Potassium Phosphate, Tribasic → (8R)-8-({[t-Butyl(dimethyl)silyl]oxy}methyl)-8-methyl-3-{1-[4-(1-methyl-1H-pyrazol-4-yl)phenyl]cyclopropyl}-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepine

Temperatur

140 °C

The compound (255 mg, 0.55 mmol) obtained in Example 4-2), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (126 mg, 0.60 mmol), tris(dibenzylideneacetone)dipalladium (25 mg, 0.03 mmol), tricyclohexylphosphine (29 mg, 0.07 mmol), and tripotassium phosphate (205 mg, 0.93 mmol) were dissolved in a mixed solvent of 1,4-dioxane (2 mL) and water (1 mL), and the mixture was stirred at 140° C. for 2 h under microwave irradiation. The reaction mixture was cooled to room temperature, then diluted with methylene chloride (60 mL), and separated into organic and aqueous layers by the addition of saturated aqueous sodium hydrogencarbonate (20 mL). The organic layer was washed with saturated sodium chloride solution and then dried with anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (elution solvent: methanol/ethyl acetate=0% to 20%) to obtain the title compound (283 mg, quant.) in a colorless solid form.

1. temperatureThe reaction mixture was cooled to room temperature
2. customseparated into organic and aqueous layers
3. additionby the addition of saturated aqueous sodium hydrogencarbonate (20 mL)
4. washThe organic layer was washed with saturated sodium chloride solution
5. dry with materialdried with anhydrous magnesium sulfate
6. distillationThe solvent was distilled off under reduced pressure
7. customthe obtained residue was purified by silica gel column chromatography (elution solvent: methanol/ethyl acetate=0% to 20%)

ORD-Eintrag

ord-8ccb4851b90d4cbaaa23749d94df6fb0

Quelldatensatz

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08927536B2