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

4-(Pyrrolidin-1-yl)piperidine-1-carboxylic acid [4-(4-amino-3-fluorophenoxy)pyridin-2-yl]amide was dissolved in ethanol (3.0 ml), and then (S)-(+)-10-camphorsulfonic acid (75.5 mg) was added thereto, followed by stirring at room temperature for 15 min. A solution of phenylacetyl isothiocyanate (45.5 mg) in toluene (3.0 ml) was added thereto, followed by stirring at room temperature for 2.5 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 brine (30 ml×3), 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=1:2, ethyl acetate, then ethyl acetate). Fractions containing the target compound were concentrated to give a solid, to which diethyl ether (3 ml) and hexane (3 ml) in this order were then added to suspend. The solid was filtered off, washed with diethyl ether (1 ml), and dried under aeration to provide the titled compound (17.8 mg, 18%) as colorless powder.

1. stirringby stirring at room temperature for 2.5 hrs
2. customThe reaction mixture was partitioned between ethyl acetate (50 ml)
3. washThe organic layer was washed with brine (30 ml×3)
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
10. customto give a solid
11. filtrationThe solid was filtered off
12. washwashed with diethyl ether (1 ml)
13. customdried under aeration

ORDレコード

ord-df71f61b6a3a4969a545c8dcb414d5f3

出典データセット

uspto-grants-2009_05

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07531532B2