Diethyl Ether → 4-[2-(Azetidin-1-yl)ethyl]piperazine-1-carboxylic acid {4-[2-fluoro-4-(3-phenylacetylthioureido)phenoxy]pyridin-2-yl}amide

4-[2-(Azetidin-1-yl)ethyl]piperazine-1-carboxylic acid [4-(4-amino-2-fluorophenoxy)pyridin-2-yl]amide (60 mg) was dissolved in ethanol (1.5 ml) under a nitrogen atmosphere, and then (S)-(+)-10-camphorsulfonic acid (101 mg) was added thereto, followed by stirring for 5 min. A 0.25 M solution of phenylacetyl isothiocyanate in toluene (0.87 ml) was added thereto, followed by stirring for 13 hrs. The reaction mixture was partitioned between ethyl acetate (50 ml) and a saturated aqueous solution of sodium hydrogencarbonate (30 ml). The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (30 ml), water (30 ml), brine (30 ml) in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, which was then purified by silica gel column chromatography (FUJI Silysia NH, eluent; heptane:ethyl acetate=1:8, ethyl acetate, then ethyl acetate:ethanol=95:5). Fractions containing the target compound were concentrated under reduced pressure to give a residue, to which diethyl ether (2 ml) and hexane (2 ml) were then added to suspend. The solid was filtered off, and dried under aeration to provide the titled compound (37.2 mg, 43.3%) as white powder.

1. stirringby stirring for 13 hrs
2. customThe reaction mixture was partitioned between ethyl acetate (50 ml)
3. washThe organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (30 ml), water (30 ml), brine (30 ml) in this order
4. dry with materialdried over anhydrous sodium sulfate
5. customThe solvent was evaporated
6. customto give a residue, which
7. customwas then purified by silica gel column chromatography (FUJI Silysia NH, eluent
8. additionFractions containing the target compound
9. concentrationwere concentrated under reduced pressure
10. customto give a residue
11. filtrationThe solid was filtered off
12. customdried under aeration

ORDレコード

ord-dcffabb5062d4d61b544ea7d7cc39498

出典データセット

uspto-grants-2009_05

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07531532B2