Cesium carbonate → HCID 22648218, compound

HRID 1835125Notes

Reaction equation

HRID 1835125 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].Cl.Cl[CH2:16][CH2:17][N:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1.C([O-])([O-])=O.[K+].[K+].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O>[CH2:1]([C:3]1[N:4]([CH2:16][CH2:17][N:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)[N:5]=[C:6]([C:11]([NH2:13])=[O:12])[C:7]=1[N+:8]([O-:10])=[O:9])[CH3:2]

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 11430Potassium CarbonateHCID 77210Morpholine, 4-(2-chloroethyl)-, hydrochloride (1:1)HCID 178438045HCID 178438045, compound

Product 1

HCID 22648218HCID 22648218, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
55 °C

Procedure

A mixture of 3-ethyl-4-nitro-1H-pyrazole-5-carboxamide (20.0 g, 109 mmol, prepared using procedure in WO9849166), 4-(2-chloroethyl)morpholine hydrochloride (22.2 g, 120 mmol), K2CO3 (29.9 g, 217 mmol) and cesium carbonate (7.08 g, 21.7 mmol) in N,N-dimethylformamide (100 ml) was stirred at 55° C. for 18 h. The reaction mixture was concentrated in vacuo and the residue was partitioned between EtOAc (350 ml) and water (500 ml). The phases were separated, and the aqueous layer extracted with further EtOAc (150 ml). The organic phases were combined, dried (Na2SO4), filtered and concentrated in vacuo. The crude product was purified by column chromatography (EtOAc/MeOH, 100:0-80:20, followed by EtOAc/MeOH/NH3, 80:20:1) to afford the title compound of preparation 21 (16.21 g, 54.5 mmol, 50%); mp 132-133° C.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe residue was partitioned between EtOAc (350 ml) and water (500 ml)
  3. customThe phases were separated
  4. extractionthe aqueous layer extracted with further EtOAc (150 ml)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by column chromatography (EtOAc/MeOH, 100:0-80:20, followed by EtOAc/MeOH/NH3, 80:20:1)
  9. customto afford

Sources & evidence

ORD record
ord-b4f9b3de05a749f5836261a363a5e8b6
Source dataset
uspto-grants-2004_08
Patent number
US06770645B2

Reaction notes

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