反应详情

A reaction flask containing a suspension of LAH (499 mg, 13.2 mmol) in THF (22 mL) was evacuated and back-filled with nitrogen three times. A solution of tert-butyl 3-(4-amino-1H-pyrazol-1-yl)pyrrolidine-1-carboxylate (830 mg, 3.3 mmol) in THF (11 mL) was added dropwise, via an addition funnel and the reaction mixture was stirred at rt under nitrogen overnight. The reaction was quenched sequentially with water (1 mL), 1N NaOH (1 mL), and water (3 mL) to afford a suspension. The precipitate was filtered off and washed with ethyl acetate. The combined filtrates were diluted with a small amount of water and transferred to a separatory funnel. The layers were separated, and the aqueous layer was extracted with ethyl acetate. The organics were combined and concentrated to give crude material (137 mg). To recover product in the aqueous layer, the aqueous extraces were lyophilized to give a solid residue. This was suspended in EtOAc and filtered. The filtrate was evaporated to give additional crude material (287 mg). The combined crude was purified via Biotage flash chromatography (25S column, eluting with 7 N NH3/MeOH in DCM (1%-4%)) to give the title compound (279 mg, 51% yield). m/z (APCI+) for C8H14N4 167.2 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.89-2.00 (m, 1H) 2.20-2.31 (m, 1H) 2.26 (s, 3H) 2.42 (td, J=8.40, 6.19 Hz, 1H) 2.60 (dd, J=9.60, 4.80 Hz, 1H) 2.64-2.77 (m, 2H) 3.79 (br. s., 2H) 4.67 (m, J=9.44, 7.23, 4.67, 4.67 Hz, 1H) 6.87 (s, 1H) 7.07 (s, 1H).

1. additionA reaction flask containing
2. customwas evacuated
3. additionback-filled with nitrogen three times
4. customThe reaction was quenched sequentially with water (1 mL), 1N NaOH (1 mL), and water (3 mL)
5. customto afford a suspension
6. filtrationThe precipitate was filtered off
7. washwashed with ethyl acetate
8. additionThe combined filtrates were diluted with a small amount of water
9. customtransferred to a separatory funnel
10. customThe layers were separated
11. extractionthe aqueous layer was extracted with ethyl acetate
12. concentrationconcentrated
13. customto give crude material (137 mg)
14. customTo recover product in the aqueous layer
15. customto give a solid residue
16. filtrationfiltered
17. customThe filtrate was evaporated
18. customto give additional crude material (287 mg)
19. customwas purified via Biotage flash chromatography (25S column, eluting with 7 N NH3/MeOH in DCM (1%-4%))