2-THIOPHENECARBOXIMIDIC ACID ETHYL ESTER → HCID 67070782, compound

HRID 732071Notes

Reaction equation

HRID 732071 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:12]=[C:11]([CH2:13][CH2:14][C:15]([NH:17][NH2:18])=[O:16])[O:10][N:9]=2)[CH:5]=[CH:6][CH:7]=1.[CH2:19]([O:21][C:22]([C:24]1[S:25][CH:26]=[CH:27][CH:28]=1)=N)[CH3:20]>C(O)C>[CH2:19]([O:21][C:22](=[N:18][NH:17][C:15](=[O:16])[CH2:14][CH2:13][C:11]1[O:10][N:9]=[C:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=2)[N:12]=1)[C:24]1[S:25][CH:26]=[CH:27][CH:28]=1)[CH3:20]

Participants

4

Reactant 2

HCID 122310432-THIOPHENECARBOXIMIDIC ACID ETHYL ESTERHCID 50743575HCID 50743575, compound

Product 1

HCID 67070782HCID 67070782, compoundYield 75.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

3-[3-(3-chloro-phenyl)-[1,2,4]oxadiazol-5-yl]-propionic acid hydrazide (266.69 mg, 1 mmol) was mixed with thiophene-2-carboximidic acid ethyl ester (191.6 mg, 1 mmol) in ethanol (6 ml) and stirred at room temperature overnight. The reaction was quenched with water, extracted with ethyl acetate, dried and concentrated in vacuo. The crude product was triturated with hexane to yield 3-[3-(3-Chloro-phenyl)-[1,2,4]oxadiazol-5-yl]-propionic acid (ethoxy-thiophen-2-yl-methylene)-hydrazide as a white solid (305 mg, 75%). 1H-NMR(CDCl3) d(ppm): 8.99 (ws, 1H), 8.09 (s, 1H), 7.98 (d, 1H), 7.41(m, 4H), 7.08 (dd, 1H), 4.27 (q, 2H), 3.34 (m, 4H) and 1.41 (t, 3H). Step 2: 3-(3-Chloro-phenyl)-5-[2-(4-methyl-5-thiophen-2-yl-4H-[1,2,4]triazol-3-yl)-ethyl]-[1,2,4]oxadiazole: 3-[3-(3-chloro-phenyl)-[1,2,4]oxadiazol-5-yl]-propionic acid (ethoxy-thiophen-2-yl-methylene)-hydrazide (81 mg, 0.2 mmol) was mixed with 2M methylamine (0.3 ml in THF) in ethanol (2 ml) at 70˜80° C. overnight. The reaction mixture was concentrated with silica gel and purified by column chromatography with 0.5˜2.0% methanol in ethyl acetate to give 54 mg (72.5%) of 3-(3-chloro-phenyl)-5-[2-(4-methyl-5-thiophen-2-yl-4H-[1,2,4]triazol-3-yl)-ethyl]-[1,2,4]oxadiazole. 1H-NMR(CDCl3) d (ppm): 8.08 (s, 1H), 7.97 (d, 1H), 7.41 (m, 4H), 7.20 (dd, 1H), 3.80 (s, 3H), 3.68 (dd, 2H), 3.38 (dd, 2H).

Workup

  1. customThe reaction was quenched with water
  2. extractionextracted with ethyl acetate
  3. customdried
  4. concentrationconcentrated in vacuo
  5. customThe crude product was triturated with hexane

Sources & evidence

ORD record
ord-8ba912fdea4d4843b2d4634c0cab365f
Source dataset
uspto-grants-2009_09
Patent number
US07585881B2

Reaction notes

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