反应详情

The title compound 2-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-5-(3-(isoquinolin-6-yloxy)propyl)thiazole-4-carboxylic acid (8) was prepared by the following procedure: To a solution of methyl 2-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-5-(3-(tosyloxy)propyl)thiazole-4-carboxylate (8F) (133 mg, 0.2 mmol) and 5-hydroxyisoquinoline (45 mg, 0.3 mmol) in DMA (3 mL) was added Cs2CO3 (50 mg, 0.3 mmol). The mixture was stirred at rt overnight and was diluted with 2N NaOH (4 mL) and stirred at 50° C. for 4 hours. The reaction mixture was neutralized with 5% HCl and the precipitate was filtered and dried. The residue was then dissolved in DMSO/MeOH (1:1) and purified by column chromatography on silica gel to provide the desired product 2-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-5-(3-(isoquinolin-6-yloxy)propyl)thiazole-4-carboxylic acid (8): 1H NMR (300 MHz, DMSO-D6) δ ppm 9.16 (1H, s), 8.34 (1H, d), 7.94 (1H, d), 7.85 (1H, d), 7.71 (4H, m), 7.38 (8H, m), 4.88 (2H, s), 4.14 (2H, t), 3.71 (2H, t), 3.00 (2H, t), 2.27 (1H, m), 2.09 (2H, m). LC/MS (APCI): m/z 622.2 (M+H).

1. customThe title compound 2-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-5-(3-(isoquinolin-6-yloxy)propyl)thiazole-4-carboxylic acid (8) was prepared by the following procedure
2. stirringstirred at 50° C. for 4 hours
3. filtrationthe precipitate was filtered
4. customdried
5. dissolutionThe residue was then dissolved in DMSO/MeOH (1:1)
6. custompurified by column chromatography on silica gel