(2S)-2-methylpyrrolidine;hydrochloride

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

Procedure: (S)-2-methyl-pyrrolidine hydrochloride (0.8 g, 6.6 mmol, 1.1 eq) was dissolved in 2-butanone (20 mL) and potassium carbonate (1.7 g, 12.6 mmol, 2.1 eq) was added. Ethyl 4-bromobutyrate (0.86 mL, 6.0 mmol, 1.0 eq) was added and the reaction mixture was refluxed for 2 days. The mixture was allowed to cool to room temperature and any solid present was filtered off and washed with ether. The filtrate was concentrated under reduced pressure to give 1.20 g of the title compound (yield 99%) which was used in the next step without further purification. the reaction mixture was refluxed for 2 days any solid present was filtered off washed with ether The filtrate was concentrated under reduced pressure

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 100 mg of 2-[2-amino-4-(1,3-dihydroisoindole-2-carbonyl)quinazolin-6-yl]benzaldehyde are dissolved in 3 ml of 1,2-dichloroethane and 3 ml of tetrahydrofuran. 43 mg of (S)-2-methylpyrrolidine hydrochloride are added, and the mixture is stirred at 40° C. for 6 h. After cooling to 25° C., 113 mg of sodium triacetoxyborohydride are added and stirred at 25° C. for a further 12 h. The mixture is poured into water, extracted three times with dichloromethane, and the combined organic phases are dried over sodium sulfate. After filtration, the filtrate is evaporated to dryness and purified by chromatography (reversed phase HPLC). After cooling to 25° C. stirred at 25° C. for a further 12 h extracted three times with dichloromethane the combined organic phases are dried over sodium sulfate After filtration the filtrate is evaporated to dryness purified by chromatography (reversed phase HPLC)

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

Procedure: The title compound was synthesized in analogy to example 1, intermediate a), from [5-(3-chloro-propoxy)-1H-pyrrolo[2,3-b]pyridin-2-yl]-(4,4-difluoro-piperidin-1-yl)-methanone, (S)-2-methyl-pyrrolidine hydrochloride (commercially available) and potassium carbonate in acetonitrile to give the desired product as a colorless solid (57%).