反应详情

温度

170 °C

Dibromomaleic anhydride (108 mg, 0.42 mmol, 1 eq) was added in one portion to a solution of 2-(2-(2-(5-(2-oxo-1,3,3a,4,6,6a-hexahydrothieno(3,4-d)imidazol-6-yl)pentanoylamino)ethoxy)ethoxy)ethylammonium 2,2,2-trifluoroacetate (205 mg, 0.42 mmol, 1 eq) in AcOH (10 mL) and the reaction mixture heated to 170° C. for 2 h. Upon cooling to 21° C. toluene was added and the AcOH azeotropically removed in vacuo (×2) to give crude product. Column chromatography (gradient 2-7% MeOH/CH2Cl2) yielded the desired compound as a white solid (123 mg, 0.20 mmol, 48% yield). m.p. 100-102° C.; [α]D20.0+71.0 (c 0.15, MeOH); 1H NMR (600 MHz, CD3OD) δ 4.53 (dd, J=5.0, 8.0 Hz, 1H, NHC(O)NHCH), 4.34 (dd, J=5.0, 8.0 Hz, 1H, NHC(O)NHCH), 3.82 (t, J=5.5 Hz, 2H, OCH2), 3.70 (t, J=5.5 Hz, 2H, OCH2), 3.63 (m, 2H, OCH2), 3.59 (m, 2H, OCH2), 3.53 (t, J=5.5 Hz, 2H, NCH2), 3.37 (t, J=5.5 Hz, 2H, NCH2), 3.24 (dt, J=5.0, 8.0 Hz, 1H, SCH), 2.96 (dd, J=5.0, 13.0 Hz, 1H, SCHH), 2.73 (d, J=13.0 Hz, 1H, SCHH), 2.26 (t, J=7.5 Hz, 2H, NHC(O)CH2CH2CH2), 1.74 (m, 4H, CH2CH2CH2), 1.49 (quintet, J=7.5 Hz, 2H, CH2CH2CH2); 13C NMR (150 MHz, CD3OD) δ 174.83 (s), 164.71 (s), 164.06 (s), 129.00 (s), 69.80 (t), 69.72 (t), 69.24 (t), 67.19 (t), 61.97 (d), 60.22 (d), 55.64 (d), 39.67 (t), 39.03 (t), 38.56 (t), 35.42 (t), 28.39 (t), 28.11 (t), 25.47 (t); IR (MeOH) 2970, 1724, 1365, 1217 cm−1; HRMS (ES) calcd for C20H28N4O6NaSBr2 [M+Na]+ 631.9916, observed 631.9937.

1. additionwas added
2. customthe AcOH azeotropically removed in vacuo (×2)
3. customto give crude product