Triethylamine → HCID 68493219, compound

HRID 509534Notes

Reaction equation

HRID 509534 reaction equation
[NH2:1][C:2]1[C:7]([C:8]([OH:10])=O)=[CH:6][C:5]([Br:11])=[CH:4][N:3]=1.C(N(CC)CC)C.[NH:19]([C:21]([C:23]1[CH:28]=[CH:27][C:26]([CH2:29][N:30]([CH3:38])[C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[CH:25][CH:24]=1)=[O:22])[NH2:20].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN(C=O)C.CCOC(C)=O.O>[NH2:1][C:2]1[C:7]([C:8]([NH:20][NH:19][C:21]([C:23]2[CH:24]=[CH:25][C:26]([CH2:29][N:30]([CH3:38])[C:31](=[O:37])[O:32][C:33]([CH3:34])([CH3:35])[CH3:36])=[CH:27][CH:28]=2)=[O:22])=[O:10])=[CH:6][C:5]([Br:11])=[CH:4][N:3]=1

Participants

7

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 68493219HCID 68493219, compoundYield 58%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 22728543Water ethylacetateSolvent

Procedure

2-amino-5-bromo-pyridine-3-carboxylic acid (776.9 mg, 3.580 mmol) and triethylamine (724.5 mg, 997.9 μL 7.160 mmol) were added to a stirred solution of tert-butyl N-[[4-(hydrazinecarbonyl)phenyl]methyl]-N-methyl-carbamate (1 g, 3.580 mmol in DMF (8 mL). To the stirred slurry was added TBTU (1.724 g, 5.370 mmol) and the mixture stirred at ambient for 60 hours. The mixture was diluted with EtOAc/water and the layers separated. The mixture was extracted with ethyl acetate (×3) and the combined extracts washed with saturated aqueous NaHCO3 (×1) and brine (×1), dried (MgSO4), filtered and concentrated in vacuo. The resultant residue was purified by column chromatography (ISCO Companion™, 12 g column, 0-100% EtOAc/Petroleum ether) and the product containing fractions concentrated in vacuo. The residue was triturated from acetonitrile to give the desired sub-title product as a cream solid (992 mg, 58% Yield). 1H NMR (400.0 MHz, DMSO) δ 1.39-1.45 (m, 9H), 2.80 (s, 3H), 4.45 (s, 2H), 7.28 (s, 2H), 7.35 (d, J=8.2 Hz, 2H), 7.90 (d, J=7.8 Hz, 2H), 8.20 (d, J=2.4 Hz, 1H), 8.24 (d, J=2.2 Hz, 1H), 10.50 (s, 1H) and 10.54 (s, 1H) ppm; MS (ES+) 480.2.

Workup

  1. customthe layers separated
  2. extractionThe mixture was extracted with ethyl acetate (×3)
  3. washthe combined extracts washed with saturated aqueous NaHCO3 (×1) and brine (×1)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe resultant residue was purified by column chromatography (ISCO Companion™, 12 g column, 0-100% EtOAc/Petroleum ether)
  8. additionthe product containing fractions
  9. concentrationconcentrated in vacuo
  10. customThe residue was triturated from acetonitrile

Sources & evidence

ORD record
ord-27019ec841394748859afddd9e731535
Source dataset
uspto-grants-2015_08
Patent number
US09096584B2

Reaction notes

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