Sodium Iodide → Indole

HRID 1602095Notes

Reaction equation

HRID 1602095 reaction equation
N1N=CN([C:6]2[CH:7]=[C:8]3[C:12](=[CH:13][CH:14]=2)[NH:11][CH:10]=[C:9]3CCCO)C=1.C(N(CC)CC)C.CS(Cl)(=O)=O.S([O-])(=O)(=O)C.C([O-])([O-])=O.[K+].[K+].[I-].[Na+]>C1COCC1.C(O)(C)C>[NH:11]1[C:12]2[C:8](=[CH:7][CH:6]=[CH:14][CH:13]=2)[CH:9]=[CH:10]1

Participants

9

Reactant 6

HCID 5238Sodium IodideHCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 85257MethanesulfonateHCID 106339143-[5-(1,2,4-triazol-4-yl)-1H-indol-3-yl]propan-1-ol

Product 1

HCID 798IndoleYield 107%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of Intermediate 1 (0.20 g, 0.83 mmol) in anhydrous THF (100 ml), at 0° C., was added triethylamine (0.167 g, 1.65 mmol) and methane sulphonyl chloride (0.19 g, 1.65 mmol) and the mixture warmed to room temperature and stirred for 1.5 h. The solvent was removed in vacuo and the residue partitioned between ethyl acetate (50 ml) and K2CO3 solution (10 ml). The aqueous was separated and extracted further with ethyl acetate (1×50 ml). The combined extracts were dried (MgSO4) and evaporated and used in the next step without further purification. To a solution of the preceding mesylate (0.264 g, 0.825 mmol), in isopropyl alcohol (25 ml), was added powdered K2CO3 (0.114 g, 0.825 mmol), sodium iodide (82 mg, 0.55 mmol) and (±)-1-H-4-(3-hydroxy-2-phenylpropyl)-piperazine (0.11 g, 0.55 mmol), and the mixture stirred at 120° C. for 16 h. The mixture was cooled to room temperature and the solvent removed in vacuo. The residue was partitioned between aq. K2CO3 solution (5 ml) and ethyl acetate (×3). The combined extracts were dried (MgSO4) and evaporated, and the residue chromatographed through silica gel eluting with CH2Cl2 /MeOH/NH3 (90:8:1) to give the title-indole (0.104 g, 43%). The 1.6 hydrogen oxalate salt was prepared. mp 137-140° C., (Found: C, 59.62: H, 6.67; N, 13.36. C26H32N6O. 1.6 (C2H2O4). 0.4 (C4H10O) requires C, 59.83; H, 6.39; N, 13.59%), m/e 445 (M+1)+, δ(360 MHz, D6 -DMSO) 1.92-2.06 (2H, m, CH2), 2.56-3.62 (17H, m, 8 of CH2 and CH), 7.18-7.34 (7H, m, Ar-H), 7.50 (1H, d, J=8.6 Hz, Ar-H), 7.79 (1H, s, Ar-H), 9.01 (2H, s, Ar-H), 11.17 (1H, s, NH).

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue partitioned between ethyl acetate (50 ml) and K2CO3 solution (10 ml)
  3. customThe aqueous was separated
  4. extractionextracted further with ethyl acetate (1×50 ml)
  5. dry with materialThe combined extracts were dried (MgSO4)
  6. customevaporated
  7. customused in the next step without further purification
  8. stirringthe mixture stirred at 120° C. for 16 h
  9. temperatureThe mixture was cooled to room temperature
  10. customthe solvent removed in vacuo
  11. customThe residue was partitioned between aq. K2CO3 solution (5 ml) and ethyl acetate (×3)
  12. dry with materialThe combined extracts were dried (MgSO4)
  13. customevaporated
  14. customthe residue chromatographed through silica gel eluting with CH2Cl2 /MeOH/NH3 (90:8:1)

Sources & evidence

ORD record
ord-c75c1fde582d4a7c8b45127bdc1338eb
Source dataset
uspto-grants-1999_11
Patent number
US05981529

Reaction notes

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