Water → N-[3-Carbamoyl-5-ethyl-1-(2-methoxyethyl)-1H-pyrazol-4-yl]-2-ethoxy-5-(4-ethylpiperazine-1-sulfonyl)pyridine-3-carboxamide

HRID 2229798Notes

Reaction equation

HRID 2229798 reaction equation
[CH2:1]([O:3][C:4]1[N:12]=[CH:11][C:10]([S:13]([N:16]2[CH2:21][CH2:20][N:19]([CH2:22][CH3:23])[CH2:18][CH2:17]2)(=[O:15])=[O:14])=[CH:9][C:5]=1[C:6]([OH:8])=O)[CH3:2].[NH2:24][C:25]1[C:26]([C:36]([NH2:38])=[O:37])=[N:27][N:28]([CH2:32][CH2:33][O:34][CH3:35])[C:29]=1[CH2:30][CH3:31].O>C(OCC)(=O)C>[C:36]([C:26]1[C:25]([NH:24][C:6](=[O:8])[C:5]2[CH:9]=[C:10]([S:13]([N:16]3[CH2:17][CH2:18][N:19]([CH2:22][CH3:23])[CH2:20][CH2:21]3)(=[O:14])=[O:15])[CH:11]=[N:12][C:4]=2[O:3][CH2:1][CH3:2])=[C:29]([CH2:30][CH3:31])[N:28]([CH2:32][CH2:33][O:34][CH3:35])[N:27]=1)(=[O:37])[NH2:38]

Participants

5

Reactant 3

HCID 962WaterHCID 46689282-Ethoxy-5-[(4-ethylpiperazino)sulfonyl]nicotinic acidHCID 112643124-amino-5-ethyl-1-(2-methoxyethyl)-1H-Pyrazole-3-carboxamide

Product 1

HCID 11478208N-[3-Carbamoyl-5-ethyl-1-(2-methoxyethyl)-1H-pyrazol-4-yl]-2-ethoxy-5-(4-ethylpiperazine-1-sulfonyl)pyridine-3-carboxamide

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
45 °C

Procedure

2-ethoxy-5-(4-ethyl-1-piperazinylsulfonyl)nicotinic acid (27.5 g, 0.08 Mol) was suspended in ethyl acetate (0.193 L) and 1,1-carbonyidimidazole (13.3 g, 0.082 Mol) was added at room temperature. The reaction mixture was heated at 45° C. for 15 minutes and then the reaction was stirred for a further 60 minutes at reflux. After cooling to ambient temperature 4-amino-5-ethyl-1-(2-methoxyethyl)-1H-pyrazole-3-carboxamide (16.5 g, 0.078 Mol) was added to the cooled mixture, and the reaction stirred for a further 17 hours under reflux. The solution was cooled and water (0.07 L) and ethyl acetate (0.17 L) added. The slurry was warmed to 40° C. and the organic separated. The organic was concentrated to by evaporating 0.23 L solvent. The slurry was cooled, granulated at 0-−10° C. filtered and the filter cake was washed with 90% water/10% ethyl acetate, (2 mL/g) to afford N-[3-carbamoyl-5-ethyl-1-(2-methoxyethyl)-1H-pyrazol-4-yl}-2-ethoxy-5-(4-ethyl-1-piperazinyl sulfonyl)nicotinamide as an off white crystalline solid, 38.7 g, 89%. m.p.=159-161° C.

Workup

  1. temperatureat reflux
  2. additionwas added to the cooled mixture
  3. stirringthe reaction stirred for a further 17 hours
  4. temperatureunder reflux
  5. temperatureThe solution was cooled
  6. temperatureThe slurry was warmed to 40° C.
  7. concentrationThe organic was concentrated
  8. customto by evaporating 0.23 L solvent
  9. temperatureThe slurry was cooled
  10. customgranulated at 0-−10° C.
  11. filtrationfiltered
  12. washthe filter cake was washed with 90% water/10% ethyl acetate, (2 mL/g)

Sources & evidence

ORD record
ord-5bb2ef6631cf4465ab3ce0e8b37ca03a
Source dataset
uspto-grants-2002_07
Patent number
US06420557B1

Reaction notes

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