Dimethylformamide → HCID 45378167, compound

HRID 1630301Notes

Reaction equation

[CH3:1][C:2]1[NH:3][CH:4]=[CH:5][N:6]=1.[CH2:7]([O:14][CH2:15][C@H:16]([NH:34][C:35](=[O:38])[CH2:36]Cl)[C:17]([NH:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][C:27]2[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=2)=[CH:22][CH:21]=1)=[O:18])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.CN(C=O)C>C(OCC)(=O)C>[CH2:7]([O:14][CH2:15][C@H:16]([NH:34][C:35](=[O:38])[CH2:36][N:3]1[CH:4]=[CH:5][N:6]=[C:2]1[CH3:1])[C:17]([NH:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][C:27]2[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=2)=[CH:22][CH:21]=1)=[O:18])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

Conditions

Temperature: 40 °C

Procedure

2-Methylimidazole (64 mg, 0.786 mmol) was added to a flask charged with (S)-3-(benzyloxy)-2-(2-chloroacetamido)-N-(4-(4-fluorophenoxy)phenyl)propanamide (150 mg, 0.393 mmol), prepared as in Example 15, and DMF (3 mL). The mixture was stirred at 40° C. for 30 minutes then diluted with ethyl acetate (20 mL). The dilution was washed with brine (20 mL), dried over sodium sulfate, filtered and concentrated. Product was purified from the residue by reverse phase HPLC to provide Compound 160, (S)-3-(benzyloxy)-N-(4-(4-fluorophenoxy)phenyl)-2-(2-(2-methyl-1H-imidazol-1-yl)acetamido)propanamide (100.8 mg, 0.201 mmol, 51% yield) as an off-white solid. 1H-NMR (400 MHz, CDCl3): 8.38 (s, 1H), 7.38-7.21 (m, 7H), 7.05-6.89 (m, 7H), 6.45 (d, 1H), 4.66 (d, 1H), 4.61 (s, 2H), 4.55 (d, 1H), 3.91 (dd, 1H), 3.55 (t, 1H), 2.38 (s, 3H). MS (EI) for C28H27FN4O4. found 502.9 (MH+).

Workup

washThe dilution was washed with brine (20 mL)
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated
customProduct was purified from the residue by reverse phase HPLC

Sources & evidence

ORD record: ord-00cea40ae79a4439a5e28e84f16521b2
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08791102B2

Reaction notes

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