反应详情

A stirred solution of 2-bromo-5-(4-bromo-2-chlorophenyl)-1,3,4-thiadiazole (700 mg, 1.975 mmol) and 5-bromo-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine (Intermediate 4) (1009 mg, 5.92 mmol) in NMP (4 mL) was heated to 120° C. for 3 hours. The reaction mixture was allowed to cool to room temperature then diluted with DCM (100 mL) and washed with saturated NaHCO3(aq) (100 mL). The organic phase was separated, dried over MgSO4, and filtered. The filtrate was concentrated in vacuo to a brown liquid. The crude material was purified by silica flash chromatography, running a gradient from 0-10% [2M NH3 in MeOH]/DCM over 30 minutes, collecting at 320 nm to afford the title compound as a light brown glass-like solid (750 mg, 86% yield). LC-MS: Rt 1.10 min; MS m/z 445.1 [M+2H]+ [Method A]. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.96 (d, J=8.59 Hz, 1H), 7.93 (d, J=2.02 Hz, 1H), 7.70 (dd, J=8.59, 2.02 Hz, 1H), 4.36 (tt, J=12.38, 3.28 Hz, 1H) 3.01 (s, 3H), 1.62 (dd, J=12.13, 3.03 Hz, 2H), 1.43 (t, J=12.13 Hz, 2H), 1.28 (br. s., 1H), 1.20 (s, 6H), 1.09 (s, 6H).

1. washwashed with saturated NaHCO3(aq) (100 mL)
2. customThe organic phase was separated
3. dry with materialdried over MgSO4
4. filtrationfiltered
5. concentrationThe filtrate was concentrated in vacuo to a brown liquid
6. customThe crude material was purified by silica flash chromatography
7. customover 30 minutes
8. customcollecting at 320 nm