Isopropylamine → 5-[3-(4-Fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-pyridine-2-carboxylic acid isopropylamide

HRID 1962988Notes

Reaction equation

HRID 1962988 reaction equation
[CH:1]([NH2:4])([CH3:3])[CH3:2].C[Al](C)C.C([O:11][C:12]([C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][C:22]2[C:23]([C:29]3[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=3)=[N:24][O:25][C:26]=2[CH2:27][OH:28])=[CH:16][N:15]=1)=O)C>O1CCOCC1>[CH:1]([NH:4][C:12]([C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][C:22]2[C:23]([C:29]3[CH:30]=[CH:31][C:32]([F:35])=[CH:33][CH:34]=3)=[N:24][O:25][C:26]=2[CH2:27][OH:28])=[CH:16][N:15]=1)=[O:11])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 6363IsopropylamineHCID 16682925TrimethylaluminumHCID 666445155-[3-(4-Fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-pyridine-2-carboxylic acid ethyl ester

Product 1

HCID 498041645-[3-(4-Fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-pyridine-2-carboxylic acid isopropylamideYield 22.1%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

To a stirred solution of isopropylamine (47.8 mg, 0.8 mmol) in dioxane (3.75 mL) was added dropwise a trimethylaluminium (603 μL, 2 M solution in toluene, 1.21 mmol) and the resulting solution stirred under argon for 30 min. A solution of 5-[3-(4-fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-pyridine-2-carboxylic acid ethyl ester (75 mg, 0.2 mmol) in dioxane (3.75 mL) was then added and the resulting solution stirred under argon for a further 1 h at 50° C. The reaction mixture was cooled and concentrated in vacuo. Purification by chromatography (silica, 0 to 10% methanol in dichloromethane) gave the title compound (17 mg, 21%) as a colourless gum. MS: m/e=386.2 [M+H]+.

Workup

  1. stirringthe resulting solution stirred under argon for a further 1 h at 50° C
  2. temperatureThe reaction mixture was cooled
  3. concentrationconcentrated in vacuo
  4. customPurification by chromatography (silica, 0 to 10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-fe44893ffe9a40128ee863109384123a
Source dataset
uspto-grants-2013_04
Patent number
US08415379B2

Reaction notes

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