Sulfuric Acid → HCID 178433995, compound

HRID 433942Notes

Reaction equation

HRID 433942 reaction equation
[OH:1][C:2]1[N:7]=[C:6]2[N:8]([CH3:12])[N:9]=[C:10]([CH3:11])[C:5]2=[CH:4][C:3]=1[C:13]#[N:14].[OH:15]S(O)(=O)=O>>[OH:1][C:2]1[N:7]=[C:6]2[N:8]([CH3:12])[N:9]=[C:10]([CH3:11])[C:5]2=[CH:4][C:3]=1[C:13]([NH2:14])=[O:15]

Participants

3

Reactant 2

HCID 1118Sulfuric AcidHCID 178433994HCID 178433994, compound

Product 1

HCID 178433995HCID 178433995, compound

Conditions

Temperature
40 °C

Procedure

6-Hydroxy-1,3-dimethylpyrazolo[5,4-b]pyridine-5-carbonitrile (0.911 g) was dissolved in concentrated H2SO4 (3.0 mL) and stirred at 40° C. for 24 hrs. The solution was poured into ice-water and the precipitated solid was filtered, washed with water, and dried under high vacuum to give 6-hydroxy-1,3-dimethylpyrazolo[5,4-b]pyridin-5-carboxamide as a white solid. A portion of this material (0.122 g) was dissolved in DMF (2.0 mL). 2-Chlorotriethylamine hydrochloride (0.192 g) and potassium carbonate (0.304 g) were added to the solution. The reaction mixture was stirred at 60° C. for 18 h. The reaction mixture was poured into water, extracted with ethyl acetate. The extract was washed with saturated NaHCO3 solution and the brine, and dried over Na2SO4. The extract was evaporated under reduced pressure to give 6-[2-(diethylamino)ethoxy]-1,3-dimethylpyrazolo[5,4-b]pyridine-5-carboxamide as a white solid. A portion of this material (0.059 g) was dissolved in hot toluene (10 mL) and azeotroped for 2 hrs. The solution was cooled to room temperature. 4-Fluoro-3-(trifluoromethyl)phenylisocyanate (0.098 g) was added to the solution. The mixture was heated at reflux for 23 hrs, and then, cooled to room temperature. The solvent was evaporated under reduced pressure, and the residue was purified with the column chromatography (ethyl acetate). A portion of this material (20mg) was dissolved in tetrahydrofuran (1.0 mL) and treated with 1N hydrochloric acid solution (1.0 mL). The mixture was lyophilized to give {6-[2-(diethylamino)ethoxy]-1,3-dimethylpyrazolo[5,4-b]pyridin-5-yl}-N-({[4-fluoro-3-trifluoromethyl)phenyl]amino}carbonyl)carboxamide hydrochloride as a white solid.

Workup

  1. filtrationthe precipitated solid was filtered
  2. washwashed with water
  3. customdried under high vacuum

Sources & evidence

ORD record
ord-de52698f8b1b43b5936e2df7aeee3f9c
Source dataset
uspto-grants-2003_12
Patent number
US06670364B2

Reaction notes

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