Hydrochloric Acid → HCID 178489065, compound

HRID 2173959Notes

Reaction equation

HRID 2173959 reaction equation
[C:1]([C:3]1[CH:47]=[CH:46][C:6]2[N:7](COCC[Si](C)(C)C)[C:8]([C:10]([C:19]3[C:27]([O:28][CH3:29])=[CH:26][C:25]([CH3:30])=[C:24]4[C:20]=3[CH:21]=[CH:22][N:23]4C(OC(C)(C)C)=O)([NH:12]S(C(C)(C)C)=O)[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)(NS(C(C)(C)C)=O)C)N(COCC[Si](C)(C)C)C=2C=1)#N.Cl.CO.C([O-])([O-])=O.[Cs+].[Cs+]>>[NH2:12][C:10]([C:8]1[NH:7][C:6]2[CH:46]=[CH:47][C:3]([C:1]#[N:2])=[CH:4][C:5]=2[N:9]=1)([C:19]1[C:27]([O:28][CH3:29])=[CH:26][C:25]([CH3:30])=[C:24]2[C:20]=1[CH:21]=[CH:22][NH:23]2)[CH3:11]

Participants

6

Reactant 5

HCID 313Hydrochloric AcidHCID 887MethanolHCID 10796Cesium carbonateHCID 86701523HCID 86701523, compoundHCID 86701524HCID 86701524, compound

Product 1

HCID 178489065HCID 178489065, compound

Conditions

Temperature
60 °C

Procedure

To a mixture of (±)-tert-butyl 4-(1-(5-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazol-2-yl)-1-(1,1-dimethylethylsulfinamido)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-(1,1-dimethylethylsulfinamido)ethyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (0.52 g, 0.76 mmol) was added 1.25 M HCl in MeOH (6.12 mL, 7.65 mmol) and heated at 60° C. for 30 minutes. The reaction was concentrated and then diluted with MeOH (5 mL). Cs2CO3 (4 g, 12.28 mmol) was added and the reaction was heated at 60° C. After 2 hours the reaction was complete. Reaction was then cooled and quenched with 10 mL of a saturated aq. solution of ammonium chloride and diluted with 50 mL of ethyl acetate. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organics layers were dried over magnesium sulfate, concentrated and purified by flash chromatography [0-10% (10% ammonium hydroxide in MeOH)-DCM] to provide the title compound. 1H NMR (400 MHz, DMSO-d6 with ˜5 μL TFA) δ ppm 11.23 (br. s., 1H) 8.82 (br. s., 3H) 7.47-7.76 (m, 1H) 7.35 (t, J=2.97 Hz, 1H) 6.87 (s, 1H) 5.94 (dd, J=3.16, 1.77 Hz, 1H) 3.50 (s, 3H) 2.04-2.37 (m, 3H). HRMS calcd. for C20H13N6O (M+H)+ 346.1663. found 346.1663.

Workup

  1. concentrationThe reaction was concentrated
  2. additiondiluted with MeOH (5 mL)
  3. temperaturethe reaction was heated at 60° C
  4. customReaction
  5. temperaturewas then cooled
  6. customquenched with 10 mL of a saturated aq. solution of ammonium chloride
  7. additiondiluted with 50 mL of ethyl acetate
  8. customThe layers were separated
  9. extractionthe aqueous layer was extracted with EtOAc
  10. dry with materialThe combined organics layers were dried over magnesium sulfate
  11. concentrationconcentrated
  12. custompurified by flash chromatography [0-10% (10% ammonium hydroxide in MeOH)-DCM]

Sources & evidence

ORD record
ord-5c57d63ca27542b080d99e49638ce738
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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