Diethyl Ether → 4-(Pyrrolidin-1-ylmethyl)piperidine-1-carboxylic acid {6-[2-fluoro-4-(3-phenylacetylthioureido)phenoxy]pyrimidin-4-yl}amide

4-(Pyrrolidin-1-ylmethyl)piperidine-1-carboxylic acid [6-(4-amino-2-fluorophenoxy)pyrimidin-4-yl]amide (100 mg) was dissolved in ethanol (1.0 ml) under a nitrogen atmosphere, and then (S)-(+)-10-camphorsulfonic acid (56 mg) was added thereto, followed by for stirring 5 min. A 0.25 M solution of phenylacetyl isothiocyanate in toluene (1.45 ml) was added thereto, followed by stirring for 1 hr. The reaction mixture was partitioned between ethyl acetate (30 ml) and a saturated aqueous solution of sodium hydrogencarbonate (20 ml). The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (20 ml), water (20 ml), brine (20 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=1:3). Fractions containing the target compound were concentrated to give a residue, to which diethyl ether (1.5 ml) and hexane (2.0 ml) in this order were then added to suspend. The solid was filtered off, and dried under aeration to provide the titled compound (37.6 mg, 26.4%) as pale yellow powder.

1. stirringby stirring for 1 hr
2. customThe reaction mixture was partitioned between ethyl acetate (30 ml)
3. washThe organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (20 ml), water (20 ml), brine (20 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; heptane:ethyl acetate=1:3)
8. additionFractions containing the target compound
9. concentrationwere concentrated
10. customto give a residue
11. filtrationThe solid was filtered off
12. customdried under aeration

ORD 기록

ord-d0166fa42e434658a930f4212d7e0d53

출처 데이터셋

uspto-grants-2009_05

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07531532B2