Diisopropylethylamine → N-(2-(5-chloro-1H-indol-3-yl)ethyl)-5-(hydroxy(phenyl)methyl)isoxazole-3-carboxamide

HRID 58758Notes

Reaction equation

HRID 58758 reaction equation
[OH:1][CH:2]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:3]1[O:7][N:6]=[C:5]([C:8]([O:10]CC)=O)[CH:4]=1.Cl.[Cl:20][C:21]1[CH:22]=[C:23]2[C:27](=[CH:28][CH:29]=1)[NH:26][CH:25]=[C:24]2[CH2:30][CH2:31][NH2:32].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>O1CCCC1.[OH-].[Na+].O.CN(C=O)C.C(OCC)(=O)C>[Cl:20][C:21]1[CH:22]=[C:23]2[C:27](=[CH:28][CH:29]=1)[NH:26][CH:25]=[C:24]2[CH2:30][CH2:31][NH:32][C:8]([C:5]1[CH:4]=[C:3]([CH:2]([OH:1])[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[O:7][N:6]=1)=[O:10]

Participants

10

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 66831982Ethyl 5-(hydroxy(phenyl)methyl)isoxazole-3-carboxylate

Product 1

HCID 66832076N-(2-(5-chloro-1H-indol-3-yl)ethyl)-5-(hydroxy(phenyl)methyl)isoxazole-3-carboxamideYield 95.6%

Reagents, catalysts & solvents 5

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 14798Sodium HydroxideSolvent

Procedure

A mixture of ethyl 5-(hydroxy(phenyl)methyl)isoxazole-3-carboxylate (0.534 g; 2.16 mmol) in tetrahydrofurane (6 mL) and sodium hydroxide in water (2M, 5.4 mL) was stirred at room temperature for 1 hour and diluted in water, extracted with dichloromethane and the waters acidified with HCl 6N in water to pH 2 extracted with ethyl acetate, the organic layer was dried and concentrated under reduced pressure. The residue was added to a mixture of 2-(5-chloro-1H-indol-3-yl)ethanamine hydrochloride (0.5 g; 2.16 mmol), HATU (0.822 g; 2.16 mmol), N,N diisopropylethylamine (0.932 mL; 5.41 mmol), in DMF (12 mL) and was stirred at room temperature overnight. The reaction mixture was diluted in ethyl acetate, washed with sodium disulphate, sodium carbonate and brine, dried and concentrated under reduced pressure. The crude mixture was purified by flash chromatography on silica (eluent 20 to 100% ethyl acetate in heptane) to yield 0.817 g (95%) of N-(2-(5-chloro-1H-indol-3-yl)ethyl)-5-(hydroxy(phenyl)methyl)isoxazole-3-carboxamide as a white solid.

Workup

  1. extractionextracted with dichloromethane
  2. extractionextracted with ethyl acetate
  3. customthe organic layer was dried
  4. concentrationconcentrated under reduced pressure
  5. stirringwas stirred at room temperature overnight
  6. washwashed with sodium disulphate, sodium carbonate and brine
  7. customdried
  8. concentrationconcentrated under reduced pressure
  9. customThe crude mixture was purified by flash chromatography on silica (eluent 20 to 100% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-66dcb875e9954b2f8c1710a26e196623
Source dataset
uspto-grants-2016_09
Patent number
US09434722B2

Reaction notes

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