Dimethylformamide → 1h-Pyrazolo[4,3-b]pyridine-5,6-dicarboxylic acid,1-methyl-,5,6-dimethyl ester

HRID 864291

Reaction equation

CN(C)[CH:3]=[O:4].P(Cl)(Cl)(Cl)=[O:7].[CH3:11][N:12]1[CH:16]=[C:15]([NH:17][C:18]([CH2:28]C)=[C:19]([C:24](OC)=O)[C:20]([O:22][CH3:23])=[O:21])[CH:14]=[N:13]1.C[N+](C)=CCl.[Cl-]>ClC(Cl)C>[CH3:11][N:12]1[C:16]2[C:15](=[N:17][C:18]([C:28]([O:4][CH3:3])=[O:7])=[C:19]([C:20]([O:22][CH3:23])=[O:21])[CH:24]=2)[CH:14]=[N:13]1

Participants

Conditions

Temperature: -5 °C

Procedure

Dimethylformamide (7.4 mL, 0.096 mol) is dissolved in 125 mL dichloroethane and the mixture cooled to -5° C. in an acetone/ice bath. Phosphorous oxychloride (8.9 mL, 0.095 mol) is added-in one portion and the clear colorless solution is allowed to warm slowly to room temperature, gradually turning yellow. The unpurified dimethyl [(1-methylpyrazol-4-yl)amino]butenedicarboxylate is dissolved in 75 mL of dichloroethane and added to the chilled Vilsmeier reagent dropwise keeping the reaction temperature below 5° C. The mixture is allowed to warm slowly to room temperature over four hours, and then is heated to reflux for one hour. The mixture is concentrated to a solid which is chromatographed using 3:1 hexanes/ethyl acetate. The fractions containing the desired product are combined and concentrated to give the product as a white solid (16.93 g, 71.4%), melting point 148°-149° C.

Workup

temperatureto warm slowly to room temperature
customthe reaction temperature below 5° C
temperatureto warm slowly to room temperature over four hours
temperatureis heated
temperatureto reflux for one hour
concentrationThe mixture is concentrated to a solid which
customis chromatographed
additionThe fractions containing the desired product
concentrationconcentrated

Sources & evidence

ORD record: ord-bda6a53387054af0b077e1d026b3e958
Source dataset: uspto-grants-1996_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05563113

Linked notes

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