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

HRID 1755331Notes

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][C@H: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+]>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].O1CCOCC1>[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][C@@H: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 (300 mg, 1.3 mmol), (S)-6-(2-methylpyrrolidin-1-yl)pyridin-2-amine (252 mg, 1.42 mmol), Pd2(dba)3 (75 mg, 0.13 mmol), BINAP (324 mg, 0.52 mmol), Cs2CO3 (1272 mg, 3.9 mmol) and dioxane (20 mL) was heated to 100° C. with stirring for 16 h under N2. The solvent was removed in vacuo and the resulting mixture was purified by chromatography (silica gel, 200-300 mesh, petroleum ether:ethyl acetate=3:1) to give (S)-6-chloro-N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine (124 mg, 29%) as a yellow solid. LC-MS: [M+H]+, 329.0, tR=1.951 min.

Workup

customThe solvent was removed in vacuo
customthe resulting mixture was purified by chromatography (silica gel, 200-300 mesh, petroleum ether:ethyl acetate=3:1)

Sources & evidence

ORD record: ord-3c84eda411054249a00adbcd2aff7a27
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09169259B2

Reaction notes

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