Ethanesulfonyl chloride → N-(4-(2,4-difluorophenoxy)-3-(7-methoxy-1-methyl-5-(morpholinomethyl)-1H-pyrrolo[2,3-c]pyridin-3-yl)phenyl)ethanesulfonamide

HRID 633600Notes

Reaction equation

HRID 633600 reaction equation
[F:1][C:2]1[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:3]=1[O:4][C:5]1[CH:11]=[CH:10][C:8]([NH2:9])=[CH:7][C:6]=1[C:12]1[C:20]2[C:15](=[C:16]([O:28][CH3:29])[N:17]=[C:18]([CH2:21][N:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)[CH:19]=2)[N:14]([CH3:30])[CH:13]=1.C(N(C(C)C)CC)(C)C.[CH2:45]([S:47](Cl)(=[O:49])=[O:48])[CH3:46].[OH-].[Na+].[Cl-].[NH4+]>ClCCl>[F:1][C:2]1[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:3]=1[O:4][C:5]1[CH:11]=[CH:10][C:8]([NH:9][S:47]([CH2:45][CH3:46])(=[O:49])=[O:48])=[CH:7][C:6]=1[C:12]1[C:20]2[C:15](=[C:16]([O:28][CH3:29])[N:17]=[C:18]([CH2:21][N:22]3[CH2:23][CH2:24][O:25][CH2:26][CH2:27]3)[CH:19]=2)[N:14]([CH3:30])[CH:13]=1

Participants

7

Reactant 5

HCID 11667Ethanesulfonyl chloride2×HCID 14798Sodium HydroxideHCID 25517Ammonium ChlorideHCID 81531Diisopropylethylamine2×HCID 904168454-(2,4-difluorophenoxy)-3-(7-methoxy-1-methyl-5-(morpholinomethyl)-1H-pyrrolo[2,3-c]pyridin-3-yl)aniline

Product 1

HCID 90416904N-(4-(2,4-difluorophenoxy)-3-(7-methoxy-1-methyl-5-(morpholinomethyl)-1H-pyrrolo[2,3-c]pyridin-3-yl)phenyl)ethanesulfonamideYield 16%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of Example 182D (54 mg, 0.112 mmol) in 5 mL dichloromethane was added diisopropylethylamine (58.9 μL, 0.337 mmol) and ethanesulfonyl chloride (26.6 μL, 0.281 mmol). The mixture was stirred at ambient temperature for 16 hours. Another 1.5 equivalents ethanesulfonyl chloride (16 μL) and 2.0 equivalents diisopropylethylamine (39 μL) were added. The mixture was continued to stir overnight. The mixture was concentrated. The residue was taken into dioxane (6 mL) and treated with sodium hydroxide (2810 μL, 2.81 mmol, 1N aqueous solution). The mixture was heated at 60° C. for 1 hour to hydrolyze the bis-sulfonamide to the manosulfonamide. To the reaction mixture, saturated ammonium chloride solution was added, extracted with ethyl acetate (3×), washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated and the residue was purified by column chromatography on silica gel with a gradient of 0-8% methanol in dichloromethane to give the title compound (10 mg, 0.017 mmol, 16% yield).

Workup

  1. stirringto stir overnight
  2. concentrationThe mixture was concentrated
  3. temperatureThe mixture was heated at 60° C. for 1 hour
  4. extractionextracted with ethyl acetate (3×)
  5. washwashed with saturated aqueous sodium chloride
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated
  9. customthe residue was purified by column chromatography on silica gel with a gradient of 0-8% methanol in dichloromethane

Sources & evidence

ORD record
ord-da2bf2f0dd68491aaee34cf233c37f1a
Source dataset
uspto-grants-2016_04
Patent number
US09321764B2

Reaction notes

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