Cesium carbonate → Methyl 3-(8-(6-(2,5-dimethylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoate

HRID 1755377Notes

Reaction equation

Br[C:2]1[C:3]2[N:4]([CH:18]=[CH:19][N:20]=2)[N:5]=[C:6]([C:8]2[CH:9]=[C:10]([CH:15]=[CH:16][CH:17]=2)[C:11]([O:13][CH3:14])=[O:12])[CH:7]=1.[CH3:21][CH:22]1[CH2:26][CH2:25][CH:24]([CH3:27])[N:23]1[C:28]1[N:33]=[C:32]([NH2:34])[CH:31]=[CH:30][CH:29]=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]>[CH3:21][CH:22]1[CH2:26][CH2:25][CH:24]([CH3:27])[N:23]1[C:28]1[N:33]=[C:32]([NH:34][C:2]2[C:3]3[N:4]([CH:18]=[CH:19][N:20]=3)[N:5]=[C:6]([C:8]3[CH:9]=[C:10]([CH:15]=[CH:16][CH:17]=3)[C:11]([O:13][CH3:14])=[O:12])[CH:7]=2)[CH:31]=[CH:30][CH:29]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of methyl 3-(8-bromoimidazo[1,2-b]pyridazin-6-yl)benzoate (0.2 g, 0.6 mmol), 6-(2,5-dimethylpyrrolidin-1-yl)pyridin-2-amine (116 mg, 0.6 mmol), Pd2(dba)3 (0.036 g, 0.06 mmol), BINAP (0.076 g, 0.12 mmol) and Cs2CO3 (0.59 g, 1.8 mmol) in dioxane (5 mL) was heated to 100° C. for 15 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, dichloromethane:MeOH=100:1) to afford methyl 3-(8-(6-(2,5-dimethylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoate (150 mg, 56%) as a brown solid. LC-MS: [M+1]+=443, tR=2.092 min.

Workup

concentrationthen concentrated in vacuo
customThe residue was purified by chromatography (silica gel, 10 g, 200˜300 mesh, dichloromethane:MeOH=100:1)

Sources & evidence

ORD record: ord-cd45cf6e41f049f181192f691b0f7564
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09169259B2

Reaction notes

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