反应详情

温度

40 °C

Silver trifluoromethanesulphonate (22.69 mg, 0.09 mmol) was added to a solution of (3R)-3-amino-1-methyl-3-[3-[4-methyl-6-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]prop-2-ynyl]pyrrolidin-2-one (which may be prepared as described in Description 14) (343 mg, 0.88 mmol) in MeCN (20 mL) at 20° C. and the reaction was stirred for 18 hrs. The reaction was heated to 40° C. and stirring was continued for 3 days. Additional AgOTf (10 mol %) was added and stirring was continued at 40° C. for 18 hrs. The solvent was evaporated and the residue was purified using a Biotage Isolera with a 25 g SNAP cartridge, eluting with 0 to 100% (mixture of 1% of 2M NH3 in MeOH; 9% MeOH; 90% EtOAc)/EtOAc affording (5R)-7-methyl-2-[4-methyl-6-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]non-1-en-6-one (D15) (359 mg, 0.924 mmol) as a light brown solid with a few % of impurities present. 300 MHz NMR δH (CDCl3) 1.89-2.00 (1H, m), 2.16-2.25 (1H, m), 2.59-2.72 (2H, m), 2.72 (3H, s), 2.92 (3H, s), 3.30-3.45 (2H, m), 3.55-3.78 (2H, m), 7.64 (1H, s), 7.79 (2H, d), 8.26 (2H, d).

1. stirringstirring
2. waitwas continued for 3 days
3. stirringstirring
4. waitwas continued at 40° C. for 18 hrs
5. customThe solvent was evaporated
6. customthe residue was purified
7. washeluting with 0 to 100% (mixture of 1% of 2M NH3 in MeOH; 9% MeOH; 90% EtOAc)/EtOAc