Cyclopropylamine → N-Cyclopropyl-6-{[3-(4-fluoro-phenyl)-5-methyl-isoxazol-4-ylmethyl]-amino}-nicotinamide

HRID 83305Notes

Reaction equation

HRID 83305 reaction equation
C[Al](C)C.[CH:5]1([NH2:8])[CH2:7][CH2:6]1.C[O:10][C:11](=O)[C:12]1[CH:17]=[CH:16][C:15]([NH:18][CH2:19][C:20]2[C:21]([C:26]3[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=3)=[N:22][O:23][C:24]=2[CH3:25])=[N:14][CH:13]=1.C(C(C(C([O-])=O)O)O)([O-])=O.[K+].[Na+]>O1CCOCC1>[CH:5]1([NH:8][C:11](=[O:10])[C:12]2[CH:17]=[CH:16][C:15]([NH:18][CH2:19][C:20]3[C:21]([C:26]4[CH:27]=[CH:28][C:29]([F:32])=[CH:30][CH:31]=4)=[N:22][O:23][C:24]=3[CH3:25])=[N:14][CH:13]=2)[CH2:7][CH2:6]1

Participants

6

Reactant 4

HCID 69828CyclopropylamineHCID 9855836Potassium sodium tartarateHCID 16682925TrimethylaluminumHCID 684433926-{[3-(4-Fluoro-phenyl)-5-methyl-isoxazol-4-ylmethyl]-amino}-nicotinic acid methyl ester

Product 1

HCID 42629450N-Cyclopropyl-6-{[3-(4-fluoro-phenyl)-5-methyl-isoxazol-4-ylmethyl]-amino}-nicotinamideYield 61.4%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

A solution of trimethylaluminium (2 M in toluene, 410 μL, 0.8 mmol) was added dropwise (exothermic) to a solution of cyclopropylamine (47 mg, 58 μL, 0.8 mmol) in dioxane (5 mL) and the resulting mixture was stirred at room temperature for 1 h. Then a solution of 6-{[3-(4-fluoro-phenyl)-5-methyl-isoxazol-4-ylmethyl]-amino}-nicotinic acid methyl ester (70 mg, 0.2 mmol) in dioxane (2.5 mL) was added. The resulting mixture was then heated at 85-95° C. for 5 h and then cooled to room temperature and then poured into a sodium potassium tartrate solution and extracted with ethyl acetate which was then washed with brine, dried over sodium sulfate and evaporated. Purification by chromatography (SiO2, heptane:ethyl acetate=100:0 to 0:100) afforded the title compound (45 mg, 60%) which was obtained as an off white foam. MS: m/e=367.0 [M+H]+.

Workup

  1. temperatureThe resulting mixture was then heated at 85-95° C. for 5 h
  2. temperaturecooled to room temperature
  3. extractionextracted with ethyl acetate which
  4. washwas then washed with brine
  5. dry with materialdried over sodium sulfate
  6. customevaporated
  7. customPurification by chromatography (SiO2, heptane:ethyl acetate=100:0 to 0:100)

Sources & evidence

ORD record
ord-3bd623ca78944411876711ca0cbf7c63
Source dataset
uspto-grants-2014_09
Patent number
US08846719B2

Reaction notes

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