反应详情

Hydroxybenzotriazole hydrate (60 mg, 0.44 mmol) and WSCDl.HCl (93 mg, 0.47 mmol) were added to a solution of 2-[3-[(3-{[(2-methoxyethyl)(2,2,2-trifluoroacetyl)amino]methyl}phenethyl)amino]-6-methyl-2-oxo-1(2H)-pyrazinyl]acetic acid (190 mg, 0.40 mmol) [see preparation 44] in N,N-dimethylformamide (3.0 ml). N-methylmorpholine (123 mg, 1.2 mmol) was added followed by (3-methyl-1H-indol-5-yl)methylamine (72 mg, 0.45 mmol) [see preparation 36]. The reaction mixture was stirred at room temperature for 18 hrs, after which time the mixture was partitioned between ethyl acetate (30 ml) and water (30 ml). The organic layer was washed with water (3×30 ml), brine (30 ml) and dried over MgSO4 and the solvent evaporated under reduced pressure. The crude product was purified by column chromatography on silica gel using an elution gradient of dichloromethane:methanol:0.88 ammonia (99:1:0.1) changing to (98:2:0.2) to afford the title compound as a oil, 113 mg (53%).

1. customafter which time the mixture was partitioned between ethyl acetate (30 ml) and water (30 ml)
2. washThe organic layer was washed with water (3×30 ml), brine (30 ml)
3. dry with materialdried over MgSO4
4. customthe solvent evaporated under reduced pressure
5. customThe crude product was purified by column chromatography on silica gel using an elution gradient of dichloromethane