Methanol → Diethylamine

Participants

Reaction Steps

To a solution of 1-[5-pyrrolidin-1-yl-7-(tetrahydro-2H-pyran-4-ylamino)-pyrazolo[1,5-a]pyrimidin-2-yl]propane-1,2-dione (87 mg, 0.243 mmol) in methanol (3 mL) and water (0.3 mL) was added 3,4-diaminopyridine (29 mg, 0.268 mmol) at room temperature. After being stirred for 24 h at same temperature, the reaction mixture was concentrated in vacuo. The crude was purified by silica gel column chromatography (chloroform:methanol=99:1 to 19:1) and HPLC(CHIRALPAK IC, 20Φ×250 mm, hexane:etanol:diethylamine=30:70:0.1, frow rate 5.0 mL/min) to give 2-(3-methylpyrido[3,4-b]pyrazin-3-yl)-5-pyrrolidin-1-yl-N-(tetrahydro-2H-pyran-4-yl)pyrazolo[1,5-a]pyrimidin-7-amine (the compound of Example 5.001 listed in the Table of Examples as described hereinafter) as a more polar compound and 2-(2-methylpyrido[3,4-b]pyrazin-2-yl)-5-pyrrolidin-1-yl-N-(tetrahydro-2H-pyran-4-yl)pyrazolo[1,5-a]pyrimidin-7-amine (the compound of Example 5.002 listed in the Table of Examples as described hereinafter) as a less polar compound. The absolute configuration was determined by X-ray analysis of 2-(2-methylpyrido[3,4-b]pyrazin-2-yl)-5-pyrrolidin-1-yl-N-(tetrahydro-2H-pyran-4-yl)pyrazolo[1,5-a]pyrimidin-7-amine.

Provenance & Evidence