Triethylamine → HCID 135567317, compound

HRID 2170221Notes

Reaction equation

HRID 2170221 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([O:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[C:6]([C:8]2[NH:9][C:10]([CH3:18])=[C:11]3[C:16]=2[CH:15]=[N:14][NH:13][C:12]3=[O:17])[CH:7]=1.C(N(CC)CC)C.[CH2:33]([S:35](Cl)(=[O:37])=[O:36])[CH3:34]>ClCCl.O1CCCC1>[CH3:18][C:10]1[NH:9][C:8]([C:6]2[CH:7]=[C:2]([NH:1][S:35]([CH2:33][CH3:34])(=[O:37])=[O:36])[CH:3]=[CH:4][C:5]=2[O:19][C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)=[C:16]2[CH:15]=[N:14][NH:13][C:12](=[O:17])[C:11]=12

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 11667Ethanesulfonyl chlorideHCID 136387534HCID 136387534, compound

Product 1

HCID 135567317HCID 135567317, compoundYield 47.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of Example 74f (0.05 g, 0.150 mmol) and triethylamine (0.084 mL, 0.602 mmol) in dichloromethane (1.504 mL) and tetrahydrofuran (1.504 mL) was added drop-wise ethanesulfonyl chloride (0.046 mL, 0.481 mmol). The reaction mixture was stirred for three hours at ambient temperature and concentrated. The residue was diluted with dioxane (3 mL) and 1 M sodium hydroxide (1 mL) and heated at 60° C. for 1 hour. The mixture was cooled and diluted with water and ethyl acetate adjusting the pH to 6 with 1 M HCl. The organic layer was washed with saturated aqueous sodium chloride, dried (anhydrous sodium sulfate), filtered, and concentrated. Purification by chromatography (silica gel, 1-5% methanol in dichloromethane) afforded the title compound (0.03 g, 45%). 1H NMR (300 MHz, DMSO-d6) δ 12.43 (s, 1H), 11.41 (s, 1H), 9.83 (s, 1H), 8.04 (s, 1H), 7.43 (d, J=2.71 Hz, 1H), 7.26-7.33 (m, 2H), 7.22 (dd, J=8.82, 2.71 Hz, 1H), 7.00-7.08 (m, 2H), 6.90 (d, J=7.46 Hz, 2H), 3.15 (q, J=7.23 Hz, 2H), 2.59 (s, 3H), 1.24 (t, J=7.46 Hz, 3H). MS (ESI+) m/z 425 [M+H]+.

Workup

  1. concentrationconcentrated
  2. additionThe residue was diluted with dioxane (3 mL) and 1 M sodium hydroxide (1 mL)
  3. temperatureheated at 60° C. for 1 hour
  4. temperatureThe mixture was cooled
  5. additiondiluted with water and ethyl acetate adjusting the pH to 6 with 1 M HCl
  6. washThe organic layer was washed with saturated aqueous sodium chloride
  7. dry with materialdried (anhydrous sodium sulfate)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification by chromatography (silica gel, 1-5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-f752b8df4fd6476c96060b8411f9596b
Source dataset
uspto-grants-2015_06
Patent number
US09050346B2

Reaction notes

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