Potassium Phosphate, Tribasic → N-(tert-butyl)-5-(1-chloro-8-phenylpyrrolo[1,2-d][1,2,4]triazin-4-yl)-2-(difluoromethyl)pyridine-3-sulfonamide

Temperatur

100 °C

To a solution of N-(tert-butyl)-2-(difluoromethyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-3-sulfonamide (0.118 g, 0.303 mmol) and 1,4-dichloro-8-phenylpyrrolo[1,2-d][1,2,4]triazine (0.080 g, 0.30 mmol) in 1,4-dioxane (4 mL) and water (0.8 mL) was added K3PO4 (0.129 g, 0.606 mmol) and the reaction mixture was purged with nitrogen for 10 minutes. Tricyclohexylphosphonium tetrafluoroborate (0.011 g, 0.030 mmol) was added followed by Pd2(dba)3 (0.014 g, 0.015 mmol) and the nitrogen purging was continued for further 5 minutes. The reaction mixture was heated at 100° C. for 4 h then allowed to cool to ambient temperature. The reaction mixture was filtered through CELITE® and the filter cake was washed with EtOAc (2×50 mL). The filtrate was washed with water (50 mL). The organic phase was separated and the aqueous phase was further extracted with EtOAc (50 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The resulting residue was purified by CombiFlash Isco (REDISEP®, SiO2, 40 g, 0-50% EtOAc/petroleum ether) to obtain N-(tert-butyl)-5-(1-chloro-8-phenylpyrrolo[1,2-d][1,2,4]triazin-4-yl)-2-(difluoromethyl)pyridine-3-sulfonamide (0.052 g, 35%) as a pale yellow solid. LCMS Method B-12: retention time 2.24 min, [M+1]=492.0. 1H NMR (400 MHz, DMSO-d6) δ ppm: 1.19 (s, 9H), 7.25 (d, J=2.8 Hz, 1H), 7.41-7.54 (m, 5H), 7.73 (t, J=52.4 Hz, 1H), 7.99 (d, J=2.8 Hz, 1H), 8.37 (s, 1H), 8.90 (br s, 1H), 9.45 (d, J=2.0 Hz, 1H).

1. customthe reaction mixture was purged with nitrogen for 10 minutes
2. temperatureto cool to ambient temperature
3. filtrationThe reaction mixture was filtered through CELITE®
4. washthe filter cake was washed with EtOAc (2×50 mL)
5. washThe filtrate was washed with water (50 mL)
6. customThe organic phase was separated
7. extractionthe aqueous phase was further extracted with EtOAc (50 mL)
8. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customThe resulting residue was purified by CombiFlash Isco (REDISEP®, SiO2, 40 g, 0-50% EtOAc/petroleum ether)

ORD-Eintrag

ord-4b5c6744a97c4315999ef22f5f54834b

Quelldatensatz

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09403834B2