Ethylenediamine → HCID 178435868, compound

HRID 2174008Notes

Reaction equation

HRID 2174008 reaction equation
[CH2:1]([C:3]1[CH:11]=[C:10]([CH3:12])[C:9]2[N:8](S(C3C=CC(C)=CC=3)(=O)=O)[CH:7]=[CH:6][C:5]=2[C:4]=1[C:23]([C:25]1[N:29](COCC[Si](C)(C)C)[C:28]2[CH:38]=[CH:39][C:40]([C:42]#[N:43])=[CH:41][C:27]=2[N:26]=1)=[O:24])[CH3:2].C(C1C=C(C)C2N(S(C3C=CC(C)=CC=3)(=O)=O)C=CC=2C=1C(C1N(COCC[Si](C)(C)C)C2C=C(C#N)C=CC=2N=1)=O)C.C[Si](C)(C)[C:89]([F:92])([F:91])[F:90].CCCC[N+](CCCC)(CCCC)CCCC.[F-].C(N)CN>C1COCC1.CCOC(C)=O>[CH2:1]([C:3]1[C:4]([C:23]([C:25]2[NH:29][C:28]3[CH:38]=[CH:39][C:40]([C:42]#[N:43])=[CH:41][C:27]=3[N:26]=2)([OH:24])[C:89]([F:92])([F:91])[F:90])=[C:5]2[C:9](=[C:10]([CH3:12])[CH:11]=1)[NH:8][CH:7]=[CH:6]2)[CH3:2]

Participants

8

Reactant 5

HCID 3301EthylenediamineHCID 552549(Trifluoromethyl)trimethylsilaneHCID 2724141Tetrabutylammonium Fluoride2×HCID 86701594HCID 86701594, compoundHCID 86701595HCID 86701595, compound

Product 1

HCID 178435868HCID 178435868, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of a mixture of 2-(5-ethyl-7-methyl-1-tosyl-1H-indole-4-carbonyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazole-5-carbonitrile and 2-(5-ethyl-7-methyl-1-tosyl-1H-indole-4-carbonyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazole-6-carbonitrile (400 mg, 0.653 mmol) and trimethyl(trifluoromethyl)silane (0.204 mL, 1.30 mmol) in THF (1 mL) was added dropwise TBAF in THF (1M, 1.95 mL, 1.95 mmol) at 0° C., and then the mixture was stirred at room temperature for 0.5 hr. To the mixture were added ethylenediamine (0.441 mL, 6.53 mmol) and TBAF in THF (1M, 6.53 mL, 6.53 mmol), and then the mixture was stirred at 60° C. for 77 h. The reaction mixture was cooled to room temperature. The reaction mixture was diluted with EtOAc and successively washed by 5% aq. NaHCO3, H2O and brine, dried over Na2SO4, and filtered. After concentration the residue was purified by silica gel flash chromatography [heptanes/(30% EtOAc in CH2Cl2)=44/55] to give the title compound. 1H NMR (400 MHz, ACETONITRILE-d3 with about 5 μL TFA) δ ppm 9.25 (br. s., 1H), 8.10 (s, 1H), 7.67 (d, J=8.30 Hz, 1H), 7.61 (dd, J=1.30, 8.30 Hz, 1H), 7.04 (t, J=3.00 Hz, 1H), 6.97 (s, 1H), 6.02 (br. s., 1H), 5.32 (br. s., 1H), 2.92-3.04 (m, 1H), 2.51-2.59 (m, 1H), 2.50 (d, J=0.76 Hz, 3H), 1.12 (t, J=7.33 Hz, 3H). HRMS calcd. for C21H17F3N4O (M+H)+ 399.1427. found 399.1420.

Workup

  1. stirringthe mixture was stirred at 60° C. for 77 h
  2. temperatureThe reaction mixture was cooled to room temperature
  3. washsuccessively washed by 5% aq. NaHCO3, H2O and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationAfter concentration the residue
  7. customwas purified by silica gel flash chromatography [heptanes/(30% EtOAc in CH2Cl2)=44/55]

Sources & evidence

ORD record
ord-17e476d4cf984c94963060921fcdf355
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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