Cesium carbonate → HCID 178489072, compound

HRID 2173935Notes

Reaction equation

HRID 2173935 reaction equation
[C:1]([C:3]1[CH:40]=[CH:39][C:6]2[N:7](COCC[Si](C)(C)C)[C:8]([C:10]([C:12]3[C:20]([O:21][CH3:22])=[CH:19][C:18]([CH3:23])=[C:17]4[C:13]=3[CH:14]=[CH:15][N:16]4C(OC(C)(C)C)=O)=[O: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)=O)N(COCC[Si](C)(C)C)C=2C=1)#N.CCCC[N+](CCCC)(CCCC)CCCC.[F-].[Cl-].[NH4+].C(=O)([O-])[O-].[Cs+].[Cs+]>C1COCC1.CCOC(C)=O>[CH3:22][O:21][C:20]1[CH:19]=[C:18]([CH3:23])[C:17]2[NH:16][CH:15]=[CH:14][C:13]=2[C:12]=1[C:10]([C:8]1[NH:7][C:6]2[CH:39]=[CH:40][C:3]([C:1]#[N:2])=[CH:4][C:5]=2[N:9]=1)=[O:11]

Participants

8

Reactant 5

HCID 10796Cesium carbonateHCID 25517Ammonium Chloride2×HCID 2724141Tetrabutylammonium FluorideHCID 86701486HCID 86701486, compoundHCID 86701487HCID 86701487, compound

Product 1

HCID 178489072HCID 178489072, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
65 °C

Procedure

A mixture of tert-butyl 4-(5-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazole-2-carbonyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate and tert-butyl 4-(6-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazole-2-carbonyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (62 mg, 0.11 mmol) was dissolved in THF (1.1 mL) and then TBAF (1.1 mL, 1.1 mmol) was added and the reaction was heated at 65° C. for 17 hours. The mixture was then cooled to room temperature and treated with 10 mL of a saturated aq. solution of ammonium chloride and then diluted with EtOAc. The organic layer was separated and washed with water (3×100 mL). The organic extract was dried over magnesium sulfate and concentrated. The resulting residue was dissolved in MeOH (4 mL), cesium carbonate (48.9 mg, 0.15 mmol) was added and the reaction was heated at 60° C. for 1 h. The reaction was cooled to room temperature, a saturated aq. solution of ammonium chloride was added, followed by EtOAc. The organic layer was separated, washed with water and the organic extracts combined, dried over magnesium sulfate, filtered and concentrated. The resulting residue was purified by flash column chromatography (0-40% EtOAc in heptanes) to provide the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 13.73 (br. s., 1H) 11.33 (br. s., 1H) 8.29 (br. s.) 8.07 (br. s.) 7.60-7.90 (m, 2H) 7.45 (t, J=2.78 Hz, 1H) 6.89 (s, 1H) 6.42 (br. s., 1H) 3.56 (s, 3H) 2.54-2.63 (m, 3H). HRMS calcd. for C19H14N4O2 (M+H)+ 331.119. found 331.1202.

Workup

  1. temperatureThe mixture was then cooled to room temperature
  2. customThe organic layer was separated
  3. washwashed with water (3×100 mL)
  4. extractionThe organic extract
  5. dry with materialwas dried over magnesium sulfate
  6. concentrationconcentrated
  7. dissolutionThe resulting residue was dissolved in MeOH (4 mL)
  8. temperaturethe reaction was heated at 60° C. for 1 h
  9. temperatureThe reaction was cooled to room temperature
  10. customThe organic layer was separated
  11. washwashed with water
  12. dry with materialdried over magnesium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customThe resulting residue was purified by flash column chromatography (0-40% EtOAc in heptanes)

Sources & evidence

ORD record
ord-9317edae6c874289ad4c8184ec9844fe
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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