Guanidine Hydrochloride → HCID 178480038, compound

HRID 59607Notes

Reaction equation

HRID 59607 reaction equation
C(Cl)(=O)C(Cl)=O.[CH3:7][N:8]1[CH:12]=[C:11]([C:13]2[CH:22]=[CH:21][CH:20]=[C:19]3[C:14]=2[CH:15]=[CH:16][C:17]([C:23]([OH:25])=O)=[CH:18]3)[CH:10]=[N:9]1.Cl.[NH2:27][C:28]([NH2:30])=[NH:29].[OH-].[Na+]>ClCCl.CN(C)C=O>[CH3:7][N:8]1[CH:12]=[C:11]([C:13]2[CH:22]=[CH:21][CH:20]=[C:19]3[C:14]=2[CH:15]=[CH:16][C:17]([C:23]([NH:29][C:28]([NH2:30])=[NH:27])=[O:25])=[CH:18]3)[CH:10]=[N:9]1

Participants

7

Reactant 4

HCID 5742Guanidine HydrochlorideHCID 14798Sodium HydroxideHCID 65578Oxalyl chlorideHCID 685128445-(1-methyl-1H-pyrazol-4-yl)-2-naphthoic acid

Product 1

HCID 178480038HCID 178480038, compoundYield 83.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

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%).

Workup

  1. additionwas added in portions during the reaction to effect dissolution))
  2. temperatureThe reaction mixture was then heated for 1 hour at 40° C.
  3. concentrationbefore being concentrated under reduced pressure
  4. stirringthe reaction mixture was then stirred for 30 minutes
  5. customThe organic phase was separated
  6. extractionthe aqueous phase was extracted with chloroform (3×30 mL)
  7. washThe combined organic extracts were washed sequentially with 1M aqueous sodium hydroxide (60 mL) and water (40 mL)
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated in vacuo
  10. customto give
  11. customa glassy solid (1.45 g after drying under high vacuum)
  12. dissolutionThis solid was dissolved in dichloromethane which
  13. customto evaporate slowly

Sources & evidence

ORD record
ord-49d4c4c43efc4d4f8f7c9049cbdb306c
Source dataset
uspto-grants-2016_09
Patent number
US09440926B2

Reaction notes

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