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レコード

ord-cab2c1a2d02f40fd900f65e39b92629a

出典データセット

uspto-grants-2009_11

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07622463B2