1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → 5-cyano-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide

Temperatur

120 °C

A microwave vial was charged with Xantphos (44.5 mg, 0.077 mmol) and Pd2(dba)3 (35.2 mg, 0.038 mmol). The vessel was flushed with Ar (g), then DMF (3843 μl) was added. The vessel was sealed and heated in a microwave reactor at 120° C. for 10 min. The mixture was cooled, then a solid mixture of 5-bromo-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide (Intermediate D; 200 mg, 0.384 mmol) and dicyanozinc (226 mg, 1.922 mmol) was added. The vial was re-sealed and heated in the microwave for 3 h at 120° C. The mixture was then diluted with water and extracted with EtOAc (3×). The combined organic extract was dried over sodium sulfate, filtered, and concentrated. The residue was purified by silica gel chromatography on a 40-g column with 50 to 100% EtOAc/Heptane to give 5-cyano-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide as an off-white solid. This material was dissolved in DCM (1 mL) and TFA (0.5 mL). The mixture was stirred for 4 h, then diluted with 2-propanol and concentrated. The residue was purified by silica gel chromatography (12-g, with 0 to 10% MeOH/DCM) to give 5-cyano-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide (12.98 mg, 0.041 mmol, 67.5% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm=8.70 (br. s., 1H), 8.60 (d, J=9.0 Hz, 1H), 8.48 (br. s., 1H), 8.34 (d, J=7.1 Hz, 1H), 8.28 (d, J=8.2 Hz, 1H), 8.10 (d, J=8.5 Hz, 1H), 7.88-7.77 (m, 1H); m/z (ESI) 317.2 (M+H)+.

1. customThe vessel was flushed with Ar (g)
2. additionDMF (3843 μl) was added
3. customThe vessel was sealed
4. temperatureThe mixture was cooled
5. additionwas added
6. customThe vial was re-sealed
7. temperatureheated in the microwave for 3 h at 120° C
8. extractionextracted with EtOAc (3×)
9. extractionThe combined organic extract
10. dry with materialwas dried over sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated
13. customThe residue was purified by silica gel chromatography on a 40-g column with 50 to 100% EtOAc/Heptane

ORD-Eintrag

ord-4eda4955354c4a9396002529bb9ea66d

Quelldatensatz

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09012443B2