Sodium Chloride → Rac-5-[3-(4-fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-2-methyl-2h-pyrazole-3-carboxylic acid (tetrahydro-furan-3-yl)-amide

HRID 1695437Notes

Reaction equation

HRID 1695437 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]=[C:17]([C:21]([OH:23])=O)[N:18]([CH3:20])[N:19]=3)=[C:11]([CH2:24][OH:25])[O:10][N:9]=2)=[CH:4][CH:3]=1.O.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)C(C)C)C.[NH2:46][CH:47]1[CH2:51][CH2:50][O:49][CH2:48]1.[Cl-].[Na+]>C1COCC1>[O:49]1[CH2:50][CH2:51][CH:47]([NH:46][C:21]([C:17]2[N:18]([CH3:20])[N:19]=[C:15]([O:14][CH2:13][C:12]3[C:8]([C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=4)=[N:9][O:10][C:11]=3[CH2:24][OH:25])[CH:16]=2)=[O:23])[CH2:48]1

Participants

7

Reactant 5

HCID 5234Sodium ChlorideHCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 3365553Oxolan-3-amineHCID 666438625-[3-(4-fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-2-methyl-2H-pyrazole-3-carboxylic acid

Product 1

HCID 59568389Rac-5-[3-(4-fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-2-methyl-2h-pyrazole-3-carboxylic acid (tetrahydro-furan-3-yl)-amideYield 50%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-[3-(4-fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-2-methyl-2H-pyrazole-3-carboxylic acid (100 mg, 0.29 mmol) in THF (10 mL) was added 1-hydroxybenzotriazole hydrate (45.0 mg, 0.29 mmol), N-ethyldiisopropylamine (126 μL, 0.76 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimidazole hydrochloride (56.3 mg, 0.29 mmol) and rac-3-aminotetrahydrofuran (25.1 mg, 0.29 mmol) and the resulting mixture stirred overnight at room temperature. The reaction mixture was then poured into aqueous sodium chloride (saturated) and the mixture was extracted with ethyl acetate. The combined organic layers were then washed with water and saturated sodium hydrogen carbonate solution and then dried over sodium sulfate, filtered and evaporated. Concentration and purification by chromatography (silica, dichloromethane:methanol=99:1 to 95:5) afforded the title compound (60 mg, 50%) as a white solid. MS: m/e=415.1 [M−H]−.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe combined organic layers were then washed with water and saturated sodium hydrogen carbonate solution
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. concentrationConcentration and purification by chromatography (silica, dichloromethane:methanol=99:1 to 95:5)

Sources & evidence

ORD record
ord-9ec924369fb543bab8d7916fdb0d2f97
Source dataset
uspto-grants-2012_04
Patent number
US08163728B2

Reaction notes

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