N,N'-Dimethylethylenediamine → Ethyl 1-(1-ethoxyethyl)-3-[4-(4-methylpiperazin-1-yl)benzoylamino]-1H-thieno[2,3-c]pyrazole-5-carboxylate

HRID 736280Notes

Reaction equation

HRID 736280 reaction equation
Br[C:2]1[C:3]2[CH:14]=[C:13]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[S:12][C:4]=2[N:5]([CH:7]([O:9][CH2:10][CH3:11])[CH3:8])[N:6]=1.[CH3:20][N:21]1[CH2:26][CH2:25][N:24]([C:27]2[CH:35]=[CH:34][C:30]([C:31]([NH2:33])=[O:32])=[CH:29][CH:28]=2)[CH2:23][CH2:22]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CNCCNC>[Cu]I.O1CCOCC1>[CH2:10]([O:9][CH:7]([N:5]1[C:4]2[S:12][C:13]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:14][C:3]=2[C:2]([NH:33][C:31](=[O:32])[C:30]2[CH:29]=[CH:28][C:27]([N:24]3[CH2:23][CH2:22][N:21]([CH3:20])[CH2:26][CH2:25]3)=[CH:35][CH:34]=2)=[N:6]1)[CH3:8])[CH3:11]

Participants

7

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 62657Potassium Phosphate, TribasicHCID 223215944-(4-Methylpiperazin-1-yl)benzamideHCID 57487832ethyl 3-bromo-1-(1-ethoxyethyl)-1H-thieno[2,3-c]pyrazole-5-carboxylate

Product 1

HCID 57848799Ethyl 1-(1-ethoxyethyl)-3-[4-(4-methylpiperazin-1-yl)benzoylamino]-1H-thieno[2,3-c]pyrazole-5-carboxylateYield 27%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

Ethyl 3-bromo-1-(1-ethoxyethyl)-1H-thieno[2,3-c]pyrazole-5-carboxylate (10.9 g, 31 mmol), 4-(4-methylpiperazin-1-yl)benzamide (9 g, 41 mmol, 1.3 eq.), copper(I)iodide (0.601 g, 3.1 mmol, 0.1 eq.), preground tripotassium phosphate (20.1 g, 94 mmol, 3 eq.) and 70 mL of anhydrous dioxane degassed beforehand with argon are placed in a 500 mL round-bottomed flask under argon. N,N′-Dimethylethylenediamine (0.336 mL, 3.16 mmol, 0.1 eq.) is added to this suspension by syringe. The reaction mixture is then heated at a temperature in the region of 110° C. for a period of 24 hours. The dioxane is then evaporated off under vacuum and the residue is diluted with ethyl acetate (300 mL) and 150 mL of water. The organic phase is washed with 100 mL of water, dried over magnesium sulfate and then concentrated to dryness under reduced pressure. The residue is purified by chromatography on silica gel, eluting at the start with a dichloromethane/methanol mixture (90/10 by volume). Ethyl 1-(1-ethoxyethyl)-3-[4-(4-methylpiperazin-1-yl)benzoylamino]-1H-thieno[2,3-c]pyrazole-5-carboxylate (4.05 g, 27%) is thus obtained in the form of a pale yellow oil, which product is used directly in the following step.

Workup

  1. customThe dioxane is then evaporated off under vacuum
  2. additionthe residue is diluted with ethyl acetate (300 mL) and 150 mL of water
  3. washThe organic phase is washed with 100 mL of water
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated to dryness under reduced pressure
  6. customThe residue is purified by chromatography on silica gel
  7. washeluting at the start with a dichloromethane/methanol mixture (90/10 by volume)

Sources & evidence

ORD record
ord-0743ef441dc74a659e897fce55178aef
Source dataset
uspto-grants-2009_09
Patent number
US07595320B2

Reaction notes

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