Isopropylamine → 6-(3-Butyl-5-methyl-isoxazol-4-ylmethoxy)-N-isopropyl-nicotinamide

HRID 1807494Notes

Reaction equation

HRID 1807494 reaction equation
C[Al](C)C.[CH:5]([NH2:8])([CH3:7])[CH3:6].CO[C:11](=[O:30])[C:12]1[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]2[C:21]([CH2:26][CH2:27][CH2:28][CH3:29])=[N:22][O:23][C:24]=2[CH3:25])=[N:14][CH:13]=1>C1(C)C=CC=CC=1.O1CCOCC1>[CH:5]([O:23][CH:24]([CH3:25])[CH3:20])([CH3:7])[CH3:6].[CH2:26]([C:21]1[C:20]([CH2:19][O:18][C:15]2[CH:16]=[CH:17][C:12]([C:11]([NH:8][CH:5]([CH3:7])[CH3:6])=[O:30])=[CH:13][N:14]=2)=[C:24]([CH3:25])[O:23][N:22]=1)[CH2:27][CH2:28][CH3:29]

Participants

7

Reactant 3

HCID 6363IsopropylamineHCID 16682925TrimethylaluminumHCID 665991586-(3-Butyl-5-methyl-isoxazol-4-ylmethoxy)-nicotinic acid methyl ester

Product 2

HCID 7914Diisopropyl EtherHCID 498047566-(3-Butyl-5-methyl-isoxazol-4-ylmethoxy)-N-isopropyl-nicotinamideYield 30.6%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
90 °C

Procedure

Trimethylaluminium (3 mL of a 2 M solution in toluene, 6 mmol) was added dropwise to a stirred solution of isopropylamine (355 mg, 6.0 mmol) in dioxane (4 mL) at room temperature and under argon. After 1 h, a solution of 6-(3-butyl-5-methyl-isoxazol-4-ylmethoxy)-nicotinic acid methyl ester (537 mg, 1.5 mmol) in dioxane (4 mL) was added and the reaction mixture warmed to 90° C. After 2 h the reaction mixture was cooled and poured onto ice/water. The resultant mixture was extracted with ethyl acetate then the combined extracts were washed with Seignette salt solution. The organic phase was dried, filtered and evaporated then purified by chromatography (silica, 0 to 60% ethyl acetate in heptane) then trituration with diisopropyl ether to give the title compound (76 mg, 15%) as a white solid. MS: m/e=332.4 [M+H]+.

Workup

  1. temperatureAfter 2 h the reaction mixture was cooled
  2. additionpoured onto ice/water
  3. extractionThe resultant mixture was extracted with ethyl acetate
  4. washthe combined extracts were washed with Seignette salt solution
  5. customThe organic phase was dried
  6. filtrationfiltered
  7. customevaporated
  8. customthen purified by chromatography (silica, 0 to 60% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-32b91403c47441a58bc7cde75647b43a
Source dataset
uspto-grants-2013_01
Patent number
US08357703B2

Reaction notes

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