Phenylhydrazine → 3-amino-N-methyl-6-{3-[(2-phenylhydrazino)carbonyl]phenyl}pyrazine-2-carboxamide

HRID 646685Notes

Reaction equation

HRID 646685 reaction equation
[NH2:1][C:2]1[N:3]=[CH:4][C:5]([C:12]2[CH:13]=[C:14]([CH:18]=[CH:19][CH:20]=2)[C:15]([OH:17])=O)=[N:6][C:7]=1[C:8]([NH:10][CH3:11])=[O:9].O[N:22]1[C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=2N=[N:23]1.CN1CCOCC1.C1(NN)C=CC=CC=1>CN(C=O)C.C(OCC)(=O)C>[NH2:1][C:2]1[C:7]([C:8]([NH:10][CH3:11])=[O:9])=[N:6][C:5]([C:12]2[CH:20]=[CH:19][CH:18]=[C:14]([C:15]([NH:23][NH:22][C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:25]=3)=[O:17])[CH:13]=2)=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 7516PhenylhydrazineHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 587105713-{5-Amino-6-[(methylamino)carbonyl]pyrazin-2-yl}benzoic acid

Product 1

HCID 686516823-amino-N-methyl-6-{3-[(2-phenylhydrazino)carbonyl]phenyl}pyrazine-2-carboxamideYield 56%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}benzoic acid (40 mg, 0.15 mmol) was dissolved in DMF (1 mL) and 1-hydroxybenzotriazole (30 mg, 0.22 mmol), 1-[(3-dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (30 mg, 0.16 mmol), and 4-methylmorpholine (30 mg, 0.28 mol) were added sequentially. After one hour phenylhydrazine (30 mg, 0.27 mmol) was added to the reaction mixture and stirring was continued at room temperature for 18 hours. It was then diluted with ethyl acetate (10 mL), washed with water, saturated sodium bicarbonate solution, and brine, dried over sodium sulfate, filtered, and concentrated. The oily residue was purified by flash chromatography (silica gel, eluted with ethyl acetate-hexanes gradient from 15% to 80% yield) to give 3-amino-N-methyl-6-{3-[(2-phenylhydrazino)carbonyl]phenyl}pyrazine-2-carboxamide (a tan color solid, 30 mg, 56% yield): 1H NMR (400 MHz, DMSO-d6): 10.42 (b, 1H), 8.92 (s, 1H), 8.84-8.82 (b, 1H), 8.57-8.57 (s,1H0, 8.41-8.39 (d, 1H), 7.94-7.89(m, 1H), 7.89-7.86 (d, 1H), 7.61-7.57 (t, 1H), 7.17-7.13 (t, 1H), 6.83-6.80 (d, 1H), 6.73-6.69(m, 1H), 2.85 (s, 3H); MS (EI) for C19H18N6O2: 440 (MH+).

Workup

  1. washwashed with water, saturated sodium bicarbonate solution, and brine
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe oily residue was purified by flash chromatography (silica gel, eluted with ethyl acetate-hexanes gradient from 15% to 80% yield)

Sources & evidence

ORD record
ord-5356ade4271a43d1aab47896aa2b5376
Source dataset
uspto-grants-2010_04
Patent number
US07704995B2

Reaction notes

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