Potassium Carbonate → N-(2-Amino-2-oxoethyl)-1-(5-(4-methoxypyridin-2-yl)pyrimidin-2-yl)-N-methyl-3-(methylthio)-1H-indole-6-carboxamide

HRID 630523Notes

Reaction equation

HRID 630523 reaction equation
[NH2:1][C:2](=[O:26])[CH2:3][N:4]([CH3:25])[C:5]([C:7]1[CH:15]=[C:14]2[C:10]([C:11]([S:23][CH3:24])=[CH:12][N:13]2[C:16]2[N:21]=[CH:20][C:19](Br)=[CH:18][N:17]=2)=[CH:9][CH:8]=1)=[O:6].B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].Br[C:51]1[CH:56]=[C:55]([O:57][CH2:58]C)[CH:54]=[CH:53][N:52]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.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].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:1][C:2](=[O:26])[CH2:3][N:4]([CH3:25])[C:5]([C:7]1[CH:15]=[C:14]2[C:10]([C:11]([S:23][CH3:24])=[CH:12][N:13]2[C:16]2[N:21]=[CH:20][C:19]([C:51]3[CH:56]=[C:55]([O:57][CH3:58])[CH:54]=[CH:53][N:52]=3)=[CH:18][N:17]=2)=[CH:9][CH:8]=1)=[O:6]

Participants

9

Reactant 5

HCID 11430Potassium CarbonateHCID 517044Potassium AcetateHCID 5651602-Bromo-4-ethoxypyridineHCID 2733548Bis(pinacolato)diboraneHCID 118676794N-(2-amino-2-oxo ethyl)-1-(5-bromopyrimidin-2-yl)-N-methyl-3-(methylthio)-1H-indole-6-carboxamide

Product 1

HCID 118666290N-(2-Amino-2-oxoethyl)-1-(5-(4-methoxypyridin-2-yl)pyrimidin-2-yl)-N-methyl-3-(methylthio)-1H-indole-6-carboxamide

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

PdCl2(dppf) (0.094 g, 0.115 mmol) was added under an argon atmosphere to a suspension of N-(2-amino-2-oxo ethyl)-1-(5-bromopyrimidin-2-yl)-N-methyl-3-(methylthio)-1H-indole-6-carboxamide (1.0 g, 2.3 mmol), bis(pinacolato)diboron (0.655 g, 2.58 mmol) and potassium acetate (0.68 g, 6.91 mmol) in dioxane (40 mL) and the mixture was stirred at 110° C. for 1 h. After cooling to room temperature, 2-bromo-4-ethoxy-pyridine (0.65 g, 3.45 mmol), a 2M potassium carbonate solution (8.0 mL) and tetrakis(triphenylphosphine)palladium(0) (0.133 g, 0.115 mmol) were added. The reaction mixture was stirred at 100° C. for 16 h, and then filtered through celite. The filter was washed with methanol/dichloromethane (1:9), the filtrate was concentrated and the residue purified by flash column chromatography [silica; methanol/dichloromethane=3.5:96.5]. White solid. Yield: 0.185 g

Workup

  1. temperatureAfter cooling to room temperature
  2. stirringThe reaction mixture was stirred at 100° C. for 16 h
  3. filtrationfiltered through celite
  4. washThe filter was washed with methanol/dichloromethane (1:9)
  5. concentrationthe filtrate was concentrated
  6. customthe residue purified by flash column chromatography [silica; methanol/dichloromethane=3.5:96.5]

Sources & evidence

ORD record
ord-ff394ee272754425a40cf4e1f490dac5
Source dataset
uspto-grants-2016_04
Patent number
US09315490B2

Reaction notes

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