Sodium hydride → N-(2-(3-methyl-1,2,4-oxadiazol-5-yl)thiophen-3-yl)-2-(naphthalen-1-yl)acetamide

HRID 2098166Notes

Reaction equation

HRID 2098166 reaction equation
[H-].[Na+].[C:3](=[N:6][OH:7])([NH2:5])[CH3:4].[C:8]1([CH2:18][C:19]([NH:21][C:22]2[CH:26]=[CH:25][S:24][C:23]=2[C:27](OC)=O)=[O:20])[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH:11]=[CH:10][CH:9]=1>C1COCC1.C(OCC)(=O)C>[CH3:4][C:3]1[N:5]=[C:27]([C:23]2[S:24][CH:25]=[CH:26][C:22]=2[NH:21][C:19](=[O:20])[CH2:18][C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH:11]=[CH:10][CH:9]=2)[O:7][N:6]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 30926N-HydroxyacetamidineHCID 25660569Methyl 3-(2-(naphthalen-1-yl)acetamido)thiophene-2-carboxylate

Product 1

HCID 46869074N-(2-(3-methyl-1,2,4-oxadiazol-5-yl)thiophen-3-yl)-2-(naphthalen-1-yl)acetamide

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Sodium hydride (60% dispersion, 15 mg, 0.39 mmol) was added to a solution of acetamide oxime (29 mg, 0.39 mmol) in THF (1 mL). The resulting mixture was stirred at room temperature for 10 minutes after which a solution of methyl 3-(2-(naphthalen-1-yl)acetamido)thiophene-2-carboxylate (107 mg, 0.33 mmol) in THF (1 mL) was added. The reaction mixture was stirred for 1 h and was subsequently diluted with ethyl acetate (10 mL). The resulting solution was washed with brine (5 mL) and the organic phase was then dried (Na2SO4), filtered and concentrated under vacuum. The residue was dissolved in THF (1 mL) and HCl (1 mL of a 10% aqueous solution) was added. The mixture was stirred for 20 minutes after which ethyl acetate (10 mL) was added. The resulting solution was washed with brine (5 mL) and the organic phase was then dried (Na2SO4), filtered, concentrated under vacuum and the residue was purified by preparative HPLC to give N-(2-(3-methyl-1,2,4-oxadiazol-5-yl)thiophen-3-yl)-2-(naphthalen-1-yl)acetamide. Retention time (min)=9.533, method [7], MS (ESI) 350.1 (M+H). 1H NMR (300 MHz, CDCl3) δ 10.10 (s, 1H), 8.26 (d, J=5.4 Hz, 1H), 8.03 (d, J=9.3 Hz, 2H), 7.59-7.49 (m, 5H), 4.27 (s, 2H), 2.14 (s, 3H).

Workup

  1. additionwas added
  2. washThe resulting solution was washed with brine (5 mL)
  3. dry with materialthe organic phase was then dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. dissolutionThe residue was dissolved in THF (1 mL)
  7. additionHCl (1 mL of a 10% aqueous solution) was added
  8. stirringThe mixture was stirred for 20 minutes after which ethyl acetate (10 mL)
  9. additionwas added
  10. washThe resulting solution was washed with brine (5 mL)
  11. dry with materialthe organic phase was then dried (Na2SO4)
  12. filtrationfiltered
  13. concentrationconcentrated under vacuum
  14. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-ce708b0d2b0049fb80575117b80c8a0c
Source dataset
uspto-grants-2013_05
Patent number
US08450363B2

Reaction notes

Loading…