Diisopropylethylamine → 2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1-H-pyrazol-3-yl]-4,4-difluoro-butyramide

温度

25 °C

In a round bottom flask under argon was placed 2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4,4-difluoro-butyric acid (166 mg, 0.50 mmol) and 1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-ylamine (prepared as in Example 49, 118 mg, 0.60 mmol) in N,N-dimethylformamide (4 mL). To this mixture was added N,N-diisopropyethylamine (250 μL, 1.5 mmol) and (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (330 mg, 0.75 mmol) and stirred overnight at 25° C. After this time, the mixture was diluted with ethyl acetate (25 mL) and washed with a saturated aqueous solution of ammonium chloride (25 mL), saturated aqueous solution of sodium bicarbonate (25 mL) and a saturated aqueous solution of sodium chloride (25 mL), dried over sodium sulfate, and then concentrated with silica gel (2 g). Purification by Biotage flash chromatography (Aspire 40 g column, 80% ethyl acetate/hexanes) afforded 2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1-H-pyrazol-3-yl]-4,4-difluoro-butyramide (185 mg, 72%) as a cream colored foam: HR-ES-MS m/z calculated for C23H25N4O5ClF2 [M+H]+ 511.1555, observed 511.1555.

1. customIn a round bottom flask under argon was placed
2. washwashed with a saturated aqueous solution of ammonium chloride (25 mL), saturated aqueous solution of sodium bicarbonate (25 mL)
3. dry with materiala saturated aqueous solution of sodium chloride (25 mL), dried over sodium sulfate
4. concentrationconcentrated with silica gel (2 g)
5. customPurification by Biotage flash chromatography (Aspire 40 g column, 80% ethyl acetate/hexanes)

ORDレコード

ord-933ef15894ae4a048471a5c319052119

出典データセット

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07741327B2