Methyl iodide → 1-(2,2-Dimethylpropyl)-5-[(1R,2S)-2-(2-hydroxyethyl)cyclopropyl]-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one

HRID 629911Notes

Reaction equation

HRID 629911 reaction equation
C([Zn]CC)C.[C:6](O)([C:8](F)(F)F)=[O:7].IC.[CH3:15][C:16]([CH3:35])([CH3:34])[CH2:17][N:18]1[C:26]2[C:21](=[N:22][C:23](/[CH:27]=[CH:28]/[CH2:29]CO)=[CH:24][CH:25]=2)[N:20]([CH3:32])[C:19]1=[O:33]>C(Cl)Cl>[CH3:35][C:16]([CH3:15])([CH3:34])[CH2:17][N:18]1[C:26]2[C:21](=[N:22][C:23]([C@@H:27]3[CH2:28][C@H:29]3[CH2:8][CH2:6][OH:7])=[CH:24][CH:25]=2)[N:20]([CH3:32])[C:19]1=[O:33]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 6422Trifluoroacetic acidHCID 711367771-(2,2-Dimethylpropyl)-5-[(1E)-4-hydroxybut-1-en-1-yl]-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-oneHCID 178418750HCID 178418750, compound

Product 1

HCID 1177023211-(2,2-Dimethylpropyl)-5-[(1R,2S)-2-(2-hydroxyethyl)cyclopropyl]-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent4×

Conditions

Temperature
0 °C

Procedure

Diethyl zinc (0.53 mL, 0.53 mmol, 2.0 equiv, 1M in hexanes) was added to anhydrous DCM (0.53 mL) and cooled to 0° C. To this solution was added TFA (41 μL, 0.53 mmol, 2.0 equiv) in anhydrous DCM (0.27 mL), and the resulting mixture was stirred at 0° C. for 15 min. Following this duration, iodomethane (43 μL, 0.53 mmol, 2.0 equiv) in anhydrous DCM (0.27 mL) as added and the resulting reaction mixture was stirred for and additional 20 min. 1-(2,2-Dimethylpropyl)-5-[(1E)-4-hydroxybut-1-en-1-yl]-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (32-3, 77 mg, 0.27 mmol, 1.0 equiv) in anhydrous DCM (0.27) as then added. After 1 h, the reaction vessel was removed from the 0° C. bath and allowed to gradually warm to RT. After 2.5 h, LCMS showed consumption of 32-3. The reaction was quenched with saturated NH4Cl (5 mL) and extracted with ethyl acetate (3×5 ml). The combined organics were dried over Na2SO4, filtered and concentrated in vacuo to give 32-4 as a white solid. Since the material was determined to be of >95% purity by 1H NMR, further purification was deemed unnecessary. MS m/z (M+H): calculated=303.4; observed=304.1.

Workup

  1. additionas added
  2. customthe resulting reaction mixture
  3. stirringwas stirred for and additional 20 min
  4. waitAfter 1 h
  5. customthe reaction vessel was removed from the 0° C. bath
  6. temperatureto gradually warm to RT
  7. waitAfter 2.5 h
  8. customconsumption of 32-3
  9. customThe reaction was quenched with saturated NH4Cl (5 mL)
  10. extractionextracted with ethyl acetate (3×5 ml)
  11. dry with materialThe combined organics were dried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-032a2e0817984a8a8c68df6d7d9c9ac4
Source dataset
uspto-grants-2016_04
Patent number
US09315518B2

Reaction notes

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