Hydrochloric Acid → HCID 178437082, compound

HRID 2262678Notes

Reaction equation

HRID 2262678 reaction equation
Br[C:2]1[CH:3]=[C:4]2[N:10]([CH:11]([CH2:14][CH3:15])[CH2:12][CH3:13])[C:9]([OH:16])=[N:8][C:5]2=[N:6][CH:7]=1.[Si]([C:21]#[CH:22])(C)(C)C.C(N(CC)CC)C.C1(P(=O)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[OH-].[K+].Cl>C1COCC1.O.[Cu]I.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.CO.CN(C=O)C>[C:21]([C:2]1[CH:3]=[C:4]2[N:10]([CH:11]([CH2:14][CH3:15])[CH2:12][CH3:13])[C:9]([OH:16])=[N:8][C:5]2=[N:6][CH:7]=1)#[CH:22]

Participants

13

Reactant 6

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 13097Triphenylphosphine OxideHCID 14797Potassium HydroxideHCID 66111TrimethylsilylacetyleneHCID 178446209HCID 178446209, compound

Product 1

HCID 178437082HCID 178437082, compoundYield 45%

Reagents, catalysts & solvents 6

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

Solid 6-bromo-1-(pentan-3-yl)-1H-imidazo[4,5-b]pyridin-2-ol (2.0 g, 7.04 mmol, 1.0 equiv), CuI (133 mg, 0.7 mmol, 0.1 equiv), and (Ph3P)2PdCl2 (491 mg, 0.7 mmol, 0.1 equiv) were added to a dry round bottom flask equipped with a stir bar. The flask was sealed and purged with nitrogen and DMF (30 mL), TMS-acetylene (4.22 mL, 8.45 mmol, 1.2 quiv), and triethylamine (4.9 mL, 35.2 mmol, 5.0 equiv) were added by syringe. The resulting mixture was heated to 100° C. for 30 min. After the reaction was allowed to cool, the mixture was concentrated in vacuo and then resuspended in EtOAc. The mixture was washed three times with water, twice with satd. aq. NaHCO3, and once with brine. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Purification by silica gel MPLC (7%-66% EtOAc/Hexanes) provided the silylated product, which contained triphenylphosphine oxide as a contaminant, was taken on directly into the deprotection. The solid was dissolved in a 1:1 mixture of THF:MeOH (30 mL), and solid KOH (1.97 g, 35.2 mmol, 5.0 equiv) was added in one portion. After 5 min, the reaction was diluted with water and acidified to pH 7 by the addition of 1 N HCl. The mixture was extracted with EtOAc, and the organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Purification by silica gel MPLC (10%-60% EtOAc/Hexanes) provided 6-ethynyl-1-(pentan-3-yl)-1H-imidazo[4,5-b]pyridin-2-ol as a white solid (713 mg, 45%). m/z=230.2 [M+H]+

Workup

  1. customequipped with a stir bar
  2. customThe flask was sealed
  3. additionwere added by syringe
  4. temperatureto cool
  5. concentrationthe mixture was concentrated in vacuo
  6. washThe mixture was washed three times with water
  7. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customPurification by silica gel MPLC (7%-66% EtOAc/Hexanes)
  11. customprovided the silylated product, which
  12. extractionThe mixture was extracted with EtOAc
  13. washthe organic layer was washed with brine
  14. dry with materialdried over anhydrous sodium sulfate
  15. filtrationfiltered
  16. concentrationconcentrated in vacuo
  17. customPurification by silica gel MPLC (10%-60% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-28b855a34cb34045a6887b9d97368559
Source dataset
uspto-grants-2010_12
Patent number
US07851484B2

Reaction notes

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