Cyclopropylamine → (2R,3R,4S,5R)-2-[5,6-dichloro-2-(cyclopropylamino)benzimidazol-1-yl]-5-methyl-tetrahydrofuran-3,4-diol
反応式
[Cl:1][C:2]1[C:22]([Cl:23])=[CH:21][C:5]2[N:6]([C@@H:13]3[O:19][C@H:18]([CH3:20])[C@@H:16]([OH:17])[C@H:14]3[OH:15])[C:7](OC(C)C)=[N:8][C:4]=2[CH:3]=1.[CH:24]1([NH2:27])[CH2:26][CH2:25]1>C1COCC1>[CH:24]1([NH:27][C:7]2[N:6]([C@@H:13]3[O:19][C@H:18]([CH3:20])[C@@H:16]([OH:17])[C@H:14]3[OH:15])[C:5]3[CH:21]=[C:22]([Cl:23])[C:2]([Cl:1])=[CH:3][C:4]=3[N:8]=2)[CH2:26][CH2:25]1参加物
4
実験手順
A mixture of 5 (0.422 g, 1 mmol) and cyclopropylamine (0.694 mL, 10 mmol) in THF (10 mL) was stirred at room temperature for 18 days (with the addition of 0.694 mL of fresh cyclopropylamine on the 9th day). Volatile materials were removed by evaporation and the residue was treated with NH3/MeOH (15 mL, sat. at 0° C.) at room temperature for 18 h. The reaction mixture was again evaporated and the residue was chromatographed on a silica column (2×15 cm, eluted successively with CHCl3, 4%, 8% MeOH/CHCL3, v/v). Evaporation of fractions 23˜35 (15 mL per fraction) and recrystallization from MeCN gave 0.296 g (83%) of 6 as white crystals. MP: ˜210° C. (dec). HRMS: (EI, with DCI probe) m/z 357.0645 (51%, M+=357.0647). 1H NMR (DMSO-d-6): δ7.48 (s, 1, 4-H), 7.35 (s,1,7-H), 7.14 (d, 1,2′-NH—, J2′NH-1Cp=2 Hz), 5.62 (d, 1,1′-H, J1′-2′=6.5 Hz), 5.26 (d, 1,3′-OH, J3′-3′OH=4.5 Hz), 5.23 (d,1, 2′-OH, J2′-2′OH′=7.0 Hz),4.33 (m, 1,2′-H, J2′-3′=5.5 Hz), 3.90 (m, 1,4′H, J4′-3′=4.5 Hz, J4′-5′=6.5 hz), 3.79 (m, 1, 3′-HO, 2.76 (m, 1,1,-Cp), 1.37 (d, 3,5′-H), 0.71, 0.53 (2×m, 4, 2-Cp and 3-Cp). 13C NMR (DMSO-d-6): δ156.68 (C2), 143.53 (C3a), 132.05 (C7a), 123.27, 120.22 (C5 and C6), 116.38 (C4), 111.05 (C7), 87.56 (C1′), 80.00 (C4′), 73.65 (C3′), 70.85 (C2′), 25.17 (1-Cp), 18.93 (C5″) 6.49, 6.15 (2-Cp and 3-Cp). Anal. Calcd. for C15H17Cl2N3O3: C, 50.29, H, 4.78, N, 11.73. Found C, 50.42, H, 5.00, N, 11.99.