benzyl N-[2-(methylamino)ethyl]carbamate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: N-Methylethylenediamine (2.0 g) was dissolved in dioxane (20 ml), the solution was added with N-carbobenzoxysuccinimide (8.07 g), and the mixture was stirred at room temperature for 4 days. The reaction mixture was added with distilled water and chloroform, the layers were separated, and the organic layer was dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=3:1 to 2:1), and then purified again by silica gel column chromatography (chloroform:methanol:28% aqueous ammonia=30:1:0.1) to obtain the title compound (243 mg). the layers were separated the organic layer was dried over anhydrous magnesium sulfate filtered The filtrate was concentrated under reduced pressure the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=3:1 to 2:1) purified again by silica gel column chromatography (chloroform:methanol:28% aqueous ammonia=30:1:0.1)

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

Procedure: A solution of benzyl 2-(methylamino)ethylcarbamate (prepared as described in example 7, 14 g, 72.1 mmol) in DMSO (20 mL) was reacted with 3-fluoro-2-cyanopyridine (see example 2, 8 g, 65.5 mmol) in a pressure vessel at 85° C. overnight. The resulting mixture was diluted with CHCl3 (100 mL) and added to the top of a silica gel column (150 mm by 7 inches) packed with 20% EtOAc/Hexanes. The column was eluted with a gradient of 20% EtOAc/Hexanes to 100% EtOAc and the clean fractions combined and evaporated to give the product as a yellow oil. added to the top of a silica gel column (150 mm by 7 inches) The column was eluted with a gradient of 20% EtOAc/Hexanes to 100% EtOAc evaporated

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

Procedure: A solution of benzyl 2-(methylamino)ethylcarbamate (0.05 g, 0.24 mmol) in CH2Cl2 (5 mL was cooled to 6° C. and treated with triethylamine (0.1 mL, 0.72 mmol) and methanesulfonyl chloride (0.02 mL, 0.24 mmol). The reaction was warmed to room temperature and stirred overnight. The reaction was washed with 10% KHSO4, the organic layer was dried over Na2SO4, filtered and evaporated to give the product. The reaction was washed with 10% KHSO4 the organic layer was dried over Na2SO4 filtered evaporated to give the product

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

Procedure: To a solution of N-methyl ethylene diamine (10 g, 135 mmol) in CHCL3 (100 mL) was added TFA (11.43 mL, 148.4 mmol) and the solution was stirred for several minutes. The reaction was then treated successively with 1-{[(benzyloxy)carbonyl]oxy}pyrrolidine-2,5-dione (Aldrich, 43.7 g, 175.3 mmol) and 18-crown-6 (71.3 g, 269.8 mmol). The reaction became slightly green. After stirring for 1 hour at room temperature, TLC (ninhydrin stain) showed no remaining starting amine. The reaction was transferred to a separatory funnel and washed with KOH solution. The aqueous layer was back-extracted several times. The organic layers were combined, dried over Na2SO4, filtered and concentrated to give 100 g of a yellow oil. The oil was dissolved in 300 ml CHCl3 and half of this volume was chromatographed on silica (150 mm×7 inches, 1 Kg silica gel, packed in CHCl3) eluting with CHCl3 saturated NH3. The pure fractions were collected and the remaining half of the crude chromatographed in the same way. Product fractions contaminated with some bis-CBZ protected material were dissolved in CHCl3 and washed with acid water. The aqueous was then basified and extracted with CHCl3. The organic layer was dried over Na2SO4, filtered and concentrated with the other pure fractions to give the product as a clear, colorless oil. After stirring for 1 hour at room temperature The reaction was transferred to a separatory funnel washed with KOH solution The aqueous layer was back-extracted several times dried over Na2SO4 filtered concentrated