Aluminium lithium hydride → (4aR,7aR)-octahydro-1H-cyclopenta[b]pyrazine

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Reaction Conditions

Reaction Steps

To a cooled (0° C.) solution of (4aR,7aR)-octahydro-2H-cyclopenta[b]pyrazin-2-one (prepared in analogy to Example 3.120, Steps 1-3) (570 mg, 4.07 mmol) in THF (27 mL) was added dropwise LAH (4.07 mL of a 2.0M solution in THF, 8.14 mmol) over 5 minutes. After the addition was complete, the mixture was capped with a reflux condenser and heated to 65° C. for 14 hours. The resulting mixture was then cooled to room temperature and carefully quenched by the addition of sodium sulfate decahydrate (1.3 g). The reaction mixture was filtered through Celite®, and the filter cake was washed with ethyl acetate. The combined filtrate was dried over magnesium sulfate, filtered, evaporated under reduced pressure and dried in vacuo to give (4aR,7aR)-octahydro-1H-cyclopenta[b]pyrazine. 1H NMR (500 MHz, DMSO-d6) δ 2.75-2.69 (m, 2H), 2.55-2.50 (m, 2H), 2.13-2.07 (m, 4H), 1.66-1.59 (m, 2H), 1.57-1.51 (m, 2H), 1.22-1.12 (m, 2H). Example 5.1 3-(2-((R)-4-acetyl-2-methylpiperazin-1-yl)-4-(5-chloropyridin-3-yl)-3-((trans-4-methyl cyclohexyl)methyl)-3H-imidazo[4,5-c]pyridin-6-yl)-1,2,4-oxadiazol-5(4H)-one

Provenance & Evidence