Ethyl isothiocyanate → 6-(2-(2,4-Difluorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-3-yl)-N-ethyl-[1,2,4]triazolo[4,3-b]pyridazin-3-amine

HRID 1930020Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1930020
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]2[CH2:24][CH2:23][CH2:22][N:12]2[C:13]=1[C:14]1[N:15]=[N:16][C:17]([NH:20][NH2:21])=[CH:18][CH:19]=1.[N:25]([CH2:28][CH3:29])=[C:26]=S>CN(C1C=CN=CC=1)C.CCO>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]2[CH2:24][CH2:23][CH2:22][N:12]2[C:13]=1[C:14]1[CH:19]=[CH:18][C:17]2[N:16]([C:26]([NH:25][CH2:28][CH3:29])=[N:21][N:20]=2)[N:15]=1

Komponenten

5

Edukt 2

HCID 10966Ethyl isothiocyanateHCID 579298742-(2,4-Difluorophenyl)-3-(6-hydrazinylpyridazin-3-yl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazole

Produkt 1

HCID 579299416-(2-(2,4-Difluorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-3-yl)-N-ethyl-[1,2,4]triazolo[4,3-b]pyridazin-3-amineAusbeute 17,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 702EthanolLösungsmittel

Reaktionsbedingungen

Temperatur
75 °C

Versuchsvorschrift

2-(2,4-Difluorophenyl)-3-(6-hydrazinylpyridazin-3-yl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazole (0.200 g, 0.609 mmol, Example #35, Step E) and isothiocyanatoethane (0.085 g, 0.975 mmol) were added to EtOH (3 mL). The suspension was heated to about 75° C. for about 3 h. DMAP (0.138 g, 0.670 mmol) was added and the solution was heated in a CEM® microwave at about 150° C. for about 10 min (250 psi maximum pressure, 10 min ramp, 300 max watts). Solvent was removed in vacuo and the material was purified by flash chromatography using MeOH/DCM (0-6% gradient) and then further purified by RP-HPLC (Table 1, Method m). The ACN was removed and the resulting precipitate was collected to afford the title compound (0.040 g, 17%): LC/MS (Table 1, Method g) Rt=1.77 min; MS m/z: 382.2 (M+1)+.

Aufarbeitung

  1. temperaturethe solution was heated in a CEM® microwave at about 150° C. for about 10 min (250 psi maximum pressure, 10 min ramp, 300 max watts)
  2. customSolvent was removed in vacuo
  3. customthe material was purified by flash chromatography
  4. customfurther purified by RP-HPLC (Table 1, Method m)
  5. customThe ACN was removed
  6. customthe resulting precipitate was collected

Quellen und Nachweise

ORD-Eintrag
ord-ca12236e47024483bdc4347a94dfdec8
Quelldatensatz
uspto-grants-2012_05
Patentnummer
US08188083B2

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