sodium;2-methoxyethanolate

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of butyl (4-chloro-quinolin-6-ylmethylene)-amine (preparation was described in example 27b) (250 mg, 1.01 mmol) and a solution of sodium (2-methoxy)-ethoxide in 2-methoxy-ethanol (2.5 mL, 10.0 mmol, 4.0M) were placed in a microwave tube and the mixture was heated to 120° C. for 30 min in a closed microwave. Then, the suspension was diluted with saturated ammonium chloride solution and the organic compound was extracted into ethyl acetate (3×50 mL). The combined extracts were washed with brine solution and dried over anhydrous magnesium sulfate. After filtration of the drying agent, the solvent was removed under the vacuum and the brown residue was dissolved in THF (2 mL) and 1 mL of HCl solution (3.0N) was added. The resulting solution was stirred for 1 h at room temperature. Then, it was neutralized with potassium carbonate solution and extracted with ethyl acetate (2×50 mL). The combined extracts were washed with brine solution and dried over anhydrous magnesium sulfate. After filtration of the drying agent, the solvent was removed under the vacuum and the brown residue was purified by using a Biotage silica gel column chromatography to obtain 160 mg (68.3% yield) of 4-(2-methoxy-ethoxy)-quinoline-6-carbaldehyde as a brown solid: EI-LRMS m/e calcd for C13H13NO3 (M+) 232.1, found 232.1. the organic compound was extracted into ethyl acetate (3×50 mL) The combined extracts were washed with brine solution dried over anhydrous magnesium sulfate After filtration of the drying agent the solvent was removed under the vacuum the brown residue was dissolved in THF (2 mL) 1 mL of HCl solution (3.0N) was added extracted with ethyl acetate (2×50 mL) The combined extracts were washed with brine solution dried over anhydrous magnesium sulfate After filtration of the drying agent the solvent was removed under the vacuum the brown residue was purified

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of butyl (4-chloro-quinolin-6-ylmethylene)-amine (preparation was described in example 27b) (250 mg, 1.01 mmol) and a solution of sodium (2-methoxy)-ethoxide in 2-methoxy-ethanol (2.5 mL, 10.0 mmol, 4.0M) were placed in a microwave tube and the mixture was heated to 120° C. for 30 min in a closed microwave. Then, the suspension was diluted with saturated ammonium chloride solution and the organic compound was extracted into ethyl acetate (3×50 mL). The combined extracts were washed with brine solution and dried over anhydrous magnesium sulfate. After filtration of the drying agent, the solvent was removed under the vacuum and the brown residue was dissolved in THF (2 mL) and 1 mL of HCl solution (3.0N) was added. The resulting solution was stirred for 1 h at room temperature. Then, it was neutralized with potassium carbonate solution and extracted with ethyl acetate (2×50 mL). The combined extracts were washed with brine solution and dried over anhydrous magnesium sulfate. After filtration of the drying agent, the solvent was removed under the vacuum and the brown residue was purified by using a Biotage silica gel column chromatography to obtain 160 mg (68.3% yield) of 4-(2-methoxy-ethoxy)-quinoline-6-carbaldehyde as a brown solid: EI-LRMS m/e calcd for C13H13NO3 (M+) 232.1, found 232.1. the organic compound was extracted into ethyl acetate (3×50 mL) The combined extracts were washed with brine solution dried over anhydrous magnesium sulfate After filtration of the drying agent the solvent was removed under the vacuum the brown residue was dissolved in THF (2 mL) 1 mL of HCl solution (3.0N) was added extracted with ethyl acetate (2×50 mL) The combined extracts were washed with brine solution dried over anhydrous magnesium sulfate After filtration of the drying agent the solvent was removed under the vacuum the brown residue was purified

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under cooling in an ice bath, a mixture of sodium hydride (suspension of 8 g of sodium hydride in mineral oil (60%) washed with hexane) in THF (10 mL) was added to methoxyethanol (100 mL) under stirring over 20 minutes to produce sodium 2-methoxyethoxide, followed by further stirring for 2 hours. A solution of sodium 2-methoxyethoxide in 2-methoxyethanol (55 mL) was added with stirring to a solution of 1-(chloromethyl)-7-ethyl-3,4-dihydroisoquinoline hydrochloride (8.5 g) in methoxyethanol (50 mL) under cooling in an ice bath, for 5 minutes. The reaction mixture was heated at 60° C., followed by stirring for 3 hours under an argon atmosphere. The reaction mixture was cooled to room temperature and diluted with THF (150 mL), followed by filtration. The filtrate was concentrated under reduced pressure. To the resulting residue was added a saturated aqueous ammonium chloride solution and the residue was extracted with EtOAc. The organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane:EtOAc) to obtain 7-ethyl-1-[(2-methoxyethyl)methyl]-3,4-dihydroisoquinoline (2.13 g). under cooling in an ice bath, for 5 minutes by stirring for 3 hours under an argon atmosphere The reaction mixture was cooled to room temperature followed by filtration The filtrate was concentrated under reduced pressure To the resulting residue was added a saturated aqueous ammonium chloride solution the residue was extracted with EtOAc The organic layer was washed with water a saturated aqueous sodium chloride solution, dried over magnesium sulfate concentrated under reduced pressure The resulting residue was purified by silica gel column chromatography (hexane:EtOAc)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-chloro-5-(chloromethyl)pyridine (1620 mg, 10 mmol) in 2-methoxyethanol (10 mL) was added sodium 2-methoxyethanolate (5.9 g, 12.00 mmol). The mixture was stirred at room temperature for 10 min and then at 50° C. for 2 hrs. Hydrazine (1.6 g, 50.0 mmol) was then added to the mixture and the reaction was heated at 120° C. for 1 hr. The mixture was purified by preparative LCMS to provide the title compound, 2-hydrazinyl-5-((2-methoxyethoxy)methyl)pyridine (540 mg, 27.4% yield). at 50° C. for 2 hrs the reaction was heated at 120° C. for 1 hr The mixture was purified by preparative LCMS

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of butyl (4-chloro-quinolin-6-ylmethylene)-amine (preparation was described in example 27b) (250 mg, 1.01 mmol) and a solution of sodium (2-methoxy)-ethoxide in 2-methoxy-ethanol (2.5 mL, 10.0 mmol, 4.0M) were placed in a microwave tube and the mixture was heated to 120° C. for 30 min in a closed microwave. Then, the suspension was diluted with saturated ammonium chloride solution and the organic compound was extracted into ethyl acetate (3×50 mL). The combined extracts were washed with brine solution and dried over anhydrous magnesium sulfate. After filtration of the drying agent, the solvent was removed under the vacuum and the brown residue was dissolved in THF (2 mL) and 1 mL of HCl solution (3.0N) was added. The resulting solution was stirred for 1 h at room temperature. Then, it was neutralized with potassium carbonate solution and extracted with ethyl acetate (2×50 mL). The combined extracts were washed with brine solution and dried over anhydrous magnesium sulfate. After filtration of the drying agent, the solvent was removed under the vacuum and the brown residue was purified by using a Biotage silica gel column chromatography to obtain 160 mg (68.3% yield) of 4-(2-methoxy-ethoxy)-quinoline-6-carbaldehyde as a brown solid: EI-LRMS m/e calcd for C13H13NO3 (M+) 232.1, found 232.1. the organic compound was extracted into ethyl acetate (3×50 mL) The combined extracts were washed with brine solution dried over anhydrous magnesium sulfate After filtration of the drying agent the solvent was removed under the vacuum the brown residue was dissolved in THF (2 mL) 1 mL of HCl solution (3.0N) was added extracted with ethyl acetate (2×50 mL) The combined extracts were washed with brine solution dried over anhydrous magnesium sulfate After filtration of the drying agent the solvent was removed under the vacuum the brown residue was purified