Methyl iodide → HCID 59722598, compound

HRID 1664851Notes

Reaction equation

HRID 1664851 reaction equation
I[CH3:2].[CH:3]1([CH:6]([OH:33])[C:7]2[N:11]3[CH2:12][C@H:13]([C:25]4[CH:30]=[CH:29][CH:28]=[C:27]([F:31])[C:26]=4[F:32])[CH2:14][CH2:15][C@@H:16]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[C:10]3=[N:9][CH:8]=2)[CH2:5][CH2:4]1.[H-].[Na+]>O1CCCC1>[CH:3]1([CH:6]([O:33][CH3:2])[C:7]2[N:11]3[CH2:12][C@H:13]([C:25]4[CH:30]=[CH:29][CH:28]=[C:27]([F:31])[C:26]=4[F:32])[CH2:14][CH2:15][C@@H:16]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[C:10]3=[N:9][CH:8]=2)[CH2:5][CH2:4]1

Participants

5

Reactant 3

HCID 6328Methyl iodide2×HCID 24758Sodium hydride2×HCID 59722707HCID 59722707, compound

Product 1

HCID 59722598HCID 59722598, compoundYield 34.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Iodomethane (9.0 μL, 0.15 mmol) was added to a solution of tert-butyl (6S,9R)-3-[cyclopropyl(hydroxy)methyl]-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-imidazo[1,2-a]azepin-9-ylcarbamate (66 mg, 0.15 mmol) and sodium hydride (60% dispersion in mineral oil; 8.3 mg, 0.23 mmol) in tetrahydrofuran (1 mL) at 0° C. After 1 h, the mixture was allowed to warm to ambient temperature. After 2 h, additional iodomethane (6.0 μL, 0.10 mmol) and sodium hydride (60% dispersion in mineral oil; 3.0 mg, 0.08 mmol) were added. After 1 h, 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 (23 mg). MS 448.2 (M+1).

Workup

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

Sources & evidence

ORD record
ord-93714841c55e4889a6842ad5567ea553
Source dataset
uspto-grants-2011_10
Patent number
US08039460B2

Reaction notes

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