(7R,8aS)-2-benzyloctahydropyrrolo[1,2-a]pyrazin-7-ol → (7R,8aS)-2-benzyl-7-[(5-cyclopropylpyrazin-2-yl)oxy]octahydropyrrolo[1,2-a]pyrazine

To (7R,8aS)-2-benzyloctahydropyrrolo[1,2-a]pyrazin-7-ol (Example 54D, 2.323 g, 10 mmol) in tetrahydrofuran (60 mL) at room temperature was added potassium tert-butoxide (14 mL, 1 M in tetrahydrofuran). After 10 minutes, 2-bromo-5-cyclopropylpyrazine (2.249 g, 11.3 mmol) in tetrahydrofuran (3 mL) was added. The mixture was stirred at room temperature for 2 days. The mixture was concentrated and diluted with dichloromethane (200 mL). This solution was washed with water (30 mL), dried over sodium sulfate, and filtered. The organic phase was concentrated. The residue was purified by chromatography on silica gel (dichloromethane/methanol=15:1) to give the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.80 (m, 2H), 0.92 (m, 2H), 1.78 (m, 3H), 2.08-2.38 (m, 5H), 2.70 (m, 1H), 2.83 (m, 2H), 3.53 (m, 3H), 5.24 (m, 1H), 7.28 (m, 5H), 8.12 (m, 2H); MS (ESI) m/z 351 (M+H)+.

1. concentrationThe mixture was concentrated
2. additiondiluted with dichloromethane (200 mL)
3. washThis solution was washed with water (30 mL)
4. dry with materialdried over sodium sulfate
5. filtrationfiltered
6. concentrationThe organic phase was concentrated
7. customThe residue was purified by chromatography on silica gel (dichloromethane/methanol=15:1)

ORD record

ord-b013478590124245be429d03647cc867

Source dataset

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08669255B2