Diisopropylethylamine → 5-[3-(4-Fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-pyridine-2-carboxylic acid ((S)-1-hydroxymethyl-propyl)-amide

HRID 1962993Notes

Reaction equation

HRID 1962993 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([CH2:13][O:14][C:15]3[CH:16]=[CH:17][C:18]([C:21](O)=[O:22])=[N:19][CH:20]=3)=[C:11]([CH2:24][OH:25])[O:10][N:9]=2)=[CH:4][CH:3]=1.O.ON1[C:32]2C=C[CH:35]=[CH:36][C:31]=2[N:30]=N1.C(N(C(C)C)C(C)C)C.Cl.CN(C)CCCN=C=NCC.C[C@H]([OH:62])CN>C1COCC1>[OH:62][CH2:32][C@@H:31]([NH:30][C:21]([C:18]1[CH:17]=[CH:16][C:15]([O:14][CH2:13][C:12]2[C:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)=[N:9][O:10][C:11]=2[CH2:24][OH:25])=[CH:20][N:19]=1)=[O:22])[CH2:36][CH3:35]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 7311736(S)-(+)-1-Aminopropan-2-olHCID 666443945-[3-(4-Fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-pyridine-2-carboxylic acid

Product 1

HCID 498044605-[3-(4-Fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-pyridine-2-carboxylic acid ((S)-1-hydroxymethyl-propyl)-amideYield 55%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-[3-(4-fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-pyridine-2-carboxylic acid (75 mg, 0.22 mmol) in THF (2 mL) was added 1-hydroxy-benzotriazole hydrate (34.1 mg, 0.22 mmol), N-ethyldiisopropylamine (95.2 μL, 0.55 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (42.6 mg, 0.22 mmol) and S-(+)-1-amino-2-propanol (16.7 mg, 0.22 mmol). The reaction mixture was stirred overnight at room temperature. Evaporation of the mixture followed by chromatography (silica, dichloro-methane:methanol=1:0 to 9:1) afforded the title compound (50 mg, 55%) as a colourless gum. MS: m/e=416.2 [M+H]+.

Workup

  1. customEvaporation of the mixture

Sources & evidence

ORD record
ord-5c561d0b7c254c1c88709301e85ce777
Source dataset
uspto-grants-2013_04
Patent number
US08415379B2

Reaction notes

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