Cesium carbonate → N-(6-(3,3-dimethylpyrrolidin-1-yl)pyridin-2-yl)-6-phenylimidazo[1,2-b]pyridazin-8-amine

HRID 1755345Notes

Reaction equation

HRID 1755345 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][C:18]1([CH3:30])[CH2:22][CH2:21][N:20]([C:23]2[N:28]=[C:27]([NH2:29])[CH:26]=[CH:25][CH:24]=2)[CH2:19]1.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][C:18]1([CH3:30])[CH2:22][CH2:21][N:20]([C:23]2[N:28]=[C:27]([NH:29][C:2]3[C:3]4[N:4]([CH:14]=[CH:15][N:16]=4)[N:5]=[C:6]([C:8]4[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=4)[CH:7]=3)[CH:26]=[CH:25][CH:24]=2)[CH2:19]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 717440288-Bromo-6-phenylimidazo[1,2-B]pyridazineHCID 80652557HCID 80652557, compound

Product 1

HCID 71525896N-(6-(3,3-dimethylpyrrolidin-1-yl)pyridin-2-yl)-6-phenylimidazo[1,2-b]pyridazin-8-amineYield 26%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 8-bromo-6-phenylimidazo[1,2-b]pyridazine (0.10 g, 0.37 mmol), 6-(3,3-dimethyl pyrrolidin-1-yl)pyridin-2-amine (0.084 g, 0.44 mmol), Pd2(dba)3 (21 mg, 0.037 mmol), BINAP (92 mg, 0.148 mmol) and Cs2CO3 (0.362 g, 1.11 mmol) in dioxane (10 mL) was heated to 100° C. for 16 h in a sealed tube under N2 atmosphere then concentrated and the residue was purified by chromatography (silica gel, 10 g, 200˜300 mesh, ethyl acetate:petroleum ether=1:10) to afford N-(6-(3,3-dimethylpyrrolidin-1-yl)pyridin-2-yl)-6-phenylimidazo[1,2-b]pyridazin-8-amine (36 mg, 26%) as a yellow solid. 1H NMR (300 MHz, DMSO): δ 9.68 (s, 1H), 8.87 (s, 1H), 8.19 (d, 1H, J=1.2 Hz), 7.95-7.92 (m, 2H), 7.64 (s, 1H), 7.53-7.40 (m, 4 h), 6.72 (d, 1H, J=7.8 Hz), 6.02 (d, 1H, J=8.1 Hz), 3.51 (t, 1H, J=6.9 Hz). 3.30 (s, 2H), 1.81 (t, 2H, J=6.9 Hz), 1.13 (s, 6H). LC-MS: [M+H]+, 385, tR=2.099 min, HPLC: 96.88% at 214 nm, 97.82% at 254 nm, tR=8.077 min.

Workup

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

Sources & evidence

ORD record
ord-ccfae50e582749d2a7b07c4bb30d7408
Source dataset
uspto-grants-2015_10
Patent number
US09169259B2

Reaction notes

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