Methyl iodide → HCID 67772019, compound

HRID 1808836Notes

Reaction equation

HRID 1808836 reaction equation
[F:1][C:2]1([F:23])[CH2:6][CH2:5][N:4]([CH2:7][C@@H:8]([NH:12][C:13](=[O:22])[C:14]2[CH:19]=[CH:18][C:17]([CH3:20])=[C:16]([CH3:21])[CH:15]=2)[CH:9]([CH3:11])[CH3:10])[CH2:3]1.[H-].[Na+].[CH3:26]I>C1COCC1>[F:23][C:2]1([F:1])[CH2:6][CH2:5][N:4]([CH2:7][C@@H:8]([N:12]([CH3:26])[C:13](=[O:22])[C:14]2[CH:19]=[CH:18][C:17]([CH3:20])=[C:16]([CH3:21])[CH:15]=2)[CH:9]([CH3:11])[CH3:10])[CH2:3]1

Participants

5

Reactant 3

HCID 6328Methyl iodide2×HCID 24758Sodium hydride2×HCID 67773711HCID 67773711, compound2×

Product 1

HCID 67772019HCID 67772019, compoundYield 27.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of (S)—N-(1-(3,3-difluoropyrrolidin-1-yl)-3-methylbutan-2-yl)-3,4-dimethylbenzamide (Compound P) (167 mg, 0.51 mmol) in THF (1 mL) was sodium hydride (0.024 mL, 0.51 mmol) added. After 30 min was MeI (0.032 mL, 0.51 mmol) added and the resultant mixture was stirred at rt overnight. Additional sodium hydride (0.013 mL, 0.51 mmol) and MeI (0.032 mL, 0.51 mmol) was added and the resulting mixture stirred for 2 h. The reaction was quenched with MeOH (0.5 mL). The solvent was removed under reduced pressure and the residue dissolved in DCM (5 mL). The organic phase was washed with NaHCO3 (saturated, 5 mL), filtered through a phase separator and concentrated under reduced pressure. The residue was purified by preparative HPLC to give the title compound (47 mg, 27%). HRMS (M+H)+: calculated 339.2248. found 339.2277.

Workup

  1. additionadded
  2. customThe reaction was quenched with MeOH (0.5 mL)
  3. customThe solvent was removed under reduced pressure
  4. dissolutionthe residue dissolved in DCM (5 mL)
  5. washThe organic phase was washed with NaHCO3 (saturated, 5 mL)
  6. filtrationfiltered through a phase separator
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-14269e75c9784236a8e3e03bc54388e3
Source dataset
uspto-grants-2013_01
Patent number
US08361998B2

Reaction notes

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