Potassium Iodide → HCID 10157486, compound

HRID 966474Notes

Reaction equation

HRID 966474 reaction equation
[CH2:1]([O:8][C:9]([C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH2:21][CH2:22]Cl)[CH:18]=2)[N:13]([CH3:24])[C:12]=1[CH3:25])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+].[CH2:34]([NH:36][CH2:37][CH3:38])[CH3:35].[K+].[Br-]>CN(C=O)C.O.CC#N>[CH2:1]([O:8][C:9]([C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH2:21][CH2:22][N:36]([CH2:37][CH3:38])[CH2:34][CH3:35])[CH:18]=2)[N:13]([CH3:24])[C:12]=1[CH3:25])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

9

Reactant 5

HCID 4875Potassium IodideHCID 8021Diethylamine2×HCID 11430Potassium CarbonateHCID 253877Potassium BromideHCID 23393870HCID 23393870, compound

Product 1

HCID 10157486HCID 10157486, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of 1-methyl-5-(2-chloro-ethoxy)-2-methyl-1H-indole-3-carboxylic acid benzyl ester (0.576 mmol, 0.206 g, Example 8, Step A) in 5.76 mL of DMF was added potassium carbonate (0.576 mmol, 0.080 g), potassium iodide (0.0576 mmol, 0.010 g), and diethylamine (2.30 mmol, 0.238 mL, Aldrich). The mixture was heated at 100° C. for 20 hours, an additional 2.30 mmol of diethylamine was added and heating was continued for 21 hours. The solution was cooled to room temperature, diluted with water (10 mL), and extracted with ethyl acetate (4×15 mL). The combined extracts were washed with water (10 mL), saturated aqueous NaCl (10 mL), dried over MgSO4, and concentrated to a brown oil (0.234 g). The product was purified by silica gel flash column chromatography (5-10% MeOH/CH2Cl2) to give a tan solid (0.114 g, 50/o): mp 73-74° C.; IR (KBr) 2968, 2918, 1692, 1186, 1101 cm−1; 1HNMR (400 MHz, DMSO-d6) δ 0.92 (t, J=7.08 Hz, 6H, N(CH2CH3)2), 2.46-2.51 (m, 4H, 2 NCH2), 2.66 (s, 3H, ArCH3), 2.68-2.73 (m, 2H, NCH2), 3.65 (s, 3H, NCH3), 3.85 (t, J=6.11 Hz, 2H, CH2OAr), 5.28 (s, 2H, CO2CH2Ph), 6.75 (dd, J=8.79, 2.44 Hz, 1H, ArH), 7.28-7.32 (m, 1H, ArH), 7.35-7.39 (m, 4H, ArH), 7.46 (d, J=7.57 Hz, 2H, ArH); MS(APCI+): m/z 395.1 (M+1). HPLC (ALLTECH/ALLTIMA C-18,50:50-2:98H2O/CH3CN+0.05% TFA): retention time=3.617 min, 96.84% purity.

Workup

  1. temperatureheating
  2. temperatureThe solution was cooled to room temperature
  3. extractionextracted with ethyl acetate (4×15 mL)
  4. washThe combined extracts were washed with water (10 mL), saturated aqueous NaCl (10 mL)
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated to a brown oil (0.234 g)
  7. customThe product was purified by silica gel flash column chromatography (5-10% MeOH/CH2Cl2)
  8. customto give a tan solid (0.114 g, 50/o)

Sources & evidence

ORD record
ord-61289bda7cc94de69cf4e1c6ad1eb929
Source dataset
uspto-grants-2005_10
Patent number
US06951848B2

Reaction notes

Loading…