Isopropylamine → Ethyl-5-phenyl-4-(2-pyridinyl)-1H-pyrazole-1-acetate

HRID 1650722

Reaction equation

HRID 1650722 reaction equation
[C:1]1([C:7](=O)[CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:16]OC(OC)N(C)C.C(N)(C)C.Cl.[NH:29]([CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])[NH2:30]>C(OC)(C)(C)C.C(OCC)(=O)C.C(O)C.C(Cl)Cl>[CH2:35]([O:34][C:32](=[O:33])[CH2:31][N:29]1[C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[C:8]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=2)[CH:16]=[N:30]1)[CH3:36]

Participants

9

Reactant 4

HCID 6363IsopropylamineHCID 741791-Phenyl-2-(2-pyridinyl)ethanoneHCID 78373Dimethylformamide dimethyl acetalHCID 11593468Acetic acid, 2-hydrazinyl-, ethyl ester, hydrochloride (1:1)

Product 1

HCID 15086050Ethyl-5-phenyl-4-(2-pyridinyl)-1H-pyrazole-1-acetateYield 61.6%

Reagents, catalysts & solvents 4

HCID 702EthanolSolvent2×HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

A solution of 26 g (0.132 mol) of 1-phenyl-2-(2-pyridinyl)ethanone and 19.3 mL (0.145 mol) of dimethylformamide dimethylacetal in 100 mL of methyl t-butyl ether was refluxed 4 hr. Because TLC on silica gel with 10% isopropylamine in ethyl acetate showed little reaction, another 20 mL of DMF dimethylacetal was added and the solution refluxed a further 6 hr. The solvent was stripped and the resulting crude, oily β-ketoenamine was dissolved in 400 mL of ethanol. The ethanol solution was heated to 40° with 22 g (0.143 mol) of ethyl hydrazinoacetate hydrochloride for about 1.5 hr. The solvent was stripped, and the resulting impure product was dissolved in a small amount of methylene dichloride and applied to a column of 850 g of silica gel. The column was eluted with 2:1 hexane-ethyl acetate to yield 25 g of yellow solid product, mp 98°-100° C. after evaporation of the solvent.

Workup

  1. temperaturethe solution refluxed a further 6 hr
  2. washThe column was eluted with 2:1 hexane-ethyl acetate

Sources & evidence

ORD record
ord-60b73e2681bd476d9b806b0a330e7602
Source dataset
uspto-grants-1990_05
Patent number
US04925857

Linked notes

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