反应详情

To a solution of 2,4-dichloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine, (Preparation S, 3.56 g, 12.57 mmol) in DME (Volume: 84 mL) at −78° C. was added KHMDS (0.91 M in THF, 15.20 ml, 13.83 mmol) dropwise. After 10 min, Met (2.36 mL, 37.7 mmol) was added. The reaction was kept at −78° C. for 10 min, then allowed to come to rt. An aliquot taken while the reaction was still cool was quenched with water and extracted with EtOAc. TLC (10% EtOAc/Hex) and LC/MS showed the clean conversion to a new product. The bulk of the material was then quenched and extracted as above. The combined organic extracts were dried over MgSO4, filtered, and the solvent removed in vacuo. SG chromatography (0 to 40% EtOAc/Hex) gave 2,4-dichloro-7-(4-fluorophenyl)-7-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine (3.01 g, 10.13 mmol, 81% yield). LC-MS (*M*+H)+=293.1 (*product reacts with methanol during analysis*). 1H NMR (500 MHz, CDCl3) δ ppm 7.21-7.29 (2H, m), 6.96-7.04 (2H, m), 2.88-3.02 (2H, m), 2.62 (1H, ddd, J=13.28, 7.93, 5.04 Hz), 2.26-2.35 (1H, m), 1.68 (3H, s).

1. waitThe reaction was kept at −78° C. for 10 min
2. customto come to rt
3. temperaturewas still cool
4. customwas quenched with water
5. extractionextracted with EtOAc
6. customThe bulk of the material was then quenched
7. extractionextracted as above
8. dry with materialThe combined organic extracts were dried over MgSO4
9. filtrationfiltered
10. customthe solvent removed in vacuo