Diisopropylethylamine → (4-(5-chloro-1H-indol-3-yl)piperidin-1-yl)(5-(2,5-difluorobenzyl)isoxazol-3-yl)methanone

HRID 1918767Notes

Reaction equation

HRID 1918767 reaction equation
Cl.[Cl:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]=[C:6]2[CH:12]1[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1.[F:18][C:19]1[CH:33]=[CH:32][C:31]([F:34])=[CH:30][C:20]=1[CH2:21][C:22]1[O:26][N:25]=[C:24]([C:27](O)=[O:28])[CH:23]=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>[Cl:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]=[C:6]2[CH:12]1[CH2:17][CH2:16][N:15]([C:27]([C:24]2[CH:23]=[C:22]([CH2:21][C:20]3[CH:30]=[C:31]([F:34])[CH:32]=[CH:33][C:19]=3[F:18])[O:26][N:25]=2)=[O:28])[CH2:14][CH2:13]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 203455215-chloro-3-(piperidin-4-yl)-1H-indole hydrochlorideHCID 668320395-(2,5-Difluorobenzyl)isoxazole-3-carboxylic acid

Product 1

HCID 66831758(4-(5-chloro-1H-indol-3-yl)piperidin-1-yl)(5-(2,5-difluorobenzyl)isoxazol-3-yl)methanoneYield 36.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The mixture of 5-chloro-3-(piperidin-4-yl)-1H-indole hydrochloride (0.070 g; 0.258 mmol), 5-(2,5-difluorobenzyl)isoxazole-3-carboxylic acid (0.062 g; 0.258 mmol), HATU (N,N,N′N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate) (0.098 g: 0.258 mmol) and N,N-diisopropylethylamine (0.113 mL; 0.634 mmol) in DMF (3 mL) was stirred for 72 hours at room temperature and was concentrated under reduced pressure. The residue 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: 0 to 10% of ethyl acetate in dichloromethane) to give 0.0428 g (36%) of (4-(5-chloro-1H-indol-3-yl)piperidin-1-yl)(5-(2,5-difluorobenzyl)isoxazol-3-yl)methanone as a white solid.

Workup

  1. concentrationwas concentrated under reduced pressure
  2. dissolutionThe residue 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: 0 to 10% of ethyl acetate in dichloromethane)

Sources & evidence

ORD record
ord-81a601a3ebe047ba9770bb8fed78cf41
Source dataset
uspto-grants-2013_12
Patent number
US08618138B2

Reaction notes

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