Diisopropylethylamine → HCID 66639821, compound

HRID 1093952Notes

Reaction equation

HRID 1093952 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:10]([NH:11][S:12]([CH2:15][C:16](OC)=O)(=[O:14])=[O:13])=[N:9][CH:8]=[CH:7][N:6]=1)=[O:4].C(N(CC)C(C)C)(C)C.FC(F)COS([C:36]([F:39])([F:38])F)(=O)=O>C(#N)C>[CH3:1][O:2][C:3]([C:5]1[C:10]([N:11]([C:3]([O:2][CH3:1])=[O:4])[S:12]([CH2:15][CH2:16][CH:36]([F:38])[F:39])(=[O:13])=[O:14])=[N:9][CH:8]=[CH:7][N:6]=1)=[O:4]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 27740892,2-Difluoroethyl trifluoromethanesulfonateHCID 59623767HCID 59623767, compound

Product 1

HCID 66639821HCID 66639821, compoundYield 110.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

To a solution of 3-methoxycarbonylmethanesulfonylamino-pyrazine-2-carboxylic acid methyl ester (Example 9.1) (1.212 g) in acetonitrile (12 ml) was added N,N-diisopropylethylamine (“Hunig's base”) (0.8 ml) at ambient temperature. The mixture was stirred at ambient temperature for 5 minutes before dropwise addition of a solution of 2,2-difluoroethyltrifluoromethanesulfonate (0.978 g) in acetonitrile (5 ml) at ambient temperature. The reaction mixture was stirred at ambient temperature for 20 hours. The reaction mixture was concentrated and the residue partitioned between ethyl acetate (30 ml) and aqueous sulfuric acid (2M) (30 ml). The phases were separated and the organic layer was concentrated. The residue was purified by column chromatography on silica gel (eluent: ethyl acetate/hexane 1:2) to give 3-[(2,2-difluoro-ethyl)-methoxycarbonyl-methanesulfonyl-amino]-pyrazine-2-carboxylic acid methyl ester (0.819 g). 1H-NMR (400 MHz, CDCl3): 8.70 (d, 1H), 8.65 (d, 1H), 6.06-6.29 (m, 1H), 4.32-4.38 (m, 2H), 4.18 (s, 2H), 4.02 (s, 3H), 3.78 (s, 3H) ppm.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customthe residue partitioned between ethyl acetate (30 ml) and aqueous sulfuric acid (2M) (30 ml)
  3. customThe phases were separated
  4. concentrationthe organic layer was concentrated
  5. customThe residue was purified by column chromatography on silica gel (eluent: ethyl acetate/hexane 1:2)

Sources & evidence

ORD record
ord-3586a787ec9243f68d63c8f1b28347f9
Source dataset
uspto-grants-2012_03
Patent number
US08133849B2

Reaction notes

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