反应详情

100 mg (0.4 mmol) of the compound from Example 23, 94 mg (0.7 mmol) of N,N-diisopropylethylamine and 95 mg (0.731 mmol) of 3,3-difluoroazetidine hydrochloride are suspended in 3 ml of ethanol and reacted at 120° C. in a single-mode microwave oven (CEM Explorer) for 40 min. The solvent is then removed, and the residue is taken up in 6 ml of DMSO. Undissolved components are removed by filtration, and the solution obtained is purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% TFA). The product-containing fractions are combined and concentrated on a rotary evaporator, and the residue is dried under high vacuum. The residue is then stirred in 5 ml of a 4 N solution of hydrogen chloride in dioxane for 30 min. The solid is filtered off, washed with tert-butyl methyl ether and dried under high vacuum.

1. customreacted at 120° C. in a single-mode microwave oven (CEM Explorer) for 40 min
2. customThe solvent is then removed
3. customUndissolved components are removed by filtration
4. customthe solution obtained
5. customis purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% TFA)
6. concentrationconcentrated on a rotary evaporator
7. customthe residue is dried under high vacuum
8. filtrationThe solid is filtered off
9. washwashed with tert-butyl methyl ether
10. customdried under high vacuum