Water → 6-[(5-Methyl-3-phenyl-isoxazol-4-ylmethyl)-amino]-pyridazine-3-carboxylic acid cyclopropylmethyl-amide

HRID 548875Notes

Reaction equation

HRID 548875 reaction equation
[NH2:1][CH2:2][CH:3]1[CH2:5][CH2:4]1.C[Al](C)C.C[O:11][C:12]([C:14]1[N:15]=[N:16][C:17]([NH:20][CH2:21][C:22]2[C:23]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[N:24][O:25][C:26]=2[CH3:27])=[CH:18][CH:19]=1)=O.O>O1CCOCC1>[CH:3]1([CH2:2][NH:1][C:12]([C:14]2[N:15]=[N:16][C:17]([NH:20][CH2:21][C:22]3[C:23]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)=[N:24][O:25][C:26]=3[CH3:27])=[CH:18][CH:19]=2)=[O:11])[CH2:5][CH2:4]1

Participants

6

Reactant 4

HCID 962WaterHCID 75646CyclopropanemethanamineHCID 16682925TrimethylaluminumHCID 671576076-[(5-Methyl-3-phenyl-isoxazol-4-ylmethyl)-amino]-pyridazine-3-carboxylic acid methyl ester

Product 1

HCID 671583246-[(5-Methyl-3-phenyl-isoxazol-4-ylmethyl)-amino]-pyridazine-3-carboxylic acid cyclopropylmethyl-amideYield 55%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

To a solution of aminomethylcyclopropane (0.11 mL, 1.2 mmol) in dioxane (5 mL) was added dropwise trimethylaluminum solution (2 M solution in hexane, 0.62 mL, 1.24 mmol). After stirring for 1 h at room temperature a suspension of 6-[(5-methyl-3-phenyl-isoxazol-4-ylmethyl)-amino]-pyridazine-3-carboxylic acid methyl ester (100 mg, 0.3 mmol) in dioxane (5 mL) was added. The reaction mixture was stirred at 90° C. for 2 h, cooled to room temperature and poured into water. Extraction (ethyl acetate/saturated aqueous Seignette salt solution) followed by drying of the organic phase over sodium sulfate and evaporation afforded an oil. Purification by chromatography (SiO2, heptane:ethyl acetate=100:0 to 0:100) afforded the title compound (60 mg, 54%) which was obtained as a light yellow foam. MS: m/e=364.5 [M+H]+.

Workup

  1. additionwas added
  2. stirringThe reaction mixture was stirred at 90° C. for 2 h
  3. temperaturecooled to room temperature
  4. extractionExtraction (ethyl acetate/saturated aqueous Seignette salt solution)
  5. dry with materialby drying of the organic phase over sodium sulfate and evaporation
  6. customafforded an oil
  7. customPurification by chromatography (SiO2, heptane:ethyl acetate=100:0 to 0:100)

Sources & evidence

ORD record
ord-d5bb4fda29b34fd294f618f5c51e14f9
Source dataset
uspto-grants-2011_05
Patent number
US07943619B2

Reaction notes

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