Sodium Chloride → 5-[3-(4-Fluoro-phenyl)-5-methyl-isoxazol-4-ylmethoxy]-2H-pyrazole-3-carboxylic acid pyrrolidin-1-ylamide

HRID 1695338Notes

Reaction equation

HRID 1695338 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:20]([OH:22])=O)[NH:18][N:19]=3)=[C:11]([CH3:23])[O:10][N:9]=2)=[CH:4][CH:3]=1.F[B-](F)(F)F.[N:29]1(OC(N(C)C)=[N+](C)C)[C:33]2[CH:34]=[CH:35][CH:36]=CC=2N=[N:30]1.C(N(CC)C(C)C)(C)C.Cl.NN1CCCC1.[Cl-].[Na+]>CN(C=O)C>[N:29]1([NH:30][C:20]([C:17]2[NH:18][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[CH3:23])[CH:16]=2)=[O:22])[CH2:33][CH2:34][CH2:35][CH2:36]1

Participants

7

Reactant 5

HCID 5234Sodium ChlorideHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 3017392Pyrrolidin-1-amine monohydrochlorideHCID 666436795-[3-(4-Fluoro-phenyl)-5-methyl-isoxazol-4-ylmethoxy]-2H-pyrazole-3-carboxylic acid

Product 1

HCID 497929225-[3-(4-Fluoro-phenyl)-5-methyl-isoxazol-4-ylmethoxy]-2H-pyrazole-3-carboxylic acid pyrrolidin-1-ylamideYield 75%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-[3-(4-fluoro-phenyl)-5-methyl-isoxazol-4-ylmethoxy]-2H-pyrazole-3-carboxylic acid (100 mg, 0.32 mmol) in DMF (5 mL) were added 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (152 mg, 0.47 mmol), N,N-diisopropyl ethyl amine (270 μL, 1.6 mmol) and N-aminopyrrolidine HCl (58 mg, 0.47 mmol). The resulting reaction mixture was stirred overnight at room temperature. The reaction mixture was then poured into aqueous sodium chloride (saturated) and extracted with ethyl acetate. The combined organic layers were then washed with water, citric acid solution and saturated sodium hydrogen carbonate solution and then dried over sodium sulfate, filtered and evaporated. Concentration and purification by chromatography (silica, dichloromethane:methanol=100:0 to 9:1) afforded the title compound (91 mg, 75%) as a white solid. MS: m/e=386.2 [M+H]+.

Workup

  1. customThe resulting reaction mixture
  2. extractionextracted with ethyl acetate
  3. washThe combined organic layers were then washed with water, citric acid solution and saturated sodium hydrogen carbonate solution
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. concentrationConcentration and purification by chromatography (silica, dichloromethane:methanol=100:0 to 9:1)

Sources & evidence

ORD record
ord-f7080502f4174adaa74fb697d30a87c9
Source dataset
uspto-grants-2012_04
Patent number
US08163728B2

Reaction notes

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