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

HRID 1514717Notes

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])=[C:30]([F:35])[CH:29]=3)=[N:23][O:24][C:25]=2[CH2:26][OH:27])=[N:15][CH:14]=1>O1CCOCC1>[F:35][C:30]1[CH:29]=[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:33]=[CH:32][C:31]=1[F:34]

Participants

Conditions

Temperature: 50 °C

Procedure

Trimethylaluminium solution (2 M in toluene, 0.80 mL, 1.60 mmol) was added to a solution of 2-methoxyethylamine (93.3 μL, 1.06 mmol) in dioxane (4 mL). The mixture was stirred for 45 min at 50° C. Then a solution of 6-[3-(3,4-difluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-nicotinic acid methyl ester (100 mg, 0.27 mmol) in dioxane (4 mL) was added and the reaction mixture was stirred overnight at 85° C. The dioxane was removed by distillation. The remaining material was purified by chromatography (silica, ethyl acetate:heptane=2:3 to 1:0) to afford the title compound (14 mg, 13%) as a white solid. MS: m/e=418.2 [M−H]−.

Workup

stirringthe reaction mixture was stirred overnight at 85° C
customThe dioxane was removed by distillation
customThe remaining material was purified by chromatography (silica, ethyl acetate:heptane=2:3 to 1:0)

Sources & evidence

ORD record: ord-3daca77e49a24e2587a8514b0e0de96a
Source dataset: uspto-grants-2012_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08222246B2

Reaction notes

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