反应详情

Sodium triacetoxyborohydride (279 mg; 1.32 mmol; 2.0 eq.) was added to a solution of tert-butyl-1-piperazinecarboxylate (1.22 g; 6.59 mmol; 10 eq.) and 4-[4-(5-methyl-1H-indazol-3-yl)-1H-1,2,3-triazol-1-yl]benzaldehyde (200 mg; 0.66 mmol; 1.0 eq.) in DMA (4 mL) and the reaction mixture was stirred overnight at RT. Sodium triacetoxyborohydride (279 mg; 1.32 mmol; 2.0 eq.) and glacial acetic acid (75.42 μl; 1.32 mmol; 2.00 eq.) then sodium cyanoborohydride (83 mg; 1.32 mmol; 2. eq.) were added to complete the reaction which was quenched with water and extracted with EtOAc (twice). Combined organic phases were washed with brine, dried over magnesium sulfate, filtered and concentrated. The resulting gum was stirred at RT in a solution of HCl in dioxane (5 mL, 4N) for 2 hours. The reaction mixture was basified to pH=9-10 and extracted with EtOAc. Organic layer was dried over magnesium sulfate, filtered and concentrated. Purification by preparative HPLC afforded the title compound as a formic acid salt. It was dissolved in MeOH and passed through a SPE-NH2 cartridge. The fractions containing the desired compound were concentrated to dryness affording a yellow gum, which was twice sonicated in 3 mL of Et2O. The suspension obtained was concentrated then dried overnight under high vacuum to afford the title compound as a beige solid. 1H NMR (300 Mz, DMSO-d6) δ: 13.23 (brs, 1H), 9.25 (s, 1H), 8.14-8.13 (m, 1H), 8.00 (d, J=8.5 Hz, 2H), 7.54 (d, J=8.5 Hz, 2H), 7.50 (d, J=8.5 Hz, 1H), 7.28 (dd, J=8.5 Hz, 1.5 Hz, 1H), 3.52 (s, 2H), 2.72-2.69 (m, 4H), 2.487 (s, 3H), 2.32-2.30 (m, 4H). HPLC (Condition A): Rt 2.22 min (purity 95.4%). MS (ESI+): 374.3, MS (ESI−): 372.3.

1. customthe reaction which
2. customwas quenched with water
3. extractionextracted with EtOAc (twice)
4. washCombined organic phases were washed with brine
5. dry with materialdried over magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. stirringThe resulting gum was stirred at RT in a solution of HCl in dioxane (5 mL, 4N) for 2 hours
9. extractionextracted with EtOAc
10. dry with materialOrganic layer was dried over magnesium sulfate
11. filtrationfiltered
12. concentrationconcentrated
13. customPurification by preparative HPLC