[C:1]([C:3]1[C:4]([CH2:18][C:19]2[CH:28]=[C:27]3[C:22]([CH:23]=[CH:24][N:25]=[CH:26]3)=[CH:21][CH:20]=2)=[C:5]([C:14]([O:16]C)=[O:15])[S:6][C:7]=1[N:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1)#[N:2].O1CCCC1.[OH-].[Na+].O.CO.C(O)(=O)C>>[C:1]([C:3]1[C:4]([CH2:18][C:19]2[CH:28]=[C:27]3[C:22]([CH:23]=[CH:24][N:25]=[CH:26]3)=[CH:21][CH:20]=2)=[C:5]([C:14]([OH:16])=[O:15])[S:6][C:7]=1[N:8]1[CH2:9][CH2:10][O:11][CH2:12][CH2:13]1)#[N:2]To the solution of methyl 4-cyano-3-(isoquinolin-7-ylmethyl)-5-(morpholin-4-yl)thiophene-2-carboxylate (0.103 g, 0.246 mmol) in tetrahydrofuran (15.0 mL, 185 mmol) was added 1.00 M of sodium hydroxide in water (3.80 mL, 3.80 mmol), followed by water (4.0 mL, 220 mmol) and methanol (4.0 mL, 99 mmol). The homogeneous solution was stirred at room temperature for 18 hours. Acetic acid (270 mg, 4.5 mmol) was added and the mixture was concentrated in rotavapor. The residue was dissolved in DCM-MeOH and then concentrated with celite. The mixture was loaded in a cartridge and chromatographed in a silica gel column using AcOH/MeOH/DCM (0/0/100 to 0.5/4.5/95) to afford a white solid product (56.5 mg, yield 60.3%). LC/MS: (FA) ES+ 380; ES− 378. 1H NMR (400 MHz, d-chloroform) δ 9.23 (s, 1H), 8.45 (d, J=5.77 Hz, 1H), 7.90 (d, J=8.53 Hz, 1H), 7.84 (s, 1H), 7.76 (d, J=5.77 Hz, 1H), 7.65 (dd, J=8.53, 1.76 Hz, 1H), 4.53 (s, 2H), 3.72 (m, 4H), 3.52 (m, 4H).
Loading…
