Tetrahydrofuran → N-(2-(5-chloro-1H-indol-3-yl)ethyl)-5-(2,5-difluorobenzoyl)isoxazole-3-carboxamide

HRID 58757Notes

Reaction equation

HRID 58757 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]([C:16]1[CH:20]=[C:19]([CH2:21][C:22]2[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:23]=2[F:29])[O:18][N:17]=1)=[O:15].[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C1C[O:51]CC1>>[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:16]1[CH:20]=[C:19]([C:21](=[O:51])[C:22]2[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:23]=2[F:29])[O:18][N:17]=1)=[O:15]

Participants

4

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 2724141Tetrabutylammonium Fluoride2×HCID 49804942N-(2-(5-chloro-1H-indol-3-yl)ethyl)-5-(2,5-difluorobenzyl)isoxazole-3-carboxamide

Product 1

HCID 49869178N-(2-(5-chloro-1H-indol-3-yl)ethyl)-5-(2,5-difluorobenzoyl)isoxazole-3-carboxamideYield 19%

Procedure

N-(2-(5-chloro-1H-indol-3-yl)ethyl)-5-(2,5-difluorobenzyl)isoxazole-3-carboxamide (0.0641 g; 0.154 mmol) was added to a solution of tetrabutylammonium fluoride in THF (1 M, 0.462 mL). The resulting mixture was stirred at room temperature overnight. As the reaction was not completed, tetrabutylammonium fluoride in THF (1 M, 2 mL) were added, the reaction mixture was stirred for four hours and concentrated under reduced pressure. The crude mixture was purified by flash chromatography on silica (eluent 1 to 20% methanol in dichloromethane) and by preparative HPLC method 2 to yield 0.013 g (19%) of N-(2-(5-chloro-1H-indol-3-yl)ethyl)-5-(2,5-difluorobenzoyl)isoxazole-3-carboxamide as a yellow solid.

Workup

  1. stirringthe reaction mixture was stirred for four hours
  2. concentrationconcentrated under reduced pressure
  3. customThe crude mixture was purified by flash chromatography on silica (eluent 1 to 20% methanol in dichloromethane) and by preparative HPLC method 2

Sources & evidence

ORD record
ord-a7caa651d5e043ed8d3537f3b0b4a802
Source dataset
uspto-grants-2016_09
Patent number
US09434722B2

Reaction notes

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