Cesium carbonate → HCID 178489073, compound

HRID 2173934Notes

Reaction equation

HRID 2173934 reaction equation
[C:1]([C:3]1[CH:40]=[CH:39][C:6]2[N:7](COCC[Si](C)(C)C)[C:8]([CH:10]([OH:30])[C:11]3[C:19]([O:20][CH3:21])=[CH:18][C:17]([CH3:22])=[C:16]4[C:12]=3[CH:13]=[CH:14][N:15]4C(OC(C)(C)C)=O)=[N:9][C:5]=2[CH:4]=1)#[N:2].C(C1C=CC2N=C(C(O)C3C(OC)=CC(C)=C4C=3C=CN4C(OC(C)(C)C)=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.C(OCC)(=O)C.CO>[OH:30][CH:10]([C:11]1[C:19]([O:20][CH3:21])=[CH:18][C:17]([CH3:22])=[C:16]2[C:12]=1[CH:13]=[CH:14][NH:15]2)[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

Participants

9

Reactant 5

HCID 10796Cesium carbonateHCID 25517Ammonium ChlorideHCID 2724141Tetrabutylammonium FluorideHCID 86701484HCID 86701484, compoundHCID 86701485HCID 86701485, compound

Product 1

HCID 178489073HCID 178489073, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of (±)-tert-butyl 4-((5-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazol-2-yl)(hydroxy)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate and (±)-tert-butyl 4-((6-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazol-2-yl)(hydroxy)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (0.3 g, 0.533 mmol) was dissolved in THF (5.33 mL). TBAF (5.34 mL, 5.34 mmol) was added to the solution and the reaction was stirred at 50° C. for 5 hours. The reaction was diluted with ethyl acetate and then with 20 mL of a saturated aq. solution of ammonium chloride. The ethyl acetate layer was separated, washed with water, dried and concentrated. The resulting residue was dissolved in MeOH (4 mL) to which cesium carbonate (0.87 g, 2.67 mmol) was added. The reaction was heated at 50° C. for 1 hour. The reaction was then concentrated and directly purified by flash chromatography (0-10% MeOH in DCM) to provide the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.93 (d, J=3.54 Hz, 1H) 10.86 (br. s., 1H) 7.81-7.95 (m, 1H) 7.60 (m) 7.40-7.56 (m) 7.14 (t, J=2.78 Hz, 1H) 6.75 (s, 1H) 6.53-6.62 (m, 1H) 6.19-6.31 (m, 2H) 3.81 (s, 3H) 2.40-2.47 (m, 3H). HRMS calcd. for C19H16N4O2 (M+H)+ 333.1346. found 333.1355.

Workup

  1. customThe ethyl acetate layer was separated
  2. washwashed with water
  3. customdried
  4. concentrationconcentrated
  5. additionwas added
  6. temperatureThe reaction was heated at 50° C. for 1 hour
  7. concentrationThe reaction was then concentrated
  8. customdirectly purified by flash chromatography (0-10% MeOH in DCM)

Sources & evidence

ORD record
ord-56972ebdbad84b1396631267a978d809
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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