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 1930020Notes

Reaction equation

[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

Participants

Conditions

Temperature: 75 °C

Procedure

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)+.

Workup

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)
customSolvent was removed in vacuo
customthe material was purified by flash chromatography
customfurther purified by RP-HPLC (Table 1, Method m)
customThe ACN was removed
customthe resulting precipitate was collected

Sources & evidence

ORD record: ord-ca12236e47024483bdc4347a94dfdec8
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08188083B2

Reaction notes

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