Sodium Carbonate → N-(2-(5-chloro-7-fluoro-2-(triethylsilyl)-1H-indol-3-yl)ethyl)-5-(2,5-difluorobenzyl)isoxazole-3-carboxamide

HRID 58642Notes

Reaction equation

HRID 58642 reaction equation
[Cl:1][C:2]1[CH:8]=[C:7](I)[C:5]([NH2:6])=[C:4]([F:10])[CH:3]=1.[F:11][C:12]1[CH:37]=[CH:36][C:35]([F:38])=[CH:34][C:13]=1[CH2:14][C:15]1[O:19][N:18]=[C:17]([C:20]([NH:22][CH2:23][CH2:24][C:25]#[C:26][Si:27]([CH2:32][CH3:33])([CH2:30][CH3:31])[CH2:28][CH3:29])=[O:21])[CH:16]=1.[Cl-].[Li+].C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.[Cl-].[Na+].O.C1(P([C-]2C=CC=C2)C2C=CC=CC=2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].[Pd](Cl)Cl.C(OCC)(=O)C>[Cl:1][C:2]1[CH:8]=[C:7]2[C:5](=[C:4]([F:10])[CH:3]=1)[NH:6][C:26]([Si:27]([CH2:32][CH3:33])([CH2:30][CH3:31])[CH2:28][CH3:29])=[C:25]2[CH2:24][CH2:23][NH:22][C:20]([C:17]1[CH:16]=[C:15]([CH2:14][C:13]2[CH:34]=[C:35]([F:38])[CH:36]=[CH:37][C:12]=2[F:11])[O:19][N:18]=1)=[O:21]

Participants

10

Reactant 4

HCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 27736504-Chloro-2-fluoro-6-iodoanilineHCID 668320895-(2,5-difluorobenzyl)-N-(4-(triethylsilyl)but-3-ynyl)isoxazole-3-carboxamide

Product 1

HCID 66831849N-(2-(5-chloro-7-fluoro-2-(triethylsilyl)-1H-indol-3-yl)ethyl)-5-(2,5-difluorobenzyl)isoxazole-3-carboxamideYield 26.3%

Reagents, catalysts & solvents 5

HCID 24290Palladium ChlorideCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-chloro-2-fluoro-6-iodoaniline (0.100 g; 0.368 mmol), 5-(2,5-difluorobenzyl)-N-(4-(triethylsilyl)but-3-ynyl)isoxazole-3-carboxamide (0.150 g; 0.347 mmol), Bis(diphenylphosphino)ferrocene]palladium(II) chloride (0.015 g; 0.018 mmol), lithium chloride (0.016 mg; 0.368 mmol), sodium carbonate (0.078 g; 0.737 mmol) in DMF (5 mL) was stirred at 100° C. overnight. The solution was reputed between ethyl acetate and brine, washed with sodium thiosulphate, dried and concentrated under reduced pressure. The crude mixture was purified by flash chromatography on silica (eluent 2 to 60% ethyl acetate in heptane) to yield 0.05 g (25%) of N-(2-(5-chloro-7-fluoro-2-(triethylsilyl)-1H-indol-3-yl)ethyl)-5-(2,5-difluorobenzyl)isoxazole-3-carboxamide as a yellow oil.

Workup

  1. washwashed with sodium thiosulphate
  2. customdried
  3. concentrationconcentrated under reduced pressure
  4. customThe crude mixture was purified by flash chromatography on silica (eluent 2 to 60% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-d8d16ac60b074360a314673fdf47c641
Source dataset
uspto-grants-2016_09
Patent number
US09434722B2

Reaction notes

Loading…