Reaction #87885

Reaction equation

Oxalyl chloride

5-(1-methyl-1H-pyrazol-4-yl)-2-naphthoic acid

guanidine hydrochloride

sodium hydroxide

→

5-(1-methyl-1H-pyrazol-4-yl)-2-naphthoylguanidine

Yield 83.2%

Solvents

dichloromethane

Conditions

Workup

1. 1
   workup.ADDITIONwas added in portions during the reaction to effect dissolution))
2. 2
   TemperatureThe reaction mixture was then heated for 1 hour at 40° C.
3. 3
   Concentrationbefore being concentrated under reduced pressure
4. 4
   workup.STIRRINGthe reaction mixture was then stirred for 30 minutes
5. 5
   OtherThe organic phase was separated
6. 6
   Extractionthe aqueous phase was extracted with chloroform (3×30 mL)
7. 7
   WashThe combined organic extracts were washed sequentially with 1M aqueous sodium hydroxide (60 mL) and water (40 mL)
8. 8
   Dryingdried (Na2SO4)
9. 9
   Concentrationconcentrated in vacuo
10. 10
    Otherto give
11. 11
    Othera glassy solid (1.45 g after drying under high vacuum)
12. 12
    workup.DISSOLUTIONThis solid was dissolved in dichloromethane which
13. 13
    Otherto evaporate slowly

Procedure

Oxalyl chloride (1.1 mL, 13 mmol) was added to a solution of 5-(1-methyl-1H-pyrazol-4-yl)-2-naphthoic acid (1.19 g, 4.71 mmol) in anhydrous dichloromethane (200 mL (which was added in portions during the reaction to effect dissolution)) containing dimethylformamide (2 drops) under nitrogen and the mixture was stirred at room temperature for 4.25 hours. The reaction mixture was then heated for 1 hour at 40° C., before being concentrated under reduced pressure. The resulting crude acid chloride was suspended in anhydrous tetrahydrofuran (50 mL) and this mixture was added dropwise to a solution of guanidine hydrochloride (2.09 g, 21.9 mmol) in 2M aqueous sodium hydroxide (15 mL, 30 mmol) and the reaction mixture was then stirred for 30 minutes. The organic phase was separated, and the aqueous phase was extracted with chloroform (3×30 mL) followed by ethyl acetate (3×30 mL). The combined organic extracts were washed sequentially with 1M aqueous sodium hydroxide (60 mL) and water (40 mL), then dried (Na2SO4) and concentrated in vacuo to give a glassy solid (1.45 g after drying under high vacuum). This solid was dissolved in dichloromethane which was then allowed to evaporate slowly to give 5-(1-methyl-1H-pyrazol-4-yl)-2-naphthoylguanidine as a yellow solid (1.15 g, 83%).

Source