Cesium carbonate → 1-Methyl-5-(3-methyl-2-nitro-phenylamino)-1H-pyrazole-4-carboxylic Acid Ethyl Ester

HRID 220940

Reaction equation

HRID 220940 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[NH2:7][C:8]1[N:12]([CH3:13])[N:11]=[CH:10][C:9]=1[C:14]([O:16][CH2:17][CH3:18])=[O:15].Br[C:20]1[C:21]([N+:27]([O-:29])=[O:28])=[C:22]([CH3:26])[CH:23]=[CH:24][CH:25]=1>O1CCOCC1.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].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>[CH2:17]([O:16][C:14]([C:9]1[CH:10]=[N:11][N:12]([CH3:13])[C:8]=1[NH:7][C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([CH3:26])[C:21]=1[N+:27]([O-:29])=[O:28])=[O:15])[CH3:18]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 142929Benzene, 1-bromo-3-methyl-2-nitro-HCID 271299Ethyl 5-amino-1-methyl-1H-pyrazole-4-carboxylate

Product 1

HCID 575553391-Methyl-5-(3-methyl-2-nitro-phenylamino)-1H-pyrazole-4-carboxylic Acid Ethyl EsterYield 54.8%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent2×

Procedure

Cesium carbonate (35.2 g, 108 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.4 g, 0.7 mmol) and tris(dibenzylideneacetone)dipalladium(0) (0.2 g, 0.2 mmol) were added to a solution of ethyl 5-amino-1-methylpyrazole-4-carboxylate (15.3 g, 90 mmol) in dioxan (50 ml) under an inert atmosphere. A solution of 3-bromo-2-nitrotoluene (16.2 g, 75 mmol) in dioxane (10 ml) was added and the mixture was stirred for 30 min at room temperature then heated at reflux for 72 h. The suspension was filtered through Celite® filter agent, washed with EtOAc and the filtrate was concentrated in vacuo. The residue was purified by flash chromatography on silica gel (eluant; 50% EtOAc:50% pet. ether) then recrystallised from EtOAc/pet. ether to yield the title compound (12.5 g, 45%).

Workup

  1. temperaturethen heated
  2. temperatureat reflux for 72 h
  3. filtrationThe suspension was filtered through Celite®
  4. filtrationfilter agent
  5. washwashed with EtOAc
  6. concentrationthe filtrate was concentrated in vacuo
  7. customThe residue was purified by flash chromatography on silica gel (eluant; 50% EtOAc:50% pet. ether)
  8. customthen recrystallised from EtOAc/pet. ether

Sources & evidence

ORD record
ord-7f6ea4725ee44fed822d4114be08db03
Source dataset
uspto-grants-2012_06
Patent number
US08202858B2

Linked notes

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