(2R,6S)-2,6-dimethyloxan-4-amine

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

Procedure: To crude (2R,6S)-2,6-dimethyltetrahydro-2H-pyran-4-amine (0.18 g) in DCE (4.2 ml) and Ethanol (4.2 ml) was added 7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-6-bromo-3-(6-fluoroquinolin-3-yl)pyrazolo[1,5-a]pyrimidine-5-carbaldehyde (0.19 g, 0.3 mmol) followed by AcOH (0.03 ml, 0.6 mmol). After stirring for 30 minutes at room temperature, NaBH3CN (37.8 mg, 0.6 mmol) was added and stirring was continued further for 30 minutes more. LC/MS showed no starting material remaining. After the solvent was rotoevaporated, the crude was dissolved with DCM (20 ml), washed with sat. NaHCO3 (1×5 ml), water (1×5 ml), brine (1×5 ml), dried over MgSO4. Solvent was removed in vacuo and the residue was purified by column chromatography on silica gel. Elution with EtOAc/Hexanes (0-60%) gave desired 6-bromo-5-(((2R,6S)-2,6-dimethyltetrahydro-2H-pyran-4-ylamino)methyl)-3-(6-fluoroquinolin-3-yl)-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine (68 mg, 30%). stirring was continued further for 30 minutes washed with sat. NaHCO3 (1×5 ml), water (1×5 ml), brine (1×5 ml) dried over MgSO4 Solvent was removed in vacuo the residue was purified by column chromatography on silica gel Elution with EtOAc/Hexanes (0-60%)

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

Procedure: To tert-butyl (2R,65)-2,6-dimethyltetrahydro-2H-pyran-4-ylcarbamate (crude, 0.6 g) was added 4M HCl in 1,4-dioxane (15 ml) at r.t. It was stirred further at room temperature for 2 h, at which time LC/MS analysis confirmed full consumption of starting material. Solvent was removed in vacuo to get the desired (2R,6S)-2,6-dimethyltetrahydro-2H-pyran-4-amine as an HCl salt. consumption of starting material Solvent was removed in vacuo