Reaktion #2259497

Reaktionsgleichung

1H-imidazole

1,1′-Sulfonylbis(1H-imidazole)

thiazol-2-amine

tert-butyl 4-(2-(1,2,3,4-tetrahydroisoquinolin-5-yl)-5-(trifluoromethyl)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate

triethylamine

sulfuryl chloride

→

tert-butyl 4-(2-(2-(N-(thiazol-2-yl)sulfamoyl)-1,2,3,4-tetrahydroisoquinolin-5-yl)-5-(trifluoromethyl)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate

Ausbeute 49.1%

Lösungsmittel

EtOAc

DCM

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigethe cooling bath was removed
2. 2
   workup.STIRRINGto stir for an additional 15 minutes
3. 3
   Waschenwashed with 1N citric acid solution
4. 4
   SonstigePurification of the resulting residue by reverse phase column chromatography [RediSep Gold C-18 100 g, 10 to 100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)]

Vorschrift

A solution of 1H-imidazole (0.238 g, 3.49 mmol) and thiazol-2-amine (TCI America, Portland, Oreg., 0.087 g, 0.872 mmol) in 6 mL DCM was cooled to −10° C. and was treated with sulfuryl chloride (0.071 ml, 0.872 mmol). After stirring for 15 minutes, the cooling bath was removed, and the reaction mixture was allowed to stir for an additional 15 minutes. The reaction mixture was treated with tert-butyl 4-(2-(1,2,3,4-tetrahydroisoquinolin-5-yl)-5-(trifluoromethyl)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate (0.200 g, 0.436 mmol) and triethylamine (0.608 ml, 4.36 mmol) and was heated to 80° C. for 20 minutes. The reaction mixture was diluted with EtOAc, washed with 1N citric acid solution and the organics concentrated. Purification of the resulting residue by reverse phase column chromatography [RediSep Gold C-18 100 g, 10 to 100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)] gave tert-butyl 4-(2-(2-(N-(thiazol-2-yl)sulfamoyl)-1,2,3,4-tetrahydroisoquinolin-5-yl)-5-(trifluoromethyl)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate (0.133 g, 0.214 mmol). This material was taken up in 1 mL THF, was treated with HCl 4N in dioxane (1.090 ml, 4.36 mmol) and was heated to 80° C. for one hour. Concentration and purification of the resulting residue by reverse phase column chromatography [RediSep Gold C-18 50 g 10 to 100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)] gave 5-(2-(1,2,3,6-tetrahydropyridin-4-yl)-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)-3,4-dihydroisoquinoline-2(1H)-sulfonamide (0.053 g, 0.102 mmol). [M+H]+=520.8 1H NMR (400 MHz, DMSO-d6) δ ppm: 7.75 (d, J=8.1 Hz, 1H), 7.49 (d, J=7.9 Hz, 1H), 7.43 (s, 1H), 7.12 (t, J=7.9 Hz, 1H), 6.90-7.04 (m, 3H), 6.54 (d, J=4.1 Hz, 1H), 5.75 (br. s., 1H), 4.11-4.40 (m, 2H), 3.52 (br. s., 2H), 3.33-3.48 (m, 1H), 3.00-3.13 (m, 2H), 2.73-2.86 (m, 1H), 2.60-2.73 (m, 1H), 2.08-2.23 (m, 1H), 1.77-2.03 (m, 2H)

Quelle