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

HRID 1473685Notes

Reaction equation

HRID 1473685 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

4

Reactant 3

HCID 10796Cesium carbonateHCID 2902745-Amino-1,2,4-thiadiazoleHCID 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)+.

Workup

  1. customThe vial was flushed with Ar (g)
  2. additionacetonitrile (0.491 ml) was added
  3. additionThe mixture was diluted with EtOAc and 1 N aq. HCl
  4. customThe layers were separated
  5. extractionthe aq. layer was extracted with EtOAc (2×)
  6. dry with materialThe combined organic extracts were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by chromatography on silica gel (12-g Redi-Sep Gold column, 0-10% MeOH/DCM)

Sources & evidence

ORD record
ord-0cdaf10154d74c1e9e2c7536be993e67
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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