反应详情

温度

-78 °C

A suspension of 1,2,4-thiadiazol-5-amine (2.67 g, 26.4 mmol) in 20 mL DCM was treated with triethylamine (3.68 ml, 26.4 mmol) and was allowed to stir for 10 minutes. The reaction mixture was then cooled to −78° C. and was treated with 1 equivalent of sulfuryl chloride. After stirring for 5 minutes, the cooling bath was removed, and the reaction mixture was allowed to stir for an additional hour. LC/MS showed mostly product so the reaction mixture was filtered then concentrated. The resulting residue was dissolved in 10 mL THF and was added to a solution of 5-(2-bromo-4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroisoquinoline hydrochloride (Intermediate D, 4.70 g, 13.20 mmol) and triethylamine (4.05 ml, 29.0 mmol) in 10 mL THF. After stirring for an additional 4 hours, the reaction mixture was poured into 1 N citric acid solution and was extracted with EtOAc. The organics were washed with brine, dried over MgSO4 and concentrated. The resulting residue was triturated with DCM providing a white solid. The washings were purified by silica gel column chromatography (0 to 100% EtOAc/heptane) and combined with the white solid yielding 5-(2-bromo-4-(trifluoromethyl)phenyl)-N-(1,2,4-thiadiazol-5-yl)-3,4-dihydroisoquinoline-2(1H)-sulfonamide (6.90 g, 13.29 mmol). [M+H]+=518.9 1H NMR (400 MHz, Acetone-d6) δ ppm: 8.04 (s, 1H), 7.97 (s, 1H), 7.81 (d, J=7.9 Hz, 1H), 7.54 (d, J=7.9 Hz, 1H), 7.28 (t, J=7.5 Hz, 1H), 7.22 (d, J=7.1 Hz, 1H), 7.01 (d, J=6.1 Hz, 1H), 4.34 (s, 2H), 3.30 (m, 2H), 2.47-2.58 (m, 2H)

1. stirringAfter stirring for 5 minutes
2. customthe cooling bath was removed
3. stirringto stir for an additional hour
4. filtrationwas filtered
5. concentrationthen concentrated
6. dissolutionThe resulting residue was dissolved in 10 mL THF
7. stirringAfter stirring for an additional 4 hours
8. extractionwas extracted with EtOAc
9. washThe organics were washed with brine
10. dry with materialdried over MgSO4
11. concentrationconcentrated
12. customThe resulting residue was triturated with DCM providing a white solid
13. customThe washings were purified by silica gel column chromatography (0 to 100% EtOAc/heptane)