Triethylamine → HCID 71617220, compound

HRID 930877Notes

Reaction equation

HRID 930877 reaction equation
[NH2:1][C:2]1[CH:16]=[CH:15][C:5]([O:6][C:7]2[CH:14]=[CH:13][C:10]([C:11]#[N:12])=[CH:9][CH:8]=2)=[C:4]([C:17]2[C:18]3[CH:27]=[CH:26][NH:25][C:19]=3[C:20](=[O:24])[N:21]([CH3:23])[CH:22]=2)[CH:3]=1.C(N(CC)CC)C.[CH2:35]([S:37](Cl)(=[O:39])=[O:38])[CH3:36].[OH-:41].[Na+].[Cl-].[NH4+]>ClCCl.O1CCOCC1>[CH2:35]([S:37]([NH:1][C:2]1[CH:16]=[CH:15][C:5]([O:6][C:7]2[CH:8]=[CH:9][C:10]([C:11]([NH2:12])=[O:41])=[CH:13][CH:14]=2)=[C:4]([C:17]2[C:18]3[CH:27]=[CH:26][NH:25][C:19]=3[C:20](=[O:24])[N:21]([CH3:23])[CH:22]=2)[CH:3]=1)(=[O:39])=[O:38])[CH3:36]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 11667Ethanesulfonyl chlorideHCID 14798Sodium HydroxideHCID 25517Ammonium ChlorideHCID 86721040HCID 86721040, compound

Product 1

HCID 71617220HCID 71617220, compoundYield 35%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

To a mixture of Example 33b (50 mg, 0.14 mmol) and triethylamine (0.043 g, 0.42 mmol) in dichloromethane (4 mL) was added dropwise ethanesulfonyl chloride (0.072 g, 0.56 mmol), and the reaction mixture stirred at ambient temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, dioxane (4 mL) and sodium hydroxide (10% w/v, 3 mL, 0.14 mmol) were added, and the reaction mixture was heated at 70° C. for 1 hour. The mixture was cooled to ambient temperature and then neutralized with saturated aqueous ammonium chloride (50 mL) to a pH of 7. The organic layer was separated and the aqueous phase was extracted with ethyl acetate (3×25 mL). The combined organic layers were washed with saturated aqueous sodium chloride, dried (anhydrous magnesium sulfate), filtered, and concentrated. The residue was purified by preparative HPLC (C18, 10-100% acetonitrile/water, 0.1% TFA) to afford the title compound (22 mg, 35%). 1H NMR (300 MHz, DMSO-d6) ppm 12.01 (s, 1H) 9.86 (s, 1H) 7.77 (s, 1H) 7.74 (d, J=8.82 Hz, 2H) 7.42 (d, J=2.37 Hz, 1H) 7.22-7.30 (m, 3H) 7.18 (s, 1H) 7.11-7.16 (m, 1H) 6.83 (d, J=8.82 Hz, 2H) 6.23-6.28 (m, 1H) 3.47 (s, 3H) 3.15 (q, J=7.35 Hz, 2H) 1.21-1.29 (m, 3H). MS (ESI+) m/z 467.2 (M+H)+.

Workup

  1. additionwere added
  2. temperaturethe reaction mixture was heated at 70° C. for 1 hour
  3. temperatureThe mixture was cooled to ambient temperature
  4. customThe organic layer was separated
  5. extractionthe aqueous phase was extracted with ethyl acetate (3×25 mL)
  6. washThe combined organic layers were washed with saturated aqueous sodium chloride
  7. dry with materialdried (anhydrous magnesium sulfate)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by preparative HPLC (C18, 10-100% acetonitrile/water, 0.1% TFA)

Sources & evidence

ORD record
ord-eeceb4a1033846b5a24c0d513caaa95f
Source dataset
uspto-grants-2016_03
Patent number
US09296741B2

Reaction notes

Loading…