Cesium carbonate → tert-butyl 7-[(5-cyclopropylpyrazin-2-yl)oxy]-6-oxohexahydropyrrolo[1,2-a]pyrazine-2(1H)-carboxylate

HRID 1184624Notes

Reaction equation

[OH:1][CH:2]1[C:17](=[O:18])[N:5]2[CH2:6][CH2:7][N:8]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:9][CH:4]2[CH2:3]1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[C:26]1[CH:31]=[N:30][C:29]([CH:32]2[CH2:34][CH2:33]2)=[CH:28][N:27]=1>C(#N)C>[CH:32]1([C:29]2[N:30]=[CH:31][C:26]([O:1][CH:2]3[C:17](=[O:18])[N:5]4[CH2:6][CH2:7][N:8]([C:10]([O:12][C:13]([CH3:15])([CH3:14])[CH3:16])=[O:11])[CH2:9][CH:4]4[CH2:3]3)=[N:27][CH:28]=2)[CH2:34][CH2:33]1

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of the product from Example 205B (89 mg, 0.347 mmol) in anhydrous acetonitrile (3.5 mL) was added cesium carbonate (226 mg, 0.695 mmol) and 2-bromo-5-cyclopropylpyrazine (104 mg, 0.521 mmol). The resulting mixture was stirred under N2 at 50° C. for 48 hours. The mixture was allowed to cool to room temperature, and then it was partitioned between water and ethyl acetate (3×). The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by column chromatography on silica gel using a solvent gradient of 0-10% methanol in dichloromethane to give the title compound (82 mg, 63%).

Workup

temperatureto cool to room temperature
customit was partitioned between water and ethyl acetate (3×)
dry with materialThe combined organic layers were dried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
customThe crude product was purified by column chromatography on silica gel using a solvent gradient of 0-10% methanol in dichloromethane

Sources & evidence

ORD record: ord-06afc14e893a4ee8bff61b3d1d00e87f
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08669255B2

Reaction notes

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