Methyl iodide → HCID 178480024, compound

HRID 30436Notes

Reaction equation

HRID 30436 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[NH:27])[CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]3[CH:19]=[C:20]4[C:24](=[CH:25][CH:26]=3)[NH:23][CH:22]=[CH:21]4)=[CH:14][CH:13]=2)=[CH:4][CH:3]=1.[H-].[Na+].I[CH3:31]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9](=[NH:27])[CH:10]=[CH:11][C:12]2[CH:13]=[CH:14][C:15]([C:18]3[CH:19]=[C:20]4[C:24](=[CH:25][CH:26]=3)[N:23]([CH3:31])[CH:22]=[CH:21]4)=[CH:16][CH:17]=2)=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 178510910HCID 178510910, compound

Product 1

HCID 178480024HCID 178480024, compoundYield 26.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 0.075 g (0.22 mmol) of 3-(4-bromo-phenyl)-N-(4-chloro-phenyl)-acrylamidine, 0.042 g (0.26 mmol) of 5-indoleboronic acid, and 0.013 g (0.011 mmol) of Pd(PPh3)4 in 3 mL of DME/water/ethanol (4/2/1) in a sealed tube was heated under microwave (45 W, 5 min). The reaction was diluted with 10 mL of saturated NaHCO3, and extracted with three 10 mL portions of ethyl acetate. The combined organic extracts were washed with 10 mL of brine, dried over Na2SO4, filtered and concentrated. The residue was purified by preparative TLC eluting with 60% ethyl acetate in hexanes plus 1% NH4OH to give 0.036 g of N-(4-chloro-phenyl)-3-[4-(1H -indol-5-yl)-phenyl]-acrylamidine. Method M: To a stirred solution of 0.10 g (0.27 mmol) of N-(4-chloro-phenyl)-3-[4-(1H -indol-5-yl)-phenyl]-acrylamidine in 3 mL of DMF was added 0.011 g (0.28 mmol) of 60% NaH at 0° C. After 1 h, 0.018 mL (0.28 mmol) of iodomethane was introduced, the reaction was warmed to room temperature overnight and quenched with 10 mL of saturated NaHCO3. It was extracted with three 10 mL portions of dichloromethane. The combined organic extracts were washed with 10 mL of brine, dried over Na2SO4, filtered and concentrated. The residue was chromatographed eluting with 40% ethyl acetate in hexanes to give 0.028 g of N-(4-chloro-phenyl)-3-[4-(1-methyl-1H-indol-5-yl)-phenyl]-acrylamidine.

Workup

  1. customquenched with 10 mL of saturated NaHCO3
  2. extractionIt was extracted with three 10 mL portions of dichloromethane
  3. washThe combined organic extracts were washed with 10 mL of brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was chromatographed
  8. washeluting with 40% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-1f11d0ebe4444a969170547bb1ba6c67
Source dataset
uspto-grants-2008_09
Patent number
US07423149B2

Reaction notes

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