Hydrochloric Acid → 3-(4-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)propanal

HRID 1969874Notes

Reaction equation

HRID 1969874 reaction equation
[O:1]1CCO[CH:2]1[CH2:6][CH2:7][C:8]1[C:9]([Cl:27])=[C:10]2[CH:16]=[CH:15][N:14]([S:17]([C:20]3[CH:26]=[CH:25][C:23]([CH3:24])=[CH:22][CH:21]=3)(=[O:19])=[O:18])[C:11]2=[N:12][CH:13]=1.Cl.C([O-])(O)=O.[Na+].C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1>C1COCC1.CC(C)=O.CCOC(C)=O.O>[Cl:27][C:9]1[C:8]([CH2:7][CH2:6][CH:2]=[O:1])=[CH:13][N:12]=[C:11]2[N:14]([S:17]([C:20]3[CH:21]=[CH:22][C:23]([CH3:24])=[CH:25][CH:26]=3)(=[O:19])=[O:18])[CH:15]=[CH:16][C:10]=12

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 516892Sodium BicarbonateHCID 585572935-(2-(1,3-dioxolan-2-yl)ethyl)-4-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 585575753-(4-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)propanalYield 94.7%

Reagents, catalysts & solvents 4

HCID 180AcetoneSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-(2-(1,3-dioxolan-2-yl)ethyl)-4-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridine (0.520 g, 1.28 mmol) in THF (4.2 mL) was added aqueous HCl (6 M, 0.639 mL, 3.83 mmol). The reaction mixture was stirred at ambient temperature for about 2 h and was heated to about 50° C. for about 1 h. The reaction was cooled to ambient temperature and water (0.64 mL) was added and the reaction stirred for about 16 h. The pH was adjusted to about 7 with saturated aqueous NaHCO3 and EtOAc (about 10 mL) was added. The layers were separated and the aqueous phase was extracted with EtOAc (10 mL). The combined organics were dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. Acetone (12 mL) and pyridinium p-toluenesulfonate (0.096 g, 0.383 mmol) were added. The reaction was heated at reflux for about 2 h. The reaction was cooled to ambient temperature and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with a gradient of 0-50% EtOAc in DCM to give 3-(4-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)propanal (0.44 g, 84%, 90% purity) as an off white foam: LC/MS (Table 1, Method b) Rt=2.50 min; MS m/z: 363 (M+H)+.

Workup

  1. temperaturewas heated to about 50° C. for about 1 h
  2. temperatureThe reaction was cooled to ambient temperature
  3. stirringthe reaction stirred for about 16 h
  4. additionwas added
  5. customThe layers were separated
  6. extractionthe aqueous phase was extracted with EtOAc (10 mL)
  7. dry with materialThe combined organics were dried over anhydrous MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. temperatureThe reaction was heated
  11. temperatureat reflux for about 2 h
  12. temperatureThe reaction was cooled to ambient temperature
  13. concentrationconcentrated under reduced pressure
  14. customThe residue was purified by silica gel chromatography
  15. washeluting with a gradient of 0-50% EtOAc in DCM

Sources & evidence

ORD record
ord-dc2b0fd6779541d2a289721ce8c1297c
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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