反应详情

温度

115 °C

In a round-bottomed flask fitted with a cold finger condenser, phenol (0.569 g, 6 mmol) and 7-methoxynaphthalene-2-sulfonic acid [1-(1-chloro-isoquinolin-7-ylmethyl)-2-oxopyrrolidin-3-(S)-yl]-amide (0.2 g, 0.4 mmol) is melted at 70° C. The mixture is stirred for 5 minutes, then ammonium acetate (0.462 g, 6 mmol) is added and heated at 115° C. for 2 hours. After this time, additional ammonium acetate (0.462 g, 6 mmol) is added. After 2 hours the reaction mixture is cooled to room temperature then partitioned between EtOAc and 0.5N NaOH. The organic layer is separated and washed with water and brine, then dried over Na2SO4, filtered and concentrated. The resulting residue is partially purified by RP-HPLC eluting with a gradient of 10% CH3CN/H2O (0.1% TFA) to 100% CH3CN. The appropriate fractions are concentrated in vacuo. The solid which precipitates out from the solution is then filtered, dried and purified again by column chromatography eluting with 5% MeOH/CH2Cl2. This product is then triturated with cold MeOH and the collected solid is suspended in MeOH and cooled to 0° C. HCl(g) is bubbled through the slurry for a few minutes during which time all the solid dissolves into the solution. The solvent is removed in vacuo and the title product (0.11 g, 0.214 mmol) is washed with ether and dried.

1. customIn a round-bottomed flask fitted with a cold finger condenser
2. temperatureAfter 2 hours the reaction mixture is cooled to room temperature
3. customthen partitioned between EtOAc and 0.5N NaOH
4. customThe organic layer is separated
5. washwashed with water and brine
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated
9. customThe resulting residue is partially purified by RP-HPLC
10. washeluting with a gradient of 10% CH3CN/H2O (0.1% TFA) to 100% CH3CN
11. concentrationThe appropriate fractions are concentrated in vacuo
12. customThe solid which precipitates out from the solution
13. filtrationis then filtered
14. customdried
15. custompurified again by column chromatography
16. washeluting with 5% MeOH/CH2Cl2
17. customThis product is then triturated with cold MeOH
18. temperaturecooled to 0° C
19. customHCl(g) is bubbled through the slurry for a few minutes during which time all the solid
20. dissolutiondissolves into the solution
21. customThe solvent is removed in vacuo