Sodium Carbonate → HCID 86724861, compound

HRID 1853092Notes

Reaction equation

HRID 1853092 reaction equation
[CH3:1][N:2]1[C:6]([CH3:7])=[C:5]([C:8]([NH:10][C:11]2[CH:16]=[CH:15][C:14](B3OC(C)(C)C(C)(C)O3)=[CH:13][CH:12]=2)=[O:9])[C:4](=[O:26])[N:3]1[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.Br[C:34]1[C:35]([NH2:41])=[N:36][CH:37]=[C:38]([Br:40])[N:39]=1.C(=O)([O-])[O-].[Na+].[Na+]>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.O1CCOCC1.O>[NH2:41][C:35]1[C:34]([C:14]2[CH:13]=[CH:12][C:11]([NH:10][C:8]([C:5]3[C:4](=[O:26])[N:3]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)[N:2]([CH3:1])[C:6]=3[CH3:7])=[O:9])=[CH:16][CH:15]=2)=[N:39][C:38]([Br:40])=[CH:37][N:36]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 6200042-Amino-3,5-dibromopyrazineHCID 68288942HCID 68288942, compound

Product 1

HCID 86724861HCID 86724861, compoundYield 39.8%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
90 °C

Procedure

A suspension of the compound prepared in Example 2 (15 g), tetrakis(triphenylphosphine)palladium (Pd(PPh3)4) (2.0 g), 3,5-dibromopyrazin-2-amine (9.5 g), and sodium carbonate (Na2CO3) (7.3 g) in 3:1 mixture of dioxane/water (350 mL) was degassed with a stream of nitrogen for 10 minutes. The reaction was heated at 90° C. for 5 hours, at which time LC/MS indicated the reaction was complete. The mixture was concentrated under reduced pressure, diluted with water (200 mL) and extracted with EtOAc (3×300 mL). The organic layers were combined, dried over Na2SO4, and evaporated under reduced pressure. The product was absorbed onto silica gel (40 g) and purified by flash chromatography (silica gel, 400 g) using a gradient of 1 to 3% MeOH in DCM as the eluent. After purification, 1H NMR showed that pinicol was present as an impurity. The product was suspended in 10% aqueous potassium carbonate (300 mL), stirred for 30 minutes, filtered and washed with water (3×100 mL). The resulting solid was then evaporated from absolute ethanol (6×50 mL) to give the title compound (6.6 g) having the following physical data as a yellow solid.

Workup

  1. customwas degassed with a stream of nitrogen for 10 minutes
  2. concentrationThe mixture was concentrated under reduced pressure
  3. additiondiluted with water (200 mL)
  4. extractionextracted with EtOAc (3×300 mL)
  5. dry with materialdried over Na2SO4
  6. customevaporated under reduced pressure
  7. customThe product was absorbed onto silica gel (40 g)
  8. custompurified by flash chromatography (silica gel, 400 g)
  9. customAfter purification, 1H NMR
  10. filtrationfiltered
  11. washwashed with water (3×100 mL)
  12. customThe resulting solid was then evaporated from absolute ethanol (6×50 mL)

Sources & evidence

ORD record
ord-63aca905a14e46c2adf984262b16dc38
Source dataset
uspto-grants-2015_02
Patent number
US08962623B2

Reaction notes

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