2-Methoxyethylamine → 6-[3-(4-Fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-N-(2-methoxy-ethyl)-nicotinamide

HRID 1514684Notes

Reaction equation

HRID 1514684 reaction equation
C[Al](C)C.[CH3:5][O:6][CH2:7][CH2:8][NH2:9].C[O:11][C:12](=O)[C:13]1[CH:18]=[CH:17][C:16]([O:19][CH2:20][C:21]2[C:22]([C:28]3[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=3)=[N:23][O:24][C:25]=2[CH2:26][OH:27])=[N:15][CH:14]=1>O1CCOCC1>[F:34][C:31]1[CH:32]=[CH:33][C:28]([C:22]2[C:21]([CH2:20][O:19][C:16]3[CH:17]=[CH:18][C:13]([C:12]([NH:9][CH2:8][CH2:7][O:6][CH3:5])=[O:11])=[CH:14][N:15]=3)=[C:25]([CH2:26][OH:27])[O:24][N:23]=2)=[CH:29][CH:30]=1

Participants

5

Reactant 3

HCID 80182-MethoxyethylamineHCID 16682925TrimethylaluminumHCID 667181316-[3-(4-Fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-nicotinic acid methyl ester

Product 1

HCID 469285746-[3-(4-Fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-N-(2-methoxy-ethyl)-nicotinamideYield 16%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

Trimethylaluminium solution (2 M in toluene, 0.51 mL, 1.00 mmol) was added to a solution of 2-methoxyethylamine (88.0 μL, 1.00 mmol) in dioxane (4 mL). After stirring for 45 min at 50° C. a solution of 6-[3-(4-fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-nicotinic acid methyl ester (90.0 mg, 0.25 mmol) in dioxane (4 mL) was added and stirring was continued overnight at 85° C. The dioxane was removed by distillation. The remaining material was purified by chromatography (silica, ethyl acetate) to yield the title compound (16.1 mg, 16%) as a white solid. MS: m/e=400.0 [M−H]−.

Workup

  1. additionwas added
  2. customThe dioxane was removed by distillation
  3. customThe remaining material was purified by chromatography (silica, ethyl acetate)

Sources & evidence

ORD record
ord-478bd62bc87c49a885ee12281db427cb
Source dataset
uspto-grants-2012_07
Patent number
US08222246B2

Reaction notes

Loading…