Acetate → HCID 178476655, compound

HRID 929657Notes

Reaction equation

HRID 929657 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8]([NH2:10])=S.CI.[CH3:13][O:14][C:15]1[CH:22]=[CH:21][CH:20]=[C:19]([O:23][CH3:24])[C:16]=1[CH2:17][NH2:18].C(N(C(C)C)CC)(C)C.[C:34]([O-:37])(=[O:36])[CH3:35]>CO.C(O)C>[C:34]([OH:37])(=[O:36])[CH3:35].[CH3:24][O:23][C:19]1[CH:20]=[CH:21][CH:22]=[C:15]([O:14][CH3:13])[C:16]=1[CH2:17][NH:18][C:8]([NH:7][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=1)=[NH:10]

Participants

8

Reactant 5

HCID 175AcetateHCID 6328Methyl iodideHCID 81531DiisopropylethylamineHCID 14904911-(2-Pyridyl)-2-thioureaHCID 28008722,6-Dimethoxybenzylamine

Product 1

HCID 178476655HCID 178476655, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 887MethanolSolvent

Procedure

0.800 g (5.117 mmol) N-pyridin-2-yl-thiourea was dissolved in 20 mL methanol and combined with 0.45 mL (10.235 mmol) methyl iodide. The mixture was heated under reflux for 15 min and subsequently stirred at room temperature. After reaction was complete the solvent was removed under vacuum, and the residue was used for the subsequent reaction without further purification. For this purpose the solid was dissolved in 20 mL ethanol, and 0.946 g (5.658 mmol) 2,6-dimethoxybenzylamine was added. After addition of 1.80 mL (10.235 mmol) diisopropylethylamine the mixture was heated under reflux for a total of 7 hr. After reaction was complete the solvent was removed under vacuum. The residue was taken up in dichloromethane and extracted with water (2×30 mL). The organic phase was dried over magnesium sulfate, and the solvent was evaporated under vacuum. 0.402 g of the desired product N-(2,6-dimethoxybenzyl)-N′-pyridin-2-yl-guanidine crystallized from acetonitrile/water (1:1), and by use of ion exchanger (Fluka, acetate on 1.5 mmol CH3COO/g/resign polymer substrate) was converted to the acetate salt. The residual mother liquor of the crystallizate was separated from impurities via preparative HPLC (Merck Chromolith RP-18 100×25 mm, eluent: water/acetonitrile/0.1 M acetic acid), resulting in isolation of a total of 0.516 g (1.489 mmol) N-(2,6-dimethoxybenzyl)-N′-pyridin-2-yl-guanidine acetate as a pure substance.

Workup

  1. temperatureThe mixture was heated
  2. temperatureunder reflux for 15 min
  3. customAfter reaction
  4. customwas removed under vacuum
  5. customthe residue was used for the subsequent reaction without further purification
  6. temperaturewas heated
  7. temperatureunder reflux for a total of 7 hr
  8. customAfter reaction
  9. customwas removed under vacuum
  10. extractionextracted with water (2×30 mL)
  11. dry with materialThe organic phase was dried over magnesium sulfate
  12. customthe solvent was evaporated under vacuum
  13. custom0.402 g of the desired product N-(2,6-dimethoxybenzyl)-N′-pyridin-2-yl-guanidine crystallized from acetonitrile/water (1:1)
  14. customThe residual mother liquor of the crystallizate was separated from impurities via preparative HPLC (Merck Chromolith RP-18 100×25 mm, eluent: water/acetonitrile/0.1 M acetic acid)

Sources & evidence

ORD record
ord-9ddcd76cd2bb4342a5af815df8f59b5b
Source dataset
uspto-grants-2016_03
Patent number
US09296697B2

Reaction notes

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