,3b,4,5,7,8,9,9a,9b,10,11,11a-dodecahydro-3H-cyclopenta[i]phenanthridin-1-yl trifluoromethanesulfonate (10.6 mmol) in tetrahydrofuran (150 mL) is added diethyl 3-pyridoborane (3.12 g, 21.2 mmol), sodium carbonate (5.06 g,) in water (30 mL), and bis(triphenylphosphine) palladium chloride (0.75 g,). The mixture is thoroughly degassed, and heated under nitrogen at 80 C. for overnight. After being filtered through a pad of Celite, the crude product is purified with silica gel column (5% to 10% methanol in dichloromethane) to give (3aS,3bS,9aR,9bS,11aS)-5-ethyl-9a,11a-dimethyl-1-(pyridin-3-yl)-3b,4,5,8,9,9a,9b,10,11,11a-decahydro-3H-cyclopenta[i]phenanthridin-7(3 aH)-one.

Reference： [1]Patent: US2010/105700,2010,A1 .Location in patent: Page/Page column 65-66

66
[ 1224436-09-2 ]
[ 89878-14-8 ]
[ 1224436-08-1 ]

Yield	Reaction Conditions	Operation in experiment
64%		To a solution of (4aR,4bS,6aS,9aS,9bR)-tert-butyl 4a,6a-dimethyl-2,7-dioxo-2,3,4,4a,4b,5,6,6a,7,8,9,9a,9b,10-tetradecahydro-1H-indeno[5,4-f]quinoline-1-carboxylate (12 g, 31 mmol) in DCM (150 mL) at 0 C. was added Tf2O (5.7 mL, 34 mmol). The mixture was stirred at 0 C. for 30 min. To the solution was added a solution of triethylamine (4.3 mL, 31 mmol) in DCM (50 mL) dropwise over 30 min. The mixture was slowly warm up to room temperature, and stirred overnight. After water (25 mL) was added, the reaction mixture was extracted with DCM (2×). The organic layers were combined, washed with NaHCO3, dried (Na2 SO4), concentrated and passed through a short silica gel column, quickly washed with DCM-MeOH (9.5:0.5), concentrated to dry to give ((4aR,4bS,6aS,9aS,9bR)-tert-butyl 4a,6a-dimethyl-2-oxo-7-(trifluoromethylsulfonyloxy)-2,3,4,4a,4b,5,6,6a,9,9a,9b,10-dodecahydro-1H-indeno[5,4-f]quinoline-1-carboxylate (8 g, 50%), which was used for next reaction without further purification. A mixture of ((4aR,4bS,6aS,9aS,9bR)-tert-butyl 4a,6a-dimethyl-2-oxo-7-(trifluoromethylsulfonyloxy)-2,3,4,4a,4b,5,6,6a,9,9a,9b,10-dodecahydro-1H-indeno[5,4-f]quinoline-1-carboxylate (930 mg, 1.79 mmol), 3-(diethylboryl)pyridine (527 mg, 3.58 mmol), (Ph3P)2 PdCl2 (63 mg, 0.11 mmol, 0.05 equiv) and Na2 CO3 (854 mg, 8.06 mmol, in 2 mL of water) was heated under nitrogen at 80 C. overnight. After being cooled to room temperature, water was added, extracted with ethyl acetate (3×). The aqueous layers were acidified with 1N HCl to pH 1.5 extracted with ethyl acetate (3×), dried (Na2 SO4), concentrated to dry to give 3-((3aS,5aS,6R,9aS9bS)-3a,6-dimethyl-7-oxo-3-(pyridin-3-yl)-3a,4,5,5a,6,7,8,9,9a,9b-decahydro-1H-cyclopenta[a]naphthalen-6-yl)propanoic acid (400 mg, 64%). MS calcd for (C23H29NO3+H)+: 368.2; MS found (electrospray): (M+H)+: 368.2; 1H NMR (CDCl3, 300 MHz) major characteristic peaks: delta 8.60 (s, 1H), 8.45 (d, 1H), 7.65 (d, 1H), 7.26 (d, 1H), 6.00 (s, 1H), 1.15 (s, 3H), 1.08 (s, 3H).

Reference： [1]Patent: US2010/105700,2010,A1 .Location in patent: Page/Page column 43

67
[ 6966-01-4 ]
[ 89878-14-8 ]
[ 1232423-31-2 ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 2320 - 2330

68
[ 358-23-6 ]
[ 89878-14-8 ]
[ 15807-55-3 ]
[ 1315356-48-9 ]
[ 1315356-46-7 ]

Yield	Reaction Conditions	Operation in experiment
79.6%		Example 46EPreparation of Compounds (45) and (46) To a solution of compound (45e) and compound (46c) (0.6 g) in THF (30 mL) was added diethyl (3-pyridyl)borane (0.255 g), bis(triphenylphosphine)palladium(II) chloride (51 mg) and 2 N aqueous Na2CO3 (0.45 g). The mixture was degassed and refilled with Argon gas three times. The mixture was heated at 80 C. overnight. The reaction was monitored by TLC. The mixture was cool to room temperature and extracted with EtOAc (2×20 mL). The organic layers were combined, washed with brine (2×20 mL) and dried over Na2SO4. The solution was concentrated and purified by column chromatography on silica gel (EtOAc/Hexanes=1:5) to give the mixture of compound (45) and compound (46) (0.4 g, 79.6%). The regioisomeric mixture was purified by preparative HPLC to isolate compound (45) and compound (46). Compound (45): Retention time at HPLC: 10.426 min [Mobile phase: B %=10-100 (gradient 20 min); B=MeCN, A=H2O (0.1% TFA); Flow rate: 0.8 mL/min; UV=266 nm column: zorbax Eclipse XDB-C8 5u, (150×4.6 mmID)]. MS calculated for (C24H3iNO2) [M+H]+366.51 Found: 366.5 ; [2M+Na]+754.02 Found: 753.6 1H NMR (CDCl3, 300 MHz): 8.65 (1H), 8.45 (1H), 7.6-7.7 (1H), 7.19 (1H), 6.0 (1H), 4.26-4.31 (1H), 4.12 (1H), 2.8-2.9 (1H), 2.2-2.3 (1H), 2.1-2.13 (1H), 1.9-2.05 (2H). 13C NMR (CDCl3, 300 MHz): 175.84, 151.51, 147.91, 147.82, 133.69, 132.82, 129.18, 123.05, 64.60, 57.11, 53.98. Compound (46): Retention time at HPLC: 10.56 min [Mobile phase: B %=10-100 (gradient 20 min); B=MeCN, A=H2O 0.1% TFA); Flow rate: 0.8 mL/min; UV=266 nm column: zorbax Eclipse XDB-C8 5u, (150*4.6 mmID)]. MS calculated for (C24H3iNO2) [M+H]+366.51 Found: 366.4; [2M+Na]+754.02 Found: 753.5 . 1H NMR (CDCl3, 300 MHz): 8.65 (1H), 8.45 (1H), 7.65 (1H), 7.18 (1H), 6.0 (1H), 4.25 (1H), 3.68 (1H), 2.7 (1H), 2.5 (1H). 13C NMR (CDCl3, 300 MHz): 176.08, 151.55, 147.92, 147.84, 133.66, 132.80, 129.09, 123.05, 69.98, 57.12, 53.78, 48.74, 47.25.

Reference： [1]Patent: US2011/178065,2011,A1 .Location in patent: Page/Page column 80

69
[ 1315357-79-9 ]
[ 89878-14-8 ]
[ 1315357-80-2 ]

Yield	Reaction Conditions	Operation in experiment
66.8%	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In tetrahydrofuran; at 80℃;Inert atmosphere;	Example 18GPreparation of Compound (17g) To a solution of compound (17f) (1.74 g) in THF (25 mL) was added diethyl (3-pyridyl)borane (1.26 g, 8.569 mmol), bis(triphenylphosphine)palladium(II) chloride (120 mg, 0.1714 mmol) and 2 N aqueous Na2CO3 (16 ml). The mixture was degassed and refilled with Argon gas three times. Then the mixture was heated at 80 C. overnight and monitored by TLC. The mixture was cooled to room temperature and extracted with dichloromethane (2×15 mL). The combined organic layers were washed with water (20 ml) and brine (2×20 mL), dried over Na2SO4. The solution was concentrated and purified by column chromatography to give 1.0 g (66.8%) of compound (17g).

Reference： [1]Patent: US2011/178065,2011,A1 .Location in patent: Page/Page column 59-60

70
C₁₉H₂₆F₃NO₄S [ No CAS ]
[ 89878-14-8 ]
C₂₃H₃₀N₂O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In water; at 80℃;Inert atmosphere;	Example 38CPreparation of Compound (37) To a solution of compound (37b) (1 g) in THF (10 mL) was added diethyl (3-pyridyl)borane (1.2 g), bis(triphenylphosphine)palladium(II) chloride (26 mg) and 2N aqueous Na2CO3 (5.5 mL). The mixture was degassed and refilled with Argon gas three times. Then the mixture was heated at 80 C. overnight and monitored by TLC. The mixture was cooled to room temperature and extracted with dichloromethane (20 mL). The combined organic layers were washed with water (20 mL) and brine (2×20 mL), dried over Na2SO4. The solution was concentrated and purified by preparative HPLC to give 70 mg of compound (37). MS calculated for (C23H30N2O) [M+H]+351.5 Found: 351.0; [M+Na]+373.5 Found: 372.9; 1H NMR (CDCl3, 300 MHz): 8.55 (1H), 8.36 (1H), 7.55 (1H), 7.11 (1H), 5.9 (1H), 3.92 (1H), 3.22 (1H), 2.4-2.6 (4H), 2.2 (1H), 1.25 (3H), 0.98 (23H). 13C NMR (CDCl3, 300 MHz): 173.53, 151.37, 147.99, 147.74, 133.61, 132.57, 128.81, 123.07, 65.31, 56.66, 54.28, 48.70, 46.88, 43.75, 19.70, 16.56; Retention time at HPLC: 8.369 min [Mobile phase: B %=10-100 (gradient 20 min); B=MeCN, A=H2O (0.1% TFA); Flow rate: 0.8 mL/min; UV=266 nm column: zorbax Eclipse XDB-C8 5u, (150*4.6 mmID)].

Reference： [1]Patent: US2011/178065,2011,A1 .Location in patent: Page/Page column 75

71
[ 956104-44-2 ]
[ 89878-14-8 ]
[ 1332391-94-2 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate;tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 105℃;Inert atmosphere;	To a solution of 6-chloro-N-(4-methoxybenzyl)-5-(trifluoromethyl)pyridin-3-amine (Intermediate 1, Step 3, 1.2 g, 3.8 mmol) and 3-(diethylboryl)pyridine (0.613 g, 4.17 mmol) in 1,4-dioxane (100 mL) was added K3P04(2.52 g, 9.48 mmol). The mixture was degassed then flushed with nitrogen before Pd2(dba)3 (173 mg, 0.02 mmol) and Xantphos (0.218 mg, 0.04 mmol) were added. The mixture was heated at 105C overnight. The reaction mixture was cooled to room temperature and filtered. The filtrate was concentrated in vacuo and the residue was purified by column chromatography on silica gel using EtOAc/PE = 1/ to afford 1 g of N- (4-methoxybenzyl)-3-(trifluoromethyl)-[2,3'-bipyridin]-5-amine.

Reference： [1]Patent: WO2011/103202,2011,A2 .Location in patent: Page/Page column 161

72
[ 73568-25-9 ]
[ 89878-14-8 ]
[ 1039775-45-5 ]

Yield	Reaction Conditions	Operation in experiment
70%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 90℃; for 5h;Inert atmosphere;	INTERMEDIATE 69 2-(Pyridin-3-yl)quinoline-3-carbaldehydeA mixture of 2-chloroquinoline-3-carbaldehyde (5.0 g, 26.1 mmol), Na2C03 (4.15 g, 39.1 mmol) and <strong>[89878-14-8]diethyl(3-pyridyl)boran</strong>e (4.22 g, 28.7 mmol) in DME (100 mL) and water (30 mL) was degassed by bubbling nitrogen gas through it for 5 minutes. Tetrakis- (triphenylphosphine)palladium(O) (0.30 g, 0.261 mmol) was added and the mixture was heated at 90C for 5 h. The mixture was allowed to cool to room temperature. The resultant precipitate was filtered off and washed with water (5 x 50 mL) and diethyl ether (5 x 50 mL) to give the title compound (4.3 g, 70%>) as a pale green solid. LCMS (ES+) 235 (M+H)+, RT 1.53 minutes.

Reference： [1]Patent: WO2012/32334,2012,A1 .Location in patent: Page/Page column 53

73
[ 1382471-65-9 ]
[ 89878-14-8 ]
[ 1382471-66-0 ]

Yield	Reaction Conditions	Operation in experiment
98.5%	With potassium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,4-dioxane; water; at 80℃;Ultrasonic degassing; Inert atmosphere;	Example 137Preparation of Compound (162)[00696] Under argon protection, a mixture of compound (161) (1.47 g, 3.10 mmol, K2C03 (2.2 g, 15.5 mmol) , 3-(diethyboryl)pyridine (700.0 mg, 4.65 mmol) , Pd(PPh3)2Cl2 (220 mg, 0.310 mmol) in 30 mL of dioxane and 10 mL of water was degassed within an ultrasonic cleaner for 30 min. The mixture was stirred at 80 C overnight. 50 mL of water and 50 mL of DCM was added. The layers were partitioned. The aqueous phase was extracted with DCM (50 mL). The combined DCM layers were washed with brine (100 mL), dried over Na2S04 and purified through FCC on silica gel ro get 1.00 g of compound (162) in 98.5 % yield. LC-MS (m/z) 391.5 [M+H]+; 1H NMR delta (400 MHz, CHC13-J): 0.97 (s, 3H), 1.12 (s, 3H), 2.05(s, 3H), 4.70 (s, 1H), 5.98 (m, 1H),6.78 (m,lH),7.20 (m,lH),7.74(m,lH),8.40 (m,lH), 8.75 (s,lH). 13C NMR delta (400 MHz, CHC13- d) 170.65, 164.52, 151.36, 147.20, 146.99, 132..55, 131.95, 127.71, 123.24, 118.46, 73.47, 53.69, 44.39, 37.07, 36.90, 36.04, 35.78, 33.87, 29.53, 28.19, 27.38, 21.44, 21.26, 19.58, 12.29.

Reference： [1]Patent: WO2012/83112,2012,A2 .Location in patent: Page/Page column 297

74
[ 1416983-46-4 ]
[ 89878-14-8 ]
[ 5958-02-1 ]

Reference： [1]Chemical Communications,2013,vol. 49,p. 5268 - 5270

75
[ 16732-70-0 ]
[ 89878-14-8 ]
[ 1012313-08-4 ]

Yield	Reaction Conditions	Operation in experiment
45%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; at 95℃; for 5h;Reflux;	Example 49 5-(l-Methanesulfonyl-piperidin-3-yl)-lH-indole-2-carboxylic acid (3,5-difluoro-phenyl)- amide a) 5-Pyridin-3-yl-lH-indole-2-carboxylic acid ethyl ester 5-Bromo-lH-indole-2-carboxylic acid ethyl ester (1.0 g), <strong>[89878-14-8]diethyl(3-pyridyl)boran</strong>e (1.097 g), tetrakis-(triphenylphosphine)-palladium (0.431 g) and potassium carbonate (1.804 g) were refluxed at 95C for 5 hours in a mixture of tetrahydrofuran (30 mL) and water (30 mL). The reaction mixture was allowed to cool to room temperature, the phases were separated, the aqueous phase was extracted three times with dichloromethane, the combined organic layers were washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was crystallized in ethyl acetate, then purified by column chromatography on silica gel using dichloromethane/methanol (98:2 v/v), again recrystallized in ethyl acetate to yield the title compound as a white solid (445 mg, 45 %).
45%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; at 95℃; for 5h;	5-Bromo-1H-indole-2-carboxylic acid ethyl ester (1.0 g), <strong>[89878-14-8]diethyl(3-pyridyl)boran</strong>e (1.097 g), tetrakis-(triphenylphosphine)-palladium (0.431 g) and potassium carbonate (1.804 g) were refluxed at 95C for 5 hours in a mixture of tetrahydrofuran (30 mL) and water (30 mL). The reaction mixture was allowed to cool to room temperature, the phases were separated, the aqueous phase was extracted three times with dichloromethane, the combined organic layers were washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was crystallized in ethyl acetate, then purified by column chromatography on silica gel using dichloromethane/methanol (98:2 v/v), again recrystallized in ethyl acetate to yield the title compound as a white solid (445 mg, 45 %). MS ISP (m/e): 267.1 (100) [(M+H)+].

Reference： [1]Patent: WO2014/60386,2014,A1 .Location in patent: Page/Page column 61
[2]Patent: EP2722329,2014,A1 .Location in patent: Paragraph 0202

76
abiraterone [ No CAS ]
[ 89878-14-8 ]
C₂₇H₃₉NOSi [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86.2%	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In tetrahydrofuran; ethanol; water; toluene; at 20 - 75℃; for 0.5h;	Compound (IV-a) (2.0 g, 4.1 mmole), <strong>[89878-14-8]diethyl(3-pyridyl)boran</strong>e (0.6 g, 4.1 mmole), Na2CO3 (0.43 g, 4.1 mmole), PdCl2(PPh3)2 (21 mg, 0.03 mmole), toluene (10 mL), THF (6 mL), EtOH (4 mL), and water (10 mL) were added to a suitable flask at 20-30 C. The mixture was heated to 70-75 C. for 0.5 hour. After the reaction was completed, the organic portion was separated after phase separation. The organic portion was washed with water (20 mL). The resulting separated organic portion was concentrated at about 40 C. under reduced pressure to near dryness. The concentrate was subjected to flash column chromatography (eluent: EtOAc/n-Heptane=1/7), and purified compound (VII-a) (1.48 g) was afforded in 86.2% yield. [0124] 1H-NMR (400 MHz, CDCl3) delta 8.64 (d, J=1.6 Hz, 1H), 8.48 (dd, J=4.8, 1.6 Hz, 1H), 7.67 (ddd, 1H), 7.26-7.22 (m, 1H), 6.02 (dd, J=3.2, 1.6 Hz, 1H), 5.39 (dd, J=5.2, 3.2 Hz, 1H), 3.56-3.48 (m, 1H), 2.37-2.20 (m, 3H), 2.12-2.04 (m, 3H), 1.86-1.45 (m, 9H), 1.16-1.09 (m, 2H), 1.08 (s, 3H), 1.07 (s, 3H), 0.14 (s, 9H)

Reference： [1]Patent: US2015/5489,2015,A1 .Location in patent: Paragraph 0123; 0124

77
[ 89878-14-8 ]
Trifluoro-methanesulfonic acid (3S,8R,9S,10R,13S,14S)-3-(tert-butyl-dimethyl-silanyloxy)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl ester [ No CAS ]
[ 1421704-60-0 ]

Yield	Reaction Conditions	Operation in experiment
81.7%	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In tetrahydrofuran; ethanol; water; toluene; at 20 - 75℃; for 1h;	Compound (IV-b) (13.3 g, 24.8 mmole), <strong>[89878-14-8]diethyl(3-pyridyl)boran</strong>e (5.5 g, 37.4 mmole), Na2CO3 (8.5 g, 80.2 mmole), PdCl2(PPh3)2 (350 mg, 0.5 mmole), toluene (67 mL), THF (40 mL), EtOH (20 mL), and water (100 mL) were added to a suitable flask at 20-30 C. The resulting mixture was heated to 70-75 C. for 1 hour. After the reaction was completed, the organic portion was separated after phase separation. The organic portion was washed with water (100 mL), separated, and concentrated at about 40 C. under reduced pressure to near dryness. The concentrate was subjected to flash column chromatography (eluent: EtOAc/n-Heptane=1/6), and purified compound (VII-b) (9.38 g) was afforded in 81.7% yield. [0126] 1H-NMR (400 MHz, CDCl3) 8.64 (d, J=1.6 Hz, 1H), 8.48 (dd, J=4.8, 1.6 Hz, 1H), 7.67 (ddd, 1H), 7.26-7.23 (m, 1H), 6.02 (dd, J=3.2, 1.6 Hz, 1H), 5.38 (dd, J=5.6, 2.0 Hz, 1H), 3.56-3.48 (m, 1H), 2.35-2.20 (m, 3H), 2.15-2.05 (m, 3H), 1.88-1.47 (m, 9H), 1.14-1.09 (m, 2H), 1.08 (s, 3H), 1.07 (s, 3H), 0.92 (s, 9H), 0.09 (s,6H)

Reference： [1]Patent: US2015/5489,2015,A1 .Location in patent: Paragraph 10

78
C₂₅H₃₅F₃O₅S [ No CAS ]
[ 89878-14-8 ]
C₂₉H₃₉NO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85.5%	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In tetrahydrofuran; ethanol; water; toluene; at 20 - 75℃; for 2h;	Compound (IV-c) (2.0 g, 4.0 mmole), <strong>[89878-14-8]diethyl(3-pyridyl)boran</strong>e (0.59 g, 4.0 mmole), Na2CO3 (0.25 g, 2.4 mmole), PdCl2(PPh3)2 (14 mg, 0.02 mmole), toluene (10 mL), THF (6 mL), EtOH (4 mL), and water (10 mL) were added to a suitable flask at 20-30 C. The mixture was heated to 70-75 C. for 2 hours. After the reaction was completed, the organic portion was separated after phase separation. The organic portion was washed with water (20 mL). The resulting separated organic portion was concentrated at about 40 C. under reduced pressure to near dryness. The concentrate was subjected to flash column chromatography (eluent: EtOAc/n-Heptane=1/4), and purified compound (VII-c) (1.48 g) was afforded in 85.5% yield. [0128] 1H-NMR (400 MHz, CDCl3) delta 8.62 (d, J 1.6 Hz, 1H), 8.46 (dd, J=4.8, 1.6 Hz, 1H), 7.65 (ddd, 1H), 7.29-7.20 (m, 1H), 6.00 (dd, J=3.2, 2.0 Hz, 1H), 5.39 (dd, J=5.6, 2.0 Hz, 1H), 4.74-4.72 (m, 1H), 3.93-3.92 (m, 1H), 3.55-3.51 (m, 2H), 2.40-2.39 (m, 2H), 2.26-2.24 (m, 2H), 2.06-2.04 (m, 3H), 1.88-1.49 (m, 14H), 1.10-1.05 (m, 2H), 1.08 (s, 3H), 1.05 (s, 3H).

Reference： [1]Patent: US2015/5489,2015,A1 .Location in patent: Paragraph 0127; 0128

79
C₃₉H₄₁F₃O₄S [ No CAS ]
[ 89878-14-8 ]
C₄₃H₄₅NO [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In tetrahydrofuran; ethanol; water; toluene; at 20 - 75℃; for 0.5h;	Compound (IV-d) (12.5 g, 18.8 mmole), <strong>[89878-14-8]diethyl(3-pyridyl)boran</strong>e (4.1 g, 28.2 mmole), Na2CO3 (8.5 g, 80.2 mmole), PdCl2(PPh3)2 (130 mg, 0.19 mmole), toluene (63 mL), THF (38 mL), EtOH (20 mL), and water (100 mL) were added to a suitable flask at 20-30 C. The mixture was heated to 70-75 C. for 0.5 hour. After the reaction was completed, the organic portion was separated after phase separation. The organic portion was washed with water (100 mL). The resulting separated organic portion was concentrated at about 40 C. under reduced pressure to near dryness. The concentrate was subjected to flash column chromatography (eluent: EtOAc/n-Heptane=1/6), and purified compound (VII-d) (9.45 g) was afforded in 85.0% yield. [0130] 1H-NMR (400 MHz, CDCl3) delta 8.62 (d, J=1.6 Hz, 1H), 8.47 (dd, J=4.8, 1.6 Hz, 1H), 7.71 (ddd, 1H), 7.56-7.54 (m, 6H), 7.33-7.23 (m, 10H), 6.02 (dd, J=2.8, 1.6 Hz, 1H), 4.95 (dd, J=4.8, 2.0 Hz, 1H), 3.40-3.37 (m, 1H), 2.89-2.11 (m, 2H), 2.10-1.94 (m, 2H), 1.71-1.27 (m, 11H), 1.03 (s, 3H), 1.02 (s, 3H), 0.98-0.81 (m, 2H).

Reference： [1]Patent: US2015/5489,2015,A1 .Location in patent: Paragraph 0129; 0130

80
C₂₀H₂₇F₃O₄S [ No CAS ]
[ 89878-14-8 ]
[ 154229-19-3 ]

Yield	Reaction Conditions	Operation in experiment
88.8%	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In tetrahydrofuran; water; at 20 - 75℃; for 0.5h;	Compound ( V) (1.68 g, 4.0 mmole), <strong>[89878-14-8]diethyl(3-pyridyl)boran</strong>e (0.88 g, 6.0 mmole), Na2CO3 (0.43 g, 4.0 mmole), PdCl2(PPh3)2 (28 mg, 0.04 mmole), THF (10 mL), and water (5 mL) were added to a suitable flask at 20-30 C. The mixture was heated to 70-75 C. for 0.5 hour. After the reaction was completed, the organic portion was separated after phase separation. The organic portion was washed with water (100 mL). The resulting separated organic portion was concentrated at about 65-70 C. till volume reached about 8 mL EtOH (10 mL) and water (10 mL) were added to the concentrate at 65-70 C. The resulting mixture was stirred at 65-70 C. for 1 hour. The mixture was cooled to 20-30 C. and stirred for 1 hour. The mixture was filtered and filtered cake was washed with water (10 mL). The wet cake was dried at about 40 C. under reduced pressure to afford abiraterone of formula (I) (1.24 g) in 88.8% yield. [0141] 1H-NMR (400 MHz, CDCl3) delta 8.64 (d, J=1.6 Hz, 1H), 8.48 (dd, J=4.8, 1.6 Hz, 1H), 7.67 (ddd, 1H), 7.26-7.22 (m, 1H), 6.02 (dd, J=3.2, 1.6 Hz, 1H), 5.42 (dd, J=5.2, 2.4 Hz, 1H), 3.60-3.53 (m, 1H), 2.38-2.25 (m, 3H), 2.13-2.04 (m, 2H), 1.93-1.45 (m, 10H), 1.18-1.10 (m, 2H), 1.09 (s, 3H), 1.07 (s, 3H)

Reference： [1]Patent: US2015/5489,2015,A1 .Location in patent: Paragraph 0140; 0141

81
3β-acetoxy-5,6-seco-5-keto-17-O-triflyl-androstan-6-al [ No CAS ]
[ 89878-14-8 ]
3β-acetoxy-5-keto-5,6-seco-17-(3-pyridyl)-androst-16-en-6-al [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With bis-triphenylphosphine-palladium(II) chloride; sodium hydrogencarbonate; In tetrahydrofuran; water; at 50℃; for 1h;	3beta-Acetoxy-5-keto-5,6-seco-17-pyridyl-androst-16-en-6-al Compound 17 (400 mg, 0.81 mmol) was coupled as described for 4, however the temperature was reduced to 50 C. Automatic purification (4 g silica, 25% to 60% EtOAc/hexanes) afforded 290 mg of the title compound as a clear oil (85%). 1H NMR (400 MHz, CDCl3) delta 9.61 (s, 1H), 8.52 (s, 1H), 8.40 (d, J=4.9 Hz, 1H), 7.53-7.44 (m, 1H), 7.16 (dd, J=7.9, 4.8 Hz, 1H), 5.87 (dd, J=3.0, 1.9 Hz, 1H), 5.31 (t, J=2.9 Hz, 1H), 2.98 (dd, J=14.4, 4.4 Hz, 1H), 2.42 (dd, J=6.1, 1.8 Hz, 1H), 2.35 (m, 1H), 2.28-2.17 (m, 1H), 2.13 (m, 1H), 2.05-1.99 (m, 2H), 1.97 (s, 3H), 1.95 (m, 4H), 1.85-1.70 (m, 3H), 1.60-1.47 (m, 3H), 1.02 (s, 3H), 0.98 (s, 3H); 13C NMR (101 MHz, CDCl3) delta 215.8, 202.1, 170.1, 151.2, 148.1, 147.7, 133.7, 132.0, 128.4, 123.1, 73.2, 55.5, 52.4, 47.3, 44.3, 43.2, 42.3, 35.3, 34.1, 33.0, 32.7, 25.2, 22.9, 21.2, 21.04, 17.7, 16.1; MS calculated for C26H33NO4 (M++H): 424.249. found 424.294.

Reference： [1]Patent: US2016/31929,2016,A1 .Location in patent: Paragraph 0116

82
3α-acetoxy-5β-androsta-16-ene-17-yl trifluoromethanesulfonate [ No CAS ]
[ 89878-14-8 ]
3α-acetoxy-17-(3-pyridyl)-5β-androsta-16-ene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In tetrahydrofuran; water; for 18h;Inert atmosphere; Reflux;	A suspension of compound 9 (698 mg, 1.50 mmol), diethyl-3-pyridylborane (265 mg, 1.80 mmol), bis(triphenylphosphine)palladium (II) chloride (11.0 mg, 0.015 mmol) in THF (15 mL) was added to an aqueous solution of sodium carbonate (2 M, 5 mL). The mixture was refluxed for 18 h under N2. The reaction was concentrated under reduced pressure, and the residue was extracted with ethyl acetate. The organic phase was washed with brine, dried over Na2S04, and concentrated under reduced pressure. Compound 10 was purified by flash column chromatography on silica gel (hexanes to 50% ethyl acetate in hexanes), yield: 90%. 1H NMR (400 MHz, CDC13) delta: 8.6 (s, 1H), 8.5 (d, J = 4.8 Hz, 1H), 7.7 (d, J = 7.6 Hz, 1H), 7.3 (dd, Jl= 4.8 Hz and J2= 7.6 Hz, 1H), 6.0 (s, 1H), 4.75 (bs, 1H), 2.24 (d, 1H), 2.0-0.9 (m, 16H), 1.0 (s, 3H), 0.98 (s, 3H) ppm.

Reference： [1]Patent: WO2016/144871,2016,A1 .Location in patent: Page/Page column 45

83
[ 89878-14-8 ]
17-iodoandrosta-5,16-dien-3β-ol 3-acetate [ No CAS ]
[ 154229-19-3 ]

Yield	Reaction Conditions	Operation in experiment
67.8%		Tetrahydrofuran (14.5 kg) was sequentially added to a 50 L glass-lined reactor.17-iodonium-5,16-diene-3beta-acetate (2.9 kg, 6.6 mol),Diethyl-(3-pyridyl)borane (1.0 kg, 6.9 mol),Bis(triphenylphosphine)palladium dichloride (50 g, 72 mmol),Stir at room temperature for 10 min,Then add 10% aqueous sodium carbonate solution (8.0kg),The reaction was refluxed for 5 h.The reaction solution was slowly cooled to room temperature.Let it stand and go to the water layer,Filter the organic phase,Add 5% sodium hydroxide in methanol (7.5kg),The temperature was controlled at 25-35 C for 5 h.Cool down to 0-5 C for 1 h,filter,The filter cake is rinsed with methanol/water = 1:1.Dry at 60 C,Abiraterone was 1.56kg,White solid.Yield: 67.8%.HPLC purity: 98.5%.
		Add tetrahydrofuran, compound C, and sequentially to a 500 mL flask.Diethyl-(3-pyridyl)borane,Bis(triphenylphosphine)palladium dichloride and tetrabutylammonium fluoride trihydrate, stirred at room temperature for 20 min, then added sodium carbonate aqueous solution,Warming up to reflux reaction (water bath setting 65 ~ 70 C),The upper layer of the reaction solution gradually turned reddish brown and reacted for 75 minutes.Start the TLC monitoring reaction and test every 15 minutes.The disappearance of Compound C spots in the reaction solution (EA: PE = 1:8, borane Rf is about 0.85,The compound CRf was about 0.8, and the phosphomolybdic acid developed color, and the reaction was stopped immediately.The reaction solution is rapidly cooled to 25 to 35 C, and the aqueous layer is allowed to stand still.Decolorization was carried out by adding activated carbon, stirred for 30 min, and filtered. Stir,Adding a pre-configured sodium hydroxide methanol solution to the organic phase,Temperature control 25 ~ 35 C reaction, TLC monitoring reaction, every 15 min test,The basic reaction to abiraterone acetate was complete (EA: Hex = 1:2, abiraterone acetate Rf was about 0.5, abiraterone Rf was about 0.2, UV color development), and the reaction was stopped.The temperature was lowered, and the temperature was controlled at 0 to 5 C for 1 h. Filtering,The obtained filter cake was added to methanol (83 g), and stirred at room temperature for 30 min.Purified water (103 g) was added and stirring was continued for 30 min. Filtering,No liquid flow, filter cake by methanol / water = 1:1 (83 methanol, 103gPurified water) is washed again. Filter by suction, filter cake and pre-cooled tetrahydrofuran(0 ~ 5 C) slurry washing, suction filtration until no liquid out, filter cake dried at 47 ~ 52 C blast air for 6h, to obtain a crude compound D. Loss on drying 2%.Crude purification of compound D: The crude abiraterone was added to tetrahydrofuran (120 g), stirred under reflux for 90 min, and slowly cooled to 0-5 C for stirring for 1 h. Drain filtration until no liquid flows out, and lasts for 20 min to obtain 34 g of abiraterone, white or off-white solid, and the weight loss on drying should not exceed 2%.
34 g		into a 500 mL flask added tetrahydrofuran, compound C, diethyl-(3-pyridyl)borane, bis(triphenylphosphine)palladium dichloride and tetrabutylammonium fluoride trihydrate respectively, stir at room temperature for 20 min, and then add an aqueous solution of sodium carbonate, warming up to reflux reaction (water bath setting 65~70 C), the upper layer of the reaction solution gradually turns reddish brown, after reacting for 75 minutes, the TLC monitoring reaction was started, test every 15 minutes, the spot of Compound C disappeared in the reaction solution (EpsilonAlpha: PE = 1:8, borane Rf was about 0.85, compound CRf was about 0.8, phosphomolybdic acid developed color), stop the reaction immediately. The reaction solution was rapidly cooled at 25~35 C, the mixture was placed in an aqueous layer, decolorized by adding activated carbon, stirred for 30 min, and filtered. Under stirring, the organic phase is added with a pre-configured sodium hydroxide methanol solution, and the temperature is controlled at 25~35 C, TLC monitors the reaction and detects it every 15 minutes, the basic reaction to abiraterone acetate is complete (EpsilonAlpha:Etaex=1:2, abiraterone acetate Rf is about 0.5, abiraterone Rf is about 0.2, UV color development), stop the reaction. Cooling down, temperature control 0~5 C stirring crystallization 1h. Filtering, the resulting filter cake was added to methanol (83 g), filter cake was added to methanol (83 g), stir at room temperature for 30 min, add purified water (103 g), and continue stirring for 30 min. Filtering, until no liquid flows out, the filter cake was washed once more with methanol/water = 1:1 (83 methanol, 1038 purified water). Filtering, the filter cake is then washed with pre-cooled tetrahydrofuran (0~5 C), filtering until no liquid flows out, the filter cake was blast dried at 47~52 C for 6 h, obtained crude compound D, Loss on drying 2%. Crude purification of compound D: the crude abiraterone added to tetrahydrofuran (120g), stirring under reflux for 90 min, slowly cooling at 0~5 C and stirring for 1h. Filtering until no liquid flows out, and lasts for 20 minutes, obtained abiraterone products 34g, white or off-white solid, weight loss should not exceed 2%.

Reference： [1]Patent: CN107840866,2018,A .Location in patent: Paragraph 0081; 0088; 0089; 0090; 0091; 0097; 0104-0106
[2]Patent: CN108546279,2018,A .Location in patent: Paragraph 0080; 0081; 0082; 0083; 0084; 0085; 0086
[3]Patent: CN108794561,2018,A .Location in patent: Paragraph 0069; 0101-0103

84
17-iodo-2,2-d₂-androst-4,16-dien-3-one [ No CAS ]
[ 89878-14-8 ]
17-(3-pyridyl-6-d)-2,2-d₂-androst-4,16-dien-3-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
58.9%	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In tetrahydrofuran; water; at 80℃; for 16h;Inert atmosphere;	At room temperature, under nitrogen protection, a mixed solution of tetrahydrofuran (6 mL) and water (2 mL) was added to a mixture of 17-iodoandrost-4,16-dien-3-one-2,2-d2 (200 mg, 0.50 mmol), <strong>[89878-14-8]3-diethylboranylpyridine</strong>-6-d (90 mg, 0.60 mmol), bis(triphenylphosphine)palladium (II) chloride (PdCl2(PPh3)2) (30 mg, 0.03 mmol), and sodium carbonate (170 mg, 1.50 mmol), and the reaction solution was kept at 80C overnight (16 hrs). After cooled to room temperature, the reaction was quenched with water (25 mL), and filtered through celite, and the filtrate was extracted with ethyl acetate (30 mL x 3). The organic layers were combined and the organic layer was washed with brine (30 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure and the concentrate was purified by column chromatography (eluent: PE/EtOAc (v/v) = 2/1) to give 100 mg of a pale yellow solid. Yield: 58.9%. LC-MS (APCI): m/z = 350.3 (M + 1)+; 1H NMR (300 MHz, MeOD) (delta/ppm) 8.60 - 8.47 (m, 1H), 8.47 - 8.30 (m, 1H), 7.91-7.78 (m, 1H), 7.45-7.31 (m, 1H), 6.17-6.01 (m, 1H), 5.75-5.71 (m, 1H), 2.63-2.26 (m, 3H), 2.23 - 2.08 (m, 2H), 2.07-1.86 (m, 3H), 1.75-1.44 (m, 5H), 1.29 (s, 3H), 1.20-1.03 (m, 5H).

Reference： [1]Patent: EP3392261,2018,A1 .Location in patent: Paragraph 0095

85
[ 32138-69-5 ]
[ 89878-14-8 ]
(3β)-17-(3-pyridyl)androst-5,16-dienyl d3-acetate [ No CAS ]

Reference： [1]Patent: EP3392261,2018,A1

86
(3β)-17-iodo-androst-5,16-dienol-16-d [ No CAS ]
[ 89878-14-8 ]
(3β)-17-(3-pyridyl)androst-5,16-dienol-16-d [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73.0%	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In tetrahydrofuran; water; at 80℃; for 2h;Inert atmosphere;	At room temperature, under nitrogen protection, a mixed solution of tetrahydrofuran (6 mL) and water (2 mL) was added to a mixture of 17-iodo-androst-5,16-diene-3beta-ol-16-d(200 mg, 0.50 mmol), 3-(diethylboryl)pyridine-(88 mg, 0.60 mmol), bis(triphenylphosphine)palladium (II) chloride (20 mg, 0.04 mmol), and sodium carbonate (248 mg, 1.80 mmol), and reacted at 80C for 2hr. After cooled to room temperature, the reaction was quenched with water (25 mL), and filtered through celite, and the filtrate was extracted with ethyl acetate (30 mL x 3). The organic layers were combined and the organic layer was washed with brine (30 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure and the concentrate was purified by column chromatography (eluent: PE/EtOAc (v/v) = 1.5/1) to give 128 mg of a white solid, yield: 73.0%, purity: 99.54%, LC-MS (APCI): m/z = 351.3 (M+1). 1H NMR (300 MHz, MeOD-d4) (delta/ppm) 8.56 (s, 1H), 8.41 (s, 1H), 7.92 (d, J=8.0 Hz, 1H), 7.44 (dd, J=7.9 , 4.9Hz, 1H), 5.40 (d, J = 5.3Hz, 1H), 3.42 (m, 1H), 2.29 (m, 3H), 2.10 (m, 3H), 1.75 (m, 7H), 1.50 (m, 2H), 1.12 (m, 8H).

Reference： [1]Patent: EP3392261,2018,A1 .Location in patent: Paragraph 0086

87
[ 89878-14-8 ]
17-iodoandrosta-5,16-dien-3β-ol 3-acetate [ No CAS ]
[ 154229-18-2 ]

Yield	Reaction Conditions	Operation in experiment
76.3%	With palladium on activated charcoal; potassium carbonate; In ethanol; at 60℃; for 3h;	In 1000 ml of the magneton with stirring, of the reflux condensation tube of three compound is added in the flask 17 - iodine male steroid - 5, 16 - diene - 3 beta - acetate 44.0 g (0.10 muM, 1.0 equiv), diethyl (3 - pyridyl) borane 14.7 g (0.10 muM, 1.0 equiv), palladium/carbon (to palladium) 0.053 g (0.0005 muM, 0 . 005 equiv), adding potassium carbonate 13.8 g (0.10 muM, 1.0 equiv), adding ethanol to 400 ml as the solvent, nitrogen replacement heating to 60 C reaction 3 hours. After the reaction, filtration and recovery of palladium/carbon catalyst, vacuum distillation (the distillation temperature is 80 C, vacuum degree is -0.09 mpa) to remove the solvent, adding 220 g water beating in addition to the salt, and filter and add 132 g acetone, heating [...] after two hours the temperature slowly to 0 C to crystallize, get acetate 30.0 g, purity of 99.4%, molar yield of 76.3%,

Reference： [1]Patent: CN109705186,2019,A .Location in patent: Paragraph 0037-0040

88
[ 32138-69-5 ]
[ 89878-14-8 ]
[ 154229-18-2 ]

Reference： [1]Patent: CN109705186,2019,A

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	89878-14-8	MDL No. :	MFCD00012348
Formula :	C₉H₁₄BN	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	OJKBCQOJVMAHDX-UHFFFAOYSA-N
M.W :	147.03	Pubchem ID :	642851
Synonyms :

Num. heavy atoms :	11
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.44
Num. rotatable bonds :	3
Num. H-bond acceptors :	1.0
Num. H-bond donors :	0.0
Molar Refractivity :	50.97
TPSA :	12.89 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) :	-5.0 cm/s

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	3.09
Log Po/w (WLOGP) :	1.82
Log Po/w (MLOGP) :	1.8
Log Po/w (SILICOS-IT) :	1.28
Consensus Log Po/w :	1.6

[ CAS No. 89878-14-8 ] {[proInfo.proName]}

Quality Control of [ 89878-14-8 ]

Related Doc. of [ 89878-14-8 ]

Product Details of [ 89878-14-8 ]

Calculated chemistry of [ 89878-14-8 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 89878-14-8 ]

Application In Synthesis of [ 89878-14-8 ]

[ 89878-14-8 ] Synthesis Path-Upstream 1~9

[ 89878-14-8 ] Synthesis Path-Downstream 1~88

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	2.0
Bioavailability Score :	0.55

Log S (ESOL) :	-2.9
Solubility :	0.183 mg/ml ; 0.00125 mol/l
Class :	Soluble
Log S (Ali) :	-3.03
Solubility :	0.138 mg/ml ; 0.000937 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.63
Solubility :	0.0346 mg/ml ; 0.000236 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.76

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

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P378
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P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
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P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
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