Cesium carbonate → 1-(1-Benzhydryl-3-azetidinyl)-5-ethyl-4-nitro-1H-pyrazole-3-carboxamide

HRID 1835129Notes

Reaction equation

HRID 1835129 reaction equation
CS(O[CH:6]1[CH2:9][N:8]([CH:10]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:7]1)(=O)=O.[CH2:23]([C:25]1[C:29]([N+:30]([O-:32])=[O:31])=[C:28]([C:33]([NH2:35])=[O:34])[NH:27][N:26]=1)[CH3:24].C(=O)([O-])[O-].[Cs+].[Cs+]>CC#N>[CH:10]([N:8]1[CH2:9][CH:6]([N:26]2[C:25]([CH2:23][CH3:24])=[C:29]([N+:30]([O-:32])=[O:31])[C:28]([C:33]([NH2:35])=[O:34])=[N:27]2)[CH2:7]1)([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 27587161-(Diphenylmethyl)azetidin-3-yl methanesulfonateHCID 178438045HCID 178438045, compound

Product 1

HCID 116471191-(1-Benzhydryl-3-azetidinyl)-5-ethyl-4-nitro-1H-pyrazole-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
75 °C

Procedure

1-Benzhydryl-3-azetidinyl methanesulfonate (8.03 g, 25.3 mmol, prepared according to the procedure in J. Org. Chem. 1991, 56, 6729-30) was added to a mixture of 3-ethyl-4-nitro-1H-pyrazole-5-carboxamide (4.64 g, 25.3 mmol, prepared using procedure in WO9849166) and cesium carbonate (8.24 g, 25.3 mmol) in MeCN (170 ml). The mixture was heated to 75° C. for 2 h and concentrated in vacuo. Water (200 ml) and EtOAc (200 ml) were added, and the mixture shaken. The insoluble solid at the interface was filtered off and dried to afford the title compound of preparation 52. The two layers of the filtrate were separated and the organic phase was dried (MgSO4), filtered and concentrated in vacuo. The residue was triturated with EtOAc (50 ml) and the resultant solid was filtered off, washed with hot DCM/MeOH (90:10, 50 ml) and dried to afford more of the title compound of preparation 52. The liquors and washings were combined and concentrated in vacuo. The residue was purified by column chromatography (DCM/MeOH, 98:2-95:5) to afford the title compound of preparation 51 plus a further small quantity of the title compound of preparation 52. The identity of the regioisomers was confirmed by nOe studies.

Workup

  1. concentrationconcentrated in vacuo
  2. additionWater (200 ml) and EtOAc (200 ml) were added
  3. filtrationThe insoluble solid at the interface was filtered off
  4. customdried
  5. customto afford

Sources & evidence

ORD record
ord-aca4bf2fefd94c8aa262f941b1b9bef6
Source dataset
uspto-grants-2004_08
Patent number
US06770645B2

Reaction notes

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