Sodium Carbonate → 5-(2,5-difluorobenzyl)-N-(2-(5-phenyl-1H-indol-3-yl)ethyl)isoxazole-3-carboxamide

HRID 58763

Reaction equation

HRID 58763 reaction equation
[C:1]1(B(O)O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[NH:16][CH:15]=[C:14]2[CH2:20][CH2:21][NH:22][C:23]([C:25]1[CH:29]=[C:28]([CH2:30][C:31]2[CH:36]=[C:35]([F:37])[CH:34]=[CH:33][C:32]=2[F:38])[O:27][N:26]=1)=[O:24].C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:38][C:32]1[CH:33]=[CH:34][C:35]([F:37])=[CH:36][C:31]=1[CH2:30][C:28]1[O:27][N:26]=[C:25]([C:23]([NH:22][CH2:21][CH2:20][C:14]2[C:13]3[C:17](=[CH:18][CH:19]=[C:11]([C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)[CH:12]=3)[NH:16][CH:15]=2)=[O:24])[CH:29]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 66831747N-(2-(5-bromo-1H-indol-3-yl)ethyl)-5-(2,5-difluorobenzyl)isoxazole-3-carboxamide

Product 1

HCID 668319975-(2,5-difluorobenzyl)-N-(2-(5-phenyl-1H-indol-3-yl)ethyl)isoxazole-3-carboxamideYield 6%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of benzene boronic acid (0.023 g; 0.191 mmol), N-(2-(5-bromo-1H-indol-3-yl)ethyl)-5-(2,5-difluorobenzyl)isoxazole-3-carboxamide (0.080 g; 0.174 mmol), tetrakis(triphenylphosphine)palladium(0) (0.020; 0.017 mmol) and sodium carbonate (0.037 g; 0.347 mmol) in DME (3 mL) and water (1 mL) was irradiated in the microwave oven at 130° C. for 20 minutes, the resulting solution was partitioned between water and EA, the organic layer was concentrated under reduced pressure. The crude mixture was purified by flash chromatography on silica (eluent 20 to 100% ethyl acetate in heptane) and by preparative HPLC method 2 to yield 0.0048 g (6%) of 5-(2,5-difluorobenzyl)-N-(2-(5-phenyl-1H-indol-3-yl)ethyl)isoxazole-3-carboxamide as a white solid.

Workup

  1. customwas irradiated in the microwave oven at 130° C. for 20 minutes
  2. customthe resulting solution was partitioned between water and EA
  3. concentrationthe organic layer was concentrated under reduced pressure
  4. customThe crude mixture was purified by flash chromatography on silica (eluent 20 to 100% ethyl acetate in heptane) and by preparative HPLC method 2

Sources & evidence

ORD record
ord-e29351ed4cb74c2f91c7b20c6c6e0e19
Source dataset
uspto-grants-2016_09
Patent number
US09434722B2

Linked notes

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