Methyl iodide → HCID 118023258, compound

HRID 929296Notes

Reaction equation

HRID 929296 reaction equation
[C:1]([O:5][C:6](=[O:27])[NH:7][CH2:8][CH2:9][C:10]([N:12]([C:15]1[C:16]([Cl:26])=[N:17][N:18]([C:20]2[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=2)[CH:19]=1)[CH2:13][CH3:14])=[O:11])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:30]I>>[C:1]([O:5][C:6](=[O:27])[N:7]([CH2:8][CH2:9][C:10]([N:12]([C:15]1[C:16]([Cl:26])=[N:17][N:18]([C:20]2[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=2)[CH:19]=1)[CH2:13][CH3:14])=[O:11])[CH3:30])([CH3:2])([CH3:3])[CH3:4]

Participants

4

Reactant 3

HCID 6328Methyl iodide2×HCID 24758Sodium hydrideHCID 118032659HCID 118032659, compound

Product 1

HCID 118023258HCID 118023258, compound

Conditions

Temperature
0 °C

Procedure

To a clean vial with a stir bar tert-butyl(3-((3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)(ethyl)amino)-3-oxopropyl)carbamate (1.5 g, 3.8 mmol) was added and sealed with a septum cap. The headspace was purged with N2, dry DMF (5.4 mL) was added via a syringe, and the reaction was cooled to a temperature of about 0° C. in an ice bath under N2. NaH (60% dispersion in oil, 0.21 g, 5.3 mmol) was carefully added and stirred at a temperature of 0° C. for 30 minutes. Methyl iodide (0.29 mL, 4.6 mmol) was then added and stirred for 30 minutes at a temperature of 0° C. With the addition of methyl iodide, reaction became light yellow slurry. The reaction was warmed up to room temperature and stirred for 2 hours. As reaction warmed up, it turned to bright orange color. The reaction was quenched by the slow addition of water (100 mL). The suspension was vigorously stirred at room temperature for 2 hours. The water was filtered off, and remaining slurry was washed with hexanes. The slurry was then dissolved in methanol and passed through the filter. The resulting solution was concentrated, dried under high vacuum to afford brown, viscous oil (1.6 g, 78%).

Workup

  1. customsealed with a septum
  2. customcap
  3. customThe headspace was purged with N2, dry DMF (5.4 mL)
  4. additionwas added via a syringe
  5. stirringstirred for 30 minutes at a temperature of 0° C
  6. temperatureThe reaction was warmed up to room temperature
  7. stirringstirred for 2 hours
  8. customAs reaction
  9. temperaturewarmed up
  10. customThe reaction was quenched by the slow addition of water (100 mL)
  11. stirringThe suspension was vigorously stirred at room temperature for 2 hours
  12. filtrationThe water was filtered off
  13. washwas washed with hexanes
  14. dissolutionThe slurry was then dissolved in methanol
  15. concentrationThe resulting solution was concentrated
  16. customdried under high vacuum
  17. customto afford brown

Sources & evidence

ORD record
ord-6c94748018f840af963c12db80c4b222
Source dataset
uspto-grants-2016_03
Patent number
US09295260B2

Reaction notes

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