Dichloromethane → HCID 136387544, compound

HRID 2170223Notes

Reaction equation

HRID 2170223 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([O:19][C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=2[F:27])=[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.ClCCl.[CH2:38]([S:40](Cl)(=[O:42])=[O:41])[CH3:39]>O1CCCC1>[F:27][C:21]1[CH:22]=[C:23]([F:26])[CH:24]=[CH:25][C:20]=1[O:19][C:5]1[CH:4]=[CH:3][C:2]([NH:1][S:40]([CH2:38][CH3:39])(=[O:42])=[O:41])=[CH:7][C:6]=1[C:8]1[NH:9][C:10]([CH3:18])=[C:11]2[C:16]=1[CH:15]=[N:14][NH:13][C:12]2=[O:17]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 11667Ethanesulfonyl chlorideHCID 136387542HCID 136387542, compound

Product 1

HCID 136387544HCID 136387544, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of Example 78c (40.5 mg, 0.110 mmol) and triethylamine (0.077 mL, 0.55 mmol) in the mixture of dichloromethane (2 mL) and tetrahydrofuran (2 mL) was added ethanesulfonyl chloride (0.038 mL, 0.40 mmol) dropwise. The reaction mixture was stirred at ambient temperature for 6 hours and concentrated. The residue was diluted with dioxane (2 mL) and 1M sodium hydroxide (1.1 mL), and heated at 50° C. for 1 hour. The reaction mixture was cooled to ambient temperature, diluted with water and ethyl acetate, adjusted the pH to 7 by addition of 1M HCl and separated. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by flash chromatography (silica gel, 1-5% methanol in dichloromethane) to afford the title compound (20 mg, 40%). 1 H NMR (300 MHz, DMSO-d6) δ 12.45 (s, 1 H) 11.45 (s, 1 H) 9.81 (s, 1 H) 8.04 (s, 1 H) 7.36-7.50 (m, 2 H) 7.13-7.27 (m, 2 H) 7.02-7.12 (m, 1 H) 6.88 (d, J=8.73 Hz, 1 H) 3.13 (q, J=7.14 Hz, 2 H) 2.63 (s, 3 H) 1.23 (t, J=7.34 Hz, 3 H). MS (ESI+) m/z 461 (M+H)+.

Workup

  1. concentrationconcentrated
  2. additionThe residue was diluted with dioxane (2 mL) and 1M sodium hydroxide (1.1 mL)
  3. temperatureheated at 50° C. for 1 hour
  4. temperatureThe reaction mixture was cooled to ambient temperature
  5. additiondiluted with water and ethyl acetate
  6. additionby addition of 1M HCl
  7. customseparated
  8. washThe organic layer was washed with saturated aqueous sodium chloride
  9. dry with materialdried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe residue was purified by flash chromatography (silica gel, 1-5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-3c4081a36c7a46cc98fddcea19af3255
Source dataset
uspto-grants-2015_06
Patent number
US09050346B2

Reaction notes

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