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

HRID 58709Notes

Reaction equation

HRID 58709 reaction equation
[F:1][C:2]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:3]=1[CH2:4][C:5]1[O:9][N:8]=[C:7]([C:10]([OH:12])=O)[CH:6]=1.Cl.[Cl:19][C:20]1[CH:21]=[C:22]2[C:26](=[CH:27][CH:28]=1)[NH:25][C:24]([CH3:29])=[C:23]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>CN(C=O)C>[Cl:19][C:20]1[CH:21]=[C:22]2[C:26](=[CH:27][CH:28]=1)[NH:25][C:24]([CH3:29])=[C:23]2[CH2:30][CH2:31][NH:32][C:10]([C:7]1[CH:6]=[C:5]([CH2:4][C:3]2[CH:13]=[C:14]([F:17])[CH:15]=[CH:16][C:2]=2[F:1])[O:9][N:8]=1)=[O:12]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 164953302-(5-chloro-2-methyl-1H-indol-3-yl)ethanamine hydrochlorideHCID 668320395-(2,5-Difluorobenzyl)isoxazole-3-carboxylic acid

Product 1

HCID 66831851N-(2-(5-chloro-2-methyl-1H-indol-3-yl)ethyl)-5-(2,5-difluorobenzyl)isoxazole-3-carboxamideYield 62.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 5-(2,5-difluorobenzyl)isoxazole-3-carboxylic acid (0.080 g, 0.334 mmol), 2-(5-chloro-2-methyl-1H-indol-3-yl)ethanamine hydrochloride (0.090 g; 0.368 mmol), HATU (0.127 g; 0.334 mmol) and N,N-diisopropylethylamine (0.144 mL; 0.836 mmol) in DMF (5 mL), was stirred at room temperature for 18 hours. The reaction mixture was partitioned between ethyl acetate and a solution of sodium hydrogen sulfate. The organic layer was washed with sodium carbonate, brine, dried and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (eluent 20 to 100% ethyl acetate in heptane) to afford 0.090 g (62%) of the title compound as a pink solid.

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate
  2. washThe organic layer was washed with sodium carbonate, brine
  3. customdried
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by flash chromatography on silica gel (eluent 20 to 100% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-0e2f451d4ac14c1d8368e979025bdd5b
Source dataset
uspto-grants-2016_09
Patent number
US09434722B2

Reaction notes

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