Sodium hydride → HCID 86287822, compound

HRID 633535Notes

Reaction equation

HRID 633535 reaction equation
[CH:1]1([CH2:6][CH2:7][OH:8])[CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].F[C:12]1[CH:17]=[CH:16][C:15]([S:18]([CH3:21])(=[O:20])=[O:19])=[CH:14][C:13]=1[C:22]1[C:30]2[C:25](=[C:26]([O:31]C)[N:27]=[CH:28][CH:29]=2)[N:24]([CH3:33])[CH:23]=1>O1CCCC1>[CH:1]1([CH2:6][CH2:7][O:8][C:12]2[CH:17]=[CH:16][C:15]([S:18]([CH3:21])(=[O:20])=[O:19])=[CH:14][C:13]=2[C:22]2[C:30]3[CH:29]=[CH:28][NH:27][C:26](=[O:31])[C:25]=3[N:24]([CH3:33])[CH:23]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 69833CyclopentaneethanolHCID 90416744HCID 90416744, compound

Product 1

HCID 86287822HCID 86287822, compoundYield 40.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

2-cyclopentylethanol (0.137 g, 1.196 mmol) in tetrahydrofuran (5 mL) was treated with NaH (0.029 g, 1.196 mmol) at ambient temperature, stirred for 5 minutes and treated with the product from Example 17C (0.1 g, 0.299 mmol). The reaction mixture was heated at 60° C. for 12 hours and partitioned with ethyl acetate and water. The organic layer was washed with saturated aqueous sodium chloride, dried (anhydrous Na2SO4), filtered, and concentrated. The resulting residue (0.15 g) was treated with 4 M HCl in dioxane (15 mL), heated at 70° C. for 12 hours, cooled, concentrated and the residue was purified by reverse phase HPLC (C18, CH3CN/water (0.1% TFA), 10-100%) to give the title compound (0.05 g, 0.121 mmol, 34.5%). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.96 (d, J=5.0 Hz, 1H), 7.84 (d, J=2.4 Hz, 1H), 7.79 (dd, J=8.7, 2.4 Hz, 1H), 7.57 (s, 1H), 7.33 (d, J=8.7 Hz, 1H), 6.94-6.86 (m, 1H), 6.42 (d, J=6.5 Hz, 1H), 4.31-3.99 (m, 5H), 3.20 (s, 3H), 1.85 (dd, J=14.6, 7.3 Hz, 1H), 1.79-1.63 (m, 4H), 1.62-1.39 (m, 4H), 1.11 (dd, J=12.0, 7.9 Hz, 2H). MS (ESI+) m/z 415.1 (M+H)+.

Workup

  1. custompartitioned with ethyl acetate and water
  2. washThe organic layer was washed with saturated aqueous sodium chloride
  3. dry with materialdried (anhydrous Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. additionThe resulting residue (0.15 g) was treated with 4 M HCl in dioxane (15 mL)
  7. temperatureheated at 70° C. for 12 hours
  8. temperaturecooled
  9. concentrationconcentrated
  10. customthe residue was purified by reverse phase HPLC (C18, CH3CN/water (0.1% TFA), 10-100%)

Sources & evidence

ORD record
ord-1a961ca2d322488aa573db0aa626c98e
Source dataset
uspto-grants-2016_04
Patent number
US09321764B2

Reaction notes

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