7-methyl-2,7-diazaspiro[3.5]nonane

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

Procedure: To a solution of 2-chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidine-6-carbaldehyde (72 mg, 0.254 mmol) in DCE (7 mL) was added 7-methyl-2,7-diaza-spiro[3.5]nonane (45 mg, 0.321 mmol). The mixture was stirred at RT for 10 min, then sodium triacetoxyborohydride (81 mg, 0.382 mmol) was added and stirring was continued for 3 h. To the reaction mixture was added water and the resulting solution was loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH and the desired product was eluted with 2 M NH3 in MeOH an concentrated in vacuo. The resultant residue was purified by column chromatography to give the title compound as a yellow oil (31 mg, 30%). stirring was continued for 3 h The cartridge was washed with MeOH the desired product was eluted with 2 M NH3 in MeOH an concentrated in vacuo The resultant residue was purified by column chromatography

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

Procedure: Prepared according to the method used in the preparation of 7-methyl-2,7-diaza-spiro[3.5]nonane using 3-fluoro-4-oxo-piperidine-1-carboxylic acid tert-butyl ester in place of formaldehyde and azetidine in place of 2,7-diaza-spiro[3.5]nonane-2-carboxylic acid tert-butyl ester hydrochloride. The title compound was obtained as a colourless oil (205 mg, 56%). Prepared

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

Procedure: To a solution of 2,7-diaza-spiro[3.5]nonane-2-carboxylic acid tert-butyl ester hydrochloride (100 mg, 0.381 mmol) in DCE (10 mL) was added an aqueous solution of formaldehyde (37% w/w, 40 μL, 0.537 mmol). The mixture was stirred at RT for 10 min, then sodium triacetoxyborohydride (121 mg, 0.571 mmol) was added and stirring was continued for 1 h. Water was added to the reaction mixture before being loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH then eluted with 2 M NH3 in MeOH to give 7-methyl-2,7-diaza-spiro[3.5]nonane-2-carboxylic acid tert-butyl ester. To a solution of 7-methyl-2,7-diaza-spiro[3.5]nonane-2-carboxylic acid tert-butyl ester in DCM (5 mL) was added TFA (1 mL) and the resulting mixture was stirred at RT for 1 h. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge, washed with MeOH then eluted with 2 M NH3 in MeOH to give the title compound as a colourless oil (45 mg, 84%). washed with MeOH then eluted with 2 M NH3 in MeOH