Diisopropylethylamine → (S)-3-cyclopentyl-N-[1-(2-methoxy-2-methyl-propyl)-1H-pyrazol-3-yl]-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide

To a solution of (S)-3-cyclopentyl-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionic acid (prepared as in Example 9, 0.1 g, 0.37 mmol) and 1-(2-methoxy-2-methyl-propyl)-1H-pyrazol-3-ylamine (prepared as in US 20080021032, Example 94, 0.065 g, 0.38 mmol) and benzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (0.19 g, 0.44 mmol) in methylene chloride (10 mL) was added N,N-diisopropylethylamine (0.19 mL, 1.10 mmol) and the resulting solution stirred at room temperature for 19 h. The solution was diluted with methylene chloride, washed with a 1 N hydrochloric acid solution (15 mL), a saturated sodium chloride solution, and dried over magnesium sulfate. The mixture was filtered and evaporated and the resulting material purified via automated flash chromatography (Analogix, SF15-40 g column, 50%-70% ethyl acetate/hexanes) to afford (S)-3-cyclopentyl-N-[1-(2-methoxy-2-methyl-propyl)-1H-pyrazol-3-yl]-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide (0.063 g, 0.21 mmol, 41%) as an off white solid; [α0]29D=−47.5° (c=0.28, chloroform); HR-ES(+) m/e calcd for C24H32N4O3 [M+Na]+ 447.2366, observed 447.2368; 1H NMR (300 MHz, DMSO-d6) δ ppm 10.88 (s, 1H), 7.70 (d, J=7.2 Hz, 1H), 7.62 (m, 2H), 7.48 (d, J=2.3 Hz, 1H), 7.45-7.54 (m, 1H), 6.43 (d, J=2.3 Hz, 1H), 5.05 (dd, J=10.7, 5.0 Hz, 1H), 4.87 (d, J=17.8 Hz, 1H), 4.53 (d, J=17.8 Hz, 1H), 3.99 (s, 2H), 3.15 (s, 3H), 1.07 (s, 3H), 1.06 (s, 3H), 0.98-2.10 (m, 11H).

1. washwashed with a 1 N hydrochloric acid solution (15 mL)
2. dry with materiala saturated sodium chloride solution, and dried over magnesium sulfate
3. filtrationThe mixture was filtered
4. customevaporated
5. customthe resulting material purified

ORD 기록

ord-23eadfb3c9894a2f82437de57ad73aa6

출처 데이터셋

uspto-grants-2013_06

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08470866B2