Diisopropylethylamine → N-(2-(5-chloro-1H-indol-3-yl)ethyl)-5-(4-fluoro-2-(trifluoromethyl)benzyl)-1,2,4-oxadiazole-3-carboxamide

HRID 1918760Notes

Reaction equation

HRID 1918760 reaction equation
[F:1][C:2]1[CH:18]=[CH:17][C:5]([CH2:6][C:7]2[O:11][N:10]=[C:9]([C:12]([O:14]CC)=O)[N:8]=2)=[C:4]([C:19]([F:22])([F:21])[F:20])[CH:3]=1.Cl.[Cl:24][C:25]1[CH:26]=[C:27]2[C:31](=[CH:32][CH:33]=1)[NH:30][CH:29]=[C:28]2[CH2:34][CH2:35][NH2:36].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>C1COCC1.[OH-].[Na+].O.CN(C=O)C>[Cl:24][C:25]1[CH:26]=[C:27]2[C:31](=[CH:32][CH:33]=1)[NH:30][CH:29]=[C:28]2[CH2:34][CH2:35][NH:36][C:12]([C:9]1[N:8]=[C:7]([CH2:6][C:5]2[CH:17]=[CH:18][C:2]([F:1])=[CH:3][C:4]=2[C:19]([F:20])([F:21])[F:22])[O:11][N:10]=1)=[O:14]

Participants

9

Reactant 4

HCID 81531DiisopropylethylamineHCID 28274945-Chloro-1H-indole-3-ethylamine monohydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66831832Ethyl 5-(4-fluoro-2-(trifluoromethyl)benzyl)-1,2,4-oxadiazole-3-carboxylate

Product 1

HCID 66831866N-(2-(5-chloro-1H-indol-3-yl)ethyl)-5-(4-fluoro-2-(trifluoromethyl)benzyl)-1,2,4-oxadiazole-3-carboxamide

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 14798Sodium HydroxideSolvent

Procedure

This compound was prepared according to method F with ethyl 5-(4-fluoro-2-(trifluoromethyl)benzyl)-1,2,4-oxadiazole-3-carboxylate (0.099 g; 0.311 mmol) in THF (1 mL) and sodium hydroxide in water (2M, 1 mL); 2-(5-chloro-1H-indol-3-yl)ethanamine hydrochloride (0.080 g; 0.346 mmol), HATU (0.131 g; 0.346 mmol), N,N diisopropylethylamine (0.149 mL; 0.865 mmol), in DMF (3 mL). The crude mixture was purified by flash column chromatography on silica (eluent 20 to 100% ethyl acetate in heptane) and by preparative HPLC method 2 to yield 0.022 (14%) of N-(2-(5-chloro-1H-indol-3-yl)ethyl)-5-(4-fluoro-2-(trifluoromethyl)benzyl)-1,2,4-oxadiazole-3-carboxamide as a white solid.

Workup

  1. customThis compound was prepared
  2. customThe crude mixture was purified by flash column chromatography on silica (eluent 20 to 100% ethyl acetate in heptane) and by preparative HPLC method 2

Sources & evidence

ORD record
ord-48c7d781744d4562825c002b4df83dfd
Source dataset
uspto-grants-2013_12
Patent number
US08618138B2

Reaction notes

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