Cesium carbonate → 6-chloro-N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine

HRID 1755359Notes

Reaction equation

Br[C:2]1[C:3]2[N:4]([CH:9]=[CH:10][N:11]=2)[N:5]=[C:6]([Cl:8])[CH:7]=1.[CH3:12][CH:13]1[CH2:17][CH2:16][CH2:15][N:14]1[C:18]1[N:23]=[C:22]([NH2:24])[CH:21]=[CH:20][CH: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]>[Cl:8][C:6]1[CH:7]=[C:2]([NH:24][C:22]2[CH:21]=[CH:20][CH:19]=[C:18]([N:14]3[CH2:15][CH2:16][CH2:17][CH:13]3[CH3:12])[N:23]=2)[C:3]2[N:4]([CH:9]=[CH:10][N:11]=2)[N:5]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 8-bromo-6-chloroimidazo[1,2-b]pyridazine (1.0 g, 4.3 mmol), 6-(2-methylpyrrolidin-1-yl)pyridin-2-amine (0.84 g, 4.73 mmol), Pd2(dba)3 (0.247 g, 0.43 mmol), BINAP (0.536 g, 0.86 mmol) and Cs2CO3 (4.21 g, 12.9 mmol) in dioxane (30 mL) was heated to 100° C. for 16 h in a sealed tube under N2 atmosphere then concentrated in vacuo. The residue was purified by chromatography (silica gel, 10 g, 200˜300 mesh, ethyl acetate:petroleum ether=1:15) to afford 6-chloro-N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine (1.2 g, 85%) as a yellow solid. LC-MS: [M+1]+=329, tR=1.930 min.

Workup

concentrationthen concentrated in vacuo
customThe residue was purified by chromatography (silica gel, 10 g, 200˜300 mesh, ethyl acetate:petroleum ether=1:15)

Sources & evidence

ORD record: ord-69349dd1c9114ab8b638f5cc24724a79
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09169259B2

Reaction notes

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