Diisopropylethylamine → N-(2-(6-chloro-5-methyl-1H-indol-3-yl)ethyl)-5-(2,5-difluorobenzyl)isoxazole-3-carboxamide

HRID 58760Notes

Reaction equation

HRID 58760 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:18][C:19]1[CH:27]=[C:26]2[C:22]([C:23]([CH2:28][CH2:29][NH2:30])=[CH:24][NH:25]2)=[CH:21][C:20]=1[CH3:31].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:18][C:19]1[CH:27]=[C:26]2[C:22]([C:23]([CH2:28][CH2:29][NH:30][C:10]([C:7]3[CH:6]=[C:5]([CH2:4][C:3]4[CH:13]=[C:14]([F:17])[CH:15]=[CH:16][C:2]=4[F:1])[O:9][N:8]=3)=[O:12])=[CH:24][NH:25]2)=[CH:21][C:20]=1[CH3:31]

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 668320395-(2,5-Difluorobenzyl)isoxazole-3-carboxylic acidHCID 668321552-(6-chloro-5-methyl-1H-indol-3-yl)ethanamine

Product 1

HCID 66831991N-(2-(6-chloro-5-methyl-1H-indol-3-yl)ethyl)-5-(2,5-difluorobenzyl)isoxazole-3-carboxamideYield 2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 5-(2,5-difluorobenzyl)isoxazole-3-carboxylic acid (0.180 g, 0.752 mmol), 2-(6-chloro-5-methyl-1H-indol-3-yl)ethanamine intermediate 142(0.157 g; 0.752 mmol), HATU (0.286 g; 0.753 mmol) and N,N diisopropylethylamine (0.324 mL; 1.88 mmol) in DMF (5 mL), was stirred at room temperature overnight. The reaction mixture was partitioned between ethyl acetate and sodium hydrogen sulphate, the organic layer was washed with sodium carbonate, brine, dried and concentrated under reduced pressure. The crude mixture was purified by flash chromatography on silica (eluent 2 to 60% ethyl acetate in heptane and eluent 1 to 10% ethyl acetate in dichloromethane) and by preparative HPLC method 2 to yield 0.0051 g (2%) of N-(2-(6-chloro-5-methyl-1H-indol-3-yl)ethyl)-5-(2,5-difluorobenzyl)isoxazole-3-carboxamide as a white solid.

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate and sodium hydrogen sulphate
  2. washthe organic layer was washed with sodium carbonate, brine
  3. customdried
  4. concentrationconcentrated under reduced pressure
  5. customThe crude mixture was purified by flash chromatography on silica (eluent 2 to 60% ethyl acetate in heptane and eluent 1 to 10% ethyl acetate in dichloromethane) and by preparative HPLC method 2

Sources & evidence

ORD record
ord-f6ee097b0ca54e04b6be3e26e6d27b7d
Source dataset
uspto-grants-2016_09
Patent number
US09434722B2

Reaction notes

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