Sodium Iodide → (R)-3-[N-Methyl-N-[2-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)ethyl]amino]pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 370005Notes

Reaction equation

HRID 370005 reaction equation
[I-].[Na+].[N:3]1[N:4]=[CH:5][N:6]([C:8]2[CH:9]=[C:10]3[C:14](=[CH:15][CH:16]=2)[NH:13][CH:12]=[C:11]3[CH2:17][CH2:18]OS(C)(=O)=O)[CH:7]=1.[C:24]([O:28][C:29]([N:31]1[CH2:35][CH2:34][C@@H:33]([NH:36][CH3:37])[CH2:32]1)=[O:30])([CH3:27])([CH3:26])[CH3:25].C(=O)([O-])[O-].[K+].[K+]>C(O)(C)C>[C:24]([O:28][C:29]([N:31]1[CH2:35][CH2:34][C@@H:33]([N:36]([CH3:37])[CH2:18][CH2:17][C:11]2[C:10]3[C:14](=[CH:15][CH:16]=[C:8]([N:6]4[CH:7]=[N:3][N:4]=[CH:5]4)[CH:9]=3)[NH:13][CH:12]=2)[CH2:32]1)=[O:30])([CH3:27])([CH3:26])[CH3:25]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 10686091methanesulphonic acid 2-[5-(1,2,4-triazol-4-yl)-1H-indol-3-yl]ethyl esterHCID 45089543tert-Butyl (3R)-3-(methylamino)pyrrolidine-1-carboxylate

Product 1

HCID 53922621(R)-3-[N-Methyl-N-[2-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)ethyl]amino]pyrrolidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

Sodium iodide (300 mg, 2.0 mmol) was added to a stirred solution/suspension of methanesulphonic acid 2-[5-(1,2,4-triazol-4-yl)-1H-indol-3-yl]ethyl ester (prepared from the corresponding alcohol, WO 95/32196) (600 mg, 2.0 mmol), (R)-3-methylaminopyrrolidine-1-carboxylic acid tert-butyl ester (600 mg, 3.0 mmol) and potassium carbonate (830 mg, 6.0 mmol) in dry isopropanol (50 ml) at room temperature under nitrogen. The mixture was stirred and heated at reflux, protected from light for 20 hours. Upon cooling, the volatiles were removed in vacuo. The residue was partitioned between dichloromethane/water. The aqueous was further extracted with dichloromethane (×2). The combined extracts were dried (Na2SO4), filtered and evaporated. The residue was purified by chromatography on silica gel, eluting with CH2Cl2 /MeOH/NH3 95:5:0.5→93:6:1→91:8:1 to give the title tryptamine (770 mg) as a thick gum. (1H nmr indicated contamination with the pyrrolidine-amine. Corrected yield of desired product≈60%≈500 mg). δ (360 MHz, CDCl3 +d4MeOH) 1.46 (9H, s, tBu), 1.70-1.85 (1H, m), 2.05-2.15 (1H, m), 2.42 (3H, s, NCH3), 2.75-3.60 (9H, m), 7.17 (1H, d, J=8.7 Hz, ArH), 7.22 (1H, s, ArH), 7.52 (1H, d, J=8.6 Hz, ArH), 7.60 (1H, s, ArH), 8.62 (2H, br s, triazole-H); MS (ES+) 411 [MH]+.

Workup

  1. customat room temperature
  2. temperatureheated
  3. temperatureat reflux
  4. temperatureUpon cooling
  5. customthe volatiles were removed in vacuo
  6. customThe residue was partitioned between dichloromethane/water
  7. extractionThe aqueous was further extracted with dichloromethane (×2)
  8. dry with materialThe combined extracts were dried (Na2SO4)
  9. filtrationfiltered
  10. customevaporated
  11. customThe residue was purified by chromatography on silica gel
  12. washeluting with CH2Cl2 /MeOH/NH3 95:5:0.5→93:6:1→91:8:1

Sources & evidence

ORD record
ord-88738d190a034d41838e77c4dfdf436f
Source dataset
uspto-grants-2000_10
Patent number
US06140347

Reaction notes

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