Sodium Bicarbonate → HCID 178428706, compound

HRID 505407Notes

Reaction equation

HRID 505407 reaction equation
[NH2:1][C:2]1[C:7]([NH:8][C:9](=O)[CH2:10][CH2:11][C:12]2[CH:17]=[C:16]([CH3:18])[CH:15]=[C:14]([NH2:19])[N:13]=2)=[CH:6][C:5](I)=[CH:4][N:3]=1.C(=O)(O)[O-].[Na+].[F:27][C:28]([F:39])([F:38])[C:29]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=1>O1CCOCC1>[CH3:18][C:16]1[CH:17]=[C:12]([CH2:11][CH2:10][C:9]2[NH:1][C:2]3=[N:3][CH:4]=[C:5]([C:32]4[CH:33]=[CH:34][C:29]([C:28]([F:39])([F:38])[F:27])=[CH:30][CH:31]=4)[CH:6]=[C:7]3[N:8]=2)[N:13]=[C:14]([NH2:19])[CH:15]=1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 27343894-(Trifluoromethyl)phenylboronic acidHCID 68462320N-(2-amino-5-iodo-pyridin-3-yl)-3-(6-amino-4-methyl-pyridin-2-yl)-propionamide

Product 1

HCID 178428706HCID 178428706, compoundYield 54.1%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

96 mg N-(2-amino-5-iodo-pyridin-3-yl)-3-(6-amino-4-methyl-pyridin-2-yl)-propionamide (compound A10) is dissolved in 3.0 ml anoxic dioxane under a nitrogen atmosphere. Subsequently, 0.7 ml of an aqueous sodium bicarbonate solution (2.0 M), 52 mg 4-(trifluoromethyl)phenyl-boronic acid, and 14 mg trans-dichloro-bis(tricyclohexylphosphane)palladium-(II) are added. The reaction mixture is refluxed at 110° C. for 20 h. Thereafter, the volatile components are removed in vacuo and the remaining residue is re-dissolved in a mixture of water/dichloromethane (1:1). The aqueous phase is extracted several times with dichloromethane. The organic layer is separated, dried using sodium sulfate, and evaporated to dryness to yield 161 mg of a colourless, crude solid. Subsequently, the residue is purified by flash chromatography on silica gel (eluent: dichloromethane/ethanol 8:1) to afford 52 mg of the title compound. M.p. 170° C. ESI-MS: 398.3 (MH+). TLC: Rf=0.25 (dichloromethane/methanol 8:1).

Workup

  1. customThereafter, the volatile components are removed in vacuo
  2. dissolutionthe remaining residue is re-dissolved in a mixture of water/dichloromethane (1:1)
  3. extractionThe aqueous phase is extracted several times with dichloromethane
  4. customThe organic layer is separated
  5. customdried
  6. customevaporated to dryness
  7. customto yield 161 mg of a colourless, crude solid
  8. customSubsequently, the residue is purified by flash chromatography on silica gel (eluent: dichloromethane/ethanol 8:1)

Sources & evidence

ORD record
ord-f088190f99884d1bb23fae5902aa43a2
Source dataset
uspto-grants-2010_08
Patent number
US07781453B2

Reaction notes

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