Triethylamine → Tert-butyl 4-(2-(3-amino-6-bromopyrazine-2-carbonyl)hydrazinecarbonyl)benzyl(methyl)carbamate

HRID 2204885Notes

Reaction equation

HRID 2204885 reaction equation
[NH:1]([C:3]([C:5]1[CH:10]=[CH:9][C:8]([CH2:11][N:12]([CH3:20])[C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[CH:7][CH:6]=1)=[O:4])[NH2:2].[NH2:21][C:22]1[C:27]([C:28](O)=[O:29])=C[C:25]([Br:31])=[CH:24][N:23]=1.C([N:34](CC)CC)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN(C=O)C.C(OCC)(=O)C.O>[NH2:21][C:22]1[C:27]([C:28]([NH:2][NH:1][C:3]([C:5]2[CH:6]=[CH:7][C:8]([CH2:11][N:12]([CH3:20])[C:13](=[O:19])[O:14][C:15]([CH3:16])([CH3:17])[CH3:18])=[CH:9][CH:10]=2)=[O:4])=[O:29])=[N:34][C:25]([Br:31])=[CH:24][N:23]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 7374452-Amino-5-bromonicotinic acidHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 67425410tert-butyl N-[[4-(hydrazinecarbonyl)phenyl]methyl]-N-methyl-carbamate

Product 1

HCID 59472138Tert-butyl 4-(2-(3-amino-6-bromopyrazine-2-carbonyl)hydrazinecarbonyl)benzyl(methyl)carbamateYield 99.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of tert-butyl N-[[4-(hydrazinecarbonyl)phenyl]methyl]-N-methyl-carbamate (1 g, 3.580 mmol) in DMF (7.769 mL) and 2-amino-5-bromo-pyridine-3-carboxylic acid (776.9 mg, 3.580 mmol) was added triethylamine (724.5 mg, 997.9 μL, 7.160 mmol) followed by TBTU (1.724 g, 5.370 mmol). The resulting mixture was stirred at room temperature for 48 h. The reaction mixture was diluted with ethyl acetate (20 mL) and water (20 mL) and the layers separated. The aqueous layer was extracted further with ethyl acetate (2×20 mL) and combined organic extracts washed with saturated aqueous sodium hydrogen carbonate solution (1×20 mL), brine (1×20 mL), dried over MgSO4 and concentrated in vacuo. The residue was triturated with CH2Cl2 to give the product as a white solid (1.71 g, 58% yield); 1H NMR (400.0 MHz, DMSO) d 1.39-1.45 (m, 9H), 2.80 (s, 3H), 4.45 (s, 2H), 4.45 (s, 2H), 7.28 (s, 2H), 7.35 (d, 2H), 7.90 (d, 2H), 8.20 (d, 2H), 8.24 (d, 1H), 10.50 (s, 1H) and 10.54 (s, 1H) ppm; MS (ES+) 480.16

Workup

  1. customthe layers separated
  2. extractionThe aqueous layer was extracted further with ethyl acetate (2×20 mL)
  3. washcombined organic extracts washed with saturated aqueous sodium hydrogen carbonate solution (1×20 mL), brine (1×20 mL)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was triturated with CH2Cl2

Sources & evidence

ORD record
ord-f89c9078361943c5bae6a21c3c07ff92
Source dataset
uspto-grants-2016_06
Patent number
US09365557B2

Reaction notes

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