Ethylenediamine → HCID 178494814, compound

HRID 2173914Notes

Reaction equation

HRID 2173914 reaction equation
[C:1]([C:3]1[CH:44]=[CH:43][C:6]2[N:7](COCC[Si](C)(C)C)[C:8]([C:10]([C:14]3[C:22]([O:23][CH:24]([F:26])[F:25])=[CH:21][C:20]([CH3:27])=[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(F)F)=CC(C)=C4C=3C=CN4C(OC(C)(C)C)=O)(OC)C)N(COCC[Si](C)(C)C)C=2C=1)#N.C(N)CN.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[F:26][CH:24]([F:25])[O:23][C:22]1[C:14]([C:10]([C:8]2[NH:7][C:6]3[CH:43]=[CH:44][C:3]([C:1]#[N:2])=[CH:4][C:5]=3[N:9]=2)([O:12][CH3:13])[CH3:11])=[C:15]2[C:19](=[C:20]([CH3:27])[CH:21]=1)[NH:18][CH:17]=[CH:16]2

Participants

6

Reactant 4

HCID 3301Ethylenediamine2×HCID 2724141Tetrabutylammonium Fluoride2×HCID 86701452HCID 86701452, compoundHCID 86701453HCID 86701453, compound

Product 1

HCID 178494814HCID 178494814, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of a mixture of (±)-tert-butyl 4-(1-(5-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazol-2-yl)-1-methoxyethyl)-5-(difluoromethoxy)-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-(difluoromethoxy)-7-methyl-1H-indole-1-carboxylate (475 mg, 0.758 mmol) in THF (7.6 mL) at room temperature, ethylenediamine (0.51 mL, 7.58 mmol) was added followed by TBAF (1M in THF, 7.6 mL, 7.6 mmol) and the reaction was stirred at 60° C. After 6 hours the reaction was cooled to room temperature, additional ethylenediamine (0.51 mL, 7.58 mmol) and TBAF (1M in THF, 7.6 mL, 7.6 mmol) were added and the reaction was stirred at 60° C. overnight. The reaction was cooled to room temperature, quenched with NH4Cl and extracted with EtOAc. The organic extract was dried over MgSO4, filtered and concentrated. The resulting residue was purified by flash chromatography (0-100% EtOAc in heptanes) to provide the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.68-12.85 (m, 1H) 11.19 (br. s., 1H) 8.09 (m) 7.83 (m) 7.69-7.74 (m) 7.47-7.58 (m) 7.31 (t, J=2.78 Hz, 1H) 6.89-6.96 (m) 6.70-6.77 (m) 6.46-6.58 (m) 3.01-3.17 (m, 3H) 2.46 (s, 3H) 2.07 (s, 3H). HRMS calcd. for C21H18F2N4O2 (M+H)+ 397.1471. found 397.1482.

Workup

  1. temperatureAfter 6 hours the reaction was cooled to room temperature
  2. stirringthe reaction was stirred at 60° C. overnight
  3. temperatureThe reaction was cooled to room temperature
  4. customquenched with NH4Cl
  5. extractionextracted with EtOAc
  6. extractionThe organic extract
  7. dry with materialwas dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe resulting residue was purified by flash chromatography (0-100% EtOAc in heptanes)

Sources & evidence

ORD record
ord-e9fad16f6f074ad99b1509110f830810
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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