反应详情

温度

0 °C

To a 0° C. stirring mixture of 1H-pyrazol-4-amine (250 mg, 3.008 mmol) and thiophene-2-carbaldehyde (281 uL, 3.008 mmol) in methanol and acetic acid (5.0 ml, 10:1 ratio) was added 5-ethyl-2-methylpyridine borane complex (444 uL, 3.008 mmol). The ice bath was removed and the flask was attached to a bubbler to allow gas evolution and expansion. The reaction was stirred overnight at room temp. Most of the volatiles were evaporated in vacuo. With the aid of a 0° C. chilling bath, a 10 M solution of NaOH in water was carefully added. The ice bath was removed and stirring was continued for nearly 1 hour. The aqueous layer was extracted with DCM (3×), washed with brine, and dried over MgSO4 and concentrated. The obtained crude product was left under vacuum to remove the volatiles. The obtained viscous oil was diluted with DCM and evaporated under a gentle stream of nitrogen overnight. Solid crystals of the amine separated out and were washed with three aliquots of Hex:EtOAc=9:1. In this way, 391 mg (2.181 mmol; 72%) of the desired product were obtained in more than 97% purity by 1H-NMR analysis. 1H NMR (400 MHz, DMSO-d6) δ 4.21 (d, J=5.6 Hz, 1H), 4.92 (t, J=6.0 Hz, 1H), 6.94 (dd, J=5.1, 3.4 Hz, 1H), 7.10-6.99 (m, 3H), 7.36 (dd, J=5.1, 1.2 Hz, 1H), 12.05 (br s, 1H).

1. additionwas added 5-ethyl-2-methylpyridine borane complex (444 uL, 3.008 mmol)
2. customThe ice bath was removed
3. stirringThe reaction was stirred overnight at room temp
4. customMost of the volatiles were evaporated in vacuo
5. temperatureWith the aid of a 0° C. chilling bath
6. additiona 10 M solution of NaOH in water was carefully added
7. customThe ice bath was removed
8. stirringstirring
9. extractionThe aqueous layer was extracted with DCM (3×)
10. washwashed with brine
11. dry with materialdried over MgSO4
12. concentrationconcentrated
13. customThe obtained crude product
14. waitwas left under vacuum
15. customto remove the volatiles
16. additionThe obtained viscous oil was diluted with DCM
17. customevaporated under a gentle stream of nitrogen overnight
18. customSolid crystals of the amine separated out
19. washwere washed with three aliquots of Hex