Triethylamine → HCID 178477709, compound

HRID 874458Notes

Reaction equation

HRID 874458 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][N:5]([CH3:27])[C:6]2[C:7]=1[CH:8]=[N:9][C:10]1[N:19]([C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=3)[CH2:18][CH:17]=[C:12]3[NH:13][C:14](=[O:16])[C:15]=2[C:11]=13.[CH2:28]([S:30](Cl)(=[O:32])=[O:31])[CH3:29].C(N(CC)CC)C>ClCCl>[Cl:26][C:23]1[CH:24]=[CH:25][C:20]([N:19]2[C:10]3=[C:11]4[C:15](=[C:6]5[N:5]([CH3:27])[CH:4]=[CH:3][C:2]([NH:1][S:30]([CH2:28][CH3:29])(=[O:32])=[O:31])=[C:7]5[CH:8]=[N:9]3)[C:14](=[O:16])[NH:13][C:12]4=[CH:17][CH2:18]2)=[CH:21][CH:22]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 11667Ethanesulfonyl chlorideHCID 178480437HCID 178480437, compound

Product 1

HCID 178477709HCID 178477709, compoundYield 70.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of Example 69e (0.04 g, 0.106 mmol), ethanesulfonyl chloride (0.054 g, 0.2423 mmol), and triethylamine (0.064 g, 0.635 mmol) in dichloromethane (3 mL) was stirred at ambient temperature for 2 hours. The solvent was removed, and the residue was treated with dioxane (3 mL) and 2.0 N NaOH (2 mL). The reaction mixture was heated at 90° C. for 2 hours. The solvents were partially removed, and the residue was partitioned between water and ethyl acetate. The aqueous layer was neutralized with 10% HCl and extracted with additional ethyl acetate twice. The combined organic layers were washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by reverse phase HPLC(C18, CH3CN/water (0.1% TFA), 0-100%) to afford 0.035 g (56.6%) of the title compound as the TFA salt. 1H NMR (500 MHz, DMSO-d6) δ 10.87 (d, J=5.8, 1H), 10.15 (s, 1H), 8.17 (d, J=2.75 Hz, 1H), 8.00 (d, J=2.75 Hz, 1H), 7.82 (s, 1H), 7.09 (d, J=5.8 Hz, 1H), 7.03-7.07 (m, 2H), 6.58-6.62 (m, 2H), 4.62 (s, 2H), 4.07 (s, 3H), 3.26 (q, J=7.32 Hz, 2H), 1.29 (t, J=7.32 Hz, 3H). MS (DCI+) m/z 470.1 (M+H)+.

Workup

  1. customThe solvent was removed
  2. additionthe residue was treated with dioxane (3 mL) and 2.0 N NaOH (2 mL)
  3. customThe solvents were partially removed
  4. customthe residue was partitioned between water and ethyl acetate
  5. extractionextracted with additional ethyl acetate twice
  6. washThe combined organic layers were washed with saturated aqueous sodium chloride
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by reverse phase HPLC(C18, CH3CN/water (0.1% TFA), 0-100%)

Sources & evidence

ORD record
ord-00e222b14b0b47f6b5c815369054292d
Source dataset
uspto-grants-2015_03
Patent number
US08980879B2

Reaction notes

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