Potassium Carbonate → N-(4-(cyclopropyl(6-methoxypyridin-3-yl)methoxy)-3-methoxybenzyl)-5-(1-methyl-1H-pyrazol-4-yl)-3-nitropyridin-2-amine

HRID 706502Notes

Reaction equation

HRID 706502 reaction equation
[CH:1]1([CH:4]([C:26]2[CH:27]=[N:28][C:29]([O:32][CH3:33])=[CH:30][CH:31]=2)[O:5][C:6]2[CH:23]=[CH:22][C:9]([CH2:10][NH:11][C:12]3[C:17]([N+:18]([O-:20])=[O:19])=[CH:16][C:15](I)=[CH:14][N:13]=3)=[CH:8][C:7]=2[O:24][CH3:25])[CH2:3][CH2:2]1.[CH3:34][N:35]1[CH:39]=[C:38](B2OC(C)(C)C(C)(C)O2)[CH:37]=[N:36]1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.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-].[Cl-].[Fe+2].[Pd+2]>[CH:1]1([CH:4]([C:26]2[CH:27]=[N:28][C:29]([O:32][CH3:33])=[CH:30][CH:31]=2)[O:5][C:6]2[CH:23]=[CH:22][C:9]([CH2:10][NH:11][C:12]3[C:17]([N+:18]([O-:20])=[O:19])=[CH:16][C:15]([C:38]4[CH:37]=[N:36][N:35]([CH3:34])[CH:39]=4)=[CH:14][N:13]=3)=[CH:8][C:7]=2[O:24][CH3:25])[CH2:3][CH2:2]1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 118114000N-(4-(cyclopropyl(6-methoxypyridin-3-yl)methoxy)-3-methoxybenzyl)-5-iodo-3-nitropyridin-2-amine

Product 1

HCID 118114063N-(4-(cyclopropyl(6-methoxypyridin-3-yl)methoxy)-3-methoxybenzyl)-5-(1-methyl-1H-pyrazol-4-yl)-3-nitropyridin-2-amineYield 55%

Reagents, catalysts & solvents 3

HCID 178478645Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent2×HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred solution of N-(4-(cyclopropyl(6-methoxypyridin-3-yl)methoxy)-3-methoxybenzyl)-5-iodo-3-nitropyridin-2-amine (2.20 g, 3.91 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.896 g, 4.30 mmol), and potassium carbonate (1.10 g, 7.95 mmol) in toluene (10 mL) and water (1 mL) was added (1,1′-bis(diphenylphosphino)ferrocene)palladium(II) dichloride (0.143 g, 0.20 mmol). The resulting mixture was heated to 100° C. and stirred under a nitrogen atmosphere. After 16 h, the mixture was allowed to cool to room temperature and was diluted with water (15 mL). The mixture was extracted with ethyl acetate (2×60 mL). The combined organic phases were dried over sodium sulfate, filtered, and concentrated. Chromatographic purification of the residue (silica gel, 33% ethyl acetate in petroleum ether elute) afforded 1.10 g (55%) of N-(4-(cyclopropyl(6-methoxypyridin-3-yl)methoxy)-3-methoxybenzyl)-5-(1-methyl-1H-pyrazol-4-yl)-3-nitropyridin-2-amine as a light brown solid.

Workup

  1. temperatureto cool to room temperature
  2. extractionThe mixture was extracted with ethyl acetate (2×60 mL)
  3. dry with materialThe combined organic phases were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customChromatographic purification of the residue (silica gel, 33% ethyl acetate in petroleum ether elute)

Sources & evidence

ORD record
ord-ea99ca81638246c7b7ed0a8a87901dbb
Source dataset
uspto-grants-2015_11
Patent number
US09174986B2

Reaction notes

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