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

HRID 1519948Notes

Reaction equation

HRID 1519948 reaction equation
[H-].[Na+].[C:3](=[N:6][OH:7])([NH2:5])[CH3:4].[CH3:8][C:9]1[C:10]([C:28](OC)=O)=[C:11]([NH:14][C:15](=[O:27])[CH2:16][C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH:20]=[CH:19][CH:18]=2)[S:12][CH:13]=1>C1COCC1>[CH3:8][C:9]1[C:10]([C:28]2[O:7][N:6]=[C:3]([CH3:4])[N:5]=2)=[C:11]([NH:14][C:15](=[O:27])[CH2:16][C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH:20]=[CH:19][CH:18]=2)[S:12][CH:13]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 30926N-HydroxyacetamidineHCID 68756461Methyl 4-methyl-2-(2-(naphthalen-1-yl)acetamido)thiophene-3-carboxylate

Product 1

HCID 46869076N-(4-methyl-3-(3-methyl-1,2,4-oxadiazol-5-yl)thiophen-2-yl)-2-(naphthalen-1-yl)acetamideYield 10.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride (60% dispersion in mineral oil, 106 mg, 2.65 mmol) was added to a solution of acetamide oxime (218 mg, 2.94 mmol) in dry THF (5 mL) at rt. Methyl 4-methyl-2-(2-(naphthalen-1-yl)acetamido)thiophene-3-carboxylate (Aldrich, 500 mg, 1.47 mmol) was added, and the reaction mixture was allowed to stir over 3 days. The mixture was concentrated under reduced pressure, then partitioned between ethyl acetate and water. The organic layer was separated, and washed with saturated NaCl solution. The organic layer was dried (MgSO4), filtered and concentrated. The residue was purified by flash chromatography (EtOAc/hexanes elution), and then triturated from acetonitrile to afford the desired product (58 mg) as a white solid. Method [7]: rt=9.42 min; 1H NMR (CDCl3) δ 11.3 (s, 1H), 8.02-7.89 (m, 3H), 7.63-7.50 (m, 4H), 6.48 (s, 1H), 4.35 (s, 2H), 2.42 (s, 3H), 2.08 (s, 3H); 13C NMR (CDCl3) δ 172.1, 168.9, 165.2, 146.4, 134.0, 133.4, 132.4, 129.4, 129.1, 129.0, 128.8, 127.2, 126.4, 125.7, 123.7, 114.0, 106.9, 42.1, 16.9, 11.4; MH+ 364.1.

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. custompartitioned between ethyl acetate and water
  3. customThe organic layer was separated
  4. washwashed with saturated NaCl solution
  5. dry with materialThe organic layer was dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by flash chromatography (EtOAc/hexanes elution)
  9. customtriturated from acetonitrile

Sources & evidence

ORD record
ord-079a3c39dbed4ed991aa40429a6588b7
Source dataset
uspto-grants-2015_07
Patent number
US09073891B2

Reaction notes

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