Triethylamine → 3,3'-(6-(4-Nitrophenyl)pyrimidine-2,4-diyl)bis(8-oxa-3-azabicyclo[3.2.1]octane)

HRID 75420Notes

Reaction equation

HRID 75420 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:14][CH:13]3[O:15][CH:10]([CH2:11][CH2:12]3)[CH2:9]2)[CH:5]=[C:4]([C:16]2[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][CH:17]=2)[N:3]=1.Cl.[CH:26]12[O:33][CH:30]([CH2:31][CH2:32]1)[CH2:29][NH:28][CH2:27]2.C(N(CC)CC)C.CCN(C(C)C)C(C)C>O1CCOCC1.C(OCC)(=O)C>[N+:22]([C:19]1[CH:20]=[CH:21][C:16]([C:4]2[N:3]=[C:2]([N:28]3[CH2:27][CH:26]4[O:33][CH:30]([CH2:31][CH2:32]4)[CH2:29]3)[N:7]=[C:6]([N:8]3[CH2:14][CH:13]4[O:15][CH:10]([CH2:11][CH2:12]4)[CH2:9]3)[CH:5]=2)=[CH:17][CH:18]=1)([O-:24])=[O:23]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 81531DiisopropylethylamineHCID 219835368-Oxa-3-aza-bicyclo(3.2.1)octane hydrochlorideHCID 866658853-[2-Chloro-6-(4-nitro-phenyl)-pyrimidin-4-yl]-8-oxa-3-aza-bicyclo[3.2.1]octane

Product 1

HCID 667505783,3'-(6-(4-Nitrophenyl)pyrimidine-2,4-diyl)bis(8-oxa-3-azabicyclo[3.2.1]octane)Yield 65.6%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

In a 100 mL round-bottomed flask was placed 3-[2-chloro-6-(4-nitro-phenyl)-pyrimidin-4-yl]-8-oxa-3-aza-bicyclo[3.2.1]octane (14, 110 mg, 0.32 mmol) in dioxane (5 ml). 8-Oxa-3-azabicyclo[3.2.1]octane, HCl (2, 0.15 g, 1 mmol) and triethylamine (0.28 ml, 2 mmol) were added. The mixture was stirred at 80° C. for 16 hours. DIPEA was added (0.3 mL) and stirring was continued at 80° C. for 64 hours. The reaction mixture was diluted with ethyl acetate and washed with sat NaHCO3. The solids between the organic phase and aqueous phase were dissolved in dichloromethane and washed with saturated NaHCO3. The combined organic phases were dried over MgSO4, filtered and concentrated. The crude product was added to a silica gel column and eluted with ethyl acetate in hexanes (10-40%) to give 89 mg of the title compound (0.21 mmol, 65%).

Workup

  1. customIn a 100 mL round-bottomed flask was placed
  2. stirringstirring
  3. waitwas continued at 80° C. for 64 hours
  4. washwashed
  5. dissolutionThe solids between the organic phase and aqueous phase were dissolved in dichloromethane
  6. washwashed with saturated NaHCO3
  7. dry with materialThe combined organic phases were dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. additionThe crude product was added to a silica gel column
  11. washeluted with ethyl acetate in hexanes (10-40%)

Sources & evidence

ORD record
ord-292e77abc6154e66ae006f41fa33b129
Source dataset
uspto-grants-2014_09
Patent number
US08835429B2

Reaction notes

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