Dimethylformamide → 1-(4-Fluorophenyl)-N-methyl-N-((3-methylpyridin-4-yl)methyl)-2-((2,3,6-trifluorobenzyl)thio)-1H-imidazole-5-carboxamide

HRID 2368535Notes

Reaction equation

HRID 2368535 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([C:13]([OH:15])=O)=[CH:11][N:10]=[C:9]2[S:16][CH2:17][C:18]2[C:23]([F:24])=[CH:22][CH:21]=[C:20]([F:25])[C:19]=2[F:26])=[CH:4][CH:3]=1.[CH3:27][N:28](C=O)[CH3:29].[CH2:32](N(CC)CC)C.CN(C(ON1N=[N:54][C:49]2[CH:50]=[CH:51][CH:52]=[CH:53]C1=2)=[N+](C)C)C.[B-](F)(F)(F)F>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:12]([C:13]([N:28]([CH3:29])[CH2:27][C:51]3[CH:50]=[CH:49][N:54]=[CH:32][C:52]=3[CH3:53])=[O:15])=[CH:11][N:10]=[C:9]2[S:16][CH2:17][C:18]2[C:23]([F:24])=[CH:22][CH:21]=[C:20]([F:25])[C:19]=2[F:26])=[CH:6][CH:7]=1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 711173271-(4-Fluorophenyl)-2-((2,3,6-trifluorobenzyl)thio)-1H-imidazole-5-carboxylic acid

Product 1

HCID 711175701-(4-Fluorophenyl)-N-methyl-N-((3-methylpyridin-4-yl)methyl)-2-((2,3,6-trifluorobenzyl)thio)-1H-imidazole-5-carboxamide

Procedure

To a solution of 1-(4-fluorophenyl)-2-((2,3,6-trifluorobenzyl)thio)-1H-imidazole-5-carboxylic acid (11) (200 mg, 0.52 mmol) in DMF (5 mL) N-methyl-1-(3-methylpyridin-4-yl)methanamine (86 mg, 0.63 mmol), and triethylamine (159 mg, 1.57 mmol) was added. At room temperature, TBTU (252 mg, 0.785 mmol) was added in one portion and the mixture was stirred at room temperature overnight. The mixture was quenched with water, and extracted with ethyl acetate. The organic layer was washed with brine, and dried over sodium sulfate. The mixture was filtered and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (10%-80% ethyl acetate in hexanes) to give 1-(4-fluorophenyl)-N-methyl-N-((3-methylpyridin-4-yl)methyl)-2-((2,3,6-trifluorobenzyl)thio)-1H-imidazole-5-carboxamide (502). 1H NMR (400 MHz, CDCl3) δ: 8.41-8.36 (m, 2H), 7.20-7.17 (m, 2H) 7.12-6.99 (m, 3H), 6.78-6.74 (m, 3H), 4.62 (s, 2H), 4.35 (s, 2H), 3.04 (s, 3H), 2.20 (s, 3H). LC-MS ESI m/z; found 501.1 [M+H]+.

Workup

  1. customThe mixture was quenched with water
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationThe mixture was filtered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography on silica gel (10%-80% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-9619090769424f569b559dc8a7952f53
Source dataset
uspto-grants-2014_04
Patent number
US08703776B2

Reaction notes

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