Hydrogen Peroxide → 2-Ethylamino-4-(4-(4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-1-yl)1,7-naphthyridin-8-yl)benzamide

HRID 1403090Notes

Reaction equation

HRID 1403090 reaction equation
[OH-:1].[Na+].OO.[CH2:5]([NH:7][C:8]1[CH:15]=[C:14]([C:16]2[N:17]=[CH:18][CH:19]=[C:20]3[C:25]=2[N:24]=[CH:23][CH:22]=[C:21]3[N:26]2[CH:30]=[C:29]([C:31]3[CH:32]=[N:33][N:34]([CH3:36])[CH:35]=3)[N:28]=[CH:27]2)[CH:13]=[CH:12][C:9]=1[C:10]#[N:11])[CH3:6].O>CS(C)=O>[CH2:5]([NH:7][C:8]1[CH:15]=[C:14]([C:16]2[N:17]=[CH:18][CH:19]=[C:20]3[C:25]=2[N:24]=[CH:23][CH:22]=[C:21]3[N:26]2[CH:30]=[C:29]([C:31]3[CH:32]=[N:33][N:34]([CH3:36])[CH:35]=3)[N:28]=[CH:27]2)[CH:13]=[CH:12][C:9]=1[C:10]([NH2:11])=[O:1])[CH3:6]

Participants

6

Reactant 4

HCID 784Hydrogen PeroxideHCID 962WaterHCID 14798Sodium HydroxideHCID 867011432-(ethylamino)-4-(4-(4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-1-yl)-1,7-naphthyridin-8yl)benzonitrile

Product 1

HCID 867011452-Ethylamino-4-(4-(4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-1-yl)1,7-naphthyridin-8-yl)benzamideYield 4%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A suspension of 3-amino-2-chloropyridine (17.6 g) and 5-(methoxymethylene)-2,2-dimethyl-1,3-dioxane-4,6-dione (25.5 g) in isopropanol (274 ml) was heated to reflux for 5 minutes. After cooling, the deposit was filtrated to obtain 5-((2-chloropyridin-3-ylamino)methylene)-2,2-dimethyl-1,3-dioxane-4,6-dione (34.8 g). The obtained 5-((2-chloropyridin-3-ylamino)methylene)-2,2-dimethyl-1,3-dioxane-4,6-di one (8.2 g) was gradually added to Dowtherm heated to 220° C., and the mixture was heated at 220° C. for 30 minutes. After cooling, hexane (300 ml) was added to the reaction solution, and the deposit was filtrated to obtain 8-chloro-1,7-naphthyridin-4(1H)-one (2.02 g). 4-(4-Chloro-1,7-naphthyridin-8-yl)-2-(ethylamino)benzonitrile (0.107 g) was obtained according to Example 5(1) using the obtained 8-chloro-1,7-naphthyridin-4(1H)-one (0.295 g) instead of compound (3a) and 4-cyano-3-(ethylamino)phenylboronic acid pinacol ester instead of 3-quinolineboronic acid. A suspension of the obtained 4-(4-chloro-1,7-naphthyridin-8-yl)-2-(ethylamino)benzonitrile (0.0491 g), 4-(1H-imidazol-4-yl)-1-methyl-1H-pyrazole hydrochloride (0.035 g), copper(II) oxide nanoparticles (0.06 g), and potassium carbonate (0.0883 g) in DMF (1.5 ml) was stirred overnight at 125° C. The reaction solution was partitioned between ethyl acetate and water. The organic layer was washed with brine. The organic layer thus washed was dried over anhydrous sodium sulfate. Then, the solvent was distilled off, and the residue was purified by neutral silica gel column chromatography (chloroform/methanol) to obtain 2-(ethylamino)-4-(4-(4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-1-yl)-1,7-naphthyridin-8yl)benzonitrile. An aqueous sodium hydroxide solution (4 M, 0.093 mL) and a 30% aqueous hydrogen peroxide solution (0.045 mL) were added to a solution of the obtained 2-(ethylamino)-4-(4-(4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-1-yl)-1,7-naphthyridin-8yl)benzonitrile in DMSO (3 mL) at room temperature, and the mixture was stirred for 30 minutes. Water was added to the reaction solution, and the deposit was collected by filtration, then washed with water and ether by sprinkling, and then dried under reduced pressure to obtain compound (72) (0.040 g, yield based on 6 steps: 4%) as a pale yellow solid.

Workup

  1. filtrationthe deposit was collected by filtration
  2. washwashed with water and ether by sprinkling
  3. customdried under reduced pressure

Sources & evidence

ORD record
ord-e613b1e060404b069d1eb0a3d9a64727
Source dataset
uspto-grants-2014_12
Patent number
US08912181B2

Reaction notes

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