Potassium Carbonate → HCID 68514066, compound

HRID 1810110Notes

Reaction equation

HRID 1810110 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH2:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH:6]=[CH:7][C:8]=1F)#[N:2].[Cl:18][C:19]1[CH:38]=[CH:37][C:22]([CH2:23][CH2:24][NH:25][C:26]([C:28]2[CH:29]=[C:30]3[C:34](=[CH:35][CH:36]=2)[NH:33][N:32]=[CH:31]3)=[O:27])=[CH:21][CH:20]=1.C([O-])([O-])=O.[K+].[K+]>CS(C)=O.CCOC(C)=O.C(=O)([O-])[O-].[Na+].[Na+]>[Cl:18][C:19]1[CH:20]=[CH:21][C:22]([CH2:23][CH2:24][NH:25][C:26]([C:28]2[CH:29]=[C:30]3[C:34](=[CH:35][CH:36]=2)[N:33]([C:8]2[CH:7]=[CH:6][C:5]([CH2:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[CH:4][C:3]=2[C:1]#[N:2])[N:32]=[CH:31]3)=[O:27])=[CH:37][CH:38]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 45925946Tert-butyl 2-(3-cyano-4-fluorophenyl)acetateHCID 68512002HCID 68512002, compound

Product 1

HCID 68514066HCID 68514066, compoundYield 22%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
90 °C

Procedure

To a stirred solution of tert-butyl 2-(3-cyano-4-fluorophenyl)acetate (110 mg, 0.468 mmol) and N-(4-chlorophenethyl)-1H-indazole-5-carboxamide (168 mg, 0.561 mmol) in DMSO (2 ml) was added K2CO3 (77.5 mg, 0.561 mmol). The reaction was heated to 90° C. overnight via an oil bath. The reaction was diluted with EtOAc and 10% aqueous sodium carbonate. The aqueous phase was extracted with EtOAc and the combined organic layers were washed with brine, dried over MgSO4, and concentrated. The crude product was purified over silica gel on a Biotage Horizon high-performance FLASH chromatography system (25+M silica gel cartridge) eluting with a gradient of 5% ethyl acetate/hexanes to 70% ethyl acetate/hexanes to provide tert-butyl 2-(4-(5-((4-chlorophenethyl)carbamoyl)-1H-indazol-1-yl)-3-cyanophenyl)acetate (0.241 g, 0.103 mmol, 22%).

Workup

  1. extractionThe aqueous phase was extracted with EtOAc
  2. washthe combined organic layers were washed with brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. customThe crude product was purified over silica gel on a Biotage Horizon high-performance FLASH chromatography system (25+M silica gel cartridge)
  6. washeluting with a gradient of 5% ethyl acetate/hexanes to 70% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-81c068b5eed143189d5ffbbb44c660e9
Source dataset
uspto-grants-2013_01
Patent number
US08362056B2

Reaction notes

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