Triethylamine → HCID 86617874, compound

HRID 2426805Notes

Reaction equation

HRID 2426805 reaction equation
[CH2:1]([C@:8]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:28])[CH:9]([OH:27])[CH2:10][NH:11][C:12](=[O:26])[C:13]1[CH:18]=[C:17]([N:19]([CH3:24])[S:20]([CH3:23])(=[O:22])=[O:21])[N:16]=[C:15]([Cl:25])[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.S(=O)(=O)=O.N1C=CC=CC=1>C(Cl)Cl.CS(C)=O>[CH2:1]([C@:8]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:28])[C:9](=[O:27])[CH2:10][NH:11][C:12](=[O:26])[C:13]1[CH:18]=[C:17]([N:19]([CH3:24])[S:20]([CH3:23])(=[O:22])=[O:21])[N:16]=[C:15]([Cl:25])[CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 168533Sulfur trioxide-pyridineHCID 86617875HCID 86617875, compound

Product 1

HCID 86617874HCID 86617874, compoundYield 84%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolvent

Procedure

To a −20° C. solution of tert-butyl (1R)-1-benzyl-3-({2-chloro-6-[methyl(methylsulfonyl)amino]isonicotinoyl}amino)-2-hydroxy-1-methylpropylcarbamate (0.400 g, 0.74 mmol) in 8 mL CH2Cl2/4 mL DMSO was added triethylamine (0.41 mL, 2.96 mmol). After 5 min, a solution of pyridine sulfur trioxide (0.471 g, 2.96 mmol) in 3 mL DMSO was added via cannula. After 16 h at ambient temperature, the reaction was quenched with brine (10 mL) and extracted with Et2O (15 mL). The aqueous layer was back extracted with Et2O (10 mL×2). The combined organics were washed with 10% aqueous sodium bisulfite (10 mL), and brine (10 mL), dried over Na2SO4, filtered and concentrated in vacuo. Purification by normal phase chromatography (20->70% EtOAc/hexanes) yielded 0.335 g (84%) of tert-butyl (1R)-1-benzyl-3-({2-chloro-6-[methyl(methylsulfonyl)amino]isonicotinoyl}amino)-1-methyl-2-oxopropylcarbamate as a white solid. NMR (CDCl3, 400 MHz) 7.69 (d, J=1.01 Hz, 1H); 7.51 (d, J=0.92 Hz, 1H); 7.31 (m, 3H); 7.12 (m, 2H); 4.62 (m, 1H); 4.41 (m, 1H); 3.44 (s, 3H); 3.11 (s, 3H); 1.48 (s, 9H); 1.31 (s, 3H); LC/MS [M−C4H7]+=483.

Workup

  1. waitAfter 16 h at ambient temperature
  2. customthe reaction was quenched with brine (10 mL)
  3. extractionextracted with Et2O (15 mL)
  4. extractionThe aqueous layer was back extracted with Et2O (10 mL×2)
  5. washThe combined organics were washed with 10% aqueous sodium bisulfite (10 mL), and brine (10 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification by normal phase chromatography (20->70% EtOAc/hexanes)

Sources & evidence

ORD record
ord-226d943c78cb403bacfea61f9762abea
Source dataset
uspto-grants-2011_06
Patent number
US07968571B2

Reaction notes

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