Ethylenediamine → HCID 178489067, compound

HRID 2173937Notes

Reaction equation

HRID 2173937 reaction equation
[C:1]([C:3]1[CH:42]=[CH:41][C:6]2[N:7](COCC[Si](C)(C)C)[C:8]([C:10]([C:14]3[C:22]([O:23][CH3:24])=[CH:21][C:20]([CH3:25])=[C:19]4[C:15]=3[CH:16]=[CH:17][N:18]4C(OC(C)(C)C)=O)([O:12][CH3:13])[CH3:11])=[N:9][C:5]=2[CH:4]=1)#[N:2].C(C1C=CC2N=C(C(C3C(OC)=CC(C)=C4C=3C=CN4C(OC(C)(C)C)=O)(OC)C)N(COCC[Si](C)(C)C)C=2C=1)#N.CCCC[N+](CCCC)(CCCC)CCCC.[F-].C(N)CN.[Cl-].[NH4+].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCCC1.C(OCC)(=O)C>[CH3:13][O:12][C:10]([C:8]1[NH:7][C:6]2[CH:41]=[CH:42][C:3]([C:1]#[N:2])=[CH:4][C:5]=2[N:9]=1)([C:14]1[C:22]([O:23][CH3:24])=[CH:21][C:20]([CH3:25])=[C:19]2[C:15]=1[CH:16]=[CH:17][NH:18]2)[CH3:11]

Participants

9

Reactant 6

HCID 3301EthylenediamineHCID 10796Cesium carbonateHCID 25517Ammonium ChlorideHCID 2724141Tetrabutylammonium FluorideHCID 86701490HCID 86701490, compoundHCID 86701491HCID 86701491, compound

Product 1

HCID 178489067HCID 178489067, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
65 °C

Procedure

To a mixture of (±)-tert-butyl 4-(1-(5-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazol-2-yl)-1-methoxy ethyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate and (±)-tert-butyl 4-(1-(6-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazol-2-yl)-1-methoxyethyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (0.494 g, 0.836 mmol) in tetrahydrofuran (8.36 mL) was added TBAF (1M in THF, 8.36 mL, 8.36 mmol) and ethylenediamine (0.28 mL, 4.18 mmol). The reaction was heated at 65° C. for 26 hours. The reaction was cooled to room temperature and treated with 10 mL of a saturated solution of aq. ammonium chloride and then diluted with ethyl acetate. The layers were separated and the organic layer was washed with water (3×100 mL), dried over magnesium sulfate and concentrated. The resulting residue was dissolved in MeOH and cesium carbonate (1.38 g, 4.25 mmol) was added and the reaction was heated at 60° C. for 1.5 hours. The reaction was cooled to room temperature, diluted with EtOAc and then washed with a saturated solution of aq. ammonium chloride. The organic extract was dried over magnesium sulfate, filtered and concentrated. The resulting residues was purified by flash chromatography (0-10% MeOH in DCM) to provide the title compound. 1H NMR (400 MHz, DMSO-d6 with about 5 μL TFA) δ ppm 11.14 (br. s., 1H) 8.23 (s, 1H) 7.66-8.01 (m, 2H) 7.39 (t, J=2.91 Hz, 1H) 6.48-6.88 (m, 2H) 3.28 (s, 3H) 3.17 (s, 3H) 2.48 (s, 3H) 2.13 (s, 3H). HRMS calcd. for C21H20N4O2 (M+H)+ 361.1659. found 361.1675.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. customThe layers were separated
  3. washthe organic layer was washed with water (3×100 mL)
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated
  6. dissolutionThe resulting residue was dissolved in MeOH
  7. temperaturethe reaction was heated at 60° C. for 1.5 hours
  8. temperatureThe reaction was cooled to room temperature
  9. washwashed with a saturated solution of aq. ammonium chloride
  10. extractionThe organic extract
  11. dry with materialwas dried over magnesium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customThe resulting residues was purified by flash chromatography (0-10% MeOH in DCM)

Sources & evidence

ORD record
ord-64cae00fcb13420eb34e89f5bcb5d9d8
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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