Sodium Carbonate → HCID 17981744, compound

HRID 2252068Notes

Reaction equation

HRID 2252068 reaction equation
[CH3:1][O:2][C:3]1[CH:30]=[CH:29][C:6]([CH2:7][N:8]2[C:12](I)=[C:11]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[N:10]=[C:9]2[CH2:20][O:21][Si](C(C)(C)C)(C)C)=[CH:5][CH:4]=1.[CH:31]([S:34]([N:37]1[C:41]2[CH:42]=[C:43](B(O)O)[CH:44]=[CH:45][C:40]=2[N:39]=[C:38]1[NH2:49])(=[O:36])=[O:35])([CH3:33])[CH3:32].C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.Cl.O.CCOC(C)=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH:31]([S:34]([N:37]1[C:41]2[CH:42]=[C:43]([C:12]3[N:8]([CH2:7][C:6]4[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:30][CH:29]=4)[C:9]([CH2:20][OH:21])=[N:10][C:11]=3[C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH:44]=[CH:45][C:40]=2[N:39]=[C:38]1[NH2:49])(=[O:35])=[O:36])([CH3:33])[CH3:32]

Participants

10

Reactant 3

HCID 10340Sodium CarbonateHCID 17981723HCID 17981723, compoundHCID 69211817HCID 69211817, compound

Product 1

HCID 17981744HCID 17981744, compoundYield 36%

Reagents, catalysts & solvents 6

HCID 178418476HCID 178418476, compoundCatalystHCID 313Hydrochloric AcidSolventHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 1-(4-methoxybenzyl)-2-tert-butyldimethylsilyloxymethyl-4-(phenyl)-5-iodoimidazole (50 mg, 0.0935 mmol) in dry toluene (0.8 mL) previously bubbled with a stream of nitrogen, add PdCl2(PPh3)2 (4.5 mg, 0.00641 mmol) in one portion. After 5 minutes, add a suspension of 1-isopropylsulfonyl-2-amino-benzimidazole-6-boronic acid (40 mg, 0.141 mmol) in ethanol (0.8 mL) previously bubbled with a stream of nitrogen, followed by sodium carbonate (2M in water, 0.32 mL, 0.640 mmol). Stir the mixture for 2.5 hours at 100° C., cool to room temperature, dilute with 10% HCl (5 mL), extract with EtOAc (15 mL), dry (Na2SO4), and concentrate in vacuo. Purify the residue by flash chromatography (SiO2, CH2Cl2/MeOH 19:1→5:1), dissolve the material obtained in MeCN (0.5 mL), and treat with HF (48% in H2O, 0.12 mL, 3.31 mmol) at room temperature for 4 hours. Dilute the mixture with EtOAc (15 nm), wash with saturated NaHCO3 (5 mL), dry (Na2SO4), and concentrate in vacuo. Purify the residue by flash chromatography (SiO2, CH2Cl2/MeCN/MeOH 85:15:5) to provide 18 mg (36% yield). MS (MS+): m/z=532 (M+H)+

Workup

  1. additionadd
  2. custompreviously bubbled with a stream of nitrogen
  3. temperaturecool to room temperature
  4. extractionextract with EtOAc (15 mL)
  5. dry with materialdry (Na2SO4)
  6. concentrationconcentrate in vacuo
  7. customPurify the residue by flash chromatography (SiO2, CH2Cl2/MeOH 19:1→5:1)
  8. dissolutiondissolve the material
  9. customobtained in MeCN (0.5 mL)
  10. washwash with saturated NaHCO3 (5 mL)
  11. dry with materialdry (Na2SO4)
  12. concentrationconcentrate in vacuo
  13. customPurify the residue by flash chromatography (SiO2, CH2Cl2/MeCN/MeOH 85:15:5)
  14. customto provide 18 mg (36% yield)

Sources & evidence

ORD record
ord-bd0a65460c7e480886b15bdd7eb9595f
Source dataset
uspto-grants-2008_01
Patent number
US07320995B2

Reaction notes

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