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CAS No. : | 343781-36-2 | MDL No. : | MFCD09033756 |
Formula : | C5H2Cl2IN | Boiling Point : | No data available |
Linear Structure Formula : | - | InChI Key : | OKXJLNYZTJLVJZ-UHFFFAOYSA-N |
M.W : | 273.89 | Pubchem ID : | 10636017 |
Synonyms : |
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Signal Word: | Warning | Class: | |
Precautionary Statements: | P280-P305+P351+P338 | UN#: | |
Hazard Statements: | H317-H319 | 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 |
---|---|---|
81% | Description 52,4-dichloro-3-iodo-pyridine (D5)To a solution of 2,4-dichloropyridine (5.2 g, 35.137 mmol) and DIPEA (3.911 g,38.651 mmol) in dry THF (40 ml) cooled at -78 0C under a nitrogen atmosphere, was added M-butyllithium (24.157 ml, 38.651 mmol, 1.6 M in hexanes) dropwise. The resulting reaction mixture was stirred at -78 0C for 45 min. and then a solution of iodine (9.81 g, 38.651 mmol) in dry THF (20 ml) was added dropwise. The mixture was stirred at -78 0C for 1 h. The mixture was allowed to warm to room temperature, diluted with EtOAc and quenched with NH4Cl (aqueous sat. solution) and Na2S2O3 (aqueous sat. solution). The combined organic extracts were separated, washed with NaHCO3 (aqueous sat. solution), dried (Na2SO4) and concentrated in vacuo. The crude product was purified by column chromatography (silica gel; Heptane/DCM up to 20% as eluent). The desired fractions were collected and concentrated in vacuo to yield intermediate compound D5 (7.8 g, 81%). | |
81% | To a solution of 2,4-dichloropyridine (5.2 g, 35.137 mmol) and diisopropylamine (3.911 g, 38.651 mmol) in dry THF (40 ml) cooled at -78 0C under a nitrogen atmosphere, was added M-butyllithium (24.157 ml, 38.651 mmol, 1.6 M in hexanes) dropwise. The resulting reaction mixture was stirred at -78 0C for 45 min., then a solution of iodine (9.81 g, 38.651 mmol) in dry THF (20 ml) was added dropwise and the mixture was further stirred at -78 0C for 1 h. The mixture was allowed to warm to r.t., diluted with EtOAc and quenched with NH4Cl (aqueous sat. solution) and Na2S2O3 (aqueous sat. solution). The organic layer was separated, washed with NaHCO3 (aqueous sat. solution), dried (Na2SO4) and concentrated in vacuo. The crude product was purified by column chromatography (silica gel; Heptane/DCM up to 20% as eluent). The desired fractions were collected and concentrated in vacuo to yield intermediate compound D 12 (7.8 g, 81%) | |
81% | To a solution of 2,4-dichloropyridine (5.2 g, 35.137 mmol) and diisopropylamine (3.911 g, 38.651 mmol) in dry THF (40 ml) cooled at -78 0C under a nitrogen atmosphere, was added n-butyllithium (24.157 ml, 38.651 mmol, 1.6 M in hexanes) dropwise. The resulting reaction mixture was stirred at -78 0C for 45 min. and then a solution of iodine (9.81 g, 38.651 mmol) in dry THF (20 ml) was added dropwise. The mixture was stirred at -78 0C for 1 h., allowed to warm to r.t., diluted with EtOAc and quenched with NH4Cl (aqueous sat. solution) and Na2S2O3 (aqueous sat. solution). The organic layer was separated, washed with NaHCO3 (aqueous sat. solution), dried (Na2SO4) and concentrated in vacuo. The crude product was purified by column chromatography (silica gel; Heptane/DCM up to 20% as eluent). The desired fractions were collected and concentrated in vacuo to yield intermediate compound D24 (7.8 g, 81%). |
81% | 2,4-Dichloro-3 -iodo-pyridine (1-5)To a solution of 2,4-dichloropyridine (5.2 g, 35.14 mmol) and DIPEA (3.91 g, 38.65 mmol) in dry THF (40 mL) cooled at -78 C under a nitrogen atmosphere, was added n-BuLi (24.16 mL, 38.65 mmol, 1.6 M in hexanes) dropwise. The resulting r.m. was stirred at -78 C for 45 min and then a solution of iodine (9.81 g, 38.651 mmol) in dry THF (20 mL) was added dropwise. The mixture was stirred at -78 C for 1 h, allowed to warm to r. , diluted with EtOAc and quenched with H4CI (aq. sat. sol.) and Na2S203 (aq. sat. sol). The organic layer was separated, washed with NaHC03 (aq. sat. sol), dried (Na2S04) and concentrated in vacuo. The crude product was purified by column chromatography (silica gel; Heptane/DCM up to 20% as eluent). The desired fractions were collected and concentrated in vacuo to yield intermediate 1-5 (7.8 g, 81%). | |
81% | Intermediate 1 (1-1)2,4-Dichloro-3-iodo-pyridine (1-1)To a solution of 2,4-dichloropyridine (5.2 g, 35.14 mmol) and diisopropylamine (3.91 g, 38.65 mmol) in dry THF (40 mL) cooled at -78 C under a nitrogen atmosphere, was added n-butyllithium (24.16 mL, 38.65 mmol, 1.6 M in hexanes) dropwise. The resulting reaction mixture was stirred at -78 C for 45 min. and then a solution of iodine (9.81 g, 38.651 mmol) in dry THF (20 mL) was added dropwise. The mixture was stirred at -78 C for 1 h., allowed to warm to r.t., diluted with EtOAc and quenched with H4CI (aqueous sat. solution) and Na2S203 (aqueous sat. solution). The organic layer was separated, washed with NaHC03 (aqueous sat. solution), dried (Na2S04) and concentrated in vacuo. The crude product was purified by column chromatography (silica gel; DCM in heptane 0/100 to 20/80). The desired fractions were collected and concentrated in vacuo to yield intermediate compound 1-1(7.8 g, 81%). | |
81% | Intermediate 7 (1-7)2,4-Dichloro-3 -iodo-pyridine (1-7) To a solution of 2,4-dichloropyridine (5.2 g, 35.14 mmol) and DIPEA (3.91 g,38.65 mmol) in dry THF (40 mL) cooled at -78 C under a nitrogen atmosphere, was added n-butyllithium (24.16 mL, 38.65 mmol, 1.6 M in hexanes) dropwise. The resulting reaction mixture was stirred at -78 C for 45 min. and then a solution of iodine (9.81 g, 38.651 mmol) in dry THF (20 mL) was added dropwise. The mixture was stirred at -78 C for 1 h., allowed to warm to r.t., diluted with EtOAc and quenched with H4CI (aqueous sat. solution) and Na2S203 (aqueous sat. solution). The organic layer was separated, washed with NaHC03 (aqueous sat. solution), dried (Na2S04) and concentrated in vacuo. The crude product was purified by column chromatography (silica gel; DCM in heptane 0/100 to 20/80). The desired fractions were collected and concentrated in vacuo to yield intermediate compound 1-7 (7.8 g, 81%). | |
81% | Intermediate 1 (1-1)2,4-Dichloro-3-iodo-pyridine (1-1)To a solution of 2,4-dichloropyridine (5.2 g, 35.14 mmol) and diisopropylamine (3.91 g, 38.65 mmol) in dry THF (40 mL) cooled at -78 C under a nitrogen atmosphere, was added n-butyllithium (24.16 mL, 38.65 mmol, 1.6 M in hexanes) dropwise. The resulting reaction mixture was stirred at -78 C for 45 min. and then a solution of iodine (9.81 g, 38.651 mmol) in dry THF (20 mL) was added dropwise. The mixture was stirred at -78 C for 1 h., allowed to warm to r.t., diluted with EtOAc and quenched with H4CI (aqueous sat. solution) and Na2S203 (aqueous sat. solution). The organic layer was separated, washed with NaHC03 (aqueous sat. solution), dried (Na2S04) and concentrated in vacuo. The crude product was purified by column chromatography (silica gel; DCM in heptane 0/100 to 20/80). The desired fractions were collected and concentrated in vacuo to yield intermediate compound 1-1 (7.8 g, 81%). | |
81% | With n-butyllithium; iodine; diisopropylamine; In tetrahydrofuran; n-heptane; at -78℃; for 1.75h;Inert atmosphere; | 2,4-Dichloro-3-iodo-pyridine (I-1) To a solution of 2,4-dichloropyridine (5.2 g, 35.14 mmol) and diisopropylamine (3.91 g, 38.65 mmol) in dry THF (40 mL) cooled at -78 C. under a nitrogen atmosphere, was added n-butyllithium (24.16 mL, 38.65 mmol, 1.6 M in hexanes) dropwise. The resulting reaction mixture was stirred at -78 C. for 45 min. and then a solution of iodine (9.81 g, 38.651 mmol) in dry THF (20 mL) was added dropwise. The mixture was stirred at -78 C. for 1 h., allowed to warm to r.t., diluted with EtOAc and quenched with NH4Cl (aqueous sat. solution) and Na2S2O3 (aqueous sat. solution). The organic layer was separated, washed with NaHCO3 (aqueous sat. solution), dried (Na2SO4) and concentrated in vacuo. The crude product was purified by column chromatography (silica gel; DCM in heptane 0/100 to 20/80). The desired fractions were collected and concentrated in vacuo to yield intermediate compound I-1 (7.8 g, 81%). |
81% | 2,4-Dichloro-3-iodo-pyridine (I-5) To a solution of 2,4-dichloropyridine (5.2 g, 35.14 mmol) and DIPEA (3.91 g, 38.65 mmol) in dry THF (40 mL) cooled at -78 C. under a nitrogen atmosphere, was added n-BuLi (24.16 mL, 38.65 mmol, 1.6 M in hexanes) dropwise. The resulting r.m. was stirred at -78 C. for 45 min and then a solution of iodine (9.81 g, 38.651 mmol) in dry THF (20 mL) was added dropwise. The mixture was stirred at -78 C. for 1 h, allowed to warm to r.t., diluted with EtOAc and quenched with NH4Cl (aq. sat. sol.) and Na2S2O3 (aq. sat. sol.). The organic layer was separated, washed with NaHCO3 (aq. sat. sol.), dried (Na2SO4) and concentrated in vacuo. The crude product was purified by column chromatography (silica gel; Heptane/DCM up to 20% as eluent). The desired fractions were collected and concentrated in vacuo to yield intermediate I-5 (7.8 g, 81%). | |
81% | To a solution of 2,4-dichloropyridine (5.2 g, 35.137 mmol) and diisopropylamine (3.911 g, 38.651 mmol) in dry THF (40 ml) cooled at -78 C under a nitrogen atmosphere, was added n-butyllithium (24.157 ml, 38.651 mmol, 1.6 M in hexanes) dropwise. The resulting reaction mixture was stirred at -78 C for 45 min and then a solution of iodine (9.81 g, 38.651 mmol) in dry THF (20 ml) was added dropwise. The mixture was stirred at -78 C for 1 h, allowed to warm to rt, diluted with EtOAc and quenched with NH4Cl (aqueous sat. solution) and Na2S203 (aqueous sat. solution). The organic layer was separated, washed with NaHC03 (aqueous sat. solution), dried (Na2S04) and concentrated in vacuo. The crude product was purified by column chromatography (silica gel; heptane/DCM up to 20% as eluent). The desired fractions were collected and concentrated in vacuo to yield 1-1 (7.8 g, 81%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With copper(l) iodide; In N,N-dimethyl-formamide; at 100℃; for 5h;Sealed tube; | Description 6 2,4-dichloro-3-trifluoromethyl-pyridine(D6)To a mixture of compound D5 (2g, 7.302 mmol) in DMF (50 ml) were added fluorosulfonyl-difluoro-acetic acid methyl ester (1.858 ml, 14.605 mmol) [C.A.S. 680- 15-9] and copper (I) iodide (2.796. g, 14.605 mmol). The reaction mixture was heated in a sealed tube at 100 0C for 5 h. After cooling, the solvent was evaporated in vacuo. The crude product was purified by column chromatography (silica gel; DCM as eluent). The desired fractions were collected and concentrated in vacuo to yield intermediate compound D6 (1.5 g, 95%). |
95% | With copper(l) iodide; In N,N-dimethyl-formamide; at 100℃; for 5h;Sealed tube; | To a mixture of intermediate compound D12 (2g, 7.302 mmol) in DMF (50 ml) were added fluorosulfonyl-difluoro-acetic acid methyl ester (1.858 ml, 14.605 mmol)[C.A.S. 680-15-9] and copper (I) iodide (2.796. g, 14.605 mmol). The reaction mixture was heated in a sealed tube at 100 0C for 5 h. After cooling, the solvent was evaporated in vacuo. The crude product was purified by column chromatography (silica gel; DCM as eluent). The desired fractions were collected and concentrated in vacuo to yield intermediate compound D 13 ( 1.5 g, 95%). |
95% | With copper(l) iodide; In N,N-dimethyl-formamide; at 100℃; for 5h;Sealed tube; | To a mixture of compound D24 (2g, 7.302 mmol) in DMF (50 ml) were added fiuorosulfonyl-difluoro-acetic acid methyl ester [C.A.S. 680-15-9] (1.858 ml, 14.605 mmol) and copper (I) iodine (2.796. g, 14.605 mmol). The reaction mixture was heated in a sealed tube at 100 0C for 5 h. After cooling, the solvent was evaporated in vacuo. The crude product was purified by column chromatography (silica gel; DCM as eluent). The desired fractions were collected and concentrated in vacuo to yield intermediate compound D25 (1.5 g, 95%). |
95% | copper(l) iodide; In N,N-dimethyl-formamide; at 100℃; for 5h;Sealed tube; | Intermediate 2 (1-2)2,4-Dichloro-3 -trifluoromethyl-pyridine (1-2)To a mixture of compound 1-1 (2g, 7.30 mmol) in DMF (50 mL) were added fluorosulfonyl-difluoro-acetic acid methyl ester [C.A.S. 680-15-9] (1.86 ml,14.60 mmol) and copper (I) iodide (2.79 g, 14.60 mmol). The reaction mixture was heated in a sealed tube at 100 C for 5 h. After cooling, the solvent was evaporated in vacuo. The crude product was purified by column chromatography (silica gel, DCM). The desired fractions were collected and concentrated in vacuo to yield intermediate compound 1-2 (1.5 g, 95%). |
95% | copper(l) iodide; In N,N-dimethyl-formamide; at 100℃; for 5h;Sealed tube; | Intermediate 8 (1-8)o-3 -trifluoromethyl-pyridine (1-2)To a mixture of compound 1-7 (2g, 7.30 mmol) in DMF (50 mL) were added fluorosulfonyl-difluoro-acetic acid methyl ester [C.A.S. 680-15-9] (1.86 ml,14.60 mmol) and copper (I) iodide (2.79 g, 14.60 mmol). The reaction mixture was heated in a sealed tube at 100 C for 5 h. After cooling, the solvent was evaporated in vacuo. The crude product was purified by column chromatography (silica gel, DCM). The desired fractions were collected and concentrated in vacuo to yield intermediate compound 1-8 (1.5 g, 95%). |
95% | With copper(l) iodide; In N,N-dimethyl-formamide; at 100℃; for 5h;Sealed vessel; | Intermediate 2 (1-2)o-3-trifluoromethyl-pyridine (1-2)To a mixture of compound 1-1 (2g, 7.30 mmol) in DMF (50 mL) were added fluorosulfonyl-difluoro-acetic acid methyl ester [C.A.S. 680-15-9] (1.86 ml, 14.60 mmol) and copper (I) iodine (2.79 g, 14.60 mmol). The reaction mixture was heated in a sealed tube at 100 C for 5 h. After cooling, the solvent was evaporated in vacuo. The crude product was purified by column chromatography (silica gel, DCM). The desired fractions were collected and concentrated in vacuo to yield intermediate compound 1-2 (1.5 g, 95%). |
95% | With copper(l) iodide; In N,N-dimethyl-formamide; at 100℃; for 5h;Sealed tube; | 2,4-Dichloro-3-trifluoromethyl-pyridine (I-2) To a mixture of compound I-1 (2 g, 7.30 mmol) in DMF (50 mL) were added fluorosulfonyl-difluoro-acetic acid methyl ester [C.A.S. 680-15-9] (1.86 ml, 14.60 mmol) and copper (I) iodide (2.79 g, 14.60 mmol). The reaction mixture was heated in a sealed tube at 100 C. for 5 h. After cooling, the solvent was evaporated in vacuo. The crude product was purified by column chromatography (silica gel, DCM). The desired fractions were collected and concentrated in vacuo to yield intermediate compound I-2 (1.5 g, 95%). |
95% | With copper(l) iodide; In N,N-dimethyl-formamide; at 100℃; for 5h;Sealed tube; | 4-Dichloro-3-trifluoromethyl-pyridine (I-6) To a mixture of intermediate I-5 (2 g, 7.30 mmol) in DMF (50 mL) were added fluorosulfonyl-difluoro-acetic acid methyl ester [C.A.S. 680-15-9] (1.86 ml, 14.60 mmol) and copper (I) iodide (2.79 g, 14.60 mmol). The r.m. was heated in a sealed tube at 100 C. for 5 h. After cooling, the solvent was evaporated in vacuo. The crude product was purified by column chromatography (silica gel, DCM). The desired fractions were collected and concentrated in vacuo to yield intermediate I-6 (1.5 g, 95%). |
95% | With copper(l) iodide; In N,N-dimethyl-formamide; at 100℃; for 5h;Sealed tube; | To a mixture of 1-1 (2 g, 7.302 mmol) in DMF (50 mL) were added fluorosulfonyl- difluoro-acetic acid methyl ester ([CAS 680-15-9], 1.858 mL, 14.605 mmol) and copper (I) iodide (2.796. g, 14.605 mmol). The reaction mixture was heated in a sealed tube at 100 C for 5 h. After cooling, the solvent was evaporated in vacuo. The crude product was purified by column chromatography (silica gel; DCM as eluent). The desired fractions were collected and concentrated in vacuo to yield 1-2 (1.5 g, 95%). |
160 g | With copper(l) iodide; In N,N-dimethyl-formamide; at 100℃; for 5h; | To a solution of <strong>[343781-36-2]2,4-dichloro-3-iodopyridine</strong> ([CAS 34378 1-36-2], 290 g, 1058 mmol)in DMF (1.7 L) was added methyl 2,2-difluoro-2-(fluorosulfonyl)acetate ([CAS 680-15-9], 403 g, 2098 mmol) and Cul (403 g, 2.13 mol), the reaction was then heated at100Cfor5h.The reation was cooled and filtered. The filtrate was diluted with H20 and extracted with Et20 and washed with a NH3 solution. The organic layer was dried (Na2SO4), filtered and concentrated in vacuo to yield intermediate 2 (160 g), which was used without further purification. |
160 g | With copper(l) iodide; In N,N-dimethyl-formamide; at 100℃; for 5h; | To a solution of <strong>[343781-36-2]2,4-dichloro-3-iodopyridine</strong> ([CAS 34378 1-36-2], 290 g, 1058 mmol)in DMF (1.7 L) was added methyl 2,2-difluoro-2-(fluorosulfonyl)acetate ([CAS 680-15-9], 403 g, 2098 mmol) and Cul (403 g, 2.13 mol), the reaction was then heated at i00Cfor5h.The reation was cooled and filtered. The filtrate was diluted with H20 and extracted with Et20 and washed with a NH3 solution. The organic layer was dried (Na2SO4),filtered and concentrated in vacuo to yield intermediate 2 (160 g), which was used without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
49% | With hydrazine hydrate; In 1,4-dioxane; at 80℃; for 16h;sealed tube; | Description 32 (4-chloro-3-iodo-pyridin-2-yl)-hydrazine (D32)To a solution of <strong>[343781-36-2]2,4-dichloro-3-iodopyridine</strong> [CAS 343781-36-3] (4.7 g, 17.16 mmol) in 1,4-dioxane (240 ml), was added hydrazine monohydrate (5.096 ml, 102.962 mmol). The reaction mixture was heated in a sealed tube at 80 0C for 16 h. After cooling, the solvent was concentrated in vacuo. The white solid residue thus obtained was dissolved in DCM and washed with NaHCO3 (aqueous saturated solution). The organic layer was separated, dried (Na2SO4) and concentrated in vacuo. The residue was washed with Et2O. The solid thus obtained was discarded. The mother liquours were concentrated in vacuo to yield intermediate compound D32 (2.31 g, 49%). |
49% | With hydrazine hydrate; In 1,4-dioxane; at 80℃; for 16h;Sealed tube; | To a solution of <strong>[343781-36-2]2,4-dichloro-3-iodopyridine</strong> [CAS 343781-36-3] (4.7 g, 17.16 mmol) in 1,4-dioxane (240 ml), was added hydrazine monohydrate (5.096 ml, 102.962 mmol). The reaction mixture was heated in a sealed tube at 80 0C for 16 h. After cooling, the solvent was concentrated in vacuo. The white solid residue thus obtained was dissolved in DCM and washed with NaHCO3 (aqueous saturated solution). The organic layer was separated, dried (Na2SO4) and concentrated in vacuo. The residue was washed with diethylether. The solid thus obtained was discarded. The mothe liquours were concentrated in vacuo to yield intermediate compound D45 (2.31 g, 49%) |
49% | With hydrazine hydrate; In 1,4-dioxane; at 80℃; | To a suspension of D24 (4.7 g, 17.16 mmol) in 1,4-dioxane (240 ml), was added hydrazine monohydrate (5.096 ml, 102.96 mmol). The reaction mixture was heated at 80 0C overnight. After cooling, the resulting solution was concentrated in vacuo. The residue thus obtained was dissolved in DCM and washed with NaHCO3 (aqueous sat. solution). The organic layer was separated, dried (Na2SO4) and concentrated in vacuo. The residue was treated with Et2O. The solid obtained was filtered off. The filtrate was concentrated in vacuo to yield intermediate D68 (2.26 g, 49%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In methanol; at 20 - 45℃; | A mixture of 4a2 (201 g, 734 mmol) and NaOMe (51.5 g, 954 mmol) in MeOH (2 L) is stirred at RT overnight then heated at 45 C for 3 h. The reaction is diluted with EtOAc, washed with water, brine, dried over MgS04, filtered and concentrated under vacuum. Upon standing crystals are formed. These are collected, washed with a small amount of (/-Pr)20 followed by heptane and dried on a stream of air to afford 4a3. |
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