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CAS No. : | 10386-27-3 | MDL No. : | MFCD07367879 |
Formula : | C6H3BrN2 | Boiling Point : | No data available |
Linear Structure Formula : | - | InChI Key : | AWSJFEKOXQBDSL-UHFFFAOYSA-N |
M.W : | 183.01 | Pubchem ID : | 11735544 |
Synonyms : |
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Signal Word: | Warning | Class: | |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With cesium fluoride;tetrakis(triphenylphosphine)palladium (0); In 2-Methyl-1,2-propanediol; | Preparation 72 2-(4-formylphenyl)-4-pyridyl cyanide Benzaldehyde-4-boronic acid (1.36 g), 2-bromo-4-cyano pyridine (1.5 g), cesium fluoride (2.72 g) and tetrakis(triphenylphosphine)palladium(0) (285 mg) were mixed together in dimethyl ethylene glycol (30 ml). The reaction mixture was refluxed for 16 hrs under a atmosphere of nitrogen after which time the cooled mixture was diluted with diethyl ether (40 ml) and washed with water (40 ml), the organic layer was separated and washed with saturated brine, dried over MgSO4 and evaporated under reduced pressure. The crude product was purified by column chromatography eluding with Dichloromethane/Diethyl ether (97.5/2.5, v/v) to afford the title compound (0.81 g). Rf 0.3 (Dichloromethane/Diethyl ether, 97.5/2.5, v/v). deltaH (400 MHz, CDCl3): 10.15 (1H, s), 8.95 (1H, d), 8.20 (2H, d), 8.05 (3H, m), 7.55 (1H, d). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | tetrakis(triphenylphosphine) palladium(0); In toluene; at 80℃;Inert atmosphere; | Example 28i 2-(Trimethylstannyl)isonicotinonitrile 2-Bromo-isoniconinonitrile (1.00 g, 5.46 mmol) was dissolved in toluene (25 mL) and 1,1,1,2,2,2-hexamethyldistannane (2.266 mL, 10.93 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.316 g, 0.27 mmol) were added and the reaction was stirred at 80 C. over night under nitrogen atmosphere. The mixture was cooled to room temperature and filtered through a pad of Celite twice and concentrated. Toluene (20 mL) was added and the mixture was concentrated to give the title compound (1.079 g, 74%), which was used without further purification in the next step. MS (EI+) m/z 268 [M]+. |
51.7% | With tetrakis(triphenylphosphine) palladium(0); In toluene; at 110℃; for 16h;Inert atmosphere; | To a stirred solution of 2-bromoisoniconitrile (2 g, 10.92 mmol) in toluene (20 mL), hexamethylditin (4.6 g, 14.20 mmol), and Pd(PPh3)4 (1.2 g, 1.09 mmol) were added at rt. The resulting solution was degassed with nitrogen for 10 min and heated to 110 C for 16 h. The reaction mixture was evaporated under reduced pressure and the crude compound was purified by flash column chromatography on neutral alumina using 50% EtOAc in petroleum ether to afford the title compound (1 ,5 g, 51.7%). LC-MS (method 1): Rt = 1.93 min; m/z = 269.08 (M+H-) |
With tetrakis(triphenylphosphine) palladium(0); In toluene; at 110℃; for 16h; | General procedure: To a stirred solution of methyl 2-chloro isonicotinate (2 g, 12 mmol) in toluene (20 mL), hexamethylditin (4.5 g, 14 mmol) was added. The reaction mixture was degassed with argon for 10 minutes, then Pd(PPI)4 (1.35 g, 10 mmol) was added, it was degassed again for 5 minutes and the resulting reaction mixture was heated at 110C for 16h. The progress of the reaction was monitored by LCMS. The reaction mixture was cooled to RT, filtered through the Celite pad, washed with EtOAc and the filtrate was concentrated to dryness. The crude compound was purified by column chromatography using neutral alumina and eluted with 5%EtOAc/pet ether to afford the title compound (1.5 g, 42%) as a colorless liquid. LC-MS (method 1): R, = 1.20 min; m/z = 301.99 (M+H+) |
With tetrakis(triphenylphosphine) palladium(0); In toluene; at 110℃; for 16h;Inert atmosphere; | General procedure: To a stirred solution of methyl 2-chloro isonicotinate (2 g, 0.0116 mol) in toluene (20 mL) was added hexamethylditin (4.5 g, 0.0140 mol). the mixture was degassed with argon for 10 minutes, then Pd(PPhs)i (1.35 g, 0.00116 mol) was added and the mixture was degassed again for 5 minutes. The resulting reaction mixture was heated at 110C for 16h. The progress of the reaction was monitored by LCMS. The reaction mixture was cooled to RT, filtered through a Celite pad, washed with EtOAc, the filtrate was concentrated to get crude compound. The crude compound was purified by column chromatography using neutral alumina and eluted with 5%EtOAc/pet ether to afford the title compound (1.5 g, 42%) as a colorless liquid. (0533) LC-MS (method 1): R, = 1.20 min; m/z = 301.99 (Mu+Eta'). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; at 80℃; for 17h;Inert atmosphere; | In a screw cap vial (2-cyclopropyl-8-methoxy-[l,2,4]triazolo[l,5-a]pyridin-5- yl)boronic acid, compound 303, (26mg, 0.1 mmol) was dissolved in DME (0.6 mL) and 1 M K2CO3 (0.2 ml_) under argon. 2-Bromo-isonicotinonitrile (18mg, 0.1 mmol) and Pd(PPh3)4 (6mg, 0.005 mmol) were added. The suspension was shaken at 800C for 17 h after which brine was added, and the aqueous phase was extracted with DCM (x 3). The combined organic phases were dried, filtered and concentrated. The crude product was purified by flash chromatography, eluent TBME : heptane 4: 1 -> 9: 1. This afforded the title compound as a solid IH NMR (300 MHz, DMSO) delta 9.23 - 9.09 (m, IH), 9.00 (dd, J = 4.9, 0.8 Hz, IH), 7.95 (dd, J = 4.9, 1.5 Hz, IH), 7.90 (d, J = 8.3 Hz, IH), 7.24 (d, J = 8.4 Hz, IH), 4.03 (s, 3H), 2.29 (tt, J = 8.1, 5.0 Hz, IH), 1.18 - 0.87 (m, 4H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
17% | With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 100℃; for 16h; | To a solution of 2-(pyridin-2-yl)-4,5,6,7-tetrahydrooxazolo[4,5-c] pyridine (I- 23.4) (40 mg, 0.2 mmol) in DMF (2 mL) was added <strong>[10386-27-3]2-bromoisonicotinonitrile</strong> (54 mg, 0.3 mmol), DIEA (52 mg, 0.4 mmol). The mixture was heated to 1000C and stirred for 16 h. The mixture was cooled to room temperature and poured into water. The mixture was extracted with EtOAc. The combined organic phase was dried over anhydrous Na2SO4 and concentrated. The residue was purified by preparative TLC to afford 2-(2- (pyridin-2-yl)-6,7-dihydrooxazolo[4,5-c]pyridin-5(4H)-yl)isonicotinonitrile (10 mg, 17percent) as a yellow solid. 1H NMR (400 MHz, CDCl3): delta 8.67 (d, IH), 8.25 (d, IH), 8.03 (d, IH), 7.75 (t, IH), 7.30 (t, IH), 6.81 (s, IH), 6.75 (d, IH), 4.52 (s, 2H), 4.07 (t, 2H), 2.91 (t, 2H); LC/MS: m/e = 304 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydroxylamine hydrochloride; sodium hydrogencarbonate; In ethanol;Reflux; | Description for D35 2-brorno-A/-hydroxy-4-pyridinecarboximidamide (D35)A mixture of <strong>[10386-27-3]2-bromo-4-pyridinecarbonitrile</strong> (0.7 g), sodium bicarbonate (0.65 g) and hydroxylamine hydrochloride (0.53 g) in ethanol (50 ml) was heated at reflux for overnight. The inorganic precipitate was filtered off. The solid was washed thoroughly with ethanol. The filtrate was concentrated. The obtained solid was dried in vacuo to afford 2-bromo-Lambda/-hydroxy-4-pyridinecarboximidamide (0.78 g). MS (ES): C6H6BrN3O requires 215; found 216.1 (M+H+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate;palladium diacetate; triphenylphosphine; In 1,4-dioxane; at 85℃; for 4h;Inert atmosphere; | Example A3. General experimental for the Suzuki coupling of aryl bromides or chlorides with boronic acidsGeneral Scheme:K2C03, Pd(OAc)2 Ph3P, dioxaneRepresentative SchePh3P, dioxaneA solution of the aryl bromide or aryl chloride (e.g., 6-bromonicotinonitrile, 1 equiv), 4,4,5,5-tetramethyl -2-vinyl-l,3,2- dioxaborolane (2 equiv), K2C03 (2 equiv), Pd(AcO)2 (0.4 equiv) and PI13P (0.8 equiv) in 1,4-dioxane was stirred under N2 at 85 °C until the reaction was complete (approximately 4 h). After cooling to room temperature, the mixture was quenched with water (50 mL) and extracted with ethyl acetate (3 x 50 mL). The combined organic layers were dried over Na2S04 and concentrated under reduced pressure. The crude vinyl-containing product (e.g., 2-vinylisonicotinonitrile) was purified by silica gel chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; at 85℃; for 3h;Inert atmosphere; | General procedure: To a solution of 2-ethynylquinoline 9 (50 mg, 0.33 mmol) in triethylamine (0.4 mL) was added PdCl2(PPh3)2 (12 mg, 0.02 mmol), copper(I) iodide 98percent (6 mg, 0.03 mmol) and 2- bromo-3-trifluoromethylpyridine (110 mg, 0.5 mmol). After the reaction was stirred at 85 °C for 3 h, it was allowed to cool to room temperature and filtered through a pad of Celite by the aid of EtOAc. The filtrate was treated with water and extracted with EtOAc (3 x 10 mL). The organic layer was washed with water and brine, dried over anhydrous MgSO4, and concentrated under reduced pressure. The crude oil was purified by column chromatography on silica gel (EtOAc/hexane = 1:1) to give 2-((3-(trifluoromethyl)pyridin-2-yl)ethynyl) quinoline 6a (48 mg, 49percent) |
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