反应详情

A solution of 0.100 g (0.20 mmol) of 1-[(E)-3-(3,4-dichloro-phenyl)-acryloyl]-4-(4-iodo-butyl)-[1,4]diazepan-5-one (example 9B) in 3.1 ml of DMA was treated with free methyl-(tetrahydro-pyran-4-yl)-amine in 1 ml of toluene [0.035 g (0.22 mmol) methyl-(tetrahydro-pyran-4-yl)-amine hydrochloride were dissolved in 0.8 ml of 0.5 N NaOH was extracted with toluene (2 ml). The organic phase was dried over Na2SO4] and stirred for 22 h at RT, 0.06 ml (0.40 mmol) of Et3N was added and stirring was continued for 18 h at 50° C. Again methyl-(tetrahydro-pyran-4-yl)-amine in 1 ml of CH2Cl2 [0.035 g (0.22 mmol) methyl-(tetrahydro-pyran-4-yl)-amine hydrochloridewere dissolved in 0.5 ml aqueous 10% NaCl solution/0.4 ml of 1 N NaOH was extracted with CH2Cl2 (1 ml). The organic phase was dried over Na2SO4] was added and heated for 9 h at 50° C. The reaction was extracted with aqueous saturated NaHCO3/Et2O (3×). The organic phases were washed with aqueous 10% NaCl, dried (Na2SO4), concentrated and evaporated. Purification by catridges, Si-Amine, 70 ml, 20 g (n-heptane/EtOAc 1:4 to 1:9) gave 0.004 g (4%) of the title compound as a light yellow semisolid. MS: 482.3 (MH+, 2Cl).

1. extractionwas extracted with toluene (2 ml)
2. dry with materialThe organic phase was dried over Na2SO4] and
3. stirringstirring
4. waitwas continued for 18 h at 50° C
5. extractionwas extracted with CH2Cl2 (1 ml)
6. dry with materialThe organic phase was dried over Na2SO4]
7. additionwas added
8. temperatureheated for 9 h at 50° C
9. extractionThe reaction was extracted with aqueous saturated NaHCO3/Et2O (3×)
10. washThe organic phases were washed with aqueous 10% NaCl
11. dry with materialdried (Na2SO4)
12. concentrationconcentrated
13. customevaporated
14. customPurification by catridges, Si-Amine, 70 ml, 20 g (n-heptane/EtOAc 1:4 to 1:9)