Carbamimidoylazanium Chloride → HCID 178448652, Verbindung

HRID 1792939Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1792939
CC(C)([O-])C.[K+].[Cl-].[NH2:8][C:9]([NH2:11])=[NH2+:10].[F:12][C:13]1[CH:14]=[CH:15][CH:16]=[C:17]2[C:21]=1[CH:20]([CH2:22][C:23](OCC)=[O:24])[N:19]([CH2:28][CH:29]([CH3:31])[CH3:30])[C:18]2=[O:32]>>[F:12][C:13]1[CH:14]=[CH:15][CH:16]=[C:17]2[C:21]=1[CH:20]([CH2:22][C:23]([NH:10][C:9]([NH2:11])=[NH:8])=[O:24])[N:19]([CH2:28][CH:29]([CH3:30])[CH3:31])[C:18]2=[O:32]

Komponenten

4

Edukt 3

HCID 5460839Carbamimidoylazanium ChlorideHCID 23665647Potassium tert-butoxideHCID 69713989Ethyl (7-fluoro-2-isobutyl-3-oxo-2,3-dihydro-1H-isoindol-1-yl)acetate

Produkt 1

HCID 178448652HCID 178448652, VerbindungAusbeute 21,4 %

Reaktionsbedingungen

Temperatur
20 °C

Versuchsvorschrift

N-[(7-Fluoro-2-isobutyl-3-oxo-2,3-dihydro-1H-isoindol-1-yl)acetyl]guanidine is prepared as described in Example 1, starting with 1.29 g of potassium tert-butoxide, 1.32 g of guanidinium chloride and 0.67 g of ethyl (7-fluoro-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 40 cm3 of water and 60 cm3 of ethyl acetate. After separation of the phases by settling, the organic phase is separated out and the aqueous phase is extracted with twice 60 cm3 of ethyl acetate. The organic extracts are combined, dried over sodium sulfate, filtered and concentrated to dryness under reduced pressure (0.6 kPa) at a temperature in the region of 55° C. The evaporation residue is taken up in diethyl ether and concentrated to dryness again under the same conditions, and then taken up in water and concentrated to dryness again under the same conditions. The residue is purified by chromatography under argon pressure (50 kPa), on a column of silica gel (particle size 15-40 μm), eluting with a mixture of dichloromethane/methanol (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 20° C. The residue is taken up in diisopropyl ether, triturated, filtered and then dried. 0.15 g of N-[(7-fluoro-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 205° C. 1H NMR (300 MHz, d6-(CD3)2SO, δ in ppm): 0.74 (d, J=6.5 Hz: 3H); 0.89 (d, J=6.5 Hz: 3H); 2.06 (mt: 1H); 2.38 (dd, J=15 and 7.5 Hz: 1H); 2.90 (dd, J=15 and 4.5 Hz: 1H); 3.04 (dd, J=13.5 and 4.5 Hz: 1H); 3.56 (dd, J=13.5 and 10 Hz: 1H); 5.23 (dd, J=7.5 and 4.5 Hz: 1H); from 6.20 to 7.00 (broad multiplet: 2H); from 7.35 to 7.60 (mt: 3H); from 7.50 to 8.20 (broad multiplet: 2H).

Aufarbeitung

  1. customN-[(7-Fluoro-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 with twice 60 cm3 of ethyl acetate
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated to dryness under reduced pressure (0.6 kPa) at a temperature in the region of 55° C
  9. concentrationconcentrated to dryness again under the same conditions
  10. concentrationconcentrated to dryness again under the same conditions
  11. customThe residue is purified by chromatography under argon pressure (50 kPa)
  12. washon a column of silica gel (particle size 15-40 μm), eluting with a mixture of dichloromethane/methanol (90/10 by volume)
  13. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 20° C
  14. customtriturated
  15. filtrationfiltered
  16. customdried

Quellen und Nachweise

ORD-Eintrag
ord-e00eddfb4ac249bf9f014dfcc2aeece2
Quelldatensatz
uspto-grants-2006_07
Patentnummer
US07078428B2

Notizen zur Reaktion

Wird geladen…