Diisopropylethylamine → (S)-4-methyl-2-[4-(naphthalen-1-yloxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-amide

온도

25 °C

A solution of (S)-4-methyl-2-[4-(naphthalen-1-yloxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-pentanoic acid (0.37 g, 1.11 mmol) in N,N-dimethylformamide (4.27 mL) at 25° C. was treated with N,N-diisopropylethylamine (0.55 mL, 3.33 mmol), (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (0.73 g, 1.66 mmol) and a solution of 1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-ylamine (prepared as in Example 49, 0.24 g, 1.22 mmol) in N,N-dimethylformamide (0.5 mL). The reaction was stirred at 25° C. overnight. At this time, the reaction was diluted with ethyl acetate (75 mL) and was washed with a saturated aqueous ammonium chloride solution (1×150 mL), a saturated aqueous sodium bicarbonate solution (1×150 mL) and a saturated aqueous sodium chloride solution (1×150 mL), dried over sodium sulfate, filtered and concentrated in vacuo. Purification by Analogix flash chromatography (40 g, 10-30% ethyl acetate/hexanes) afforded (S)-4-methyl-2-[4-(naphthalen-1-yloxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-amide (0.43 g, 76%) as a light orange solid: HR-ES-MS m/z calculated for C29H34N4O5 [M+H]+ 519.2602, observed 519.2604; 1H NMR (300 MHz, DMSO-d6) δ ppm 0.91 (d, J=6.3 Hz, 3H), 0.96 (d, J=6.3 Hz, 3H), 1.25 (s, 3H), 1.30 (s, 3H), 1.41-1.69 (m, 2H), 1.70-1.85 (m, 1H), 3.74 (dd, J=8.3, 5.9 Hz, 1H), 4.00 (dd, J=8.3, 6.5 Hz, 1H), 4.11 (t, J=5.6 Hz, 2H), 4.28-4.44 (m, 2H), 4.65-4.77 (m, 2H), 4.90 (dd, J=10.4, 4.7 Hz, 1H), 6.46 (d, J=2.1 Hz, 1H), 7.51 (d, J=7.2 Hz, 1H), 7.54-7.67 (m, 4H), 7.91 (d, J=8.2 Hz, 1H), 7.99-8.09 (m, 2H), 10.80 (s, 1H).

1. washwas washed with a saturated aqueous ammonium chloride solution (1×150 mL)
2. dry with materiala saturated aqueous sodium bicarbonate solution (1×150 mL) and a saturated aqueous sodium chloride solution (1×150 mL), dried over sodium sulfate
3. filtrationfiltered
4. concentrationconcentrated in vacuo
5. customPurification by Analogix flash chromatography (40 g, 10-30% ethyl acetate/hexanes)

ORD 기록

ord-8efa5c322b334191bb1cbc471b290607

출처 데이터셋

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07741327B2