Sodium hydride → 12-Methoxy-4-(2-propan-2-yl-1,2,4-triazol-3-yl)-9-oxa-3,6,13-triazatricyclo[8.4.0.02,6]tetradeca-1(14),2,4,10,12-pentaene

HRID 2044329Notes

Reaction equation

HRID 2044329 reaction equation
Cl[C:2]1[CH:7]=[C:6]([O:8][CH3:9])[N:5]=[CH:4][C:3]=1[C:10]1[N:11]([CH2:23][CH2:24][OH:25])[CH:12]=[C:13]([C:15]2[N:16]([CH:20]([CH3:22])[CH3:21])[N:17]=[CH:18][N:19]=2)[N:14]=1.[H-].[Na+]>CN(C=O)C>[CH:20]([N:16]1[C:15]([C:13]2[N:14]=[C:10]3[N:11]([CH2:23][CH2:24][O:25][C:2]4[CH:7]=[C:6]([O:8][CH3:9])[N:5]=[CH:4][C:3]=43)[CH:12]=2)=[N:19][CH:18]=[N:17]1)([CH3:22])[CH3:21]

Participants

4

Reactant 2

HCID 24758Sodium hydride2×HCID 582047142-[2-(4-Chloro-6-methoxy-pyridin-3-yl)-4-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-imidazol-1-yl]-ethanol

Product 1

HCID 5820487112-Methoxy-4-(2-propan-2-yl-1,2,4-triazol-3-yl)-9-oxa-3,6,13-triazatricyclo[8.4.0.02,6]tetradeca-1(14),2,4,10,12-pentaeneYield 79.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 2-[2-(4-chloro-6-methoxy-pyridin-3-yl)-4-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-imidazol-1-yl]-ethanol (7.52 g, 20.7 mmol) in DMF (100 mL) was cooled to 0° C. and treated with sodium hydride (804 mg, 20.1 mmol), the reaction mixture stirred at 0° C. for 10 min then allowed to warm to RT and stirred for 72 h. Further sodium hydride (150 mg) was added and stirring continued until no starting material remained before removal of solvent in vacuo. The residue was dissolved in ethyl acetate and the resultant solution washed three times with saturated brine then dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was triturated in pentane/diethyl ether (5:1) to give the title compound as a brown solid (5.38 g, 79%). LCMS RT=2.86, [M+H]+=327. 1H NMR 400 MHz (CDCl3) δ: 9.35 (1H, s), 7.87 (1H, s), 7.63 (1H, s), 6.37 (1H, s), 6.03-6.02 (1H, m), 4.54-4.53 (2H, m), 4.53-4.33 (2H, m), 3.99 (3H, s), 1.57 (6H, d, J=6.63 Hz).

Workup

  1. temperatureto warm to RT
  2. stirringstirred for 72 h
  3. stirringstirring
  4. customremained before removal of solvent in vacuo
  5. dissolutionThe residue was dissolved in ethyl acetate
  6. washthe resultant solution washed three times with saturated brine
  7. dry with materialthen dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe resultant residue was triturated in pentane/diethyl ether (5:1)

Sources & evidence

ORD record
ord-52abfb3ba12d48cd8542cb1ab142e3db
Source dataset
uspto-grants-2013_11
Patent number
US08586574B2

Reaction notes

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