Sodium Carbonate → HCID 178476654, compound

HRID 929678Notes

Reaction equation

HRID 929678 reaction equation
[CH3:1][O:2][C:3]1[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH3:22])[C:4]=1[CH2:5][NH:6][C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13](I)=[CH:12][N:11]=1)=[NH:8].[C:23]1([O:29]B(O)O)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C(=O)([O-])[O-].[Na+].[Na+]>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.COCCOC.O.C(O)C>[C:17]([OH:21])(=[O:29])[CH3:18].[CH3:1][O:2][C:3]1[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH3:22])[C:4]=1[CH2:5][NH:6][C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[CH:12][N:11]=1)=[NH:8]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 78412Phenyl dihydrogen orthoborateHCID 178491352N-(2,6-dimethoxybenzyl)-N'-(5-iodopyridin-2-yl)guanidine

Product 1

HCID 178476654HCID 178476654, compoundYield 12.4%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 86587095Dimethoxyethane ethanol waterSolvent

Conditions

Temperature
120 °C

Procedure

0.251 g (0.609 mmol) N-(2,6-dimethoxybenzyl)-N′-(5-iodopyridin-2-yl)guanidine, 0.100 g (0.792 mmol) phenylboric acid, 0.194 g (1.829 mmol) sodium carbonate, and 0.035 g (0.030 mmol) tetrakis-(triphenylphosphine) palladium(0) were combined and added to 7.0 mL of a solvent mixture of 1,2-dimethoxyethane/water/ethanol (7:3:2). The mixture was degassed under a strong nitrogen stream and reacted by heating for 60 min at 120° C. in a CEM microwave (230 watts). To prevent precipitation of product, the reaction mixture was first diluted with dichloromethane and then shaken out with water. After separation of the phases the aqueous phase was repeatedly extracted with dichloromethane, and the combined organic phases were neutralized with 150 mL 2 N sodium hydroxide solution and then washed again with water (2×100 mL). After drying over magnesium sulfate and evaporation of the solvent, purification was performed via preparative HPLC (Merck Chromolith RP-18 100×25 mm, eluent: water/acetonitrile/0.1 M acetic acid), with a flow rate of 20 mL/min and with gradients of 10% to 40% of the acetonitrile fraction in 15 min. Following freeze drying with a lyophilizing agent, 16 mg of the desired product N-(2,6-dimethoxybenzyl)-N′-(5-phenylpyridin-2-yl)guanidine was isolated in the form of the acetate salt (base/acetate in a ratio of 1:1).

Workup

  1. customThe mixture was degassed under a strong nitrogen stream
  2. customreacted
  3. customprecipitation of product
  4. additionthe reaction mixture was first diluted with dichloromethane
  5. customAfter separation of the phases the aqueous phase
  6. extractionwas repeatedly extracted with dichloromethane
  7. washwashed again with water (2×100 mL)
  8. dry with materialAfter drying over magnesium sulfate and evaporation of the solvent, purification
  9. customdrying with a lyophilizing agent

Sources & evidence

ORD record
ord-3ab82855bc334b7b87632cadd495418a
Source dataset
uspto-grants-2016_03
Patent number
US09296697B2

Reaction notes

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