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

HRID 1695391Notes

Reaction equation

HRID 1695391 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]([CH3:24])[O:10][N:9]=2)=[CH:4][CH:3]=1.F[B-](F)(F)F.[N:30]1(OC(N(C)C)=[N+](C)C)[C:34]2[CH:35]=[CH:36][CH:37]=CC=2N=[N:31]1.C(N(CC)C(C)C)(C)C.Cl.NN1CCCC1.[Cl-].[Na+]>CN(C=O)C>[N:30]1([NH:31][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[CH3:24])[CH:16]=2)=[O:23])[CH2:34][CH2:35][CH2:36][CH2:37]1

Participants

7

Reactant 5

HCID 5234Sodium ChlorideHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 3017392Pyrrolidin-1-amine monohydrochlorideHCID 66643617HCID 66643617, compound

Product 1

HCID 595684585-[3-(4-Fluoro-phenyl)-5-methyl-isoxazol-4-ylmethoxy]-2-methyl-2H-pyrazole-3-carboxylic acid pyrrolidin-1-ylamideYield 58%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-[3-(4-fluoro-phenyl)-5-methyl-isoxazol-4-ylmethoxy]-2-methyl-2H-pyrazole-3-carboxylic acid (200 mg, 0.6 mmol) in DMF (5 mL) were added 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (291 mg, 0.91 mmol), N,N-diisopropyl ethyl amine (510 μL, 3.0 mmol) and N-aminopyrrolidine HCl (111 mg, 0.91 mmol). The resulting reaction mixture was 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, 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) afforded the title compound (139 mg, 58%) as a colorless oil. MS: m/e=400.2 [M+H]+.

Workup

  1. customThe resulting reaction mixture
  2. extractionthe mixture was extracted 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)

Sources & evidence

ORD record
ord-73e3a4dcec9f415ba07b459b4fd5df8a
Source dataset
uspto-grants-2012_04
Patent number
US08163728B2

Reaction notes

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