右旋樟脑磺酸 → 4-[2-(Azetidin-1-yl)ethyl]piperazine-1-carboxylic acid [6-(2-fluoro-4-{3-[2-(4-fluorophenyl)acetyl]thioureido}phenoxy)pyrimidin-4-yl]amide

4-[2-(Azetidin-1-yl)ethyl]piperazine-1-carboxylic acid [6-(4-amino-2-fluorophenoxy)pyrimidin-4-yl]amide (31 mg) was dissolved in ethanol (1 ml) under a nitrogen atmosphere, and then (S)-(+)-10-camphorsulfonic acid (47 mg) was added thereto, followed by stirring for 5 min. A 0.25 M solution of 2-(4-fluorophenyl)acetyl isothiocyanate in toluene (0.448 ml) was added thereto, followed by stirring for 15 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, which was then purified by LC-MS. Fractions containing the target compound were concentrated to give a residue, which was then 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), and dried over anhydrous sodium sulfate. The solvent was evaporated to provide the titled compound (0.9 mg) as a colorless oil.

1. stirringby stirring for 15 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, which
11. customwas then purified by LC-MS
12. additionFractions containing the target compound
13. concentrationwere concentrated
14. customto give a residue, which
15. customwas then partitioned between ethyl acetate (50 ml)
16. washThe organic layer was washed with brine (30 ml)
17. dry with materialdried over anhydrous sodium sulfate
18. customThe solvent was evaporated

ORD记录

ord-12579c2a184a438fb1664454b281e649

来源数据集

uspto-grants-2009_05

DOI

10.6084/m9.figshare.5104873.v1

专利号

US07531532B2