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

HRID 1755376Notes

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

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of methyl 3-(8-bromoimidazo[1,2-b]pyridazin-6-yl)benzoate (0.10 g, 0.3 mmol), 6-(3,3-dimethylpyrrolidin-1-yl)pyridin-2-amine (60 mg, 0.3 mmol), Pd2(dba)3 (0.014 g, 0.03 mmol), BINAP (0.038 g, 0.06 mmol) and Cs2CO3 (0.3 g, 0.9 mmol) in dioxane (10 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-(3,3-dimethylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoate (110 mg, 83%) as a brown solid. LC-MS: [M+1]+=443, tR=2.065 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-9468d9c51377496fa4c6b329c435c5c7
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09169259B2

Reaction notes

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