Cesium carbonate → (NZ,3R)-N-[3-(3,5-dichlorophenyl)-5-(hydroxymethyl)-1,3-thiazol-2-ylidene]-3-fluoropyrrolidine-1-carboxamide

In a 4 mL vial charged with a stir bar, (3R)-3-fluoro-N-[5-(hydroxymethyl)-1,3-thiazol-2-yl]pyrrolidine-1-carboxamide (43 mg, 0.18 mmol, Example 36B) was added followed by copper iodide (8 mg, 0.04 mmol) and cesium carbonate (88 mg, 0.27 mmol). A loose cap with septum was placed on the vial and then the vial was placed under vacuum for 30 minutes. The solid mixture was purged with nitrogen gas a couple of times. Then ethyl 2-cyclohexanecarboxylate (12 mg, 0.07 mmol) dissolved in dry dimethyl sulfoxide (0.4 mL) was added to the mixture followed by 1,3-dichloro-5-iodobenzene (60 mg, 0.22 mmol) dissolved in dry dimethyl sulfoxide (0.7 mL). The vial was capped and the resulting mixture was shaken at room temperature for 1 hour followed by shaking at 95° C. overnight. Then 1 mL of concentrated ammonium hydroxide solution was added. The reaction was filtered and concentrated to dryness. The residue was purified by reverse phase HPLC (C18, gradient 10-95% acetonitrile/water/0.1% trifluoroacetic acid) to provide the title compound.

1. additionIn a 4 mL vial charged with a stir bar
2. customA loose cap with septum
3. customThe solid mixture was purged with nitrogen gas a couple of times
4. additionwas added to the mixture
5. customThe vial was capped
6. stirringby shaking at 95° C. overnight
7. filtrationThe reaction was filtered
8. concentrationconcentrated to dryness
9. customThe residue was purified by reverse phase HPLC (C18, gradient 10-95% acetonitrile/water/0.1% trifluoroacetic acid)

ORD record

ord-e56755ecbb2b4532a6f314f11f028c5e

Source dataset

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08383657B2