Water → HCID 10433340, compound

HRID 984468Notes

Reaction equation

HRID 984468 reaction equation
I[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[CH:5]2.ClC1C=CC=C(C=O)C=1[S:20][C:21]1[CH:26]=[CH:25][C:24](/[CH:27]=[CH:28]/[C:29]([N:31]2[CH2:36][CH2:35][N:34]([C:37](=[O:39])[CH3:38])[CH2:33][CH2:32]2)=[O:30])=[CH:23][C:22]=1[Cl:40].C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[NH:7]1[C:8]2[C:4](=[CH:3][C:2]([S:20][C:21]3[CH:26]=[CH:25][C:24](/[CH:27]=[CH:28]/[C:29]([N:31]4[CH2:32][CH2:33][N:34]([C:37](=[O:39])[CH3:38])[CH2:35][CH2:36]4)=[O:30])=[CH:23][C:22]=3[Cl:40])=[CH:10][CH:9]=2)[CH:5]=[CH:6]1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 27823135-Iodo-1H-indoleHCID 10434523HCID 10434523, compound

Product 1

HCID 10433340HCID 10433340, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

To a stirred solution of 5-iodoindole (255 mg, 1.05 mmol) in 5.0 mL of anhydrous DMF was added the potassium thiolate (457 mg, 1.26 mmol) from Example 65B, followed by K2CO3 (174 mg, 1.26 mmol), and cuprous iodide (20 mg, 0.11 mmol). The resulting mixture was then heated at 120° C. for overnight. The reaction mixture was then allowed to cool to ambient temperature and poured into water. The aqueous mixture was extracted twice with 25 mL of ethyl acetate. The combined organic layer was then washed with water and brine, dried over Na2SO4, filtered, concentrated on a rotavap under reduced pressure. The crude product was purified using Gilson Preparative HPLC as described in Example 38B to give the title compound (115 mg, 25% based on the iodide) as a light-brown solid. 1H NMR (d6-DMSO, 300 MHz) δ 2.03 (s, 3H), 3.40-3.78 (m, 8H), 6.5.1 (d, J=8.4 Hz, 1H), 6.53 (s, 1H), 7.23 (dd, J=2.1, 8.4 Hz, 1H), 7.27 (d, J=15.6 Hz, 1H), 7.39 (d, J=15.6 Hz, 1H), 7.41 (dd, J=1.8, 8.4 Hz, 1H), 7.49 (t, J=2.7 Hz, 1H), 7.56 (d, J=8.4 Hz, 1H), 7.85 (d, J=1.8 Hz, 1H), 7.99 (d, J=1.8 Hz, 1H). MS (APCI+) (M+NH4)+ at m/z 440, 442. Anal. Calcd for C23H22ClN3O2S.0.53 CH2Cl2: C, 58.28; H, 4.79; N, 8.66. Found: C, 58.31; H, 4.93; N, 8.65.

Workup

  1. temperatureto cool to ambient temperature
  2. extractionThe aqueous mixture was extracted twice with 25 mL of ethyl acetate
  3. washThe combined organic layer was then washed with water and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated on a rotavap under reduced pressure
  7. customThe crude product was purified

Sources & evidence

ORD record
ord-ddf3a8aa1ee94f4a95343de533258b86
Source dataset
uspto-grants-2005_03
Patent number
US06867203B2

Reaction notes

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