2-Thiophenecarboxamide → ethyl 1-(1-ethoxyethyl)-3-[(thiophene-2-carbonyl)amino]-1H-thieno[2,3-c]pyrazole-5-carboxylate

HRID 1363073Notes

Reaction equation

HRID 1363073 reaction equation
N[C@@H]1CCCC[C@H]1N.[S:9]1[CH:13]=[CH:12][CH:11]=[C:10]1[C:14]([NH2:16])=[O:15].P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[C:26]1[C:27]2[CH:38]=[C:37]([C:39]([O:41][CH2:42][CH3:43])=[O:40])[S:36][C:28]=2[N:29]([CH:31]([O:33][CH2:34][CH3:35])[CH3:32])[N:30]=1>O1CCOCC1.[Cu]I>[CH2:34]([O:33][CH:31]([N:29]1[C:28]2[S:36][C:37]([C:39]([O:41][CH2:42][CH3:43])=[O:40])=[CH:38][C:27]=2[C:26]([NH:16][C:14]([C:10]2[S:9][CH:13]=[CH:12][CH:11]=2)=[O:15])=[N:30]1)[CH3:32])[CH3:35]

Participants

7

Reactant 4

HCID 220632-ThiophenecarboxamideHCID 438061,2-Diaminocyclohexane, trans-HCID 62657Potassium Phosphate, TribasicHCID 57487832ethyl 3-bromo-1-(1-ethoxyethyl)-1H-thieno[2,3-c]pyrazole-5-carboxylate

Product 1

HCID 57487836ethyl 1-(1-ethoxyethyl)-3-[(thiophene-2-carbonyl)amino]-1H-thieno[2,3-c]pyrazole-5-carboxylateYield 25.6%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
25 °C

Procedure

1.1 g (5.8 mmol) of copper(I) iodide, 0.69 cm3 (5.8 mmol) of trans-1,2-diaminocyclohexane, 4.4 g (34.6 mmol) of 2-thiophenecarboxamide and then 12.2 g (57.6 mmol) of tripotassium phosphate are successively added to a solution of 10.0 g (28.8 mmol) of ethyl 3-bromo-1-(1-ethoxyethyl)-1H-thieno[2,3-c]pyrazole-5-carboxylate in 167 cm3 of dioxane, stirred at a temperature in the region of 25° C., under argon. The reaction mixture is refluxed for 20 hours and is then cooled to a temperature in the region of 25° C. and filtered through Clarcel®. The solid is washed with twice 170 cm3 of ethyl acetate. The filtrate is extracted with three times 170 cm3 of saturated brine and the organic phase is then dried over sodium sulfate, filtered and then concentrated to dryness under reduced pressure (2.7 kPa) at a temperature in the region of 35° C. The residue is purified by chromatography on a column of about 300 g of silica gel (particle size 40-63 μm), eluting with a cyclohexane/ethyl acetate mixture (90/10 and then 85/15 by volume). The fractions containing the expected product are combined and concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. 2.9 g of ethyl 1-(1-ethoxyethyl)-3-[(thiophene-2-carbonyl)amino]-1H-thieno[2,3-c]pyrazole-5-carboxylate are thus obtained in the form of a yellow solid. (Rf=0.18, thin-layer chromatography on silica gel, eluent: cyclohexane/ethyl acetate (80/20 by volume)).

Workup

  1. temperatureThe reaction mixture is refluxed for 20 hours
  2. temperatureis then cooled to a temperature in the region of 25° C.
  3. filtrationfiltered through Clarcel®
  4. washThe solid is washed with twice 170 cm3 of ethyl acetate
  5. extractionThe filtrate is extracted with three times 170 cm3 of saturated brine
  6. dry with materialthe organic phase is then dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated to dryness under reduced pressure (2.7 kPa) at a temperature in the region of 35° C
  9. customThe residue is purified by chromatography on a column of about 300 g of silica gel (particle size 40-63 μm)
  10. washeluting with a cyclohexane/ethyl acetate mixture (90/10
  11. additionThe fractions containing the expected product
  12. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C

Sources & evidence

ORD record
ord-6301708a2c71434aa1ac3e520dba2a7a
Source dataset
uspto-grants-2011_02
Patent number
US07884123B2

Reaction notes

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