Cesium carbonate → N-(5,6-dimethoxypyridin-2-yl)-6-phenylimidazo[1,2-b]pyridazin-8-amine

HRID 1755358Notes

Reaction equation

Br[C:2]1[C:3]2[N:4]([CH:14]=[CH:15][N:16]=2)[N:5]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:7]=1.[CH3:17][O:18][C:19]1[CH:20]=[CH:21][C:22]([NH2:27])=[N:23][C:24]=1[O:25][CH3:26].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:17][O:18][C:19]1[CH:20]=[CH:21][C:22]([NH:27][C:2]2[C:3]3[N:4]([CH:14]=[CH:15][N:16]=3)[N:5]=[C:6]([C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=3)[CH:7]=2)=[N:23][C:24]=1[O:25][CH3:26]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 8-bromo-6-phenylimidazo[1,2-b]pyridazine (0.15 g, 0.55 mmol), 5,6-dimethoxypyridin-2-amine (0.092 g, 0.61 mmol), Pd2(dba)3 (32 mg, 0.055 mmol), BINAP (68 mg, 0.11 mmol) and Cs2CO3 (0.54 g, 1.65 mmol) in dioxane (20 mL) was heated to 100° C. for 16 h in a sealed tube under N2 atmosphere then concentrated and the residue purified by chromatography (silica gel, 10 g, 200˜300 mesh, ethyl acetate:petroleum ether=1:6) to afford N-(5,6-dimethoxypyridin-2-yl)-6-phenylimidazo[1,2-b]pyridazin-8-amine (49 mg, 26%) as a yellow solid. 1H NMR (300 MHz, CD3OD): δ 8.56 (s, 1H), 8.01-7.92 (m, 3H), 7.60 (s, 1H), 7.51-7.48 (m, 3H), 7.35 (d, 1H, J=8.4 Hz), 6.73 (d, 1H, J=8.4 Hz), 4.09 (s, 3H), 3.85 (s, 3H). LC-MS: [M+H]+, 348, tR=1.735 min, HPLC: 98.28% at 214 nm, 98.33% at 254 nm, tR=5.85 min.

Workup

concentrationthen concentrated
customthe residue purified by chromatography (silica gel, 10 g, 200˜300 mesh, ethyl acetate:petroleum ether=1:6)

Sources & evidence

ORD record: ord-1e10c539081d4caea136f20095f98cc4
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09169259B2

Reaction notes

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