HCID 145726187, compound → HCID 86620137, compound

HRID 1664876Notes

Reaction equation

HRID 1664876 reaction equation
[CH3:1][Mg]Br.[C:4]([S:8](/[N:10]=[CH:11]/[C:12]1[N:16]2[CH2:17][C@H:18]([C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([F:36])[C:31]=3[F:37])[CH2:19][CH2:20][C@@H:21]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[C:15]2=[N:14][CH:13]=1)=[O:9])([CH3:7])([CH3:6])[CH3:5]>O1CCCC1>[C:4]([S:8]([NH:10][CH:11]([C:12]1[N:16]2[CH2:17][C@H:18]([C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([F:36])[C:31]=3[F:37])[CH2:19][CH2:20][C@@H:21]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[C:15]2=[N:14][CH:13]=1)[CH3:1])=[O:9])([CH3:5])([CH3:6])[CH3:7]

Participants

4

Reactant 2

HCID 145726187HCID 145726187, compoundHCID 178418573HCID 178418573, compound2×

Product 1

HCID 86620137HCID 86620137, compoundYield 117.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Methylmagnesium bromide (0.24 mL, 0.71 mmol) was added to a solution of tert-butyl [(6S,9R)-3-{(E)-[(tert-butylsulfinyl)imino]methyl}-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-imidazo[1,2-a]azepin-9-yl]carbamate (117 mg, 0.24 mmol) in tetrahydrofuran (4 mL) at 0° C. After 5 min, the mixture was warmed to ambient temperature. After 1.5 h, additional methylmagnesium bromide (0.24 mL, 0.71 mmol) was added. After 1.5 h, the reaction mixture was cooled to 0° C. and quenched with saturated aqueous ammonium chloride and water. The mixture was extracted with ethyl acetate (3×). The organic extracts were washed with saturated brine, dried with magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% dichloromethane→94% dichloromethane/methanol) gave the title compound (144 mg). MS 511.2 (M+1).

Workup

  1. waitAfter 1.5 h
  2. waitAfter 1.5 h
  3. temperaturethe reaction mixture was cooled to 0° C.
  4. customquenched with saturated aqueous ammonium chloride and water
  5. extractionThe mixture was extracted with ethyl acetate (3×)
  6. washThe organic extracts were washed with saturated brine
  7. dry with materialdried with magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification by silica gel chromatography (100% dichloromethane→94% dichloromethane/methanol)

Sources & evidence

ORD record
ord-4f6ecab90bd340a3a4d5e6f225d3adab
Source dataset
uspto-grants-2011_10
Patent number
US08039460B2

Reaction notes

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