1,4-二氧杂螺[4.5]癸烷-8-基肼

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (1,4-Dioxa-spiro[4.5]dec-8-yl)-hydrazine (46 g, 368 mL of above solution) was cooled in an ice bath, then triethylamine (47 mL) and ethanol (368 mL) were added. When the internal temperature reached 7.6° C., 2,4,6-trichloro-pyrimidine-5-carbaldehyde (32 g, synthesized by method of WO 02/066482) was added as a solid over 1.5 min. The internal temperature jumped to 12.6° C., and continued to rise to 17° C. during 4 min. After stirring a total of 28 min, water (367 mL) was added and the slurry was filtered. The cake was washed well twice with water (300 mL), then hexane (300 mL) and air dried over house vacuum overnight. This gave a damp cake that was washed twice with hexane (400 mL). Air-drying over house vacuum over weekend gave 35.29 g (70.8%) of 4,6-dichloro-1-(1,4-dioxa-spiro[4.5]dec-8-yl)-1H-pyrazolo[3,4-d]pyrimidine, containing ˜6.5% of 2,4,6-Trichloro-pyrimidine-5-carbaldehyde. It was important to have a minimal amount of 2,4,6-trichloro-pyrimidine-5-carbaldehyde, which consumes 2 equivalents of 8-oxa-3-aza-bicyclo[3.2.1]octane in the next step. reached 7.6° C. jumped to 12.6° C. was added the slurry was filtered The cake was washed well twice with water (300 mL) hexane (300 mL) and air dried over house vacuum overnight This gave a damp cake that was washed twice with hexane (400 mL) Air-drying over house vacuum over weekend

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (1,4-Dioxa-spiro[4.5]dec-8-yl)-hydrazine (46 g, 368 mL of above solution) was cooled in an ice bath, then triethylamine (47 mL) and ethanol (368 mL) were added. When the internal temperature reached 7.6° C., 2,4,6-trichloro-pyrimidine-5-carbaldehyde (32 g, synthesized by method of WO 02/066482) was added as a solid over 1.5 min. The internal temperature jumped to 12.6° C., and continued to rise to 17° C. during 4 min. After stirring a total of 28 min, water (367 mL) was added and the slurry was filtered. The cake was washed well twice with water (300 mL), then hexane (300 mL) and air dried over house vacuum overnight. This gave a damp cake that was washed twice with hexane (400 mL). Air-drying over house vacuum over weekend gave 35.29 g (70.8%) of 4,6-dichloro-1-(1,4-dioxa-spiro[4.5]dec-8-yl)-1H-pyrazolo[3,4-d]pyrimidine, containing ˜6.5% of 2,4,6-Trichloro-pyrimidine-5-carbaldehyde. It was important to have a minimal amount of 2,4,6-trichloro-pyrimidine-5-carbaldehyde, which consumes 2 equivalents of 8-oxa-3-aza-bicyclo[3.2.1]octane in the next step. reached 7.6° C. jumped to 12.6° C. was added the slurry was filtered The cake was washed well twice with water (300 mL) hexane (300 mL) and air dried over house vacuum overnight This gave a damp cake that was washed twice with hexane (400 mL) Air-drying over house vacuum over weekend