反应详情

温度

20 °C

N-[2-(2-Isobutyl-5-isopropoxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl)-acetyl]-guanidine is prepared as described in Example 9, starting with 20 cm3 of absolute ethanol, 0.086 g of sodium, 0.36 g of guanidinium chloride and 0.42 g of ethyl (5-isopropyloxy-2-isobutyl-3-oxo-2,3-dihydro-1H-isoindol-1-yl)acetate. The reaction mixture is stirred at a temperature in the region of 20° C. for 18 hours and then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The residue is then taken up in 50 cm3 of ethyl acetate and the organic phase is washed twice with 30 cm3 of aqueous 1 N sodium hydroxide solution and then twice with 50 cm3 of aqueous 1N hydrochloric acid solution. The acidic aqueous phase is treated with aqueous 30% sodium hydroxide solution to pH 14, and then extracted with 3 times 30 cm3 of ethyl acetate. The organic extracts are combined, washed with 50 cm3 of saturated brine, dried over magnesium sulfate and concentrated under reduced pressure (2 kPa) at a temperature in the region of 40° C. The residue is triturated with diethyl ether and then filtered and dried in a desiccator under reduced pressure (2 Pa) at a temperature in the region of 40° C. for 2 hours. 0.0175 g of N-[2-(2-Isobutyl-5-isopropoxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl)-acetyl]-guanidine is thus obtained in the form of a white powder melting at 208° C. 1H NMR (300 MHz, d6-(CD3)2SO, δ in ppm): 0.75 (d, J=6.5 Hz: 3H); 0.90 (d, J=6.5 Hz: 3H); 1.30 (mt: 6H); 2.01 (mt: 1H); 2.40 (dd, J=15 and 6.5 Hz: 1H); 2.65 (dd, J=15 and 6.5 Hz: 1H); 3.00 (dd, J=13.5 and 5.5 Hz: 1H); 3.53 (dd, J=13.5 and 10 Hz: 1H) 4.68 (mt: 1H); 4.96 (broad t, J=6.5 Hz: 1H); from 6.40 to 7.10 (broad multiplet: 2H); 6.98 (dd, J=8.5 and 2 Hz: 1H); 7.09 (d, J=2 Hz: 1H); 7.54 (d, J=8.5 Hz: 1H); from 7.60 to 8.20 (broad multiplet: 2H).

1. customN-[2-(2-Isobutyl-5-isopropoxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl)-acetyl]-guanidine is prepared
2. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C
3. washthe organic phase is washed twice with 30 cm3 of aqueous 1 N sodium hydroxide solution
4. additionThe acidic aqueous phase is treated with aqueous 30% sodium hydroxide solution to pH 14
5. extractionextracted with 3 times 30 cm3 of ethyl acetate
6. washwashed with 50 cm3 of saturated brine
7. dry with materialdried over magnesium sulfate
8. concentrationconcentrated under reduced pressure (2 kPa) at a temperature in the region of 40° C
9. customThe residue is triturated with diethyl ether
10. filtrationfiltered
11. customdried in a desiccator under reduced pressure (2 Pa) at a temperature in the region of 40° C. for 2 hours