2-Pyrazinecarboxylic acid → N-[2-amino-2,2-bis(4-fluorophenyl)-1-methylethyl]-2-pyrazinecarboxamide

HRID 1455308Notes

Reaction equation

HRID 1455308 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)([NH2:12])[CH:9]([NH2:11])[CH3:10])=[CH:4][CH:3]=1.[N:20]1[CH:25]=[CH:24][N:23]=[CH:22][C:21]=1[C:26](O)=[O:27].CN(C)CCCN=C=NCC>N1C=CC=CC=1>[NH2:12][C:8]([C:13]1[CH:14]=[CH:15][C:16]([F:19])=[CH:17][CH:18]=1)([C:5]1[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=1)[CH:9]([NH:11][C:26]([C:21]1[CH:22]=[N:23][CH:24]=[CH:25][N:20]=1)=[O:27])[CH3:10]

Participants

5

Reactant 3

HCID 10472-Pyrazinecarboxylic acidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 218859191,1-Bis(4-fluorophenyl)-1,2-propanediamine

Product 1

HCID 69053565N-[2-amino-2,2-bis(4-fluorophenyl)-1-methylethyl]-2-pyrazinecarboxamideYield 84.8%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

1,1-bis(4-fluorophenyl)-1,2-propanediamine (94 mg) and pyrazinecarboxylic acid (53 mg) was dissolved in pyridine (1 mL), and to the solution was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (103 mg). The mixture was stirred at room temperature for 24 hrs. The reaction mixture was concentrated, and the obtained residue was dissolved in chloroform, followed by washing with saturated sodium hydrogen carbonate aqueous solution. The aqueous layer was extracted with chloroform twice, and the combined chloroform layers were dried over magnesium sulfate. After evaporating the solvent in vacuo, the obtained residue was purified by silica gel column chromatography (C-300; hexane: ethyl acetate=1:1→1:3) to give N-[2-amino-2,2-bis(4-fluorophenyl)-1-methylethyl]-2-pyrazinecarboxamide (112 mg) as the mixture with pyrazinecarboxylic acid methyl ester. The mixture was dissolved in methanol (1 mL), and to the solution was added 2N sodium hydroxide aqueous solution (0.5 mL), and the solution was stirred at room temperature for one hr. The reaction mixture was diluted with chloroform, followed by washing with water. The aqueous layer was extracted with chloroform twice, and the combined chloroform layers were dried over anhydrous magnesium sulfate. The solvent was evaporated in vacuo to give the pure amide compound (95 mg).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionthe obtained residue was dissolved in chloroform
  3. washby washing with saturated sodium hydrogen carbonate aqueous solution
  4. extractionThe aqueous layer was extracted with chloroform twice
  5. dry with materialthe combined chloroform layers were dried over magnesium sulfate
  6. customAfter evaporating the solvent in vacuo
  7. customthe obtained residue was purified by silica gel column chromatography (C-300; hexane: ethyl acetate=1:1→1:3)

Sources & evidence

ORD record
ord-bf32b29e007b4c31b55a58a5c04933cb
Source dataset
uspto-grants-2009_01
Patent number
US07482358B2

Reaction notes

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