Sodium Carbonate → N,N-Di(Boc)-3-ethynyl-5-[4-(isopropylsulfonyl)phenyl]pyrazin-2-amine

HRID 467494Notes

Reaction equation

HRID 467494 reaction equation
[C:1]([O:5][C:6]([N:8]([C:16]1[C:21]([C:22]#[C:23][Si](C)(C)C)=[N:20][C:19]([C:28]2[CH:33]=[CH:32][C:31]([S:34]([CH:37]([CH3:39])[CH3:38])(=[O:36])=[O:35])=[CH:30][CH:29]=2)=[CH:18][N:17]=1)[C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[Na+].[Na+]>CO>[C:1]([O:5][C:6]([N:8]([C:16]1[C:21]([C:22]#[CH:23])=[N:20][C:19]([C:28]2[CH:29]=[CH:30][C:31]([S:34]([CH:37]([CH3:39])[CH3:38])(=[O:36])=[O:35])=[CH:32][CH:33]=2)=[CH:18][N:17]=1)[C:9](=[O:15])[O:10][C:11]([CH3:13])([CH3:14])[CH3:12])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

4

Reactant 2

HCID 10340Sodium CarbonateHCID 68044859tert-Butyl N-tert-butoxycarbonyl-N-[5-(4-isopropylsulfonylphenyl)-3-(2-trimethylsilylethynyl)pyrazin-2-yl]carbamate

Product 1

HCID 59471983N,N-Di(Boc)-3-ethynyl-5-[4-(isopropylsulfonyl)phenyl]pyrazin-2-amineYield 89%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

tert-Butyl N-tert-butoxycarbonyl-N-[5-(4-isopropylsulfonylphenyl)-3-(2-trimethylsilylethynyl)pyrazin-2-yl]carbamate (42.6 g, 74.25 mmol) was dissolved/suspended in methanol (510 mL) and 2M aqueous sodium carbonate (425.8 mL, 851.6 mmol) was added to the rapidly stirred mixture. An oil separated out and more methanol (100 mL) was added to dissolve. The mixture was stirred at ambient temperature for 1 hour. The slurry was poured into a mixture of EtOAc/water (800 mL/1 L). The organic phase was separated and the aqueous extracted with EtOAc (2×250 mL). The combined organic extracts were washed with brine, dried (MgSO4), filtered and concentrated in vacuo. The residue was slurried in 5% EtOAc/Petroleum Ether and stirred for 90 minutes at ambient temperature. The precipitate was isolated by filtration, washed with Petroleum Ether and dried to give the sub-title product as a white solid (33.1 g, 89% Yield). 1H NMR (400.0 MHz, DMSO) δ 1.18 (d, 6H), 1.37 (s, 18H), 3.50 (sept, 1H), 4.99 (s, 1H), 8.03 (d, 2H), 8.44 (d, 2H) and 9.35 (s, 1H) ppm; MS (ES+) 502.1.

Workup

  1. customAn oil separated out
  2. additionmore methanol (100 mL) was added
  3. dissolutionto dissolve
  4. additionThe slurry was poured into a mixture of EtOAc/water (800 mL/1 L)
  5. customThe organic phase was separated
  6. extractionthe aqueous extracted with EtOAc (2×250 mL)
  7. washThe combined organic extracts were washed with brine
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. stirringstirred for 90 minutes at ambient temperature
  12. customThe precipitate was isolated by filtration
  13. washwashed with Petroleum Ether
  14. customdried

Sources & evidence

ORD record
ord-98b5396e4fd84a16bdd604fe7238448f
Source dataset
uspto-grants-2014_01
Patent number
US08623869B2

Reaction notes

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