Citric Acid → 5-bromo-N-(5-fluorothiazol-2-yl)-3,4-dihydroisoquinoline-2(1H)-sulfonamide

A solution of 5-fluorothiazol-2-amine hydrochloride (Milestone Pharmatech, Brunswick, N.J., 6.22 g, 40.2 mmol) and 1H-imidazole (10.96 g, 161 mmol) in 200 mL DCM was cooled to −78° C. and was treated with sulfuryl chloride (3.27 ml, 40.2 mmol). After stirring for 10 minutes, the reaction mixture was placed into a 0° C. bath and was allowed to stir for an additional hour. To this mixture was added 30 mL of heptane and the solvent was decanted. The remaining solid was treated with 5-bromo-1,2,3,4-tetrahydroisoquinoline hydrochloride (ASW Medchem, Brunswick, N.J., 5.00 g, 20.12 mmol) then treated sequentially with 100 mL THF and DIPEA (42.2 ml, 241 mmol). The reaction mixture was heated to reflux for one hour before being cooled and poured into 1N citric acid. The desired product was extracted with ethyl acetate. The organics were concentrated and the resulting residue was purified directly by silica gel column chromatography (0 to 100% EtOAc/heptane, 2% MeOH) yielding 5-bromo-N-(5-fluorothiazol-2-yl)-3,4-dihydroisoquinoline-2(1H)-sulfonamide (3.25 g, 8.29 mmol). [M+H]+=393.9

1. customwas placed into a 0° C.
2. stirringto stir for an additional hour
3. customthe solvent was decanted
4. temperatureThe reaction mixture was heated
5. temperatureto reflux for one hour
6. temperaturebefore being cooled
7. extractionThe desired product was extracted with ethyl acetate
8. concentrationThe organics were concentrated
9. customthe resulting residue was purified directly by silica gel column chromatography (0 to 100% EtOAc/heptane, 2% MeOH)

ORD record

ord-121fb25062784ed5a64c93d0ef08bc54

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09051311B2