Hydrochloric Acid → 3-Ethyl-1-[2-(4-morpholinyl)ethyl]-4-nitro-1H-pyrazole-5-carboxamide

HRID 393900Notes

Reaction equation

HRID 393900 reaction equation
[CH2:1]([C:3]1[C:7]([N+:8]([O-:10])=[O:9])=[C:6]([C:11]([NH2:13])=[O:12])[NH:5][N:4]=1)[CH3:2].C(=O)([O-])[O-].[K+].[K+].C(=O)([O-])[O-].[Cs+].[Cs+].Cl[CH2:27][CH2:28][N:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1.Cl>>[CH2:1]([C:3]1[C:7]([N+:8]([O-:10])=[O:9])=[C:6]([C:11]([NH2:13])=[O:12])[N:5]([CH2:27][CH2:28][N:29]2[CH2:34][CH2:33][O:32][CH2:31][CH2:30]2)[N:4]=1)[CH3:2]

Participants

6

Reactant 5

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 11430Potassium CarbonateHCID 767274-(2-Chloroethyl)morpholineHCID 178438045HCID 178438045, compound

Product 1

HCID 226482153-Ethyl-1-[2-(4-morpholinyl)ethyl]-4-nitro-1H-pyrazole-5-carboxamide

Procedure

A mixture of 3-ethyl-4-nitro-1H-pyrazole-5-carboxamide (prepared as in WO 98/49166) (20.0 g, 0.11 mol), potassium carbonate (29.9 g, 0.22 mmol) and cesium carbonate (7.08 g, 21.7 mmol) were stirred together at room temperature. After 15 minutes 4(2-chloroethyl)morpholine.HCl (22.2 g, 0.12 mol) was added and the reaction mixture was heated at 55° C. for 16 h. The reaction mixture was concentrated in vacuo, and then partitioned between water (500 mL) and ethyl acetate (350 mL). Solid sodium carbonate was added until the pH reached 10, and then the organic layer was separated. The aqueous layer was extracted with further ethyl acetate (150 mL). The combined organic layers were concentrated in vacuo, combined with 1.6 g of a previous identical batch and purified by flash column chromatography (eluting with methanol:ethyl acetate:NH3 0:100:0 to 20:80:1). Two products were separated. The first product was triturated from diethyl ether to yield 3-ethyl-1-[2-(4-morpholinyl)ethyl]-4-nitro-1H-pyrazole-5-carboxamide as cream coloured crystals (16.2 g, 54.5 mmol).

Workup

  1. temperaturethe reaction mixture was heated at 55° C. for 16 h
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. custompartitioned between water (500 mL) and ethyl acetate (350 mL)
  4. additionSolid sodium carbonate was added until the pH
  5. customthe organic layer was separated
  6. extractionThe aqueous layer was extracted with further ethyl acetate (150 mL)
  7. concentrationThe combined organic layers were concentrated in vacuo
  8. custompurified by flash column chromatography (eluting with methanol:ethyl acetate:NH3 0:100:0 to 20:80:1)
  9. customTwo products were separated
  10. customThe first product was triturated from diethyl ether

Sources & evidence

ORD record
ord-32183c1228424cafbc64e8ac702b7b42
Source dataset
uspto-grants-2004_10
Patent number
US06809200B2

Reaction notes

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