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

HRID 58704

Reaction equation

HRID 58704 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.[C:48]1([CH2:54][C:55]([NH:57][NH2:58])=O)[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1.C1(C)C=CC(S(Cl)(=O)=O)=CC=1>C(Cl)(Cl)Cl.ClCCl>[CH2:54]([C:55]1[O:17][C:15]([C:14]([NH:13][CH2:12][CH2:11][C:5]2[C:4]3[C:8](=[CH:9][CH:10]=[C:2]([Cl:1])[CH:3]=3)[NH:7][CH:6]=2)=[O:18])=[N:58][N:57]=1)[C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1

Participants

9

Reactant 6

HCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 70301Benzeneacetic acid, hydrazideHCID 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 668318505-benzyl-N-(2-(5-chloro-1H-indol-3-yl)ethyl)-1,3,4-oxadiazole-2-carboxamideYield 2.6%

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 (0.350 mg; 1.31 mmol) in chloroform (20 mL) was added thionyl chloride (0.955 mL; 13.12 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 (0.180 g, 0.631 mmol) was dissolved in dichloromethane (12 mL) and a mixture of triethylamine (0.355 mL; 2.53 mmol) and 2-phenylacetic acid hydrazide (0.092 g; 0.600 mmol) in dichloromethane (2 mL) was added at 0° C. The mixture was stirred at room temperature for 3 days and p-toluenesulfonyl chloride (0.122 g, 0.631 mmol) was added. The resulting mixture was stirred 18 h 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 0.006 g (2.5%) of 5-benzyl-N-(2-(5-chloro-1H-indol-3-yl)ethyl)-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 3 days
  4. stirringThe resulting mixture was stirred 18 h 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-d9f9d46efcd24e76a5e4ba5bce750045
Source dataset
uspto-grants-2016_09
Patent number
US09434722B2

Linked notes

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