Sodium hydride → 2-(1-(2-(4-fluorobenzyloxy)ethyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)-4-methyl-N-(pyridin-3-ylmethyl)thiazole-5-carboxamide

HRID 560867Notes

Reaction equation

HRID 560867 reaction equation
[OH:1][CH2:2][CH2:3][N:4]1[C:8](=[O:9])[N:7]([C:10]2[S:11][C:12]([C:16]([NH:18][CH2:19][C:20]3[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=3)=[O:17])=[C:13]([CH3:15])[N:14]=2)[CH:6]=[N:5]1.[H-].[Na+].Br[CH2:29][C:30]1[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=1>O1CCCC1.C(OCC)(=O)C>[F:36][C:33]1[CH:34]=[CH:35][C:30]([CH2:29][O:1][CH2:2][CH2:3][N:4]2[C:8](=[O:9])[N:7]([C:10]3[S:11][C:12]([C:16]([NH:18][CH2:19][C:20]4[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=4)=[O:17])=[C:13]([CH3:15])[N:14]=3)[CH:6]=[N:5]2)=[CH:31][CH:32]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 680214-Fluorobenzyl bromideHCID 250966952-(1-(2-hydroxyethyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)-4-methyl-N-(pyridin-3-ylmethyl)thiazole-5-carboxamide

Product 1

HCID 594812832-(1-(2-(4-fluorobenzyloxy)ethyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)-4-methyl-N-(pyridin-3-ylmethyl)thiazole-5-carboxamideYield 46%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To the solution of 2-(1-(2-hydroxyethyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)-4-methyl-N-(pyridin-3-ylmethyl)thiazole-5-carboxamide (0.11 g, 0.31 mmol) in anhydrous tetrahydrofuran was added sodium hydride (60% in mineral oil, 0.015 g, 0.35 mmol) at 0° C. The reaction mixture was stirred for 30 minutes, followed by the addition of 1-(bromomethyl)-4-fluorobenzene (0.04 mL, 0.31 mmol). The resulting mixture was stirred at ambient temperature for 17 hours, diluted with ethyl acetate and washed with water and brine. The organic solution was dried over anhydrous sodium sulphate, filtered and concentrated in vacuo. The residue was purified by column chromatography eluted with ethyl acetate to afford the title compound as a white solid in 46% yield (0.06 g): mp 235-236° C. (ethyl acetate): 1H NMR (300 MHz, DMSO-d6) δ 9.14 (br s, 1H), 9.11-9.06 (m, 1H), 8.95 (t, J=5.5 Hz, 1H), 8.73 (s, 1H), 8.56-8.48 (m, 1H), 8.15-8.08 (m, 1H), 7.65-7.56 (m, 2H), 7.32-7.22 (m, 2H), 5.81 (s, 2H), 4.57 (d, J=5.5 Hz, 2H), 3.79 (t, J=5.4 Hz, 2H), 3.64 (t, J=5.4 Hz, 2H), 2.54 (s, 3H): 13C NMR (75 MHz, DMSO-d6) δ 162.0, 161.4, 152.6, 152.1, 150.6, 145.1, 143.8, 143.7, 141.1, 131.9, 131.9, 131.0, 128.7, 121.9, 116.6, 62.9, 58.6, 48.3, 40.7, 17.5: MS (ES+) m/z 469.2 (M+1).

Workup

  1. stirringThe resulting mixture was stirred at ambient temperature for 17 hours
  2. washwashed with water and brine
  3. dry with materialThe organic solution was dried over anhydrous sodium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by column chromatography
  7. washeluted with ethyl acetate

Sources & evidence

ORD record
ord-6b6956a885744f779ae0bba511f093fe
Source dataset
uspto-grants-2011_11
Patent number
US08063084B2

Reaction notes

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