Triethylamine → HCID 10718457, compound

HRID 1415908Notes

Reaction equation

HRID 1415908 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N:17]2[CH2:21][C@H:20]([CH2:22][NH:23][C:24](=[O:26])[CH3:25])[O:19][C:18]2=[O:27])[CH:5]=[CH:6][C:7]=1[N:8]1[CH:12]=[CH:11][C:10]([CH2:13][CH2:14][CH2:15]O)=[CH:9]1.C(N(CC)CC)C.CS(Cl)(=O)=O.[CH3:40][S:41]([NH2:44])(=[O:43])=[O:42].[H-].[Na+]>ClCCl.CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]([N:17]2[CH2:21][C@H:20]([CH2:22][NH:23][C:24](=[O:26])[CH3:25])[O:19][C:18]2=[O:27])[CH:5]=[CH:6][C:7]=1[N:8]1[CH:12]=[CH:11][C:10]([CH2:13][CH2:14][CH2:15][NH:44][S:41]([CH3:40])(=[O:43])=[O:42])=[CH:9]1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 24758Sodium hydrideHCID 31297Methanesulfonyl chlorideHCID 72879MethanesulfonamideHCID 10690868HCID 10690868, compound

Product 1

HCID 10718457HCID 10718457, compoundYield 26%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 100 mg (0.266 mmol) of the compound of Example 25 (previously dried at 60° C. under 0.1 mmHg for 18 h prior to use) and 88 mg (120 μL, 0.88 mmol) of triethylamine in 2 mL dichloromethane at 0° C. was treated with 85 mg (58 μL, 0.73 mmol) of methanesulfonyl chloride, followed by stirring at 0° C. for 30 min. The solution was diluted with dichloromethane and extracted with water (2×) and saturated sodium bicarbonate solution. Drying (Na2SO4) and concentration in vacuo afforded a solid which was dissolved in 2 mL DMF and treated via cannula to a 0° C. solution of 38 mg (0.40 mmol) of methanesulfonamide in 2 mL DMF which had been previously treated with 10 mg (17 mg of 60% in oil, 0.43 mmol) of sodium hydride. The solution was then warmed at 60° C. for 18 h. The solution was cooled and the DMF removed in vacuo, and the residue was dissolved in ethyl acetate and extracted with water (2×). Drying (Na2SO4) and concentration in vacuo afforded a solid which was subjected to radial chromatography on a 2 mm chromatotron plate, eluting with 1-4% (v/v) methanol in dichloromethane. These procedures afforded 31 mg (26%) of the title compound as a white solid. 1H NMR (CDCl3) δ 7.61, 7.56, 7.35, 7.23, 6.92, 6.81, 6.19, 6.06, 4.81, 4.29, 4.07, 3.82, 3.67, 3.22, 2.95, 2.62, 2.04, 1.90. ##STR5##

Workup

  1. customat 0° C.
  2. extractionextracted with water (2×) and saturated sodium bicarbonate solution
  3. customDrying
  4. concentration(Na2SO4) and concentration in vacuo
  5. customafforded a solid which
  6. temperatureThe solution was then warmed at 60° C. for 18 h
  7. temperatureThe solution was cooled
  8. customthe DMF removed in vacuo
  9. dissolutionthe residue was dissolved in ethyl acetate
  10. extractionextracted with water (2×)
  11. customDrying
  12. concentration(Na2SO4) and concentration in vacuo
  13. customafforded a solid which
  14. washeluting with 1-4% (v/v) methanol in dichloromethane

Sources & evidence

ORD record
ord-b91a184f6ccd4928ac52e711b8fce655
Source dataset
uspto-grants-1999_06
Patent number
US05910504

Reaction notes

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