Potassium Sodium Tartrate → 6-[3-(5-Fluoro-pyridin-2-yl)-5-methyl-isoxazol-4-ylmethoxy]-N-morpholin-4-yl-nicotinamide

HRID 1516198Notes

Reaction equation

HRID 1516198 reaction equation
C[Al](C)C.[NH2:5][N:6]1[CH2:11][CH2:10][O:9][CH2:8][CH2:7]1.C[O:13][C:14](=O)[C:15]1[CH:20]=[CH:19][C:18]([O:21][CH2:22][C:23]2[C:24]([C:29]3[CH:34]=[CH:33][C:32]([F:35])=[CH:31][N:30]=3)=[N:25][O:26][C:27]=2[CH3:28])=[N:17][CH:16]=1.[C@H](O)(C([O-])=O)[C@@H](O)C([O-])=O.[Na+].[K+]>O1CCOCC1>[F:35][C:32]1[CH:33]=[CH:34][C:29]([C:24]2[C:23]([CH2:22][O:21][C:18]3[CH:19]=[CH:20][C:15]([C:14]([NH:5][N:6]4[CH2:11][CH2:10][O:9][CH2:8][CH2:7]4)=[O:13])=[CH:16][N:17]=3)=[C:27]([CH3:28])[O:26][N:25]=2)=[N:30][CH:31]=1

Participants

6

Reactant 4

HCID 9357Potassium Sodium TartrateHCID 20315N-AminomorpholineHCID 16682925TrimethylaluminumHCID 665989716-[3-(5-Fluoro-pyridin-2-yl)-5-methyl-isoxazol-4-ylmethoxy]-nicotinic acid methyl ester

Product 1

HCID 595639786-[3-(5-Fluoro-pyridin-2-yl)-5-methyl-isoxazol-4-ylmethoxy]-N-morpholin-4-yl-nicotinamideYield 40%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

A solution of trimethylaluminium (2 M in toluene, 0.58 mL, 1.1 mmol) was added dropwise (exothermic) to a solution of N-aminomorpholine (111 μL, 1.2 mmol) in dioxane (2.5 mL) and the resulting mixture was stirred at room temperature for 1 h. Then a solution of 6-[3-(5-fluoro-pyridin-2-yl)-5-methyl-isoxazol-4-ylmethoxy]-nicotinic acid methyl ester (100 mg, 0.29 mmol) in dioxane (2.5 mL) was added. The resulting mixture was then heated at 90° C. overnight and then cooled to room temperature and then poured into Seignette salt solution and extracted with ethyl acetate which was then washed with brine, dried over sodium sulfate and evaporated. Purification by chromatography (silica, dichloromethane:methanol=9:1) afforded the title compound (47 mg, 40%) which was obtained as a white solid. MS: m/e=414.3 [M+H]+.

Workup

  1. temperatureThe resulting mixture was then heated at 90° C. overnight
  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 (silica, dichloromethane:methanol=9:1)

Sources & evidence

ORD record
ord-fee17536519547fba9c80df9f76b6afe
Source dataset
uspto-grants-2012_07
Patent number
US08227461B2

Reaction notes

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