反应详情

A solution of 4-methyl-3-morpholinecarboxylic acid hydrochloride (Chem-Impex International) (60.0 mg, 0.33 mmol) in acetonitrile (2 mL) was treated with HATU (126 mg, 0.33 mmol) and DIPEA (0.157 ml, 0.901 mmol). The resulting mixture was stirred for 15 min at ambient temperature and then N-[1-{[3-(aminomethyl)phenyl]methyl}-4-(methyloxy)-1H-indazol-3-yl]-5-chloro-2-thiophenesulfonamide hydrochloride (for a preparation see Intermediate 4) (150 mg, 0.300 mmol) was added, and the resulting mixture was stirred at ambient temperature for 1 h. The reaction mixture was diluted with DCM (3 mL) and water (3 mL). Organic phase was separated and the aqueous layer was further extracted with 3 mL of DCM. The combined organic solutions were washed with water (3 mL), dried through an hydrophobic frit and concentrated in a nitrogen blow-down apparatus. The residue was dissolved in 1:1 MeOH-DMSO 2 mL and purified by Mass Directed AutoPrep (Method C) on Xbridge column using acetonitrile water with an ammonium carbonate modifier. The solvent was evaporated under reduced pressure to give the required product (53.1 mg, 30%). LCMS (System F) RT=0.85 min, ES+ve m/z 590/592 (M+H)+.

1. additionwas added
2. stirringthe resulting mixture was stirred at ambient temperature for 1 h
3. customOrganic phase was separated
4. extractionthe aqueous layer was further extracted with 3 mL of DCM
5. washThe combined organic solutions were washed with water (3 mL)
6. customdried through an hydrophobic frit
7. concentrationconcentrated in a nitrogen blow-down apparatus
8. dissolutionThe residue was dissolved in 1:1 MeOH-DMSO 2 mL
9. custompurified by Mass Directed AutoPrep (Method C) on Xbridge column
10. customThe solvent was evaporated under reduced pressure