Sodium hydride → HCID 46909349, compound

HRID 1183208Notes

Reaction equation

HRID 1183208 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+].[F:28][CH2:29][CH2:30]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][CH2:30][CH2:29][F:28])=[CH:17][CH:16]=2)=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 69804Ethane, 1-fluoro-2-iodo-HCID 46909255HCID 46909255, compound2×

Product 1

HCID 46909349HCID 46909349, 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]methano 1 (product of Example 23, 20 mg, 0.054 mmol) was dissolved in DMF (1 mL), to which was added NaH (0.25 mmol) and 1-fluoro-2-iodoethane (0.25 mmol) at 0° C. The reaction was warmed to rt and then heated at 55° C. for 2 hours. After it was cooled t rt, 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 (40-100% EtOAc in hexanes) to afford the title compound. 1H NMR (500 MHz, (CDCl3): 9.83 (s, 1H), 8.38 (s, 1H), 7.88 (d, 2H), 7.63 (d, 1H), 7.19 (d, 1H), 7.18 (d, 2H), 4.63 (m, 1H), 4.58 (m, 1H), 4.02 (s, 3H), 3.76 (m, 1H), 4.71 (m, 1H), 3.57 (d, 2H), 1.85 (m, 1H), 1.46 (m, 1H), 1.03 (m, 2H). LCMS: m/z 418 (M+H)+. Human FAAH lysate assay: IC50=69.3 nM.

Workup

  1. temperatureheated at 55° C. for 2 hours
  2. temperatureAfter it was cooled t rt
  3. customthe reaction was quenched with 1 mL of aqueous NH4Cl
  4. additiondiluted with 5 mL of EtOAc
  5. washThe mixture was washed with water (two times) and brine
  6. customThe organic layer was dried
  7. concentrationconcentrated
  8. customto give the crude product that
  9. customwas purified by column (40-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-6cb04f4d8a01445498c377c2ba4a3e6f
Source dataset
uspto-grants-2014_03
Patent number
US08664253B2

Reaction notes

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