Aluminium lithium hydride → HCID 46909255, compound

HRID 1183206Notes

Reaction equation

HRID 1183206 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[C:24](OCC)=[O:25])=[CH:17][CH:16]=2)=[N:6][CH:7]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[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

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 86664899HCID 86664899, compound

Product 1

HCID 46909255HCID 46909255, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

The product of Step 1 (150 mg, 0.362 mmol) was dissolved in THF (2 mL), to which was added 100 mg of LAH (2.63 mmol) at 0° C. The reaction was stirred at 0° C. for 10 min and was quenched by Fischer work up: careful successive dropwise addition of 0.1 mL of water, 0.1 mL of 15% NaOH solution, and 0.3 mL of water provided a granular inorganic precipitate that was easy to rinse and filter. The granular precipitate was filtered and washed with EtOAc. The combined organic solution was concentrated to give the crude product that was purified by column (95-100% EtOAc in hexanes) to afford the title compound. 1H NMR (500 MHz, (CDCl3): 8.39 (s, 1H), 8.05 (s, 1H), 7.86 (d, 2H), 7.48 (d, 1H), 7.06 (d, 2H), 6.81 (d, 1H), 3.67 (s, 3H), 3.61 (d, 2H), 3.02 (broad s, 1H), 1.83 (m, 1H), 1.45 (m, 1H), 0.97 (m, 2H). LCMS: m/z 372 (M+H)+. Human FAAH lysate assay: IC50=88.4 nM.

Workup

  1. customwas quenched by Fischer work up
  2. additioncareful successive dropwise addition of 0.1 mL of water, 0.1 mL of 15% NaOH solution, and 0.3 mL of water
  3. customprovided a granular inorganic precipitate that
  4. washto rinse
  5. filtrationfilter
  6. filtrationThe granular precipitate was filtered
  7. washwashed with EtOAc
  8. concentrationThe combined organic solution was concentrated
  9. customto give the crude product that
  10. customwas purified by column (95-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-c84de86a44274c2b9cc474e3c86af74d
Source dataset
uspto-grants-2014_03
Patent number
US08664253B2

Reaction notes

Loading…