1,8-Diazabicyclo(5.4.0)undec-7-ene → 3-[6-(2-Cyclopropylethylcarbamoyl)pyridazin-3-ylamino]azetidine-1-carboxylic acid tert-butyl ester

HRID 1171804Notes

Reaction equation

HRID 1171804 reaction equation
[CH:1]1([CH2:4][CH2:5][NH:6][C:7]([C:9]2[N:10]=[N:11][C:12](Cl)=[CH:13][CH:14]=2)=[O:8])[CH2:3][CH2:2]1.[C:16]([N:23]1[CH2:26][CH:25]([NH2:27])[CH2:24]1)([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17].N12CCCN=C1CCCCC2>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O1CCOCC1>[C:19]([O:18][C:16]([N:23]1[CH2:26][CH:25]([NH:27][C:12]2[N:11]=[N:10][C:9]([C:7](=[O:8])[NH:6][CH2:5][CH2:4][CH:1]3[CH2:3][CH2:2]3)=[CH:14][CH:13]=2)[CH2:24]1)=[O:17])([CH3:22])([CH3:20])[CH3:21]

Participants

6

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 1516507Tert-butyl 3-aminoazetidine-1-carboxylateHCID 655615656-Chloro-N-(2-cyclopropylethyl)pyridazine-3-carboxamide

Product 1

HCID 672049743-[6-(2-Cyclopropylethylcarbamoyl)pyridazin-3-ylamino]azetidine-1-carboxylic acid tert-butyl esterYield 43%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 6-chloropyridazine-3-carboxylic acid (2-cyclopropylethyl)amide (0.350 g, 1.55 mmol), 1-BOC-3-aminoazetidine (0.400 g, 2.32 mmol), tetrabutylammonium bromide (0.120 g, 0.36 mmol) and 1,8-diazabicyclo[5,4,0]undec-7-ene (1.000 g, 6.00 mmol) in 1,4-dioxane (30 mL) was heated under reflux overnight. The solvent was evaporated. The residue was washed with 1 M citric acid (50 mL) and ethyl ether (50 mL) was added. Ultrasonication of the mixture followed by filtration afforded 3-[6-(2-cyclopropylethylcarbamoyl)pyridazin-3-ylamino]azetidine-1-carboxylic acid tert-butyl ester as a white solid in 43% yield (0.240 g).

Workup

  1. temperaturewas heated
  2. temperatureunder reflux overnight
  3. customThe solvent was evaporated
  4. washThe residue was washed with 1 M citric acid (50 mL) and ethyl ether (50 mL)
  5. additionwas added
  6. customUltrasonication of the mixture
  7. filtrationfollowed by filtration

Sources & evidence

ORD record
ord-139acd746805433cac6f0cf2c75062ba
Source dataset
uspto-grants-2010_11
Patent number
US07829712B2

Reaction notes

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