tert-butyl (2S)-2-[(cyclopropylamino)methyl]pyrrolidine-1-carboxylate

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

Procedure: 3.78 mL (13 mmol) of titanium isopropoxide and 2 g (10 mmol) of (S)-1-tert-butoxycarbonyl-pyrrolidine-2-carbaldehyde are added to a solution of 1.7 mL (30 mmol) of cyclopropylamine in 10 mL of anhydrous methanol. The solution is stirred for 5 hours at room temperature then 378 mg (10 mmol) of sodium borohydride is added. Stirring is continued for a further 2 hours then 2 mL of water is added. The reaction mixture is filtered then the solvents are evaporated. Water is added and the compound is extracted with diethyl ether. The organic phases are dried over magnesium sulfate, filtered and evaporated to give 2.34 g (97%) of (S)—N-cyclopropyl-1-tert-butoxycarbonyl-pyrrolidin-2-ylmethyl-amine in the form of a colourless oil. Stirring is continued for a further 2 hours The reaction mixture is filtered the solvents are evaporated Water is added the compound is extracted with diethyl ether The organic phases are dried over magnesium sulfate filtered evaporated

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

Procedure: (S)-8-[(1-tert-butoxycarbony-pyrrolidin-2-ylmethyl)-cyclopropyl-sulfamoyl]-4-oxo-4,5-dihydro-3H-pyrrolo[2,3-c]quinoline-1-propyl carboxylate is prepared according to synthesis 111, from 326 mg (1 mmol) of 8-chlorosulfonyl-4-oxo-4,5-dihydro-3H-pyrrolo[2,3-c]quinoline-1-carboxylic acid and 288 mg (1.2 mmol) of (S)-1-tert-butoxycarbonyl-2-cyclopropylaminomethyl-pyrrolidine to give, after esterification according to general method C (using di-n-propylsulfate as the dialkylsulfate) and purification by chromatography on silica (eluent dichloromethane/methanol 99/1 then 95/5), 99 mg (17% in two stages) of (S)-8-[(1-tert-butoxycarbonyl-pyrrolidin-2-ylmethyl)-cyclopropyl-sulfamoyl]-4-oxo-4,5-dihydro-3H-pyrrolo[2,3-c]quinoline-1-propyl carboxylate in the form of a white solid. to give purification by chromatography on silica (eluent dichloromethane/methanol 99/1