Cyclopropylamine → N-Cyclopropyl-6-[3-(3,4-difluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-nicotinamide

HRID 1514713Notes

Reaction equation

C[Al](C)C.[CH:5]1([NH2:8])[CH2:7][CH2:6]1.C[O:10][C:11](=O)[C:12]1[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]2[C:21]([C:27]3[CH:32]=[CH:31][C:30]([F:33])=[C:29]([F:34])[CH:28]=3)=[N:22][O:23][C:24]=2[CH2:25][OH:26])=[N:14][CH:13]=1>O1CCOCC1>[CH:5]1([NH:8][C:11](=[O:10])[C:12]2[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]3[C:21]([C:27]4[CH:32]=[CH:31][C:30]([F:33])=[C:29]([F:34])[CH:28]=4)=[N:22][O:23][C:24]=3[CH2:25][OH:26])=[N:14][CH:13]=2)[CH2:7][CH2:6]1

Participants

Conditions

Temperature: 50 °C

Procedure

Trimethylaluminium solution (2 M in toluene, 0.8 mL, 1.60 mmol) was added to a solution of cyclopropylamine (62.0 mg, 1.06 mmol) in dioxane (5 mL). The mixture was stirred for 1 h 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 (5 mL) was added. 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=8:2 to 1:0) to afford the title compound (27 mg, 25%) as a colourless oil. MS: m/e=402.3 [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=8:2 to 1:0)

Sources & evidence

ORD record: ord-8e819937ffed412b8ada60dd0a8eed21
Source dataset: uspto-grants-2012_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08222246B2

Reaction notes

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