Imidazole → 3-Imidazol-1-yl-6-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylmethyl)-quinoline

HRID 655291Notes

Reaction equation

Br[C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([CH2:12][C:13]1[N:17]3[N:18]=[C:19]([CH3:22])[CH:20]=[CH:21][C:16]3=[N:15][N:14]=1)=[CH:7][CH:6]=2.N1CCC[C@H]1C(O)=O.C([O-])([O-])=O.[K+].[K+].[NH:37]1[CH:41]=[CH:40][N:39]=[CH:38]1>CS(C)=O.[Cu]I>[N:37]1([C:2]2[CH:3]=[N:4][C:5]3[C:10]([CH:11]=2)=[CH:9][C:8]([CH2:12][C:13]2[N:17]4[N:18]=[C:19]([CH3:22])[CH:20]=[CH:21][C:16]4=[N:15][N:14]=2)=[CH:7][CH:6]=3)[CH:41]=[CH:40][N:39]=[CH:38]1

Participants

Conditions

Temperature: 120 °C

Procedure

To a reaction vial was added 3-bromo-6-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylmethyl)-quinoline (71 mg, 0.2 mmol, 1.0 equiv), CuI (7 mg, 0.04 mmol, 0.008 equiv), L-proline (9 mg, 0.08 mmol, 0.4 equiv) and K2CO3 (83 mg, 0.60 mmol, 3.0 equiv). The system was evacuated and filled with nitrogen (3×). A solution of degassed imidazole (27 mg, 0.4 mmol, 2.0 equiv) in DMSO (1 mL) was then added. The reaction was heated at 120° C. for 18 hours. The solvent was removed in vacuo and the residue absorbed onto silica gel and purified by flash chromatography (SiO2, CH2Cl2:CH3OH 100:0-90:10 to return the title compound (15 mg, 22% yield). Analytical data presented in Table 2.

Workup

customThe system was evacuated
additionfilled with nitrogen (3×)
customThe solvent was removed in vacuo
customthe residue absorbed onto silica gel
custompurified by flash chromatography (SiO2, CH2Cl2:CH3OH 100:0-90:10

Sources & evidence

ORD record: ord-8113fd05a7594e8d9aa37e929998105d
Source dataset: uspto-grants-2011_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08071581B2

Reaction notes

Loading…