Carbamimidoylazanium Chloride → HCID 178448660, compound

HRID 733255Notes

Reaction equation

HRID 733255 reaction equation
CC(C)([O-])C.[K+].[Cl-].[NH2:8][C:9]([NH2:11])=[NH2+:10].[F:12][C:13]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]2[C:14]=1[C:15](=[O:33])[N:16]([CH2:29][CH:30]([CH3:32])[CH3:31])[CH:17]2[CH2:23][C:24](OCC)=[O:25]>>[F:12][C:13]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]2[C:14]=1[C:15](=[O:33])[N:16]([CH2:29][CH:30]([CH3:31])[CH3:32])[CH:17]2[CH2:23][C:24]([NH:10][C:9]([NH2:11])=[NH:8])=[O:25]

Participants

4

Reactant 3

HCID 5460839Carbamimidoylazanium ChlorideHCID 23665647Potassium tert-butoxideHCID 86591369ethyl (4,7-difluoro-2-isobutyl-3-oxo-2,3-dihydro-1H-isoindol-1-yl)acetate

Product 1

HCID 178448660HCID 178448660, compoundYield 10.3%

Conditions

Temperature
20 °C

Procedure

N-[(4,7-Difluoro-2-isobutyl-3-oxo-2,3-dihydro-1H-isoindol-1-yl)acetyl]guanidine is prepared as described in Example 1, starting with 2.68 g of potassium tert-butoxide, 2.74 g of guanidinium chloride and 1.49 g of ethyl (4,7-difluoro-2-isobutyl-3-oxo-2,3-dihydro-1H-isoindol-1-yl)acetate. The reaction mixture is stirred at a temperature in the region of 20° C. for 20 hours and is then filtered. The filtrate is taken up in 80 cm3 of water and 120 cm3 of ethyl acetate. After separation of the phases by settling, the organic phase is separated out and the aqueous phase is extracted twice with 120 cm3 of ethyl acetate. The organic extracts are combined, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (0.6 kPa) at a temperature in the region of 40° C. The evaporation residue is purified by chromatography under argon pressure (50 kPa) on a column of silica gel (particle size 15-40 μm), eluting with successive mixtures of dichloromethane/methanol (95/5 and then 90/10 by volume). The fractions comprising the expected product are combined and concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 35° C. The residue is taken up in diethyl ether, triturated, filtered and then dried in a desiccator under reduced pressure (2 kPa) at a temperature in the region of 20° C. 0.16 g of N-[(4,7-difluoro-2-isobutyl-3-oxo-2,3-dihydro-1H-isoindol-1-yl)acetyl]-guanidine is thus obtained in the form of a pale yellow solid melting at 212° C. Mass spectrum: DCI: m/e 325 (M+H)+, m/e 263 (base peak).

Workup

  1. customN-[(4,7-Difluoro-2-isobutyl-3-oxo-2,3-dihydro-1H-isoindol-1-yl)acetyl]guanidine is prepared
  2. filtrationis then filtered
  3. customAfter separation of the phases
  4. customthe organic phase is separated out
  5. extractionthe aqueous phase is extracted twice with 120 cm3 of ethyl acetate
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated to dryness under reduced pressure (0.6 kPa) at a temperature in the region of 40° C
  9. customThe evaporation residue is purified by chromatography under argon pressure (50 kPa) on a column of silica gel (particle size 15-40 μm)
  10. washeluting with successive mixtures of dichloromethane/methanol (95/5
  11. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 35° C
  12. customtriturated
  13. filtrationfiltered
  14. customdried in a desiccator under reduced pressure (2 kPa) at a temperature in the region of 20° C

Sources & evidence

ORD record
ord-cda2fb8a73aa47239c9db625c92c0e4a
Source dataset
uspto-grants-2009_09
Patent number
US07589117B2

Reaction notes

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