Water → HCID 22557472, compound

HRID 984059Notes

Reaction equation

HRID 984059 reaction equation
[O:1]([C:8]1[CH:13]=[CH:12][C:11](B(O)O)=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:17][C:18]1[C:19]([C:26]([NH2:28])=[O:27])=[N:20][C:21](Cl)=[C:22]([NH2:24])[N:23]=1.C(=O)([O-])[O-].[Na+].[Na+].O>C1(C)C=CC=CC=1.C(O)C.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>[NH2:17][C:18]1[C:19]([C:26]([NH2:28])=[O:27])=[N:20][C:21]([C:11]2[CH:12]=[CH:13][C:8]([O:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[CH:9][CH:10]=2)=[C:22]([NH2:24])[N:23]=1

Participants

8

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 6043433,5-diamino-6-chloropyrazine-2-carboxamideHCID 27343774-Phenoxyphenylboronic acid

Product 1

HCID 22557472HCID 22557472, compoundYield 27.4%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Procedure

To a mixture of 4-phenoxyphenylboronic acid (0.22 g, 1.02 mmol), 3,5-diamino-6-chloropyrazine-2-carboxamide (0.176 g, 0.919 mmol), sodium carbonate (0.33 g, 2.06 mmol) in toluene (14 mL), ethanol (3.5 mL), and water (3.5 mL) was added tetrakis(triphenylphosphine)palladium (60 mg). The mixture was refluxed overnight. The reaction was allowed to cool to room temperature, then partitioned between water and ethyl acetate. The aqueous layer was extracted one more time with ethyl acetate. The combined organic layers were washed with water, dried over sodium sulfate, filtered, and evaporated under reduced pressure to give the crude product as a solid. Flash chromatography (Silica gel; 6:4 ethyl acetate/dichloromethane to 7:3 ethyl acetate/dichloromethane) and subsequent recrystalization from chloroform afforded 81 mg (27%) of the desired product as white solid. 1H NMR (CDCl3): δ 7.58 (d, J=9.0 Hz, 2H), 7.37 (t, J=7.8 Hz, 2H), 7.38 (bs, 1H), 7.15 (t, J=8.4 Hz, 1H), 7.10-7.05 (m, 4H), 5.26 (bs, 1H), 4.97 (s, 4H).

Workup

  1. temperatureThe mixture was refluxed overnight
  2. custompartitioned between water and ethyl acetate
  3. extractionThe aqueous layer was extracted one more time with ethyl acetate
  4. washThe combined organic layers were washed with water
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated under reduced pressure
  8. customto give the crude product as a solid
  9. customFlash chromatography (Silica gel; 6:4 ethyl acetate/dichloromethane to 7:3 ethyl acetate/dichloromethane) and subsequent recrystalization from chloroform

Sources & evidence

ORD record
ord-98d2ce912cc6450ca64e53c926ccf2e1
Source dataset
uspto-grants-2005_03
Patent number
US06867210B2

Reaction notes

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