Diisopropylethylamine → 3-(4-((2-(1H-imidazol-5-yl)acetamido)methyl)-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamido)phenyl dimethylcarbamate

To a suspension of 2-(1H-imidazol-5-yl)acetic acid (0.238 g, 1.47 mmol) and HATU (0.372 g, 0.978 mmol) in CH2Cl2 (5 mL) was added N,N-diisopropylethylamine (0.51 mL, 2.93 mmol). The resulting solution was allowed to stir for 20 min. at room temperature. To this solution was added the acetate salt of 3-(4-(aminomethyl)-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamido)phenyl dimethylcarbamate (from example 20, 0.500 g, 0.978 mmol) and N,N-diisopropylethylamine (0.17 mL) in CH2Cl2 (5 mL). The reaction was allowed to stir at room temperature for 6h, and then diluted with H2O (10 mL) and CH2Cl2 (20mL). The mixture was extracted with CH2Cl2 (2×10 mL), and the combined organics were washed with NaHCO3 (10 mL) and brine (10 mL), dried over MgSO4, and concentrated under vacuum. The residue was purified by flash chromatography (3-10% MeOH:CH2Cl2) to afford the title compound (0.393 g, 72% yield) as a white solid. This solid was suspended in water, and acetic acid was added until the solution became clear. This solution was frozen and lyophilized to the di-acetate salt of the title compound (0.477 g).

1. extractionThe mixture was extracted with CH2Cl2 (2×10 mL)
2. washthe combined organics were washed with NaHCO3 (10 mL) and brine (10 mL)
3. dry with materialdried over MgSO4
4. concentrationconcentrated under vacuum
5. customThe residue was purified by flash chromatography (3-10% MeOH:CH2Cl2)

ORDレコード

ord-71224663e6224a029a18263a351951d2

出典データセット

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08193202B2