반응 #91793

반응 방정식

5-aminomethyl-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride

cyclohexylisocyanate

triethylamine

→

1-cyclohexyl-3-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-urea

수율 77.0%

용매

THF

반응 조건

후처리

1. 1
   온도then cooled to rt
2. 2
   여과The mixture was filtered
3. 3
   workup.ADDITIONthe filtrate diluted with EtOAc (100 mL)
4. 4
   세척The organic layer was washed with dil. aq. HCl (100 mL), water (2×100 mL)
5. 5
   건조dried (MgSO4)
6. 6
   농축concentrated
7. 7
   기타The crude product was purified by prep-HPLC (40/60 CH3CN/H2O)
8. 8
   농축concentrated
9. 9
   기타dried in vacuo

실험 절차

To a stirred mixture of 5-aminomethyl-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride (1.00 g, 3.10 mmol) and cyclohexylisocyanate (0.39 g, 3.10 mmol) in THF (35 mL), was added triethylamine (0.88 mL, 6.20 mmol) at room temperature under nitrogen. The mixture was heated to 40° C. for 18 h then cooled to rt. The mixture was filtered and the filtrate diluted with EtOAc (100 mL). The organic layer was washed with dil. aq. HCl (100 mL), water (2×100 mL), dried (MgSO4) and concentrated. The crude product was purified by prep-HPLC (40/60 CH3CN/H2O). The product fractions were combined, concentrated and dried in vacuo to give 1-cyclohexyl-3-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-urea as a white solid (0.65 g, 77% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 40/60 CH3CN/0.1% H3PO4, 3.16 min (99.05%); mp: 208-210° C.; 1H NMR (DMSO-d6) δ 1.01-1.36 (m, 5H), 1.46-1.83 (m, 5H), 2.00-2.14 (m, 1H), 2.53-2.66 (m, 2H), 2.79-3.01 (m, 1H), 3.34-3.44 (m, 1H), 4.36 (d, J=6.0 Hz, 2H), 5.14 (dd, J=5.3, 12.8 Hz, 1H), 6.00 (d, J=7.9 Hz, 1H), 6.42 (t, J=5.9 Hz, 1H), 7.67-7.79 (m, 2H), 7.87 (d, J=7.6 Hz, 1H), 11.12 (s, 1H); 13C NMR (DMSO-d6) δ 22.01, 24.50, 25.27, 30.93, 33.23, 42.67, 47.97, 48.97, 121.54, 123.39, 129.50, 131.53, 133.07, 149.49, 157.28, 167.05, 167.22, 169.83, 172.73; LCMS: MH=413; Anal Calcd for C21H24N4O5+0.2H2O: C, 60.76; H, 5.90; N, 13.47. Found: C, 60.61; H, 5.74; N, 13.31.

출처