Methane → HCID 58070279, compound

HRID 81380Notes

Reaction equation

HRID 81380 reaction equation
BrC1N=C(C#C[Si](C)(C)C)C(N)=NC=1.[CH3:15][C:16]1[CH:17]=CC(S(O)(=O)=O)=C[CH:21]=1.[Br:26][C:27]1[N:28]=[C:29]([C:44]#[C:45][Si:46]([CH3:49])([CH3:48])[CH3:47])[C:30]([N:33]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[C:34](=[O:36])[O-:35])=[N:31][CH:32]=1.CC(OC(OC(OC(C)(C)C)=O)=O)(C)C.C>CCOC(C)=O.CN(C1C=CN=CC=1)C>[C:40]([O:39][C:37]([N:33]([C:30]1[C:29]([C:44]#[C:45][Si:46]([CH3:47])([CH3:49])[CH3:48])=[N:28][C:27]([Br:26])=[CH:32][N:31]=1)[C:34](=[O:35])[O:36][C:16]([CH3:17])([CH3:21])[CH3:15])=[O:38])([CH3:42])([CH3:43])[CH3:41]

Participants

8

Reactant 5

HCID 297MethaneHCID 6101p-Toluenesulfonic acidHCID 90495Di-tert-butyl dicarbonateHCID 533931895-Bromo-3-((trimethylsilyl)ethynyl)pyrazin-2-amineHCID 86680731N-[5-bromo-3-(2-trimethylsilylethynyl)pyrazin-2-yl]-N-tertbutoxycarbonyl-carbamate

Product 1

HCID 58070279HCID 58070279, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8857Ethyl AcetateSolvent2×

Procedure

A solution of 5-bromo-3-((trimethylsilyl)ethynyl)pyrazin-2-amine (Compound C-2) PTSA salt 3 (2350 g, 5.31 mol) in EtOAc (11.5 L) is stirred with a 20% w/w aq. solution of KHCO3 (4.5 kg, 1.5 eq.) for at least 30 min. The layers are separated and the organic layer is concentrated then dissolved in EtOAc (7 L) and added to a reactor. DMAP (19.5 g, 0.16 mol) is added followed a solution of Boc2O (2436 g, 11.16 mol) in EtOAc (3 L) is added lowly. The reaction is stirred for at least 30 min to ensure complete reaction then activated charcoal (Darco G-60, 720 g) and Celite (720 g) are added and stirred for at least 2 h. The mixture is filtered washing the solid pad with EtOAc (2×1.8 L). The filtrate is concentrated to afford tert-butyl N-tert-butoxycarbonyl-N-[5-bromo-3-((trimethylsilyl)ethynyl)pyrazin-2-yl]carbamate (Compound C-3) that is used directly in the next step.

Workup

  1. customThe layers are separated
  2. concentrationthe organic layer is concentrated
  3. dissolutionthen dissolved in EtOAc (7 L)
  4. additionadded to a reactor
  5. additionis added lowly
  6. customreaction
  7. stirringstirred for at least 2 h
  8. filtrationThe mixture is filtered
  9. washwashing the solid pad with EtOAc (2×1.8 L)
  10. concentrationThe filtrate is concentrated

Sources & evidence

ORD record
ord-8e13d50c4b5f459cbacffa6ab52b8660
Source dataset
uspto-grants-2014_09
Patent number
US08846686B2

Reaction notes

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