Diisopropylethylamine → 5-(2,5-Difluorobenzyl)isoxazole-3-carboxamide

HRID 58656Notes

Reaction equation

HRID 58656 reaction equation
ClC1C=C2C(CCN)=C([Si](CC)(CC)CC)NC2=[N:6]C=1.[F:21][C:22]1[CH:36]=[CH:35][C:34]([F:37])=[CH:33][C:23]=1[CH2:24][C:25]1[O:29][N:28]=[C:27]([C:30](O)=[O:31])[CH:26]=1.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>[F:21][C:22]1[CH:36]=[CH:35][C:34]([F:37])=[CH:33][C:23]=1[CH2:24][C:25]1[O:29][N:28]=[C:27]([C:30]([NH2:6])=[O:31])[CH:26]=1

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 668320582-(5-chloro-2-(triethylsilyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)ethanamine

Product 1

HCID 1317370185-(2,5-Difluorobenzyl)isoxazole-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-(5-chloro-2-(triethylsilyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)ethanamine (0.128 g; 0.413 mmol), 5-(2,5-difluorobenzyl)isoxazole-3-carboxylic acid intermediate 74 (0.104 g; 0.434 mmol), HATU (N,N,N′,N′-Tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate) (0.165 g: 0.434 mmol) and N,N-diisopropylethylamine (0.108 mL; 0.619 mmol) in DMF (3 mL) was stirred overnight at room temperature and concentrated under reduced pressure. The crude material was dissolved in dichloromethane and the organic layer was washed with water and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel (eluent: 1 to 10% of ethyl acetate in dichloromethane) to give 0.108 g (49%) of N-(2-(5-chloro-2-(triethylsilyl)-1H-pyrrolo[2, 3-1)]pyridin-3-yl)ethyl)-5-(2,5-difluorobenzyl)isoxazole-3-carboxamide as a solid.

Workup

  1. concentrationconcentrated under reduced pressure
  2. dissolutionThe crude material was dissolved in dichloromethane
  3. washthe organic layer was washed with water
  4. concentrationconcentrated under reduced pressure
  5. customThe crude material was purified by flash chromatography on silica gel (eluent: 1 to 10% of ethyl acetate in dichloromethane)

Sources & evidence

ORD record
ord-6d00a5e5f8a64ea5a44e3dac9a734d40
Source dataset
uspto-grants-2016_09
Patent number
US09434722B2

Reaction notes

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