N-(1-Cyano-piperidin-4-yl)-N-cyclopropyl-4-oxazol-5-yl-benzamide → N-Cyclopropyl-N-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yl]-4-oxazol-5-yl-benzamide

HRID 68801

Reaction equation

[OH:1][NH:2][C:3](=[NH:7])[CH:4]([CH3:6])[CH3:5].[C:8]([N:10]1[CH2:15][CH2:14][CH:13]([N:16]([CH:30]2[CH2:32][CH2:31]2)[C:17](=[O:29])[C:18]2[CH:23]=[CH:22][C:21]([C:24]3[O:28][CH:27]=[N:26][CH:25]=3)=[CH:20][CH:19]=2)[CH2:12][CH2:11]1)#N>O1CCCC1.C(OCC)(=O)C.[Cl-].[Zn+2].[Cl-]>[CH:30]1([N:16]([CH:13]2[CH2:14][CH2:15][N:10]([C:8]3[O:1][N:2]=[C:3]([CH:4]([CH3:6])[CH3:5])[N:7]=3)[CH2:11][CH2:12]2)[C:17](=[O:29])[C:18]2[CH:19]=[CH:20][C:21]([C:24]3[O:28][CH:27]=[N:26][CH:25]=3)=[CH:22][CH:23]=2)[CH2:32][CH2:31]1

Participants

Conditions

Temperature: 50 °C

Procedure

A 0.5 M solution of zinc chloride in tetrahydrofuran (5.20 mL) is added dropwise at room temperature to a mixture of N-hydroxy-isobutyramidine (266 mg) and N-(1-cyano-piperidin-4-yl)-N-cyclopropyl-4-oxazol-5-yl-benzamide (600 mg) in ethyl acetate (25 mL). The reaction mixture is stirred at 50° C. for 3 h and cooled to room temperature. The precipitate is filtered off and heated to 100° C. for 2 h in a mixture of ethanol (10 mL) and glacial acetic acid (5 mL). The solvents are evaporated and the residue is chromatographed on silica gel [ethyl acetate/cyclohexane/methanol 9:9:2] to give the title compound. LC (method 6): tR=1.66 min; Mass spectrum (ESI+): m/z=422 [M+H]+.

Workup

temperaturecooled to room temperature
filtrationThe precipitate is filtered off
temperatureheated to 100° C. for 2 h in a mixture of ethanol (10 mL) and glacial acetic acid (5 mL)
customThe solvents are evaporated
customthe residue is chromatographed on silica gel [ethyl acetate/cyclohexane/methanol 9:9:2]

Sources & evidence

ORD record: ord-afb49415878d4bd684e661bd22e0678e
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08822471B2

Linked notes

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