Sodium hydride → HCID 58382232, compound

HRID 1628090Notes

Reaction equation

HRID 1628090 reaction equation
[Br:1][C:2]1[N:3]=[C:4]([C:9]#[C:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)[C:5]([NH2:8])=[N:6][CH:7]=1.C(C1C=CC(OC)=CC=1)#C.BrC1C(N)=NC=C(Br)N=1.[H-].[Na+].[CH3:40][Si:41]([CH3:48])([CH3:47])[CH2:42][CH2:43][O:44][CH2:45]Cl>CN(C=O)C>[Br:1][C:2]1[N:3]=[C:4]2[CH:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=3)[N:8]([CH2:45][O:44][CH2:43][CH2:42][Si:41]([CH3:48])([CH3:47])[CH3:40])[C:5]2=[N:6][CH:7]=1

Participants

7

Reactant 5

HCID 24758Sodium hydride2×HCID 2510201-Ethynyl-4-methoxybenzeneHCID 6200042-Amino-3,5-dibromopyrazineHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 58382310HCID 58382310, compound

Product 1

HCID 58382232HCID 58382232, compoundYield 84%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a round bottom flask was added 5-bromo-3-((4-methoxyphenyl)ethynyl)pyrazin-2-amine (11.9 g, 39.1 mmol, prepared using A from 1-ethynyl-4-methoxybenzene with 3,5-dibromopyrazin-2-amine), DMF (98 mL) and NaH (60% in mineral oil) (2.03 g, 50.8 mmol). The reaction mixture was stirred at room temperature for about 2 h and then 2-(trimethylsilyl)ethoxymethyl chloride (7.63 mL, 43.0 mmol) was added. The reaction mixture was stirred at rt for about 2 h. To the reaction mixture was added NaH (60% in mineral oil) (0.469 g, 19.55 mmol). The reaction mixture was stirred for about 24 h at rt. The reaction mixture was quenched with water (400 mL) and extracted with EtOAc (3×250 mL). The organic layer was washed with brine (250 mL), dried with MgSO4, filtered and concentrated in vacuo. The crude material was purified by flash chromatography (300 g Silicycle® column, DCM/MeOH 1:0 to 10:1) to give the title compound (14.3 g; 84%): LC/MS (Table 2, Method b) Rt=3.11 min; MS m/z 436.2 (M+H)+.

Workup

  1. customprepared
  2. stirringThe reaction mixture was stirred at rt for about 2 h
  3. stirringThe reaction mixture was stirred for about 24 h at rt
  4. customThe reaction mixture was quenched with water (400 mL)
  5. extractionextracted with EtOAc (3×250 mL)
  6. washThe organic layer was washed with brine (250 mL)
  7. dry with materialdried with MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude material was purified by flash chromatography (300 g Silicycle® column, DCM/MeOH 1:0 to 10:1)

Sources & evidence

ORD record
ord-47d649f758564b55b07926f0d036ba02
Source dataset
uspto-grants-2014_07
Patent number
US08785639B2

Reaction notes

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