反应详情

A solution of tert-butyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (ASW Medchem, Brunswick, N.J., 2.340 g, 6.51 mmol) in 7 mL THF was treated with HCl 4 N in dioxane (8.14 ml, 32.6 mmol) and was allowed to stir at room temperature overnight. LC/MS showed mostly product, so the reaction mixture was concentrated. The resulting residue was triturated with heptane, and the solid was dried and collected. A separate flask charged with 1,2,4-thiadiazol-5-amine (1.317 g, 13.03 mmol), 26 mL DCM, and triethylamine (4.54 ml, 32.6 mmol) was cooled to −78° C. and was treated with sulfuryl chloride (1.059 ml, 13.03 mmol). After stirring for one hour, the reaction mixture was filtered through a syringe filter and was treated with the 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydroisoquinoline derived above. After stirring overnight, LC/MS showed product so the reaction mixture was filtered then concentrated. Purification of the resulting residue by silica gel column chromatography (0 to 100% EtOAc/heptane) gave 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N-(1,2,4-thiadiazol-5-yl)-3,4-dihydroisoquinoline-2(1H)-sulfonamide (0.711 g, 1.684 mmol). [M+H]+=423.3

1. concentrationso the reaction mixture was concentrated
2. customThe resulting residue was triturated with heptane
3. customthe solid was dried
4. customcollected
5. temperaturewas cooled to −78° C.
6. stirringAfter stirring for one hour
7. filtrationthe reaction mixture was filtered through a syringe
8. filtrationfilter
9. additionwas treated with the 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydroisoquinoline
10. stirringAfter stirring overnight
11. filtrationwas filtered
12. concentrationthen concentrated
13. customPurification of the resulting residue by silica gel column chromatography (0 to 100% EtOAc/heptane)