反应详情

To a solution of tert-butyl ((S)-2-(4-chlorophenyl)-3-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-oxopropyl)(isopropyl)carbamate (50 g) in 1-propanol (128 g) was added HCl in 1-propanol (45.2 g, 5.5N). The solution was heated until complete deprotection. The solution was cooled to room temperature and then a solution of piperazine (7.3 g) in 1-propanol (36.5 g) was added dropwise. The resulting solid piperazine.HCl was filtered off and the filtrate was carbon treated, concentrated and solvent-switched to ethyl acetate. The resulting solid (S)-2-(4-chlorophenyl)-1-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-(isopropylamino)propan-1-one monohydrochloride was filtered and washed with ethyl acetate and dried under vacuum (Yield 22.9 g, 99.8% purity by LC).

1. temperatureThe solution was heated until complete deprotection
2. filtrationHCl was filtered off
3. additiontreated
4. concentrationconcentrated
5. filtrationThe resulting solid (S)-2-(4-chlorophenyl)-1-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-(isopropylamino)propan-1-one monohydrochloride was filtered
6. washwashed with ethyl acetate
7. customdried under vacuum (Yield 22.9 g, 99.8% purity by LC)