Sodium Carbonate → 2-fluoro-N-(3-isopropoxyphenyl)-4-methyl-3-(2-(methylamino)quinazolin-6-yl)benzamide

HRID 2092293Notes

Reaction equation

HRID 2092293 reaction equation
[F:1][C:2]1[C:20](I)=[C:19]([CH3:22])[CH:18]=[CH:17][C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([O:13][CH:14]([CH3:16])[CH3:15])[CH:8]=1)=[O:5].[CH3:23][NH:24][C:25]1[N:34]=[CH:33][C:32]2[C:27](=[CH:28][CH:29]=[C:30](B3OC(C)(C)C(C)(C)O3)[CH:31]=2)[N:26]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:1][C:2]1[C:20]([C:30]2[CH:31]=[C:32]3[C:27](=[CH:28][CH:29]=2)[N:26]=[C:25]([NH:24][CH3:23])[N:34]=[CH:33]3)=[C:19]([CH3:22])[CH:18]=[CH:17][C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([O:13][CH:14]([CH3:16])[CH3:15])[CH:8]=1)=[O:5]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 16086139N-Methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)quinazolin-2-amineHCID 588297502-fluoro-3-iodo-N-(3-isopropoxyphenyl)-4-methylbenzamide

Product 1

HCID 588290582-fluoro-N-(3-isopropoxyphenyl)-4-methyl-3-(2-(methylamino)quinazolin-6-yl)benzamideYield 57.1%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of 2-fluoro-3-iodo-N-(3-isopropoxyphenyl)-4-methylbenzamide (630 mg, 1525 μmol), N-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinazolin-2-amine (522 mg, 1830 μmol) and sodium carbonate (2 M aqueous solution) (1525 μL, 3049 μmol) in DME (25 mL) was flushed with nitrogen and then tetrakis(triphenylphosphine)palladium (0) (176 mg, 152 μmol) was added. The mixture was refluxed for 24 h and thne cooled to RT. Solvent was removed in vacuo and the residue was purified by flash chromatography eluting with EtOAc/hexane (25-60%) to give the title compound (387 mg, 57%). MS (M+H)+ 445.

Workup

  1. customwas flushed with nitrogen
  2. temperatureThe mixture was refluxed for 24 h
  3. customSolvent was removed in vacuo
  4. customthe residue was purified by flash chromatography
  5. washeluting with EtOAc/hexane (25-60%)

Sources & evidence

ORD record
ord-e92b329307f5445286d8a336adf92398
Source dataset
uspto-grants-2013_05
Patent number
US08440674B2

Reaction notes

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