Sodium Carbonate → N-(3-methyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)-7-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)imidazo[1,2-a]pyridine-3-carboxamide

HRID 706621

Reaction equation

HRID 706621 reaction equation
Br[C:2]1[CH:7]=[CH:6][N:5]2[C:8]([C:11]([NH:13][C:14]3[CH:22]=[CH:21][CH:20]=[C:19]4[C:15]=3[C:16]([CH3:31])=[N:17][N:18]4[CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([CH3:30])[N:25]=3)=[O:12])=[CH:9][N:10]=[C:4]2[CH:3]=1.[CH3:32][N:33]1[CH:38]=[C:37](B2OC(C)(C)C(C)(C)O2)[CH:36]=[CH:35][C:34]1=[O:48].C(=O)([O-])[O-].[Na+].[Na+]>C(COC)OC.CN(C)C=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:31][C:16]1[C:15]2[C:19](=[CH:20][CH:21]=[CH:22][C:14]=2[NH:13][C:11]([C:8]2[N:5]3[CH:6]=[CH:7][C:2]([C:37]4[CH:36]=[CH:35][C:34](=[O:48])[N:33]([CH3:32])[CH:38]=4)=[CH:3][C:4]3=[N:10][CH:9]=2)=[O:12])[N:18]([CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([CH3:30])[N:25]=2)[N:17]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 454801941-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-oneHCID 679764107-bromo-N-(3-methyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide

Product 1

HCID 57387148N-(3-methyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)-7-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)imidazo[1,2-a]pyridine-3-carboxamideYield 51.3%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 18463208dimethoxyethane N,N-dimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

7-Bromo-N-(3-methyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide (0.05 g, 0.12 mmol) was dissolved in dimethoxyethane:dimethylformamide (1:1, 0.8 mL) in a 2 dram vial, and 1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-one (0.04 g, 0.17 mmol), PdCl2(dppf)*dcm (0.005 g, 0.006 mmol), and 2 M sodium carbonate (0.17 mL, 0.34 mmol) were added. Nitrogen was bubbled through the reaction mixture for 5 minutes before capping the vial and heating in a sand bath at 90° C. overnight. The reaction mixture was diluted with ethyl acetate and water. A greenish precipitate formed and was collected. The crude material was purified by preparatory thin layer chromatography (silica, 20×20 cm, 0.5 mm) developed in a chamber with 10% MeOH/DCM. The UV active band with Rf=0.1 was isolated and the silica washed with 10% MeOH/DCM. The filtrate was concentrated to give N-(3-methyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)-7-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)imidazo[1,2-a]pyridine-3-carboxamide as a beige solid (31 mg).

Workup

  1. customNitrogen was bubbled through the reaction mixture for 5 minutes
  2. additionThe reaction mixture was diluted with ethyl acetate and water
  3. customA greenish precipitate formed
  4. customwas collected
  5. customThe crude material was purified by preparatory thin layer chromatography (silica, 20×20 cm, 0.5 mm)
  6. customThe UV active band with Rf=0.1 was isolated
  7. washthe silica washed with 10% MeOH/DCM
  8. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-d63acd04cdd6428f95fef0246b68e518
Source dataset
uspto-grants-2015_11
Patent number
US09174981B2

Linked notes

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