Name: 96424-68-9|2-Bromo-3-chloropyridine|97%
Brand: Ambeed
SKU: A392051
Price: 5.0 USD
Availability: InStock
Rating: 98 (30 reviews)

1
[ 73583-41-2 ]
[ 626-60-8 ]
[ 96424-68-9 ]
[ 107399-32-6 ]

Reference： [1]Tetrahedron,1986,vol. 42,p. 2253 - 2262

2
[ 96424-68-9 ]
[ 77332-89-9 ]

Yield	Reaction Conditions	Operation in experiment
86%	With chloro-trimethyl-silane; sodium iodide; In propiononitrile; for 2h;Inert atmosphere; Reflux;	2-Bromo-3-chloropyridine (6.25 g, 0.033 mol) and sodium iodide (14.5 g, 0.10 mol) were dissolved in propionitrile (26 mL). Chloro(trimethyl)silane (4.1 mL, 32 mmol) was then added dropwise to the mixture. After the bubbling stopped, the reaction mixture was brought to reflux under nitrogen for two hours. The mixture was diluted in EtOAc (75 mL) and washed three times with water (50 mL). The organic layer was then dried over sodium sulfate, filtered, and concentrated in vacuo to give title compound as pale yellow solid (6.69 g, 86%):1H NMR (400 MHz, d6-DMSO): delta 7.42-7.45 (q, 1H), 7.94-7.97 (m, 1H), 8.30-8.32 (m, 1H)LCMS Rt=1.38 minutes MS m/z 240 [MH]+

Reference： [1]Patent: US2012/10183,2012,A1 .Location in patent: Page/Page column 52
[2]European Journal of Organic Chemistry,2002,p. 4181 - 4184

3
[ 931-49-7 ]
[ 96424-68-9 ]
3-chloro-2-cyclohex-1-enylethynyl-pyridine [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2006,vol. 128,p. 10694 - 10695

4
[ 96424-68-9 ]
[ 149771-44-8 ]
[ 201162-50-7 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 120℃; for 48h;	tert-Butyl 3,8-diazabicyclo[3.2.1]octane-8-carboxylate (435 mg, 2.26 mmol), <strong>[96424-68-9]2-bromo-3-chloropyridine</strong> (400 mg, 1.88 mmol), and potassium carbonate (390 mg, 2.83 mmol) were combined in dry dimethylformamide (10 mL) and stirred at 120 C. for 48 hours. The mixture was allowed to cool room temperature, diluted with ethyl acetate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by chromatography on silica gel (85:15 hexanes:ethyl acetate) to provide the title compound. MS (ESI) m/z: 268 (100%), 324.0 (M+H)+; 1H NMR (CDCl3) delta 1.48 (s, 9H), 1.92 (m, 2H), 2.07 (m, 2H), 3.13 (d, 2H), 3.59 (br, 2H), 4.30 (br, 2H), 6.84 (dd, 1H), 7.58 (dd, 1H), 8.17 (dd, 1H).
	With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 120℃; for 48h;	Example 23J tert-butyl 3-(3-chloro-2-pyridinyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate tert-Butyl 3,8-diazabicyclo[3.2.1]octane-8-carboxylate (435 mg, 2.26 mmol), <strong>[96424-68-9]2-bromo-3-chloropyridine</strong> (400 mg, 1.88 mmol), and potassium carbonate (390 mg, 2.83 mmol) were combined in dry dimethylformamide (10 mL) and stirred at 120 C. for 48 hours. The mixture was allowed to cool room temperature, diluted with ethyl acetate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by chromatography on silica gel (85:15 hexanes:ethyl acetate) to provide the title compound. MS (ESI) m/z: 268 (100%), 324.0 (M+H)+; 1H NMR (CDCl3) delta1.48 (s, 9H), 1.92 (m, 2H), 2.07 (m, 2H), 3.13 (d, 2H), 3.59 (br, 2H), 4.30 (br, 2H), 6.84 (dd, 1H), 7.58 (dd, 1H), 8.17 (dd, 1H).

Reference： [1]Patent: US2005/9841,2005,A1 .Location in patent: Page/Page column 15
[2]Patent: US2005/80095,2005,A1 .Location in patent: Page/Page column 17

5
[ 96424-68-9 ]
[ 201162-53-0 ]
[ 824982-31-2 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 120℃; for 48h;	tert-Butyl 3,8-diazabicyclo[3.2.1]octane-3-carboxylate (454 mg, 2.36 mmol) and <strong>[96424-68-9]2-bromo-3-chloropyridine</strong> (418 mg, 1.97 mmol) were combined in dry N,N-dimethylformamide (10 mL) and treated with potassium carbonate (408 mg, 2.95 mmol). After stirring at 120 C. for 48 hours, the mixture was allowed to cool to room temperature, diluted with ethyl acetate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by chromatography on silica gel (4:1, hexanes:ethyl acetate) to provide the title compound. MS (ESI) m/z: 324 (M+H)+; 1H NMR (CDCl3) delta 1.47 (s, 9H), 1.77 (m, 2H), 1.93 (m, 2H), 3.22 (d, 1H), 3.31 (d, 1H), 3.76 (d, 1H), 3.90 (d, 1H), 4.53 (d, 2H), 6.76 (dd, 1H), 7.56 (dd, 1H), 8.09 (dd, 1H).
	With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 20 - 120℃; for 48h;	Example 34D tert-butyl 8-(3-chloro-2-pyridinyl)-3,8-diazabicyclo[3.2.1]octane-3-carboxylate tert-Butyl 3,8-diazabicyclo[3.2.1]octane-3-carboxylate (454 mg, 2.36 mmol) and <strong>[96424-68-9]2-bromo-3-chloropyridine</strong> (418 mg, 1.97 mmol) were combined in dry N,N-dimethylformamide (10 mL) and treated with potassium carbonate (408 mg, 2.95 mmol). After stirring at 120 C. for 48 hours, the mixture was allowed to cool to room temperature, diluted with ethyl acetate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by chromatography on silica gel (4:1, hexanes:ethyl acetate) to provide the title compound. MS (ESI) m/z: 324 (M+H)+; 1H NMR (CDCl3) delta 1.47 (s, 9H), 1.77 (m, 2H), 1.93 (m, 2H), 3.22 (d, 1H), 3.31 (d, 1H), 3.76 (d, 1H), 3.90 (d, 1H), 4.53 (d, 2H), 6.76 (dd, 1H), 7.56 (dd, 1H), 8.09 (dd, 1H).

Reference： [1]Patent: US2005/9841,2005,A1 .Location in patent: Page/Page column 16-17
[2]Patent: US2005/80095,2005,A1 .Location in patent: Page/Page column 19

6
[ 96424-68-9 ]
[ 64603-90-3 ]
[ 828266-00-8 ]

Yield	Reaction Conditions	Operation in experiment
		1,2,3,6-Tetrahydro-4-pyridinecarboxylic acid (7.0 g, 47 mmol) and <strong>[96424-68-9]2-bromo-3-chloropyridine</strong> (11.0 g, 57 mmol) were combined in DMSO (100 mL) and treated with anhydrous K2CO3 (8.0 g, 58 mmol). The mixture was heated at 90 C. overnight, allowed to cool to room temperature, and then concentrated under reduced pressure. The residue in dichloromethane (200 mL) was cooled to -78 C. and treated with an excess of TFA (10 mL, 130 mmol) dropwise. The mixture was allowed to warm to room temperature and the layers were separated. The organic layer was washed with brine, dried over Na2SO4, filtered, and the filtrate concentrated under reduced pressure to provide the title compound which was used in the next step without further purification.
		Example 1D 3'-chloro-3,6-dihydro-2H-1,2'-bipyridine-4-carboxylic acid 1,2,3,6-Tetrahydro-4-pyridinecarboxylic acid (7.0 g, 47 mmol) and <strong>[96424-68-9]2-bromo-3-chloropyridine</strong> (11.0 g, 57 mmol) were combined in DMSO (100 mL) and treated with anhydrous K2CO3 (8.0 g, 58 mmol). The mixture was heated at 90 C. overnight, allowed to cool to room temperature, and then concentrated under reduced pressure. The residue in dichloromethane (200 mL) was cooled to -78 C. and treated with an excess of TFA (10 mL, 130 mmol) dropwise. The mixture was allowed to warm to room temperature and the layers were separated. The organic layer was washed with brine, dried over Na2SO4, filtered, and the filtrate concentrated under reduced pressure to provide the title compound which was used in the next step without further purification.

Reference： [1]Patent: US2005/9841,2005,A1 .Location in patent: Page/Page column 11
[2]Patent: US2005/80095,2005,A1 .Location in patent: Page/Page column 14

7
[ 4746-97-8 ]
[ 96424-68-9 ]
[ 1147097-55-9 ]

Yield	Reaction Conditions	Operation in experiment
64%		To a -60 C. solution of n-butyl lithium (23 mL, 2.5M in hexane, 58.2 mmol) in diethyl ether (40 mL) was added a solution of <strong>[96424-68-9]2-bromo-3-chloropyridine</strong> (Alfa, 8.0 g, 41.6 mmol) in diethyl ether (60 mL) over 15 minutes. The reaction mixture was stirred for 40 minutes followed by a slow addition (about 15 minutes) of a solution of 1,4-dioxaspiro[4.5]decan-8-one (Aldrich, 8.44 g, 54.0 mmol) in diethyl ether (100 mL), and stirred until reaction mixture warmed up to ambient temperature (about 3 hours). The mixture was quenched with saturated NH4Cl, diluted with ethyl acetate and washed with water. The organic layer was separated, concentrated and the residue crystallized from ethyl acetate-hexanes to obtain 5.5 g of the title compound. Two more crystallizations of the mother liquors yielded 1.61 g more material. Total yield 7.13 g (64%). 1H NMR (300 MHz, DMSO-d6) delta ppm 1.59 (d, J=12.69 Hz, 2H), 1.80 (d, J=12.69 Hz, 2H), 1.94 (td, J=12.69, 4.36 Hz, 2H), 2.30-2.41 (m, 2H), 3.88 (s, 4H), 5.36 (s, 1H), 7.36 (dd, J=7.93, 4.76 Hz, 1H), 7.88 (dd, J=7.93, 1.59 Hz, 1H), 8.48 (dd, J=4.76, 1.59 Hz, 1H). MS (DCI) m/z 270.10 (M+H)+.

Reference： [1]Patent: US2009/124671,2009,A1 .Location in patent: Page/Page column 16

8
[ 96424-68-9 ]
[ 107-12-0 ]
[ 1147098-31-4 ]

Yield	Reaction Conditions	Operation in experiment
91%		To a -78 C. solution of diisopropylamine (3.04 g, 4.28 mL, 30 mmol) was added n-butyl lithium (13.2 mL, 2.5M in hexane, 33 mmol). The reaction mixture was stirred for 20 minutes at -78 C., followed by the addition of propionitrile (1.65 g, 2.15 mL, 30 mmol). The reaction mixture was stirred for an additional 50 minutes, followed by the slow addition of <strong>[96424-68-9]2-bromo-3-chloropyridine</strong> (1.92 g, 10 mmol) in THF (10 mL). The reaction was then allowed to warm to ambient temperature and stirred overnight. The reaction mixture was quenched with water and extracted with two portions of diethyl ether. The combined organic phases were washed with brine, concentrated, and the residue chromatographed on silica gel eluding with 30% ethyl acetate-hexane to obtain the title compound (1.52 g, 91%). 1H NMR (300 MHz, DMSO-d6) delta ppm 8.59 (dd, J=1.5, 4.7, 1H), 8.02 (dd, J=1.5, 8.1, 1H), 7.48 (dd, J=4.7, 8.1, 1H), 4.73 (q, J=7.1, 1H), 1.59 (d, J=7.1, 3H). MS (DCI) m/z 167 (M+H)+.

Reference： [1]Patent: US2009/124671,2009,A1 .Location in patent: Page/Page column 28

9
[ 96424-68-9 ]
[ 1011460-68-6 ]
[ 1147097-97-9 ]

Yield	Reaction Conditions	Operation in experiment
86%	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; for 8h;Heating / reflux;	To a solution of <strong>[96424-68-9]2-bromo-3-chloropyridine</strong> (Matrix, 1.651 g, 8.58 mmol), 4,4,6-trimethyl-2-(3,3,3-trifluoroprop-1-en-2-yl)-1,3,2-dioxaborinane (Frontier, 2.0 g, 9.01 mmol), and potassium carbonate (4.74 g, 34.3 mmol) in degassed 1,2-dimethoxyethane (50 mL) and water (25 mL) was added tetrakis(triphenylphosphine)palladium (496 mg, 0.429 mmol). The reaction mixture was refluxed for 8 hours, cooled to ambient temperature, diluted with water (200 mL), extracted twice with diethyl ether (200 mL), washed with brine, dried (Na2SO4) and concentrated to a yellow liquid. The residue was purified by silica gel chromatography (AnaLogix SF25-40G; 50 micron silica; elution with 0-20% ethyl acetate in hexane at 30 mL/min) to provide the title compound (1.530 g, 7.37 mmol, 86% yield) as a colorless liquid. 1H NMR (300 MHz, DMSO-d6) delta ppm 8.61 (dd, J=4.6, 1.4, 1H), 8.10 (dd, J=8.2, 1.4, 1H), 7.53 (dd, J=8.3, 4.6, 1H), 6.51-6.46 (m, 1H), 6.13-6.10 (m, 1H); MS (EI) m/e 207 (M)+.

Reference： [1]Patent: US2009/124671,2009,A1 .Location in patent: Page/Page column 22

10
[ 96424-68-9 ]
[ 128563-89-3 ]
[ 1147098-10-9 ]

Yield	Reaction Conditions	Operation in experiment
53.4%		To a 200 mL round bottom flask containing diethyl ether (40 mL) was added n-butyllithium (IM) (3.41 ml, 8.52 mmol) (Aldrich) followed by addition of <strong>[96424-68-9]2-bromo-3-chloropyridine</strong> (1.639 g, 8.52 mmol) (Aldrich) and the reaction was stirred for 1 hr at -65 C. Example 32D (1.45 g, 8.52 mmol) was added to the reaction in 20 mL of diethyl ether and stirred for 30 minutes. The reaction mixture was slowly warmed to room temperature and stirred for 2 hours, quenched with saturated NaHCO3 and extracted with EtOAc (200 mL), dried (NaSO4), filtered, and concentrated in vacuo. The material was purified on SiO2 and eluted with hexane/ethyl acetate (20%) to give a colorless oil (1.295 g) in 53.4% yield. 1H NMR (300 MHz, CDCl3) delta ppm 8.52-8.34 (m, 1H), 7.77-7.60 (m, 1H), 7.20 (ddd, J=4.6, 6.1, 7.9, 1H), 4.04-3.85 (m, 4H), 2.99-2.79 (m, 2H), 2.56-2.33 (m, 1H), 2.24-1.99 (m, 2H), 1.33-1.12 (m, 2H), 1.03-0.81 (d, 3H). MS (DCI+) M/Z 284 (M+H)+.

Reference： [1]Patent: US2009/124671,2009,A1 .Location in patent: Page/Page column 25

11
(5-chloro-2-formylphenyl)boronic acid [ No CAS ]
[ 96424-68-9 ]
[ 1228267-26-2 ]

Yield	Reaction Conditions	Operation in experiment
40%	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; water; for 5h;Reflux;	After <strong>[96424-68-9]2-bromo-3-chloro-pyridine</strong> (13.26 g, 69.1 mmol) and 5-chloro-2-formyl-benzeneboronic acid (13.98 g, 76 mmol) were dissolved in tetrahydrofuran (THF) (200 mL), 2M potassium carbonate aqueous solution (70 mL) was added thereto, and tetrakistripbenylphasphino palladium (Pd(PPh3)4) (1.6 g, 2 mol%) was put thereinto, agitated and refluxed for 5 hours. The temperature was lowered to normal temperature, the water layer was removed, and the organic layer was dried with anhydrous magnesium sulfate and filtered. The filtered solution was concentrated under the reduced pressure, recrystallized with hexane to prepare the compound A-27 (7 g, 40 %). MS: [M+H\|+=252

Reference： [1]Patent: EP2311826,2011,A2 .Location in patent: Page/Page column 59-60

12
[ 52670-38-9 ]
[ 96424-68-9 ]
[ 1323111-64-3 ]

Yield	Reaction Conditions	Operation in experiment
89%	With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; at 100℃; for 2h;	General procedure: In a dry Schlenk tube, the dihalopyridine, CuI (6 mol %), and PdCl2(PPh3)2 (3 mol %) were added in Et3N (2 mL per mmol of pyridine). After stirring for 10 min, the (hetero)arylacetylene (1.0 or 1.1 equiv) was added, and the solution was heated to 100 C in a silicone bath for 2 h. The reactions were monitored by TLC, following the disappearance of the starting materials. After completion, the mixture was allowed to cool to room temperature. Then ethyl acetate and water were added and the organic phase was separated, dried (MgSO4), and filtered. Removal of the solvent under reduced pressure gave either oils, which were submitted to column chromatography or pure products corresponding to the expected (hetero)arylethynylpyridines.

Reference： [1]Tetrahedron,2012,vol. 68,p. 7082 - 7094
[2]Synthesis,2011,p. 1723 - 1732

13
[ 96424-68-9 ]
[ 1527-91-9 ]
[ 1350629-03-6 ]

Reference： [1]Organic Letters,2011,vol. 13,p. 6516 - 6519

14
[ 96424-68-9 ]
[ 411235-57-9 ]
[ 1355066-87-3 ]

Yield	Reaction Conditions	Operation in experiment
62%	With potassium phosphate;palladium diacetate; tricyclohexylphosphine; In water; toluene; at 100℃; for 6h;Inert atmosphere;	Preparation 403-Chloro-2-cvclopropylpyridine3-Chloro-2-bromopyridine (5.0 g, 26 mmol) and potassium phosphate tribasic (19.3 g, 90.9 mmol) were suspended in toluene (40.0 ml_) and water (2.0 ml_). The mixture was sonicated for 10 minutes, then cydopropylboronic acid (1 .12 g, 13.0 mmol), palladium diacetate (0.093 g, 0.414 mmol) and tncydohexylphosphine (0.243 g, 0.867 mmol) were added to the reaction mixture, which was heated into a pre heated DrySyn at 100C, under a nitrogen atmosphere for 2 hours. Then cydopropylboronic acid (1 .12 g, 13.0 mmol), palladium diacetate (0.093 g, 0.414 mmol) and tncydohexylphosphine (0.243 g, 0.867 mmol) were added to the reaction mixture and the mixture was stirred for 2 hours. Then cydopropylboronic acid (1 .12 g, 13.0 mmol), palladium diacetate (0.093 g, 0.414 mmol) and thcyclohexylphosphine (0.243 g, 0.867 mmol) were added to the reaction mixture and the mixture was stirred for 2 hours more. The reaction mixture was stirred at room temperature for 16 hours, diluted with EtOAc (40.0 mL) and water (40.0 mL) and filtered on a pad of arbocel under a stream of nitrogen. The organic layer was separated and washed with aqueous citric acid (1 0%, 3 x 25.0 m L), followed by aqueous hydrochloric acid (1 M, 3 x 20.0 mL). The organic layer was discarded and the aqueous layer basified again with careful addition of a saturated aqueous solution of sodium hydrogen carbonate (100.0 mL). The product was extracted with TBME (3 x 20.0 mL). The combined organics were washed once more with aqueous citric acid (10%, 25.0 mL). The organic layer was then dried over sodium sulfate, filtered, and concentrated in vacuo to yield the title compound as a pale brown oil (2.45 g, 16.02 mmol, 62%).1H NMR (400 MHz, d6-DMSO): delta 0.94-1 .01 (m, 4H), 2.40-2.48 (m, 1 H), 7.13-7.16 (m, 1 H), 7.78-7.81 (m, 1 H), 8.33-8.34 (m, 1 H).LCMS Rt = 2.27 minutes MS m/z 154 [MH]+
62%	With potassium phosphate;palladium diacetate; tricyclohexylphosphine; In water; toluene; at 20 - 100℃; for 22h;Inert atmosphere;	Preparation 363-Chloro-2-cvclopropyl pyridine; 3-Chloro-2-bromopyridine (5.0 g, 26 mmol) and potassium phosphate tribasic (19.3 g, 90.9 mol) were suspended in toluene (40.0 ml_) and water (2.0 ml_). The mixture was sonicated for 10 minutes, then cyclopropylboronic acid (1.12 g, 13.0 mmol), palladium diacetate (0.093 g, 0.414 mol) and tricyclohexylphosphine (0.243 g, 0.867 mol) were added to the reaction mixture, which was heated into a pre heated DrySyn at 100C, under a nitrogen atmosphere for 2 hours. Then cyclopropylboronic acid (1.12 g, 13.0 mmol), palladium diacetate (0.093 g, 0.41 mol) and tricyclohexylphosphine (0.243 g, 0.87 mol) were added to the reaction mixture and the mixture was stirred for 2 hours. Then cyclopropylboronic acid (1.12 g, 13.0 mmol), palladium diacetate (0.093 g, 0.41 mol) and tricyclohexylphosphine (0.243 g, 0.87 mol) were added to the reaction mixture and the mixture was stirred for 2 hours more. The reaction mixture was then left to stir at room temperature for 16 hours. The reaction mixture was diluted with EtOAc (40.0 ml_) and water (40.0 ml_) and was filtered on a pad of arbocel under a stream of nitrogen. The organic layer was separated and washed with a 10% solution of aqueous citric acid (3 x 25.0 ml_), followed by an aqueous hydrochloric acid solution (3 x 1.0 M, 20.0 ml_). The organic layer was discarded and the aqueous layer basified again with careful addition of a saturated aqueous solution of sodium hydrogen carbonate (100.0 ml_). The product was extracted with fert-butyl methyl ether (3 x 20.0 ml_). The combined organics were washed once more with a 10% solution of aqueous citric acid (25.0 ml_). The organic layer was then dried over sodium sulfate, filtered, and concentrated in vacuo to yield the title compound as a pale brown oil (2.45g, 62%).1H NMR (400 MHz, d6-DMSO): delta 0.94-1.01 (m, 4H), 2.40-2.48 (m, 1 H), 7.13-7.16 (m, 1 H), 7.78-7.81 (m, 1 H), 8.33-8.34 (m, 1 H).LCMS Rt = 2.27 minutes MS m/z 154 [MH]+
62%	With potassium phosphate;palladium diacetate; tricyclohexylphosphine; In water; toluene; at 100℃; for 6h;Inert atmosphere;	3-Chloro-2-bromopyridine (5.0 g, 26 mmol) and potassium phosphate tribasic (19.3 g, 90.9 mol) were suspended in toluene (40.0 mL) and water (2.0 mL). The mixture was sonicated for 10 minutes, then cyclopropylboronic acid (1.12 g, 13.0 mmol), palladium diacetate (0.093 g, 0.414 mol) and tricyclohexylphosphine (0.243 g, 0.867 mol) were added to the reaction mixture, which was heated into a pre heated DrySyn at 100 C., under a nitrogen atmosphere for 2 hours. Then cyclopropylboronic acid (1.12 g, 13.0 mmol), palladium diacetate (0.093 g, 0.41 mol) and tricyclohexylphosphine (0.243 g, 0.87 mol) were added to the reaction mixture and the mixture was stirred for 2 hours. Then cyclopropylboronic acid (1.12 g, 13.0 mmol), palladium diacetate (0.093 g, 0.41 mol) and tricyclohexylphosphine (0.243 g, 0.87 mol) were added to the reaction mixture and the mixture was stirred for 2 hours more. The reaction mixture was then left to stir at room temperature for 16 hours. The reaction mixture was diluted with EtOAc (40.0 mL) and water (40.0 mL) and was filtered on a pad of Arbocel under a stream of nitrogen. The organic layer was separated and washed with a 10% solution of aqueous citric acid (3×25.0 mL), followed by an aqueous hydrochloric acid solution (1.0 M, 3×20.0 mL). The organic layer was discarded and the aqueous layer basified again with careful addition of a saturated aqueous solution of sodium hydrogen carbonate (100.0 mL). The product was extracted with tert-butyl methyl ether (3×20.0 mL). The combined organics were washed once more with a 10% solution of aqueous citric acid (25.0 mL). The organic layer was then dried over sodium sulfate, filtered, and concentrated in vacuo to yield the title compound as a pale brown oil (2.45 g, 62%).1H NMR (400 MHz, d6-DMSO): delta 0.94-1.01 (m, 4H), 2.40-2.48 (m, 1H), 7.13-7.16 (m, 1H), 7.78-7.81 (m, 1H), 8.33-8.34 (m, 1H).LCMS Rt=2.27 minutes MS m/z 154 [MH]+

With potassium phosphate;palladium diacetate; tricyclohexylphosphine; In water; toluene; at 80 - 95℃; for 18.5h;Inert atmosphere;

Preparation 40: 3-chloro-2-cvclopropylpyridine; <strong>[96424-68-9]2-bromo-3-chloropyridine</strong> (70 g, 363.8 mmol), cycloproyl boronic acid (31 .3 g, 363.8 mmol), and potassium phosphate tribasic (193 g, 909.5 mmol) were suspended in a mixture of toluene (600 mL) and water (120 mL) with rapid stirring. The suspension was heated to 80 C, and the solvent de-gassed by direct bubbling of N2 gas through the suspension for 30 mins. The reaction was then heated to 95 C, and tricyclohexyl phosphine (10.2 g, 36.4 mmol) rapidly followed by palladium acetate (4.10 g, 18.2 mmol) were added. The reaction was left to stir and heated at 95 C for 18 hours. The reaction was cooled to room temperature, and run through a plug of arbocel, eluting with ethyl acetate. The solvent was removed to leave a dark yellow oil. TBME was added (300 mL), and the organics washed with 2M HCI solution (3 x 200 mL). The organics were discarded. TBME (300 mL) was added to the combined aqueous layers, and solid sodium bicarbonate was added until the aqueous layer reached pH 7. The mixture was transferred to a separating funnel, the organic layer was removed, and the aqueous layer was extracted into TBME (2 x 100 mL). The combined organics were dried over magnesium sulfate, filtered and the solvent removed to leave an orange oil. The material was purified by column chromatography (silica), eluting with 4: 1 heptane:ethyl acetate, affording the title compound as a pale yellow oil (38.6 g).1 H NMR (400 MHz, CDCI3) delta ppm 0.95-1 .10 (m, 4H), 2.45-2.57 (m, 1 H), 6.98 (dd, 1 H), 7.39 (d, 1 H), 8.30 (d, 1 H)LCMS Rt = 2.61 minutes, MS m/z 154 [MH]+

Reference： [1]Patent: WO2012/7869,2012,A2 .Location in patent: Page/Page column 87-88
[2]Patent: WO2012/7877,2012,A2 .Location in patent: Page/Page column 76-77
[3]Patent: US2012/10183,2012,A1 .Location in patent: Page/Page column 52
[4]Patent: WO2012/95781,2012,A1 .Location in patent: Page/Page column 109-110

15
[ 96424-68-9 ]
[ 1355067-20-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: potassium phosphate / tricyclohexylphosphine; palladium diacetate / toluene; water / 6 h / 100 °C / Inert atmosphere 2: 4,4'-di-tert-butyl-2,2'-bipyridine; (1,5-cyclooctadiene)(methoxy)iridium(I) dimer / n-heptane / 18 h / 20 °C / Inert atmosphere
	Multi-step reaction with 2 steps 1: potassium phosphate / palladium diacetate; tricyclohexylphosphine / water; toluene / 6 h / 100 °C / Inert atmosphere 2: (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; 4,4'-di-tert-butyl-2,2'-bipyridine / hexane / 18 h / 20 °C / Inert atmosphere
	Multi-step reaction with 2 steps 1: potassium phosphate / palladium diacetate; tricyclohexylphosphine / water; toluene / 18.5 h / 80 - 95 °C / Inert atmosphere 2: (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; 4,4'-di-tert-butyl-2,2'-bipyridine / 1,4-dioxane / 18 h / 90 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: PFIZER INC - US2012/10183, 2012, A1
[2]Current Patent Assignee: PFIZER INC - WO2012/7869, 2012, A2
[3]Current Patent Assignee: PFIZER INC - WO2012/95781, 2012, A1

16
[ 96424-68-9 ]
[ 411235-57-9 ]
[ 1355070-88-0 ]

Yield	Reaction Conditions	Operation in experiment
16%	With potassium phosphate;palladium diacetate; tricyclohexylphosphine; In water; toluene; at 100℃; for 6h;Inert atmosphere;	Preparation 982,3-Dicvclopropylpyridine3-Chloro-2-bromopyridine (5.0 g, 26.0 mmol) and potassium phosphate tribasic (19.3 g, 90.9 mmol) were suspended in toluene (40 mL) and water (2 mL). The reaction mixture was sonicated for 10 minutes, and then cyclopropylboronic acid (1 .12 g, 13.0 mmol), palladium acetate (0.093 g, 0.414 mmol) and tricyclohexylphosphine (0.243 g, 0.867 mmol) were added to the reaction mixture, which was then placed in a pre heated DrySyn bath at 100 C. The reaction mixture was then left to stir under nitrogen for two hours. Additional cyclopropylboronic acid (1 .12 g, 13.0 mmol), palladium acetate (0.093 g, 0.414 mol) and tricyclohexylphosphine (0.243 g, 0.867 mmol) were added to the reaction m ixture which was stirred for a further two hours. Additional cyclopropylboronic acid (1 .12 g, 13.0 mmol), palladium acetate (0.093 g, 0.414 mmol) and tricyclohexylphosphine (0.243 g, 0.867 mmol) were again added to the reaction mixture which was stirred for a further two hours. The mixture was then left to stir at room temperature for 16 hours. The reaction mixture was diluted in ethyl acetate (40 mL) and water (40 mL) and was filtered on a pad of arbocel under a stream of nitrogen. The organic layer was then separated and washed three times with a 10% solution of aqueous citric acid (25 mL). The organic layer was discarded and the aqueous layer brought back to basic pH with careful addition of a saturated aqueous solution of sodium hydrogen carbonate (100 mL). The product was extracted three times with terf-butyl methyl ether (20 mL). The organic layers were combined, then dried over sodium sulfate, filtered, and concentrated in vacuo. The title compound was isolated as an orange oil (0.66 g, 16%):1H NMR (400 MHz, DMSO-d6): delta 0.60-0.64 (m, 2H), 0.88-0.96 (m, 6H), 2.06-2.14 (m, 1 H), 2.45-2.52 (m, 1 H), 6.99 (d, 1 H), 7.27 (d, 1 H), 8.17 (d, 1 H)LCMS Rt = 0.74 minutes MS m/z 160 [MH]+

Reference： [1]Patent: WO2012/7869,2012,A2 .Location in patent: Page/Page column 104-105

17
2-(2-fluoro-3-nitrophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane [ No CAS ]
[ 96424-68-9 ]
[ 1386460-42-9 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; water; at 120℃; for 1h;microwave irradiation;	To a solution of <strong>[96424-68-9]2-bromo-3-chloropyridine</strong> [96424-68-9] (144 mg, 0.75 mmol) and 2-fluoro-3- nitrophenylboronic acid pinacol ester [1 189042-70-3] (200 mg, 0.75 mmol) in dioxane (4 mL) and water (1 mL) was added potassium carbonate (259 mg, 1.87 mmol) and Pd(dppf)CI2 CH2CI2 adduct (61.2 mg, 0.075 mmol). The solution was heated for 60 min at 120C under microwave irradiation. The reaction mixture was diluted with EtOAc and the resulting solution was washed successively with saturated aqueous NaHC03 solution and brine, then dried (Phase separator) and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (c-hexane/EtOAc 4:1) to give the title compound. MS (LC-MS): 253 [M+H]+; tR (HPLC conditions k): 3.45 min.

Reference： [1]Patent: WO2012/93101,2012,A1 .Location in patent: Page/Page column 263

18
[ 67237-53-0 ]
[ 96424-68-9 ]
[ 1392013-59-0 ]

Yield	Reaction Conditions	Operation in experiment
70%	With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; at 100℃; for 2h;	General procedure: In a dry Schlenk tube, the dihalopyridine, CuI (6 mol %), and PdCl2(PPh3)2 (3 mol %) were added in Et3N (2 mL per mmol of pyridine). After stirring for 10 min, the (hetero)arylacetylene (1.0 or 1.1 equiv) was added, and the solution was heated to 100 C in a silicone bath for 2 h. The reactions were monitored by TLC, following the disappearance of the starting materials. After completion, the mixture was allowed to cool to room temperature. Then ethyl acetate and water were added and the organic phase was separated, dried (MgSO4), and filtered. Removal of the solvent under reduced pressure gave either oils, which were submitted to column chromatography or pure products corresponding to the expected (hetero)arylethynylpyridines.

Reference： [1]Tetrahedron,2012,vol. 68,p. 7082 - 7094
[2]Helvetica Chimica Acta,2019,vol. 102

19
[ 2510-23-8 ]
[ 96424-68-9 ]
[ 1392013-60-3 ]