4-Toluenesulfonyl chloride → N-(2-(5-chloro-1H-indol-3-yl)ethyl)-5-cyclohexyl-1,3,4-oxadiazole-2-carboxamide

HRID 58705Notes

Reaction equation

HRID 58705 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][CH2:12][NH:13][C:14](=[O:18])[C:15]([OH:17])=O.S(Cl)(Cl)=O.ClC1C=C2C(=CC=1)NC=C2CCNC(=O)C(Cl)=O.C(N(CC)CC)C.[CH:48]1([C:54]([NH:56][NH2:57])=O)[CH2:53][CH2:52][CH2:51][CH2:50][CH2:49]1.C1(C)C=CC(S(Cl)(=O)=O)=CC=1>C(Cl)(Cl)Cl.ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][CH2:12][NH:13][C:14]([C:15]1[O:17][C:54]([CH:48]2[CH2:53][CH2:52][CH2:51][CH2:50][CH2:49]2)=[N:56][N:57]=1)=[O:18]

Participants

9

Reactant 6

HCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 240039CyclohexanecarbohydrazideHCID 668319752-(2-(5-chloro-1H-indol-3-yl)ethylamino)-2-oxoacetic acidHCID 866638412-(2-(5-chloro-1H-indol-3-yl)ethylamino)-2-oxoacetyl chloride

Product 1

HCID 66831875N-(2-(5-chloro-1H-indol-3-yl)ethyl)-5-cyclohexyl-1,3,4-oxadiazole-2-carboxamideYield 1.5%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
80 °C

Procedure

To a suspension of 2-(2-(5-chloro-1H-indol-3-yl)ethylamino)-2-oxoacetic acid (0.920 mg; 3.45 mmol) in chloroform (50 mL) was added thionyl chloride (2.51 mL; 34.50 mmol) and the mixture was stirred at 80° C. for 3 h and was then evaporated to dryness. The resulting 2-(2-(5-chloro-1H-indol-3-yl)ethylamino)-2-oxoacetyl chloride (0.480 g; 1.68 mmol) was dissolved in dichloromethane (12 mL) and a mixture of triethylamine (0.945 mL; 6.73 mmol) and cyclohexanecarboxylic acid hydrazide (0.232 g; 1.60 mmol) in dichloromethane (8 mL) was added at 0° C. The mixture was stirred at room temperature for 2 h and p-toluenesulfonyl chloride (0.324 g, 1.68 mmol) was added. The resulting mixture was stirred overnight at room temperature, diluted with dichloromethane, washed with an aqueous solution of sodium carbonate, and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (eluent: 12 to 100% ethyl acetate in heptane) to give 0.0088 g (1.40%) of N-(2-(5-chloro-1H-indol-3-yl)ethyl)-5-cyclohexyl-1,3,4-oxadiazole-2-carboxamide as a white solid.

Workup

  1. customwas then evaporated to dryness
  2. additionwas added at 0° C
  3. stirringThe mixture was stirred at room temperature for 2 h
  4. stirringThe resulting mixture was stirred overnight at room temperature
  5. washwashed with an aqueous solution of sodium carbonate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by flash column chromatography on silica gel (eluent: 12 to 100% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-ec42d7ad6f884722a67acfa8e4f09825
Source dataset
uspto-grants-2016_09
Patent number
US09434722B2

Reaction notes

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