Cesium carbonate → 4-(2-chloro-3'-fluoro-5-methoxy-[1,1'-biphenyl]-4-yl)-N-(1,2,4-thiadiazol-5-yl)quinazoline-7-sulfonamide

Reaction equation

[Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[C:17]3[C:12](=[CH:13][C:14]([S:18]([O:21]C4C(F)=C(F)C(F)=C(F)C=4F)(=[O:20])=O)=[CH:15][CH:16]=3)[N:11]=[CH:10][N:9]=2)[C:5]([O:33][CH3:34])=[CH:4][C:3]=1[C:35]1[CH:40]=[CH:39][CH:38]=[C:37]([F:41])[CH:36]=1.[S:42]1[C:46]([NH2:47])=[N:45][CH:44]=[N:43]1.C(=O)([O-])[O-].[Cs+].[Cs+]>>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[C:17]3[C:12](=[CH:13][C:14]([S:18]([NH:47][C:46]4[S:42][N:43]=[CH:44][N:45]=4)(=[O:20])=[O:21])=[CH:15][CH:16]=3)[N:11]=[CH:10][N:9]=2)[C:5]([O:33][CH3:34])=[CH:4][C:3]=1[C:35]1[CH:40]=[CH:39][CH:38]=[C:37]([F:41])[CH:36]=1

Participants

Reactant 3

HCID 10796Cesium carbonate

HCID 2902745-Amino-1,2,4-thiadiazole

HCID 86687767Perfluorophenyl 4-(2-chloro-3'-fluoro-5-methoxy-[1,1'-biphenyl]-4-yl)quinazoline-7-sulfonate

Product 1

HCID 866877684-(2-chloro-3'-fluoro-5-methoxy-[1,1'-biphenyl]-4-yl)-N-(1,2,4-thiadiazol-5-yl)quinazoline-7-sulfonamide

Procedure

A vial was charged with perfluorophenyl 4-(2-chloro-3′-fluoro-5-methoxy-[1,1′-biphenyl]-4-yl)quinazoline-7-sulfonate (0.060 g, 0.098 mmol), 1,2,4-thiadiazol-5-amine (10.93 mg, 0.108 mmol), and cesium carbonate (0.096 g, 0.295 mmol). The vial was flushed with Ar (g), then acetonitrile (0.491 ml) was added. The reaction was stirred overnight at room temperature. The mixture was diluted with EtOAc and 1 N aq. HCl. The layers were separated, and the aq. layer was extracted with EtOAc (2×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography on silica gel (12-g Redi-Sep Gold column, 0-10% MeOH/DCM) to give 4-(2-chloro-3′-fluoro-5-methoxy-[1,1′-biphenyl]-4-yl)-N-(1,2,4-thiadiazol-5-yl)quinazoline-7-sulfonamide as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ=9.55-9.42 (m, 1H), 8.44-8.35 (m, 2H), 8.01 (td, J=2.0, 8.8 Hz, 1H), 7.96-7.89 (m, 1H), 7.67 (dd, J=1.5, 2.3 Hz, 1H), 7.63-7.54 (m, 1H), 7.49-7.41 (m, 2H), 7.38-7.28 (m, 2H), 3.75 (d, J=2.2 Hz, 3H). m/z (ESI) 529.8 (M+H)+.