Triethylamine → 2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-ethanesulfonic acid (5-chloro-2-{2-[4-(4-fluoro-benzyl)-2-methyl-piperazin-1-yl]-2-oxo-ethoxy}-phenyl)-amide

HRID 480190Notes

Reaction equation

HRID 480190 reaction equation
[NH2:1][C:2]1[CH:26]=[C:25]([Cl:27])[CH:24]=[CH:23][C:3]=1[O:4][CH2:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=2)[CH2:10][CH:9]1[CH3:22])=[O:7].C(N(CC)CC)C.[O:35]=[C:36]1[C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[C:38](=[O:45])[N:37]1[CH2:46][CH2:47][S:48](Cl)(=[O:50])=[O:49].C(=O)([O-])O.[Na+]>C(Cl)Cl>[Cl:27][C:25]1[CH:24]=[CH:23][C:3]([O:4][CH2:5][C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=3)[CH2:10][CH:9]2[CH3:22])=[O:7])=[C:2]([NH:1][S:48]([CH2:47][CH2:46][N:37]2[C:36](=[O:35])[C:44]3[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=3)[C:38]2=[O:45])(=[O:49])=[O:50])[CH:26]=1

Participants

6

Reactant 4

HCID 8471Triethylamine3×HCID 3087392-Phthalimidoethanesulfonyl chloride3×HCID 516892Sodium BicarbonateHCID 114861502-(2-Amino-4-chloro-phenoxy)-1-[4-(4-fluoro-benzyl)-2-methyl-piperazin-1-yl]-ethanone

Product 1

HCID 699590132-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-ethanesulfonic acid (5-chloro-2-{2-[4-(4-fluoro-benzyl)-2-methyl-piperazin-1-yl]-2-oxo-ethoxy}-phenyl)-amideYield 36.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of of 2-(2-amino-4-chloro-phenoxy)-1-[4-(4-fluoro-benzyl)-2-methyl-piperazin-1-yl]-ethanone (0.050 g, 0.13 mmol) in methylene chloride (1 mL) at ambient temperature was added triethylamine (0.027 mL, 0.19 mmol) and 2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethanesulfonyl chloride (0.045 g, 0.17 mmol). The reaction was stirred overnight at ambient temperature. Additional triethylamine ((0.027 mL, 0.19 mmol) and 2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethanesulfonyl chloride (0.045 g, 0.17 mmol) was added. The reaction was stirred one hour, then additional triethylamine (0.055 mL, 0.34 mmol) was added. The reaction was stirred and hour, then additional 2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethanesulfonyl chloride (0.090 g, 0.34 mmol) was added. After stirring an additional 1 hour, the reaction was treated with saturated aqueous sodium hydrogen carbonate and extracted with methylene chloride (3×). The combined organics were dried over magnesium sulfate, filtered and concentrated in vacuo. Purification via radial chromatography (2 mm plate) gave the title compound (0.030 g).

Workup

  1. stirringThe reaction was stirred one hour
  2. stirringThe reaction was stirred and hour
  3. stirringAfter stirring an additional 1 hour
  4. extractionextracted with methylene chloride (3×)
  5. dry with materialThe combined organics were dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification via radial chromatography (2 mm plate)

Sources & evidence

ORD record
ord-92ee45ff1350409d8657e3cc5afcda14
Source dataset
uspto-grants-2003_11
Patent number
US06649611B2

Reaction notes

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