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Diisopropylethylamine → N-(2-(5-chloro-1H-indol-3-yl)ethyl)-4-phenylisoxazole-3-carboxamide

HRID 58780
Notes
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Reaction equation

HRID 58780 reaction equation
[C:1]1([C:7]2[C:8]([C:12]([O:14]CC)=O)=[N:9][O:10][CH:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.[Cl:18][C:19]1[CH:20]=[C:21]2[C:25](=[CH:26][CH:27]=1)[NH:24][CH:23]=[C:22]2[CH2:28][CH2:29][NH2:30].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.C(OCC)(=O)C>[Cl:18][C:19]1[CH:20]=[C:21]2[C:25](=[CH:26][CH:27]=1)[NH:24][CH:23]=[C:22]2[CH2:28][CH2:29][NH:30][C:12]([C:8]1[C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)=[CH:11][O:10][N:9]=1)=[O:14]
ParticipantsProcedureWorkupSources & evidenceReaction notes

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 13449587HCID 13449587, compound

Product 1

HCID 66831904N-(2-(5-chloro-1H-indol-3-yl)ethyl)-4-phenylisoxazole-3-carboxamide
Yield 30%

Reagents, catalysts & solvents 5

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

Procedure

A mixture of ethyl 4-phenylisoxazole-3-carboxylate (0.030 g; 0.130 mmol) in THF (1 mL) and sodium hydroxide in water (2M, 1 mL) was stirred at room temperature for 2.5 hours. The reaction mixture was then diluted with water and the aqueous layer was extracted with dichloromethane. The aqueous layer was acidified with HCl 6N until pH 2 and extracted with ethyl acetate. The organic layer was dried over magnesium sulphate and concentrated under reduced pressure. The crude residue was added to a mixture of 2-(5-chloro-1H-indol-3-yl)ethanamine hydrochloride (0.030 g; 0.130 mmol), HATU (0.50 g; 0.130 mmol), N,N diisopropylethylamine (0.055 mL; 0.324 mmol), in DMF (2 mL) and was stirred at room temperature for 72 hours. The reaction mixture was diluted with ethyl acetate and was washed with sodium hydrogensulphate, sodium carbonate and brine. The organic layer was dried over magnesium sulphate and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica (eluent 20 to 100% ethyl acetate in heptane) and then by preparative HPLC method 2 to yield 0.0136 g (30%) of the title compound as a white solid.

Workup

  1. extractionthe aqueous layer was extracted with dichloromethane
  2. extractionextracted with ethyl acetate
  3. dry with materialThe organic layer was dried over magnesium sulphate
  4. concentrationconcentrated under reduced pressure
  5. stirringwas stirred at room temperature for 72 hours
  6. washwas washed with sodium hydrogensulphate, sodium carbonate and brine
  7. dry with materialThe organic layer was dried over magnesium sulphate
  8. concentrationconcentrated under reduced pressure
  9. customThe crude material was purified by flash chromatography on silica (eluent 20 to 100% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-3e21c43e95164d44bbfbbcf3a33c9c86
Source dataset
uspto-grants-2016_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09434722B2

Reaction notes

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