Sodium Carbonate → methyl 2-[2-(5-bromo-1-methyl-1H-pyrazol-4-yl)-2-oxoethyl]-2-formylhydrazinecarboxylate

HRID 1498046Notes

Reaction equation

HRID 1498046 reaction equation
COC1C=CC(CN[CH:9]=[N:10][NH:11][C:12]([O:14][CH3:15])=[O:13])=CC=1.Br[CH2:19][C:20]([C:22]1[CH:23]=[N:24][N:25]([CH3:28])[C:26]=1[Br:27])=[O:21].C(=O)([O-])[O-:30].[Na+].[Na+].C(N(CC)C(C)C)(C)C>C(#N)C.O>[Br:27][C:26]1[N:25]([CH3:28])[N:24]=[CH:23][C:22]=1[C:20](=[O:21])[CH2:19][N:10]([CH:9]=[O:30])[NH:11][C:12]([O:14][CH3:15])=[O:13]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 866697172-bromo-1-(5-bromo-1-methyl-1H-pyrazol-4-yl)ethanoneHCID 178502533HCID 178502533, compound

Product 1

HCID 86669721methyl 2-[2-(5-bromo-1-methyl-1H-pyrazol-4-yl)-2-oxoethyl]-2-formylhydrazinecarboxylateYield 27.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

Methyl 2-{[(4-methoxybenzyl)amino]methylene}hydrazinecarboxylate (3.28 g, 13.8 mmol), 2-bromo-1-(5-bromo-1-methyl-1H-pyrazol-4-yl)ethanone (3.90 g, 13.8 mmol) and sodium carbonate (1.16 g, 13.8 mmol) were combined in a mixture of N,N-diisopropylethylamine (99.5%, 2.30 mL, 13.8 mmol) and acetonitrile (30 mL). The reaction was heated at 80° C. for 18 hours, at which time water was added, and heated was continued for 10 minutes. After removal of solvent in vacuo, the aqueous residue was partitioned between water and ethyl acetate (100 mL). The aqueous layer was extracted with ethyl acetate (4×100 mL), and the combined organic layers were dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification using silica gel chromatography (Gradient: 0% to 100% ethyl acetate in heptane) provided the product (1.20 g), contaminated with some impurities. This material was taken directly to the following step. LCMS m/z 319.0 (M+1). 1H NMR (400 MHz, CD3OD) δ, product peaks: 3.74 (s, 3H), 3.92 (s, 3H), 4.82 (br s, 2H), 8.14 (s, 1H), 8.24 (s, 1H).

Workup

  1. additionwas added
  2. temperatureheated
  3. customAfter removal of solvent in vacuo
  4. customthe aqueous residue was partitioned between water and ethyl acetate (100 mL)
  5. extractionThe aqueous layer was extracted with ethyl acetate (4×100 mL)
  6. dry with materialthe combined organic layers were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customPurification

Sources & evidence

ORD record
ord-a573d8e296bd47f899e95cf5682ff1c1
Source dataset
uspto-grants-2015_12
Patent number
US09200000B2

Reaction notes

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