Tetrahydrofuran → 8-Chloro-6-Cyclopentyl-4,4-dimethyl-5,6-dihydro-4H-2,3,6,7,9,10b-hexaazabenzo[e]azulene

2-Chloro-9-cyclopentyl-8,9-dihydro-7,7-dimethyl-5H-pyrimido[4,5-b][1,4]diazepin-6(7H)-one (0.21 g, 0.73 mmol) in phosphorus oxychloride (6 ml) was heated at 110° C. for 4 hours. The reaction mixture was concentrated in vacuo and redissolved in dichloromethane (4 ml). This latest solution was then added dropwise to a 1M solution of hydrazine in tetrahydrofuran (7.27 ml, 7.27 mmol). The reaction mixture was stirred overnight at room temperature. A saturated solution of NaHCO3 was added and the mixture was extracted with ethyl acetate. The organic layer was dried (MgSO4), filtered and concentrated in vacuo. The resulting mixture was dissolved in trimethylorthoformate (4 ml) and heated to 110° C. for 90 minutes. The reactionnel mixture was evaporated in vacuo and purified by silica gel chromatography eluting with ethyl acetate to give the title compound as an off-white solid (0.16 g, 69% yield). NMR DMSO D6 1.37 (6H, s), 1.52-1.88 (8H, m), 3.44 (2H, s), 5.23 (1H, quint.), 8.56 (1H, s), 9.02 (1H, s); MS (ES+) 319.

1. concentrationThe reaction mixture was concentrated in vacuo
2. dissolutionredissolved in dichloromethane (4 ml)
3. extractionthe mixture was extracted with ethyl acetate
4. dry with materialThe organic layer was dried (MgSO4)
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. dissolutionThe resulting mixture was dissolved in trimethylorthoformate (4 ml)
8. temperatureheated to 110° C. for 90 minutes
9. customThe reactionnel mixture was evaporated in vacuo
10. custompurified by silica gel chromatography
11. washeluting with ethyl acetate

ORD 기록

ord-8e6a26a5cc784782bfa2e175c50d8a1d

출처 데이터셋

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08394952B2