Methyl iodide → HCID 46909256, compound

HRID 1183207Notes

Reaction equation

HRID 1183207 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([S:8][C:9]2[N:13]([CH3:14])[CH:12]=[N:11][C:10]=2[C:15]2[CH:20]=[CH:19][C:18]([C@H:21]3[CH2:23][C@@H:22]3[CH2:24][OH:25])=[CH:17][CH:16]=2)=[N:6][CH:7]=1.[H-].[Na+].[CH3:28]I>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([S:8][C:9]2[N:13]([CH3:14])[CH:12]=[N:11][C:10]=2[C:15]2[CH:20]=[CH:19][C:18]([C@H:21]3[CH2:23][C@@H:22]3[CH2:24][O:25][CH3:28])=[CH:17][CH:16]=2)=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 46909255HCID 46909255, compound2×

Product 1

HCID 46909256HCID 46909256, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

[(1S,2S)-2-(4-{5-[(5-Chloropyridin-2-yl)thio]-1-methyl-1H-imidazol-4-yl}phenyl)cyclopropyl]methanol (product of Example 23, 20 mg, 0.054 mmol) was dissolved in DMF (1 mL), to which was added NaH (0.25 mmol) and MeI (0.25 mmol) at 0° C. The reaction was warmed to rt and stirred for 30 min. The reaction was quenched with 1 mL of aqueous NH4Cl and diluted with 5 mL of EtOAc. The mixture was washed with water (two times) and brine. The organic layer was dried and concentrated to give the crude product that was purified by column (60-100% EtOAc in hexanes) to afford the title compound. 1H NMR (500 MHz, (CDCl3): 9.82 (s, 1H), 8.37 (s, 1H), 7.88 (d, 2H), 7.58 (d, 1H), 7.15 (d, 2H), 7.07 (d, 1H), 3.97 (s, 3H), 3.42 (d, 2H), 3.39 (s, 3H), 1.82 (m, 1H), 1.44 (m, 1H), 0.99 (m, 2H). LCMS: m/z 386 (M+H)+. Human FAAH lysate assay: IC50=35.5 nM.

Workup

  1. customThe reaction was quenched with 1 mL of aqueous NH4Cl
  2. additiondiluted with 5 mL of EtOAc
  3. washThe mixture was washed with water (two times) and brine
  4. customThe organic layer was dried
  5. concentrationconcentrated
  6. customto give the crude product that
  7. customwas purified by column (60-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-b43867efe3f04c19a57c5bebd46a5d1d
Source dataset
uspto-grants-2014_03
Patent number
US08664253B2

Reaction notes

Loading…