Isopropylamine → 6-{[3-(4-Fluoro-phenyl)-5-methyl-isoxazol-4-ylmethyl]-amino}-N-isopropyl-nicotinamide

HRID 331903Notes

Reaction equation

HRID 331903 reaction equation
C[Al](C)C.[CH:5]([NH2:8])([CH3:7])[CH3:6].CO[C:11](=[O:33])[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>[F:32][C:29]1[CH:30]=[CH:31][C:26]([C:21]2[C:20]([CH2:19][NH:18][C:15]3[CH:16]=[CH:17][C:12]([C:11]([NH:8][CH:5]([CH3:7])[CH3:6])=[O:33])=[CH:13][N:14]=3)=[C:24]([CH3:25])[O:23][N:22]=2)=[CH:27][CH:28]=1

Participants

6

Reactant 4

HCID 6363IsopropylamineHCID 9855836Potassium sodium tartarateHCID 16682925TrimethylaluminumHCID 684433926-{[3-(4-Fluoro-phenyl)-5-methyl-isoxazol-4-ylmethyl]-amino}-nicotinic acid methyl ester

Product 1

HCID 684426016-{[3-(4-Fluoro-phenyl)-5-methyl-isoxazol-4-ylmethyl]-amino}-N-isopropyl-nicotinamideYield 71.9%

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 isopropylamine (48 mg, 70 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 (53 mg, 70%) which was obtained as an off white foam. MS: m/e=369.4 [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-91834f1a86d548daa154321ec0f0571f
Source dataset
uspto-grants-2014_11
Patent number
US08877782B2

Reaction notes

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