2-[2-methoxyethyl(methyl)amino]ethanol

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

Procedure: A mixture of 2-methylaminoethanol (5.4 g), 2-bromoethyl methyl ether (10 g), triethylamine (10 ml) and acetonitrile (70 ml) was stirred and heated to reflux for 16 hours. The mixture was cooled to ambient temperature and filtered. The filtrate was evaporated and the residue was triturated under diethyl ether. The organic solution was separated and evaporated to give 2-[N-(2-methoxyethyl)-N-methylamino]ethanol (3 g, 31%); NMR Spectrum: (CDCl3) 2.35 (s, 3H), 2.6 (t, 2H), 2.65 (t, 2H), 3.35 (s, 3H), 3.5 (t, 2H), 3.6 (t, 2H). heated to reflux for 16 hours filtered The filtrate was evaporated the residue was triturated under diethyl ether The organic solution was separated evaporated

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

Procedure: A mixture of 2-(methylamino)ethanol (5.4 g, 72 mmol), 2-bromoethyl methyl ether (10 g, 72 mmol) and triethylamine (10 ml, 72 mmol) in acetonitrile (70 ml) was refluxed overnight. After cooling, the solid was filtered and the filtrate was evaporated. The residue was triturated with ether. The ether layer was separated and evaporated to give 2-(N-(2-methoxyethyl)-N-methylamino)ethanol (3g, 31%). was refluxed overnight After cooling the solid was filtered the filtrate was evaporated The residue was triturated with ether The ether layer was separated evaporated

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

Procedure: A mixture of 2-(methylamino)ethanol (5.4 g, 72 mmol), 2-bromoethyl methyl ether (10 g, 72 mmol) and triethylamine (10 ml, 72 mmol) in acetonitrile (70 ml) was refluxed overnight. After cooling, the solid was filtered and the filtrate was evaporated. The residue was triturated with ether. The ether layer was separated and evaporated to give 2-(N-(2-methoxyethyl)-N-methylamino)ethanol (3g, 31%). was refluxed overnight After cooling the solid was filtered the filtrate was evaporated The residue was triturated with ether The ether layer was separated evaporated

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

Procedure: A mixture of 2-methylaminoethanol (5.4 g), 2-bromoethyl methyl ether (10 g), triethylamine (10 ml) and acetonitrile (70 ml) was stirred and heated to reflux for 16 hours. The mixture was cooled to ambient temperature and filtered. The filtrate was evaporated and the residue was triturated under diethyl ether. The organic solution was separated and evaporated to give 2-[N-(2-methoxyethyl)-N-methylamino]ethanol (3 g, 31%); NMR Spectrum: (CDCl3) 2.35 (s, 3H), 2.6 (t, 2H), 2.65 (t, 2H), 3.35 (s, 3H), 3.5 (t, 2H), 3.6 (t, 2H). heated to reflux for 16 hours filtered The filtrate was evaporated the residue was triturated under diethyl ether The organic solution was separated evaporated

Conditions: temp:83.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1.2 g (0.0032 mole) of 8-(2-chloroethoxy)-5-(2-chlorophenyl)-7-cyano-1,3-dihydro-2H-1,4-benzodiazepin-2-one (Iss, prepared in Example 35), 2.85 g (0.032 mole) of 2-((2-methoxyethyl)methylamino) ethanol, 20 mL of tetrahydrofuran and 4.8 g (0.032 mole) of sodium iodide was heated in an oil bath at 83° C. under an argon atmosphere for 20 hours. The mixture was cooled and then partitioned between ethyl acetate and 0.6 M sodium bicarbonate solution. The ethyl acetate layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was chromatographed on silica gel, eluting with acetonitrile-methanol (80:20) to give 0.233 g of 5-(2-chlorophenyl)-7-cyano-1,3-dihydro-8-(2-((2-methoxyethyl)methylamino)-ethoxy)-2H-1,4-benzodiazepin-2-one (Iv). The mixture was cooled partitioned between ethyl acetate and 0.6 M sodium bicarbonate solution The ethyl acetate layer was washed with brine dried over anhydrous sodium sulfate filtered concentrated under reduced pressure The residue was chromatographed on silica gel eluting with acetonitrile-methanol (80:20)

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

Procedure: A mixture of 2-methylaminoethanol (5.4 g), 2-bromoethyl methyl ether (10 g), triethylamine (10 ml) and acetonitrile (70 ml) was stirred and heated to reflux for 16 hours. The mixture was cooled to ambient temperature and filtered. The filtrate was evaporated and the residue was triturated under diethyl ether. The organic solution was separated and evaporated to give 2-[N-(2-methoxyethyl)-N-methylamino]ethanol (3 g, 31%); NMR Spectrum: (CDCl3) 2.35 (s, 3H), 2.6 (t, 2H), 2.65 (t, 2H), 3.35 (s, 3H), 3.5 (t, 2H), 3.6 (t, 2H). heated to reflux for 16 hours filtered The filtrate was evaporated the residue was triturated under diethyl ether The organic solution was separated evaporated

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

Procedure: A mixture of 2-(methylamino)ethanol (5.4 g, 72 mmol), 2-bromoethyl methyl ether (10 g, 72 mmol) and triethylamine (10 ml, 72 mmol) in acetonitrile (70 ml) was refluxed overnight. After cooling, the solid was filtered and the filtrate was evaporated. The residue was triturated with ether. The ether layer was separated and evaporated to give 2-(N-(2-methoxyethyl)-N-methylamino)ethanol (3g, 31%). was refluxed overnight After cooling the solid was filtered the filtrate was evaporated The residue was triturated with ether The ether layer was separated evaporated

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

Procedure: A mixture of 2-methylaminoethanol (5.4 g), 2-bromoethyl methyl ether (10 g), triethylamine (10 ml) and acetonitrile (70 ml) was stirred and heated to reflux for 16 hours. The mixture was cooled to ambient temperature and filtered. The filtrate was evaporated and the residue was triturated under diethyl ether. The organic solution was separated and evaporated to give 2-[N-(2-methoxyethyl)-N-methylamino]ethanol (3 g, 31%); NMR Spectrum: (CDCl3) 2.35 (s, 3H), 2.6 (t, 2H), 2.65 (t, 2H), 3.35 (s, 3H), 3.5 (t, 2H), 3.6 (t, 2H). heated to reflux for 16 hours filtered The filtrate was evaporated the residue was triturated under diethyl ether The organic solution was separated evaporated