Hydrochloric Acid → HCID 178483311, compound

HRID 2173960Notes

Reaction equation

HRID 2173960 reaction equation
C(O[C:6]([N:8](C)[C:9]([C:30]1[C:38]([O:39][CH3:40])=[CH:37][C:36]([CH3:41])=[C:35]2[C:31]=1[CH:32]=[CH:33][N:34]2C(OC(C)(C)C)=O)([C:11]1[N:15](COCC[Si](C)(C)C)[C:14]2[CH:24]=[CH:25][C:26]([C:28]#[N:29])=[CH:27][C:13]=2[N:12]=1)[CH3:10])=O)(C)(C)C.C(OC(N(C)C(C1C(OC)=CC(C)=C2C=1C=CN2C(OC(C)(C)C)=O)(C1N(COCC[Si](C)(C)C)C2C=C(C#N)C=CC=2N=1)C)=O)(C)(C)C.Cl.O1CCOCC1.C(=O)([O-])[O-].[Cs+].[Cs+]>CO>[CH3:40][O:39][C:38]1[C:30]([C:9]([C:11]2[NH:15][C:14]3[CH:24]=[CH:25][C:26]([C:28]#[N:29])=[CH:27][C:13]=3[N:12]=2)([NH:8][CH3:6])[CH3:10])=[C:31]2[C:35](=[C:36]([CH3:41])[CH:37]=1)[NH:34][CH:33]=[CH:32]2

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 86701526HCID 86701526, compoundHCID 86701527HCID 86701527, compound

Product 1

HCID 178483311HCID 178483311, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
0 °C

Procedure

A mixture of (±)-tert-butyl 4-(1-((tert-butoxycarbonyl)(methyl)amino)-1-(5-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazol-2-yl)ethyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate and (±)-tert-butyl 4-(1-((tert-butoxycarbonyl)(methyl)amino)-1-(6-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazol-2-yl)ethyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (0.21 g, 0.304 mmol) was dissolved in anhydrous MeOH (0.61 mL) and cooled to 0° C. A 4 M HCl solution in dioxane (1.52 mL, 6.09 mmol) was added and the reaction was stirred in the ice bath for 5 hours. Anhydrous MeOH (0.6 mL) was added to the reaction followed by cesium carbonate (2.98 g, 9.13 mmol). The mixture was heated at 60° C. for 1 hour. At this point the reaction was concentrated and diluted with a saturated solution of aq. ammonium chloride and ethyl acetate. The layers were separated and the organic phase was dried over magnesium sulfate, concentrated and purified by flash chromatography [0-5% MeOH (containing 10% ammonium hydroxide) in DCM] to provide the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.87 (br. s., 1H) 7.93 (m) 7.56 (m) 7.43-7.50 (m, 1H) 7.22 (br. s., 1H) 6.69 (s, 1H) 6.57 (br. s., 1H) 3.22 (s, 3H) 2.44 (s, 3H) 2.06 (s, 3H) 1.91 (s, 3H). HRMS calcd. for C21H21N5O (M+H) 360.1824. found 360.1831.

Workup

  1. temperatureThe mixture was heated at 60° C. for 1 hour
  2. concentrationAt this point the reaction was concentrated
  3. additiondiluted with a saturated solution of aq. ammonium chloride and ethyl acetate
  4. customThe layers were separated
  5. dry with materialthe organic phase was dried over magnesium sulfate
  6. concentrationconcentrated
  7. custompurified by flash chromatography [0-5% MeOH (containing 10% ammonium hydroxide) in DCM]

Sources & evidence

ORD record
ord-f27ff28cbc12495eb0d83ad61cd7a745
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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