Phenylacetyl isocyanate → 4-[2-(Azetidin-1-yl)ethyl]piperazine-1-carboxylic acid {4-[2-fluoro-4-(3-phenylacetylureido)phenoxy]pyridin-2-yl}amide

To a solution of 4-[2-(azetidin-1-yl)ethyl]piperazine-1-carboxylic acid [4-(4-amino-2-fluorophenoxy)pyridin-2-yl]amide (71 mg) in N,N-dimethylformamide (2 ml) was added a solution of 0.25 M 2-phenylacetyl isocyanate in hexane (2.05 ml) under a nitrogen atmosphere, followed by stirring for 1 hr. The reaction mixture was partitioned between ethyl acetate (100 ml) and a saturated aqueous solution of sodium hydrogencarbonate (50 ml). The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (50 ml), water (50 ml), brine (50 ml) 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; ethyl acetate, then ethyl acetate:methanol=9:1). Fractions containing the target compound were concentrated to give a residue, which was then suspended in diethyl ether (1.5 ml) and hexane (3 ml). The solid was filtered off and dried under aeration to provide the titled compound (63.0 mg, 64.0%) as white powder.

1. customThe reaction mixture was partitioned between ethyl acetate (100 ml)
2. washThe organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (50 ml), water (50 ml), brine (50 ml)
3. dry with materialdried over anhydrous sodium sulfate
4. customThe solvent was evaporated
5. customto give a residue, which
6. customwas then purified by silica gel column chromatography (Fuji Silysia NH, eluent
7. additionFractions containing the target compound
8. concentrationwere concentrated
9. customto give a residue, which
10. filtrationThe solid was filtered off
11. customdried under aeration

ORD-Eintrag

ord-20fdd9d1734b459badc196021a92d26c

Quelldatensatz

uspto-grants-2009_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07531532B2