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HRID1504420

反应详情

EQUATION

反应方程式

HRID 1504420 的结构方程式

REACTANTS

反应物

3
结构：O=C([O-])[O-].[Cs+].[Cs+]
HCID10796

Cesium carbonate

CCs2O3

结构：Nc1nncs1
HCID19909

2-Amino-1,3,4-thiadiazole

C2H3N3S

结构：COc1cc(-c2cccc(F)c2)c(Cl)cc1-n1c(=O)ccc2cc(S(=O)(=O)Oc3c(F)c(F)c(F)c(F)c3F)ccc21
HCID117737251

未命名化合物

PRODUCTS

生成物

1
结构：COc1cc(-c2cccc(F)c2)c(Cl)cc1-n1c(=O)ccc2cc(S(=O)(=O)Nc3nncs3)ccc21
HCID117736985

未命名化合物

收率 102.8%

PROCEDURE

实验过程

A vial was charged with perfluorophenyl 1-(2-chloro-3′-fluoro-5-methoxy-[1,1′-biphenyl]-4-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonate (0.140 g, 0.224 mmol), 2-amino-1,3,4-thiadiazole (0.027 g, 0.268 mmol), and cesium carbonate (0.219 g, 0.671 mmol). The vial was flushed with Ar (g), then acetonitrile (2.2 mL) was added. The reaction was stirred overnight at RT. The mixture was diluted with EtOAc and NH4Cl (sat.). The layers were separated, and the aqueous layer was extracted with EtOAc (2×). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated. The residue was purified by chromatography on silica gel (25-g SNAP Ultra column, 0-50% EtOAc/Heptane) to give 125 mgs of 1-(2-chloro-3′-fluoro-5-methoxy-[1,1′-biphenyl]-4-yl)-2-oxo-N-(1,3,4-thiadiazol-2-yl)-1,2-dihydroquinoline-6-sulfonamide as an off-white solid. This material was purified by chiral SFC on Chiralpak AS-H column (40% MeOH/60% CO2) to give (P)-1-(2-chloro-3′-fluoro-5-methoxy-[1,1′-biphenyl]-4-yl)-2-oxo-N-(1,3,4-thiadiazol-2-yl)-1,2-dihydroquinoline-6-sulfonamide as peak 1 and (M)-1-(2-chloro-3′-fluoro-5-methoxy-[1,1′-biphenyl]-4-yl)-2-oxo-N-(1,3,4-thiadiazol-2-yl)-1,2-dihydroquinoline-6-sulfonamide as peak 2, both as off-white solids. Data for peak 1: NMR (400 MHz, DMSO-d6) δ=14.36 (br. s., 1H), 8.77 (s, 1H), 8.31 (d, J=2.15 Hz, 1H); 8.24 (d, J=9.59 Hz, 1H), 7.84 (dd, J=2.15, 8.90 Hz, 1H), 7.68 (s, 1H), 7.60 (dt, J=6.36, 8.07 Hz, 1H), 7.41-7.48 (m, 2H), 7.36 (s, 1H), 7.29-7.34 (m, 1H), 6.78-6.85 (m, 2H), 3.74 (s, 3H). m/z (ESI) 544.0 (M+H)+. Data for peak 2: 1H NMR (400 MHz, DMSO-d6) δ=14.36 (br. s., 1H), 8.77 (s, 1H), 8.31 (d, J=2.25 Hz, 1H), 8.24 (d, J=9.49 Hz, 1H); 7.84 (dd, J=2.20, 8.95 Hz, 1H), 7.68 (s, 1H), 7.59 (dt, J=6.36, 8.07 Hz, 1H), 7.41-7.48 (m, 2H), 7.36 (s, 1H), 7.30-7.35 (m, 1H), 6.81 (dd, J=6.80, 9.24 Hz, 2H), 3.74 (s, 3H). m/z (ESI) 544.0 (M+H)+.

WORKUP

后处理

  1. customThe vial was flushed with Ar (g)
  2. additionacetonitrile (2.2 mL) was added
  3. additionThe mixture was diluted with EtOAc and NH4Cl (sat.)
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with EtOAc (2×)
  6. dry with materialThe combined organic extracts were dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by chromatography on silica gel (25-g SNAP Ultra column, 0-50% EtOAc/Heptane)