Methyl iodide → HCID 59722604, compound

HRID 1664852Notes

Reaction equation

HRID 1664852 reaction equation
I[CH3:2].[F:3][C:4]1[C:9]([F:10])=[CH:8][CH:7]=[CH:6][C:5]=1[C@H:11]1[CH2:17][N:16]2[C:18]([CH:21]([OH:23])[CH3:22])=[CH:19][N:20]=[C:15]2[C@H:14]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[CH2:13][CH2:12]1.[H-].[Na+]>O1CCCC1>[F:3][C:4]1[C:9]([F:10])=[CH:8][CH:7]=[CH:6][C:5]=1[C@H:11]1[CH2:17][N:16]2[C:18]([CH:21]([O:23][CH3:2])[CH3:22])=[CH:19][N:20]=[C:15]2[C@H:14]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[CH2:13][CH2:12]1

Participants

5

Reactant 3

HCID 6328Methyl iodide2×HCID 24758Sodium hydride2×HCID 59722677HCID 59722677, compound

Product 1

HCID 59722604HCID 59722604, compoundYield 38%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Iodomethane (6.0 μL, 0.10 mmol) was added to a solution of tert-butyl (6S,9R)-6-(2,3-difluorophenyl)-3-(1-hydroxyethyl)-6,7,8,9-tetrahydro-5H-imidazo[1,2-a]azepin-9-ylcarbamate (40 mg, 0.10 mmol) and sodium hydride (60% dispersion in mineral oil; 6.7 mg, 0.15 mmol) in tetrahydrofuran (1 mL) at 0° C. After 2 h, the mixture was allowed to warm to ambient temperature. Additional iodomethane (6.0 μL, 0.10 mmol) and sodium hydride (60% dispersion in mineral oil; 2.2 mg, 0.05 mmol) were added every 1.5 h over a total of 4.5 h, after which the reaction was quenched with water and the mixture was extracted with dichloromethane (3×). The organic layer was washed with water, saturated brine, dried over magnesium sulfate, filtered and concentrated. Purification by reverse phase HPLC (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.1% trifluoroacetic acid) gave the title compound (16 mg). MS 422.2 (M+1).

Workup

  1. customafter which the reaction was quenched with water
  2. extractionthe mixture was extracted with dichloromethane (3×)
  3. washThe organic layer was washed with water, saturated brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by reverse phase HPLC (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-b04510b43ec84b1e8e90585a1d892f74
Source dataset
uspto-grants-2011_10
Patent number
US08039460B2

Reaction notes

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