Sodium Iodide → HCID 16725698, compound

HRID 1864004Notes

Reaction equation

HRID 1864004 reaction equation
[NH2:1][C:2]1[C:3]([C:7]2[N:8]([CH2:32][CH3:33])[C:9]3[C:14]([O:15][CH2:16][CH:17]4[S:22][CH2:21][CH2:20][N:19](C(OC(C)(C)C)=O)[CH2:18]4)=[CH:13][N:12]=[C:11](Cl)[C:10]=3[N:31]=2)=[N:4][O:5][N:6]=1.[Na+].[I-].C1CCN2C(=NCCC2)CC1.[CH3:47][C:48]([OH:52])([C:50]#[CH:51])[CH3:49].[NH4+].[Cl-]>[Zn].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CO.C(Cl)Cl.O1CCOCC1>[NH2:1][C:2]1[C:3]([C:7]2[N:8]([CH2:32][CH3:33])[C:9]3[C:14]([O:15][CH2:16][CH:17]4[S:22][CH2:21][CH2:20][NH:19][CH2:18]4)=[CH:13][N:12]=[C:11]([C:51]#[C:50][C:48]([CH3:49])([OH:52])[CH3:47])[C:10]=3[N:31]=2)=[N:4][O:5][N:6]=1

Participants

10

Reactant 5

HCID 5238Sodium IodideHCID 82582-Methyl-3-butyn-2-olHCID 25517Ammonium ChlorideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 86619282HCID 86619282, compound

Product 1

HCID 16725698HCID 16725698, compoundYield 37%

Reagents, catalysts & solvents 4

HCID 23994ZincCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
80 °C

Procedure

A thick-walled pressure vessel was charged with 1,1-dimethylethyl 2-({[2-(4-amino-1,2,5-oxadiazol-3-yl)-4-chloro-1-ethyl-1H-imidazo[4,5-c]pyridin-7-yl]oxy}methyl)-4-thiomorpholinecarboxylate (enantiomer E1) (0.18 g, 1.35 mmol), Zn dust (0.03 g, 0.40 mmol), NaI (0.06 g, 0.40 mmol), DBU (0.61 mL, 4.00 mmol), TEA (0.56 mL, 4.00 mmol), 2-methyl-3-butyn-2-ol (0.48 mL, 5.70 mmol), (Ph3P)4Pd (0.08 g, 0.08 mmol) and dioxane (35 mL). After purging the mixture with nitrogen for 10 min., the vessel was sealed and heated at 80° C. for 2.5 h. After allowing the reaction to cool to ambient temperature, sat NH4Cl was added and the reaction was extracted with EtOAc. The combined organic extracts were washed with water, brine and dried over sodium sulfate. The solvent was removed under reduced pressure and the residue subjected to flash chromatography (MeOH/CH2Cl2, silica gel). The Boc-protected product was dissolved in 25% TFA/CH2Cl2 (10 mL). After 30 min., the solvent was removed under reduced pressure. The residue was partitioned between 1N NaOH and ethyl acetate. The aqueous layer was extracted with additional ethyl acetate. The combined organic extracts were washed with brine, dried over sodium sulfate. The solvent was removed under reduced pressure. Flash chromatography (MeOH/CH2Cl2, silica gel) gave 0.22 g (37% yield) of the desired compound. MS (ES+) m/z 444 (M+H)+.

Workup

  1. customAfter purging the mixture with nitrogen for 10 min.
  2. customthe vessel was sealed
  3. customthe reaction
  4. temperatureto cool to ambient temperature
  5. additionwas added
  6. extractionthe reaction was extracted with EtOAc
  7. washThe combined organic extracts were washed with water, brine
  8. dry with materialdried over sodium sulfate
  9. customThe solvent was removed under reduced pressure
  10. dissolutionwas dissolved in 25% TFA/CH2Cl2 (10 mL)
  11. customthe solvent was removed under reduced pressure
  12. customThe residue was partitioned between 1N NaOH and ethyl acetate
  13. extractionThe aqueous layer was extracted with additional ethyl acetate
  14. washThe combined organic extracts were washed with brine
  15. dry with materialdried over sodium sulfate
  16. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-6d5ad7ea935644b3beb133977d1c1058
Source dataset
uspto-grants-2009_12
Patent number
US07625890B2

Reaction notes

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