Morpholine → 2-[2-(3,5-Difluoro-Phenyl)-acetylamino]-pentanoic acid [1-(2-morpholin-4-yl-ethyl)-1H-imidazol-4-yl]-amide

HRID 553192Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([NH:12][CH:13]([CH2:29][CH2:30][CH3:31])[C:14]([NH:16][C:17]2[N:18]=[CH:19][N:20]([CH2:22][CH2:23]OS(C)(=O)=O)[CH:21]=2)=[O:15])=[O:11])[CH:5]=[C:6]([F:8])[CH:7]=1.C(=O)([O-])[O-].[K+].[K+].[NH:38]1[CH2:43][CH2:42][O:41][CH2:40][CH2:39]1>C(#N)C>[N:38]1([CH2:23][CH2:22][N:20]2[CH:21]=[C:17]([NH:16][C:14](=[O:15])[CH:13]([NH:12][C:10](=[O:11])[CH2:9][C:4]3[CH:5]=[C:6]([F:8])[CH:7]=[C:2]([F:1])[CH:3]=3)[CH2:29][CH2:30][CH3:31])[N:18]=[CH:19]2)[CH2:43][CH2:42][O:41][CH2:40][CH2:39]1

Participants

Conditions

Temperature: 65 °C

Procedure

Methanesulfonic acid 2-(4-{2-[2-(3,5-difluoro-phenyl)-acetylamino]-pentanoylamino}-imidazol-1-yl)-ethyl ester (1 equiv) was dissolved in acetonitrile and treated with potassium carbonate (1.5 equic) and morpholine (3 equiv). The reaction was heated to 65° C. for 18 h and quenched with water, extracted with methylene chloride, dried, and concentrated. The residue was purified by column chromatography to afford the title compound: C13 NMR (100 MHz, CDCl3) 14.0, 18.9, 36.0, 43.1, 45.1, 53.1, 53.9, 58.9, 67.1, 102.6, 102.9, 107.9, 112.3, 112.6, 133.5, 137.6, 139.0, 161.0, 162.0, 169.3, 169.4; MS m/z 450.1 (M+1).

Workup

customquenched with water
extractionextracted with methylene chloride
customdried
concentrationconcentrated
customThe residue was purified by column chromatography

Sources & evidence

ORD record: ord-96e387bb7c1048289b23161ea2caad42
Source dataset: uspto-grants-2011_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07951958B2

Reaction notes

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