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

HRID 1514683Notes

Reaction equation

HRID 1514683 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])=[CH:29][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:28]=[CH:29][C:30]([F:33])=[CH:31][CH:32]=4)=[N:22][O:23][C:24]=3[CH2:25][OH:26])=[N:14][CH:13]=2)[CH2:7][CH2:6]1

Participants

5

Reactant 3

HCID 69828CyclopropylamineHCID 16682925TrimethylaluminumHCID 667181316-[3-(4-Fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-nicotinic acid methyl ester

Product 1

HCID 46928573N-Cyclopropyl-6-[3-(4-fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-nicotinamideYield 42%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

Trimethylaluminium solution (2M in toluene, 0.51 mL, 1.00 mmol) was added to a solution of cyclopropylamine (71.9 μL, 1.00 mmol) in dioxane (4.0 mL). After 45 min stirring at 50° C. a solution of 6-[3-(4-fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-nicotinic acid methyl ester (90 mg, 0.25 mmol) in dioxane (4.0 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 afford the title compound (40 mg, 42%) as light brown solid. MS: m/e=382.1 [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-13492c1a6dec43f38213a50f91f06853
Source dataset
uspto-grants-2012_07
Patent number
US08222246B2

Reaction notes

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