Diisopropylethylamine → 5-bromo-N-(5-(4-methoxyphenyl)-1H-pyrazol-3-yl)pentanamide

HRID 1695208Notes

Reaction equation

HRID 1695208 reaction equation
[Br:1][CH2:2][CH2:3][CH2:4][CH2:5][C:6](Cl)=[O:7].[CH3:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[NH:21][N:20]=[C:19]([NH2:22])[CH:18]=2)=[CH:13][CH:12]=1.C(N(C(C)C)CC)(C)C>CC(N(C)C)=O>[CH3:9][O:10][C:11]1[CH:12]=[CH:13][C:14]([C:17]2[NH:21][N:20]=[C:19]([NH:22][C:6](=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2][Br:1])[CH:18]=2)=[CH:15][CH:16]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 5211735-Bromovaleryl chlorideHCID 27564693-Amino-5-(4-methoxyphenyl)pyrazole

Product 1

HCID 577800445-bromo-N-(5-(4-methoxyphenyl)-1H-pyrazol-3-yl)pentanamide

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent2×

Procedure

A solution of 5-bromovaleryl chloride (2.1 mL, 15.7 mmol) in dry dimethylacetamide (DMA) (35 mL) was cooled to −10° C. (ice water bath) under N2; a solution of 5-(4-methoxy-phenyl)-1H-pyrazol-3-ylamine (3.0 g, 15.7 mmol) and diisopropylethylamine (2.74 mL, 15.7 mmol) in dry DMA (15 mL) was added over 30 min. After two hours at −10° C., LCMS shows completion of the reaction (acylation on the pyrazole ring was also detected). The reaction was quenched by addition of H2O (ca. 50 mL), and the thick white precipitate formed upon addition of water is recovered by filtration. When the reaction was allowed to reach room temperature before quenching, a putative exchange of Br with Cl caused reactivity problems in subsequent steps. Washing with Et2O (3×10 mL) efficiently removed the byproduct (acylation on pyrazole ring). 4.68 g of the title compound was obtained as a white powder (13.3 mmol, 85% yield). Mp=149.5-151.5° C.

Workup

  1. customcompletion of the reaction (acylation on the pyrazole ring
  2. customThe reaction was quenched by addition of H2O (ca. 50 mL)
  3. customthe thick white precipitate formed upon addition of water
  4. filtrationis recovered by filtration
  5. customto reach room temperature
  6. custombefore quenching
  7. washWashing with Et2O (3×10 mL)
  8. customefficiently removed the byproduct (acylation on pyrazole ring)

Sources & evidence

ORD record
ord-da1880ef546947c9b404fe30e9695940
Source dataset
uspto-grants-2012_04
Patent number
US08163729B2

Reaction notes

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