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CAS No. : | 2402-78-0 |
Formula : | C5H3Cl2N |
M.W : | 147.99 |
SMILES Code : | ClC1=CC=CC(Cl)=N1 |
MDL No. : | MFCD00006244 |
InChI Key : | FILKGCRCWDMBKA-UHFFFAOYSA-N |
Pubchem ID : | 16989 |
GHS Pictogram: | ![]() |
Signal Word: | Danger |
Hazard Statements: | H301-H315-H319 |
Precautionary Statements: | P264-P270-P280-P301+P310+P330-P302+P352-P305+P351+P338-P332+P313-P337+P313-P405-P501 |
Class: | 6.1 |
UN#: | 2811 |
Packing Group: | Ⅲ |
* 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 |
---|---|---|
89% | at 0 - 20℃; Heating / reflux | A mixture of NaOH (14.7 g, 0.37 mol), hydrazine monohydrate (15 ml) and 2,6-diacetylpyridine (6g, 36.8 mmol) suspended in diethylene glycol (27 ml_) was cautiously heated to 120 °C for 16 hours. The mixture was cooled to room temperature and partitioned between H2O and ether. The ether extracts were washed with 1 N NaOH, dried over MgSO4 and concentrated to a clear oil. Flash column chromatography (0percent to 15percent EtOAc in hexanes) gave the product as a clear oil (2.9 g, 58percent). 1H NMR (400 MHz, CDCI3): 5 1.29 (t, J=7.8 Hz, 3 H), 2.80 (d, J=7.8 Hz, 2 H), 6.97 (d, J=2.0 Hz, 2 H), 7.51 (t, J=7.6 Hz, 1 H). 2,6-Diethyl-pyridine has also been prepared as follows:A solution of ethylmagnesium bromide in ethyl ether [prepared from Mg (16.5 g, 0.68 mol) and ethyl bromide (50 mL, 0.68 mol) in 500 ml_ of ether] was added dropwise to a mixture of 2,6-dichloropyridine (50 g, 0.34 mol) and NiCI2(dppp) (1.0 g, 2 mol) in anhydrous ethyl ether(500 mL).at 0 °C unde(r N3 atmosphere. After addition, the resulting mixture was stirred,. , ' >.,"?, '['A V ' "' > 'ambient temperature oveifngh'tj was then heated to reflux for about 3 hours. The suspensiatonwas poured into cushed ice (200 g) and the mixture was saturated with NH4CI. The organic layer was separated and the aqueous phase was extracted with ether (200 mL x 3). The combined organic layers were washed with water, brine, dried over Na2SO4 and concentrated to give the product (41 .1 g, 89percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To a solution of diisopropyl amine (4 mL) in THF (60 mL) was added dropwise a 1.55 M n-butyl lithium/n-hexane solution (20 mL) at -78C, followed by stirring at the same temperature for 30 minutes. To this solution was added dropwise a mixture of 2,6-dichloropyridine (2.0 g) and THF (10 mL), followed by stirring at the same temperature for additional 1 hour. A mixture of triisopropyl borate (6.8 mL) and THF (10 mL) was added dropwise thereto, followed by stirring at room temperature for 20 hours. The reaction mixture was diluted with water, and then neutralized with hydrochloric acid, and extracted with ethyl acetate. The organic layer was washed with water, dried over magnesium sulfate, and then concentrated under reduced pressure to obtain (2,6-dichloropyridin-3-yl)boronic acid (2.6 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | tetrakis(triphenylphosphine) palladium(0); In toluene; for 11h;Reflux; | Step 1 [Show Image] 2,6-dichloropyridine 11 (8.88 g, 60.0 mmol) and 2-(tributylstannyl)pyridine (7.36 g, 20.0mmol) were dissolved in toluene (74 ml). To the solution was added tetrakis triphenyl phosphinepalladium (2.31 g, 2.0 mmol) and the mixture was stirred under heat refluxing for 11 hours. The reactant was condensed under reduced pressure and the residue was purified by silica gel chromatography to give quantitatively the desired Compound 12 (3.9 g). 1H-NMR (DMSO-d6) deltapppm: 7.50-7.53 (m, 1H), 7.59 (d, 1H, J = 8.0 Hz), 7.93-8.05 (m, 2H), 8.30 (d, 1H, J = 8.0 Hz), 8.38 (d, 1H, J = 8.0 Hz), 8.72 (d, 1H, J = 4.4 Hz). |
100% | tetrakis(triphenylphosphine) palladium(0); In toluene; for 11h;Reflux; | 2,6-dichloropyridine 11 (8.88 g, 60.0 mmol) and 2-(tributylstannyl)pyridine (7.36 g, 20.0 mmol) were dissolved in toluene (74 ml). To the solution was added tetrakis triphenyl phosphinepalladium (2.31 g, 2.0 mmol) and the mixture was stirred under heat refluxing for 11 hours. The reactant was condensed under reduced pressure and the residue was purified by silica gel chromatography to give quantitatively the desired Compound 12 (3.9 g) 1H-NMR (DMSO-d6) ? ppm: 7.50-7.53 (m, 1H), 7.59 (d, 1H, J=8.0 Hz), 7.93-8.05 (m, 2H), 8.30 (d, 1H, J=8.0 Hz), 8.38 (d, 1H, J=8.0 Hz), 8.72 (d, 1H, J=4.4 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With copper(l) iodide; In water; at 180.0℃; for 2.0h;Sealed tube; Microwave irradiation; | General procedure: Compounds I-VII (4.22 mmol), catalytic amounts of CuI (10 mg, 0.052 mmol) and water (100 muL) were treated with 6equiv of the respective amine and sealed in a 5 mL microwave vial. Pd(PPh3)4 (10 mg, 0.008 mmol) was added in the case of anilines. After the reaction was completed (see Table 1), 2 equiv of solid K2CO3 were added. The resulting product was obtained after filtration and washing with water as an analytically pure crystalline solid. Otherwise all volatiles were then evaporated and purified by flash column chromatography (A) or bulb-to-bulb distillation (B). In the case of methylamine and ethylamine the corresponding aqueous solution was used without extra water addition. |
With sodium hydroxide; In water; at 120.0℃; for 16.0h; | To a stirring solution of 2,6-dichloro-pyridine (15 g, 0.10 mol) and methylamine (40 wt %, H2O, 20 mL) in a sealed tube, NaOH (8 g, 0.20 mol) was added, the heterogeneous solution was heated at 120 C. for 16 h, the mixture was cooled down to RT before poured into 200 mL ice-H2O. After filtration, the title productproduct was collected as an off-white solid. MS m/z 143 (MH)+. | |
With sodium hydroxide; In water; at 80.0℃; for 16.0h; | To a stirred solution of 2,6-dichloropyridine (1.0 g, 6.76 mmol) in methylamine (40% in water) (1.3 ml) was added NaOH (0.54 g, 13.5 mmol) at rt. The reaction mixture was heated at 80C for 16 h. The reaction mixture was cooled to rt, poured into cold water (20 ml). The obtained precipitates were collected by filtration, washed with water (15 ml) and dried under vacuum yielding 6-chloro-N- methylpyridin-2-amine (0.399 g, 2.80 mmol). This material was used for the next step without furtherpurification. LCMS: Method C, 1.82 mm, MS: ES+ 143.03; ?H NMR (400 MHz, DMSO-d6) (5ppm 7.38(dd, J=7.6 Hz, 8.0 Hz, 1 H), 6.90 (d, J4.0 Hz, 1 H), 6.48 (d, J=7.6 Hz, 1 H), 6.37 (d, J=8.4 Hz, 1 H), 2.73(d, J=4.8 Hz, 3 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With pyridine; at 20 - 100℃; | Reference example 67: 2-(6-chloro-pyridin-2-ylaminoVethanol. 2-Arnino-ethanol (0.82 g, 13.5 mmol) was added to a solution of 2,6- dichloropyridine (2.0 g, 13.5 mmol) in pyridine (10 mL) at room temperature and then heated at 100 C overnight The reaction mixture was concentrated in vacuo to obtain a residue which was dissolved in ethyl acetate. The solution was washed with water, brine, dried over anhydrous sodium sulfate and evaporated in vacuo to afford 2-(6- chloro-pyridin-2-ylamino)-ethanol (2.3 g, 99%) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | To a solution of <strong>[56456-49-6]4-chloro-2-fluorobenzyl alcohol</strong> (15.0 g, 93.4 mmol) in DMF (250 mL) was added NaH (4.48 g, 112 mmol, 60% susp.) at 0 C. After stirring at 15 C. for 40 min, 2,6-dichloropyridine (16.6 g, 112 mmol) was added. The resulting mixture was stirred at 15 C. for 3 h. The mixture was poured into water (1 L) and extracted with EtOAc (2*200 mL). The combined organic layers were washed with sat. NH4Cl (500 mL), brine (500 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by flash chromatography (PE) to give 2-chloro-6-((4-chloro-2-fluorobenzyl)oxy)pyridine (19.2 g, 75%) as a solid. 1H NMR (CDCl3) delta 7.55 (t, 1H), 7.47 (t, 1H), 7.15 (t, 2H), 6.94 (d, 1H), 6.71 (d, 1H), 5.40 (s, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate; caesium carbonate; In N,N-dimethyl-formamide; at 120℃; for 7h;Schlenk technique; Inert atmosphere; | General procedure: An oven-dried Schlenk flask was evacuated and back-filled with argon three times. (Hetero)aryl (di)halide (1 equiv), base (1.5 equiv per halogen) and a solution of SPO (1.2 equiv per halogen) in anhydrous solvent (5 mL/mmol per halogen) were added to the flask. The solution was bubbled with argon for 10 min and Pd(OAc)2 (1 mol% per halogen) and ferrocene-based bidentate phosphine ligand (2 mol% per halogen) were added to the flask simultaneously [2.5 mol% Pd(OAc)2 per halogen and 5 mol% dppf per halogen for compounds 2j, 2l, 2r, 2t, 2w]. The resulting mixture was heated at the indicated temperature for the given time. Workup procedures are described below for two different conditions. Final purification of crude products was achieved by column chromatography on silica gel (40-60 μm) using CH2Cl2-MeOH as eluent. Reaction scale and yields are shown in Table 1 (2a-w), Scheme 1 (3a-h) and Scheme 2 (4a-g). Notice that all compounds with two phosphine oxide groups are beige-to-brown solids or slowly solidifying viscous brown oils. Conditions I: ligand: dppf, solvent: DMF, base: Cs2CO3 (2d-n, 2q, 2r, 2t-w, 4a-g) or K2CO3 (3a-h), temperature: 120 C, time: 7 h (20 h for 2j, 2l, 2r, 2w). Workup: after cooling, the reaction mixture was poured into a fourfold excess of brine. The mixture was extracted three times with CH2Cl2 (40 mL/mmol each). The combined organic layers were washed with brine to remove traces of DMF, dried over Na2SO4 and then evaporated to dryness. Conditions II: ligand: dippf, solvent: toluene, base: t-BuOK, temperature: 110 C, time: 7 h. Workup: after cooling, the reaction mixture was evaporated to dryness. Then, the mixture was diluted with CH2Cl2 (40 mL/mmol) and washed with water and brine (40 mL/mmol). The organic layer was dried over Na2SO4 and the CH2Cl2 was removed under reduced pressure. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate; caesium carbonate; In N,N-dimethyl-formamide; at 120℃; for 7h;Schlenk technique; Inert atmosphere; | General procedure: An oven-dried Schlenk flask was evacuated and back-filled with argon three times. (Hetero)aryl (di)halide (1 equiv), base (1.5 equiv per halogen) and a solution of SPO (1.2 equiv per halogen) in anhydrous solvent (5 mL/mmol per halogen) were added to the flask. The solution was bubbled with argon for 10 min and Pd(OAc)2 (1 mol% per halogen) and ferrocene-based bidentate phosphine ligand (2 mol% per halogen) were added to the flask simultaneously [2.5 mol% Pd(OAc)2 per halogen and 5 mol% dppf per halogen for compounds 2j, 2l, 2r, 2t, 2w]. The resulting mixture was heated at the indicated temperature for the given time. Workup procedures are described below for two different conditions. Final purification of crude products was achieved by column chromatography on silica gel (40-60 μm) using CH2Cl2-MeOH as eluent. Reaction scale and yields are shown in Table 1 (2a-w), Scheme 1 (3a-h) and Scheme 2 (4a-g). Notice that all compounds with two phosphine oxide groups are beige-to-brown solids or slowly solidifying viscous brown oils. Conditions I: ligand: dppf, solvent: DMF, base: Cs2CO3 (2d-n, 2q, 2r, 2t-w, 4a-g) or K2CO3 (3a-h), temperature: 120 C, time: 7 h (20 h for 2j, 2l, 2r, 2w). Workup: after cooling, the reaction mixture was poured into a fourfold excess of brine. The mixture was extracted three times with CH2Cl2 (40 mL/mmol each). The combined organic layers were washed with brine to remove traces of DMF, dried over Na2SO4 and then evaporated to dryness. Conditions II: ligand: dippf, solvent: toluene, base: t-BuOK, temperature: 110 C, time: 7 h. Workup: after cooling, the reaction mixture was evaporated to dryness. Then, the mixture was diluted with CH2Cl2 (40 mL/mmol) and washed with water and brine (40 mL/mmol). The organic layer was dried over Na2SO4 and the CH2Cl2 was removed under reduced pressure. |
Tags: 2402-78-0 synthesis path| 2402-78-0 SDS| 2402-78-0 COA| 2402-78-0 purity| 2402-78-0 application| 2402-78-0 NMR| 2402-78-0 COA| 2402-78-0 structure
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