Nitrogen → Tert-butyl 1-(pyridazin-3-yl)cyclopropylcarbamate

HRID 1025231Notes

Reaction equation

HRID 1025231 reaction equation
O1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH2:8][CH2:7]1.[N:17]#[N:18].C([O-])(O)=O.[Na+].BrN1C(=O)CCC1=O>CC(C)=O.O.C1COCC1>[N:17]1[CH:5]=[CH:4][CH:3]=[C:2]([C:6]2([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH2:8][CH2:7]2)[N:18]=1

Participants

8

Reactant 4

HCID 947NitrogenHCID 67184N-bromobutanimideHCID 516892Sodium BicarbonateHCID 67117129tert-Butyl (1-(furan-2-yl)cyclopropyl)carbamate

Product 1

HCID 67291864Tert-butyl 1-(pyridazin-3-yl)cyclopropylcarbamate

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-20 °C

Procedure

A solution of tert-butyl 1-(furan-2-yl)cyclopropylcarbamate (2.15 g, 9.64 mmol, 1.0 eq) in acetone (86 ml) and water (86 ml) was purged N2 and cooled to −20° C. NaHCO3 (1.62 g, 19.28 mmol, 2.0 eq) and N-bromosuccinimide (2.23 g, 12.52 mmol, 1.3 eq) were added to the mixture at −20° C. which was stirred at the same temperature for 2 hr. To the reaction mixture at −20° C. was added THF (4.3 ml) and the temperature raised to 0° C. over 30 min. Acetone was removed from the reaction mixture by a stream of N2 and to the residue at 0° C. was added isopropanol (86 ml) followed by hydrazine hydrate (12.9 ml). The reaction mixture was stirred at r.t. overnight. Product formation was confirmed by LCMS. After removal of the solvent by vacuum, the residue was diluted with water and extracted with EtOAc. The organic was washed with brine, dried over Na2SO4, filtered and concentrated. The crude product was purified by silica gel (60-120) column chromatography using 4% MeOH/CHCl3 as eluent. Yield: 0.8 g (36%). 1H NMR (400 MHz, CDCl3): δ8.95 (d, J=3.6 Hz, 1H), 7.53 (d, J=8 Hz, 1H), 7.39 (m, 1H), 5.45 (bs, 1H), 1.82 (m, 2H), 1.46 (s, 9H) 1.24 (m, 2H). LCMS: (ES+) m/z=236.2 (M+H)+

Workup

  1. temperaturethe temperature raised to 0° C. over 30 min
  2. customAcetone was removed from the reaction mixture by a stream of N2 and to the residue at 0° C.
  3. additionwas added isopropanol (86 ml)
  4. stirringThe reaction mixture was stirred at r.t. overnight
  5. customAfter removal of the solvent by vacuum
  6. additionthe residue was diluted with water
  7. extractionextracted with EtOAc
  8. washThe organic was washed with brine
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe crude product was purified by silica gel (60-120) column chromatography

Sources & evidence

ORD record
ord-acd189a4f0c5420ea355f122b5d7cbf7
Source dataset
uspto-grants-2014_05
Patent number
US08722688B2

Reaction notes

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