Sodium Chloride → 5-[3-(4-Chloro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-2-methyl-2H-pyrazole-3-carboxylic acid (2-hydroxy-1,1-dimethyl-ethyl)-amide

HRID 1695449Notes

Reaction equation

HRID 1695449 reaction equation
[Cl: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](O)=[O:22])[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][C:47]([CH3:51])([CH3:50])[CH2:48][OH:49].[Cl-].[Na+]>C1COCC1>[OH:49][CH2:48][C:47]([NH:46][C:21]([C:17]1[N:18]([CH3:20])[N:19]=[C:15]([O:14][CH2:13][C:12]2[C:8]([C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=3)=[N:9][O:10][C:11]=2[CH2:24][OH:25])[CH:16]=1)=[O:22])([CH3:51])[CH3:50]

Participants

7

Reactant 5

HCID 5234Sodium ChlorideHCID 118072-Amino-2-methyl-1-propanolHCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 666437235-[3-(4-chloro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-2-methyl-2H-pyrazole-3-carboxylic acid

Product 1

HCID 497930925-[3-(4-Chloro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-2-methyl-2H-pyrazole-3-carboxylic acid (2-hydroxy-1,1-dimethyl-ethyl)-amideYield 26.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-[3-(4-chloro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-2-methyl-2H-pyrazole-3-carboxylic acid (100 mg, 0.28 mmol) in THF (2.7 mL) was added 1-hydroxybenzotriazole hydrate (43.0 mg, 0.28 mmol), N-ethyldiisopropylamine (120 μL, 0.69 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimidazole hydrochloride (43.0 mg, 0.28 mmol) and 2-amino-2-methyl-1-propanol (25.3 mg, 0.28 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 (32 mg, 26%) as a white solid. MS: m/e=435.3 [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-aeeba5c75cf94b1d9d515a0cb00a486f
Source dataset
uspto-grants-2012_04
Patent number
US08163728B2

Reaction notes

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