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

HRID 1755347Notes

Reaction equation

HRID 1755347 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][O:22][CH2:23][CH:24]1[CH2:28][CH2:27][CH2:26][N:25]1[C:29]1[N:34]=[C:33]([NH2:35])[CH:32]=[CH:31][CH:30]=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][O:22][CH2:23][CH:24]1[CH2:28][CH2:27][CH2:26][N:25]1[C:29]1[N:34]=[C:33]([NH:35][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:32]=[CH:31][CH:30]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 86682703HCID 86682703, compoundHCID 866827206-(2-(Methoxymethyl)pyrrolidin-1-yl)pyridin-2-amine

Product 1

HCID 86682721Methyl 3-(8-(6-(2-(methoxymethyl)pyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoateYield 36.3%

Reagents, catalysts & solvents 2

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

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-(2-(methoxymethyl)pyrrolidin-1-yl)pyridin-2-amine (0.083 g, 0.4 mmol), Pd2(dba)3 (0.019 g, 0.033 mmol), BINAP (0.083 g, 0.134 mmol) and Cs2CO3 (0.326 g, 1.0 mmol) in dioxane (20 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 methyl 3-(8-(6-(2-(methoxymethyl)pyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoate (0.050 g) as a yellow solid. LC-MS: [M+1]+=459, tR=1.985 min. This contained some unidentified impurities and was used directly without further purification.

Workup

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

Sources & evidence

ORD record
ord-0985f44236c940068ecdfce53bba94e7
Source dataset
uspto-grants-2015_10
Patent number
US09169259B2

Reaction notes

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