Iodine → HCID 67311406, compound

HRID 1400617Notes

Reaction equation

HRID 1400617 reaction equation
II.[CH3:3][C:4]1[CH:12]=[CH:11][C:10]2[N:9]([CH:13]=[C:14]([C:16]3[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=3)[CH3:15])[C:8]3[CH2:22][CH2:23][N:24]([C:26]([O:28][CH2:29][C:30]([Cl:33])([Cl:32])[Cl:31])=[O:27])[CH2:25][C:7]=3[C:6]=2[CH:5]=1.[CH2:34](I)I>C1COCC1.[Cu].[Zn]>[CH3:3][C:4]1[CH:12]=[CH:11][C:10]2[N:9]([CH:13]=[C:14]([C:16]3[CH:17]=[CH:18][N:19]([CH3:34])[CH2:20][CH:21]=3)[CH3:15])[C:8]3[CH2:22][CH2:23][N:24]([C:26]([O:28][CH2:29][C:30]([Cl:33])([Cl:32])[Cl:31])=[O:27])[CH2:25][C:7]=3[C:6]=2[CH:5]=1

Participants

6

Reactant 3

HCID 807IodineHCID 6346DiiodomethaneHCID 67309725HCID 67309725, compound

Product 1

HCID 67311406HCID 67311406, compoundYield 31.7%

Reagents, catalysts & solvents 2

HCID 10290809Zinc copper coupleCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
85 °C

Procedure

Zinc-copper couple (800 mg) was dissolved in THF and a crystal of iodine was added. The reaction mixture was stirred at 85° C. until the brown color disappeared. A mixture of 2,2,2-trichloroethyl 3,4-dihydro-8-methyl-5-(2-(pyridin-4-yl)prop-1-enyl)-1H-pyrido[4,3-b]indole-2(5H)-carboxylate (400 mg, 0.83 mmol) and methylene iodide (447 mg, 1.67 mmol) was added at the same temperature and the mixture was heated at 85° C. overnight. The reaction mixture was filtered under vacuum and the filtrate purified by reverse phase HPLC to obtain 2,2,2-trichloroethyl 3,4-dihydro-8-methyl-5-(2-(N-methyl-pyridin-4-yl)prop-1-enyl)-1H-pyrido[4,3-b]indole-2(5H)-carboxylate (130 mg TFA salt). To the purified compound (130 mg) was added acetic acid (2 mL) and zinc dust (35 mg). The reaction mixture was stirred at RT for 2 days. MeOH (10 mL) was added and the mixture filtered under vacuum. The filtrate residue was washed with additional MeOH (2×10 mL) and concentrated under reduced pressure. The product obtained was purified on reverse phase chromatography. Yield: 25 mg (TFA salt). 1H NMR (CD3OD, TFA salt): δ (ppm): 8.8 (d, 2H), 8.3 (d, 2H), 7.8 (s, 1H), 7.4 (s, 1H), 7.1 (s, 2H), 4.5 (s, 2H), 4.4 (s, 3H), 3.6 (bs, 2H), 3.1 (bs, 2H), 2.4 (s, 3H), 2.2 (s, 3H).

Workup

  1. additionwas added at the same temperature
  2. temperaturethe mixture was heated at 85° C. overnight
  3. filtrationThe reaction mixture was filtered under vacuum
  4. customthe filtrate purified by reverse phase HPLC

Sources & evidence

ORD record
ord-097661090d804d61a386b56bbbdc3d07
Source dataset
uspto-grants-2014_12
Patent number
US08906925B2

Reaction notes

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