反应详情

After dissolving 4-[2-(pyrrolidin-1-yl)ethyl]piperazine-1-carboxylic acid [6-(4-amino-2-fluorophenoxy)pyrimidin-4-yl]amide (49 mg) in ethanol (2 ml) under a nitrogen atmosphere, D-10-camphorsulfonic acid (53 mg) was added and the mixture was stirred for 5 minutes. A 0.25 M solution of 2-phenylacetyl isothiocyanate in toluene (0.684 ml) was added to the reaction mixture and stirring was carried out for 1 hour. The reaction mixture was partitioned between ethyl acetate (50 ml) and saturated aqueous sodium hydrogencarbonate (30 ml). The organic layer was washed with saturated aqueous sodium hydrogencarbonate (30 ml), water (30 ml) and brine (30 ml) in that order and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and then the resultant residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; heptane:ethyl acetate=1:8). Fractions containing the target compound were concentrated under reduced pressure, and then diethyl ether (1.0 ml) and hexane (1.5 ml) were added to the resultant residue to produce a suspension of the solid. After filtering the solid, it was subjected to aeration drying to provide the title compound (5.8 mg, 8.4%) as white powder.

1. stirringstirring
2. waitwas carried out for 1 hour
3. customThe reaction mixture was partitioned between ethyl acetate (50 ml) and saturated aqueous sodium hydrogencarbonate (30 ml)
4. washThe organic layer was washed with saturated aqueous sodium hydrogencarbonate (30 ml), water (30 ml) and brine (30 ml) in that order
5. dry with materialdried over anhydrous sodium sulfate
6. distillationThe solvent was distilled off under reduced pressure
7. customthe resultant residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; heptane:ethyl acetate=1:8)
8. additionFractions containing the target compound
9. concentrationwere concentrated under reduced pressure
10. additiondiethyl ether (1.0 ml) and hexane (1.5 ml) were added to the resultant residue
11. customto produce
12. additiona suspension of the solid
13. filtrationAfter filtering the solid, it
14. customdrying