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

Temperature

65 °C

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

1. additionAfter the addition
2. customthe mixture was capped with a reflux condenser
3. temperatureThe resulting mixture was then cooled to room temperature
4. customcarefully quenched by the addition of sodium sulfate decahydrate (1.3 g)
5. filtrationThe reaction mixture was filtered through Celite®
6. washthe filter cake was washed with ethyl acetate
7. dry with materialThe combined filtrate was dried over magnesium sulfate
8. filtrationfiltered
9. customevaporated under reduced pressure
10. customdried in vacuo

ORD record

ord-5dd3d9c339fe496cb1708df7766b6f4a

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08846657B2