Trimethylaluminum → HCID 131730123, compound

HRID 2196692Notes

Reaction equation

HRID 2196692 reaction equation
C[Al](C)C.[I:5][C:6]1[N:15]([S:16]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)(=[O:18])=[O:17])[C:9]2=[N:10][CH:11]=[C:12]([NH2:14])[CH:13]=[C:8]2[CH:7]=1.[F:25][C:26]1[C:35]([N:36]([S:43]([CH2:46][CH2:47][CH3:48])(=[O:45])=[O:44])[S:37]([CH2:40][CH2:41][CH3:42])(=[O:39])=[O:38])=[CH:34][CH:33]=[C:32]([F:49])[C:27]=1[C:28](OC)=[O:29]>C1(C)C=CC=CC=1.C(OCC)(=O)C>[F:25][C:26]1[C:35]([N:36]([S:37]([CH2:40][CH2:41][CH3:42])(=[O:39])=[O:38])[S:43]([CH2:46][CH2:47][CH3:48])(=[O:44])=[O:45])=[CH:34][CH:33]=[C:32]([F:49])[C:27]=1[C:28]([NH:14][C:12]1[CH:13]=[C:8]2[CH:7]=[C:6]([I:5])[N:15]([S:16]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)(=[O:17])=[O:18])[C:9]2=[N:10][CH:11]=1)=[O:29]

Participants

6

Reactant 3

HCID 16682925TrimethylaluminumHCID 58095328HCID 58095328, compoundHCID 67155717HCID 67155717, compound

Product 1

HCID 131730123HCID 131730123, compoundYield 87%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Trimethylaluminum (0.51 mL, 1.01 mmol, 2.0M solution in toluene) was added dropwise via a syringe to a cold (0° C.) suspension of 2-iodo-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-amine (0.135 g, 0.338 mmol) in toluene (10 mL). The cold bath was removed and the mixture was stirred at room temperature for 20 minutes. Methyl 2,6-difluoro-3-(N-(propylsulfonyl)propylsulfonamido)benzoate (0.149 g, 0.372 mmol) was added, and the reaction mixture was heated to 90° C. under N2 for 2 hours. The reaction mixture was cooled to room temperature and diluted with ethyl acetate (50 mL) 30% Aqueous potassium sodium tartrate solution (50 mL) was carefully added, and the resulting emulsion was stirred at room temperature for 30 minutes. The aqueous layer was extracted with ethyl acetate (2×50 mL). The combined organic layers were dried, filtered and concentrated. The crude product was purified by column chromatography, eluting with hexanes/ethyl acetate (4:1), hexanes/ethyl acetate (2:1) to give 2,6-difluoro-N-(2-iodo-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)-3-(N-(propylsulfonyl)propylsulfonamido)benzamide (0.225 g, 87%) as a foam.

Workup

  1. customThe cold bath was removed
  2. temperaturethe reaction mixture was heated to 90° C. under N2 for 2 hours
  3. temperatureThe reaction mixture was cooled to room temperature
  4. additionwas carefully added
  5. stirringthe resulting emulsion was stirred at room temperature for 30 minutes
  6. extractionThe aqueous layer was extracted with ethyl acetate (2×50 mL)
  7. customThe combined organic layers were dried
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was purified by column chromatography
  11. washeluting with hexanes/ethyl acetate (4:1), hexanes/ethyl acetate (2:1)

Sources & evidence

ORD record
ord-e67c08d415a54856858d594a0d398129
Source dataset
uspto-grants-2012_12
Patent number
US08338452B2

Reaction notes

Loading…