Ethylenediamine → (+/-)-2-(hydroxy(5-methoxy-7-methyl-1H-indol-4-yl)methyl)-1H-indole-6-carbonitrile

HRID 2174094Notes

Reaction equation

HRID 2174094 reaction equation
C(OC([N:8]1[C:16]2[C:11](=[C:12]([CH:20]([C:22]3[N:23](COCC[Si](C)(C)C)[C:24]4[C:29]([CH:30]=3)=[CH:28][CH:27]=[C:26]([C:31]#[N:32])[CH:25]=4)[OH:21])[C:13]([O:18][CH3:19])=[CH:14][C:15]=2[CH3:17])[CH:10]=[CH:9]1)=O)(C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-].C(N)CN>C1COCC1>[OH:21][CH:20]([C:12]1[C:13]([O:18][CH3:19])=[CH:14][C:15]([CH3:17])=[C:16]2[C:11]=1[CH:10]=[CH:9][NH:8]2)[C:22]1[NH:23][C:24]2[C:29]([CH:30]=1)=[CH:28][CH:27]=[C:26]([C:31]#[N:32])[CH:25]=2

Participants

5

Reactant 3

HCID 3301EthylenediamineHCID 2724141Tetrabutylammonium FluorideHCID 86701729tert-Butyl-4-((6-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indol-2-yl)(hydroxy)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate

Product 1

HCID 86701730(+/-)-2-(hydroxy(5-methoxy-7-methyl-1H-indol-4-yl)methyl)-1H-indole-6-carbonitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

tert-Butyl-4-((6-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indol-2-yl)(hydroxy)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (70 mg, 0.125 mmol) was dissolved in THF (1.3 mL) and TBAF (1.3 mL, 1.246 mmol) was added. Ethylenediamine (0.084 mL, 1.25 mmol) was then added. The reaction was heated at 65° C. for 4 days. The reaction cooled to room temperature and quenched with saturated aq. ammonium chloride (10 mL) and then diluted with DCM. The layers were separated and the organic layer was washed with water, dried over MgSO4 filtered and concentrated. The resulting residue was absorbed onto silica and purified via flash chromatography (0-75% EtOAc:heptanes) to obtain the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.39 (s, 1H) 10.80 (s, 1H) 7.66-7.85 (m, 1H) 7.50 (d, J=8.08 Hz, 1H) 7.21 (dd, J=8.15, 1.45 Hz, 1H) 7.14 (t, J=2.78 Hz, 1H) 6.76 (s, 1H) 6.56 (d, J=4.42 Hz, 1H) 6.42 (dd, J=3.03, 2.02 Hz, 1H) 6.07-6.14 (m, 1H) 5.88 (d, J=4.55 Hz, 1H) 3.82 (s, 3H) 2.45 (d, J=0.63 Hz, 3H). MS (ESI−) m/z 330.05 (M−H).

Workup

  1. temperatureThe reaction cooled to room temperature
  2. customquenched with saturated aq. ammonium chloride (10 mL)
  3. additiondiluted with DCM
  4. customThe layers were separated
  5. washthe organic layer was washed with water
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe resulting residue was absorbed onto silica
  10. custompurified via flash chromatography (0-75% EtOAc:heptanes)

Sources & evidence

ORD record
ord-1f2572797a4446f1b1f2a9451608e309
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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