反应详情

A solution of tert-butyl 2-(5-(2-(benzyloxy)-6-fluoro-4-(1H-pyrazol-4-yl)phenyl)-1,3,4-thiadiazol-2-yl)-2,7-diazaspiro[3.5]nonane-7-carboxylate (86 mg, 0.149 mmol) in a 1:1: mixture MeOH:DCM (3 mL) was added to a nitrogen flushed flask containing 10% Pd/C (8.6 mg). The reaction mixture was placed under a hydrogen atmosphere (balloon) and stirred at room temperature for 18 hours. The reaction mixture was flushed with nitrogen and an additional 8.6 mg of 10% Pd/C was added. The reaction was diluted with 1:1 MeOH:DCM (3 mL), and again placed under a hydrogen atmosphere (balloon) and stirred at room temperature for an additional 5 days. The reaction mixture was flushed with nitrogen, diluted with 10% MeOH in DCM (50 mL) and filtered through celite. The filtrate was concentrated in vacuo to afford a pale brown/off-white solid. The solid was re-dissolved in 25% MeOH in DCM (10 mL) and added to a nitrogen flushed flash containing 10% Pd/C (8.6 mg). The reaction mixture was placed under a hydrogen atmosphere (balloon) and left to stir at room temperature for 18 hours. The reaction mixture was diluted with 10% MeOH in DCM (50 mL) and filtered through celite. The filtrate was concentrated in vacuo to afford the crude product as a brown solid. The crude material was purified by flash chromatography using a 10 g silica cartridge running a MeOH/DCM gradient and collecting by mass to afford an the title compound as a pale brown solid (54 mg, 74% yield). LC-MS: Rt 1.33 min; MS m/z 487.3 [M+H]+ [Method A]. 1H NMR (400 MHz, DMSO-d6) δ 13.09 (s, 1H), 11.92 (s, 1H), 8.36 (d, J=1.7 Hz, 1H), 8.04 (d, J=1.9 Hz, 1H), 7.22 (dd, J=12.6, 1.6 Hz, 1H), 7.14-7.19 (m, 1H), 3.92 (s, 4H), 3.28-3.31 (m, 4H), 1.69-1.79 (m, 4H), 1.40 (s, 9H).

1. customThe reaction mixture was flushed with nitrogen
2. additionan additional 8.6 mg of 10% Pd/C was added
3. additionThe reaction was diluted with 1:1 MeOH
4. stirringstirred at room temperature for an additional 5 days
5. customThe reaction mixture was flushed with nitrogen
6. additiondiluted with 10% MeOH in DCM (50 mL)
7. filtrationfiltered through celite
8. concentrationThe filtrate was concentrated in vacuo
9. customto afford a pale brown/off-white solid
10. additionadded to a nitrogen
11. customflushed flash
12. additioncontaining 10% Pd/C (8.6 mg)
13. waitleft
14. stirringto stir at room temperature for 18 hours
15. additionThe reaction mixture was diluted with 10% MeOH in DCM (50 mL)
16. filtrationfiltered through celite
17. concentrationThe filtrate was concentrated in vacuo
18. customto afford the crude product as a brown solid
19. customThe crude material was purified by flash chromatography
20. customcollecting by mass