反应详情

A solution of (3Z)-1-cyclopropyl-4-(dimethylamino)-3-[2-(methylsulfanyl)pyrimidin-4-yl]but-3-en-2-one (3) (810 mg, 2.92 mmol), N-methylguanidine (480 mg, 4.38 mmol), and K2CO3 (1211 mg, 8.76 mmol) in DMF (28 mL) was stirred at 120° C. for 2 hours, followed by stifling at rt for 18 hours. The reaction was partitioned between water and EtOAc. The organic layer was separated, and the aqueous layer was back-extracted. The organic extracts were combined, washed with brine, dried over sodium sulfate, then concentrated in vacuo. The crude product was purified by Biotage™ silica gel chromatography [100 g SNAP column, 30% EtOAc/heptane to 100% EtOAc] to afford the desired product as a white solid (720 g, 86% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 0.12 (br. s., 2 H) 0.37 (d, J=7.07 Hz, 2 H) 1.07 (br. s., 1 H) 2.81 (d, J=6.57 Hz, 2H) 2.87 (d, J=5.05 Hz, 3 H) 7.39 (d, J=5.05 Hz, 1 H) 7.49 (br. s., 1 H) 8.49 (br. s., 1 H) 8.60 (d, J=5.05 Hz, 1 H). MS (ES+): m/z=288.2/289.2/290.2 (100/20/10) [MH+]. HPLC: tR=1.28 minutes over 3 minutes. Purity: 100% [HPLC (LC/MS) at 220 nm].

1. customThe reaction was partitioned between water and EtOAc
2. customThe organic layer was separated
3. extractionthe aqueous layer was back-extracted
4. washwashed with brine
5. dry with materialdried over sodium sulfate
6. concentrationconcentrated in vacuo
7. customThe crude product was purified by Biotage™ silica gel chromatography [100 g SNAP column, 30% EtOAc/heptane to 100% EtOAc]